TY - JOUR T1 - Altered expression of miR-181a and miR-146a does not change the expression of surface NCRs in human NK cells. AN - 1863698278; 28145491 AB - MicroRNAs (miRNAs) play an important role in regulating gene expression and immune responses. Of interest, miR-181a and miR-146a are key players in regulating immune responses and are among the most abundant miRNAs expressed in NK cells. Bioinformatically, we predicted miR-181a to regulate the expression of the natural cytotoxicity receptor NCR2 by seeded interaction with the 3'-untranslated region (3'-UTR). Whereas, miR-146a expression was not significantly different (P = 0.7361), miR-181a expression was, on average 10-fold lower in NK cells from breast cancer patients compared to normal subjects; P < 0.0001. Surface expression of NCR2 was detected in NK cells from breast cancer patients (P = 0.0384). While cytokine receptor-induced NK cell activation triggered overexpression of miR-146a when stimulated with IL-2 (P = 0.0039), IL-15 (P = 0.0078), and IL-12/IL-18 (P = 0.0072), expression of miR-181a was not affected. Overexpression or knockdown of miR-181a or miR-146a in primary cultured human NK cells did not affect the level of expression of any of the three NCRs; NCR1, NCR2 or NCR3 or NK cell cytotoxicity. Expression of miR-181a and miR-146a did not correlate to the expression of the NCRs in NK cells from breast cancer patients or cytokine-stimulated NK cells from healthy subjects. JF - Scientific reports AU - Rady, Mona AU - Watzl, Carsten AU - Claus, Maren AU - Khorshid, Ola AU - Mahran, Laila AU - Abou-Aisha, Khaled AD - Microbiology and Immunology Department, German University in Cairo (GUC), New Cairo, Egypt. ; Immunology Department, Leibniz Research Center for Working Environment and Human Factors (IfADo), Dortmund, Germany. ; Medical Oncology Department, National Cancer Institute (NCI), Cairo, Egypt. ; Pharmacology and Toxicology Department, German University in Cairo (GUC), New Cairo, Egypt. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 SP - 41381 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1863698278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Altered+expression+of+miR-181a+and+miR-146a+does+not+change+the+expression+of+surface+NCRs+in+human+NK+cells.&rft.au=Rady%2C+Mona%3BWatzl%2C+Carsten%3BClaus%2C+Maren%3BKhorshid%2C+Ola%3BMahran%2C+Laila%3BAbou-Aisha%2C+Khaled&rft.aulast=Rady&rft.aufirst=Mona&rft.date=2017-02-01&rft.volume=7&rft.issue=&rft.spage=41381&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep41381 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-02-01 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1038/srep41381 ER - TY - JOUR T1 - Veterans' Location in Health Professional Shortage Areas: Implications for Access to Care and Workforce Supply AN - 1862136670 AB - Objective To describe the distribution of Veterans in areas of the United States where there are potentially inadequate supplies of health professionals, and to explore opportunities suggested by this distribution for fostering health workforce flexibility. Data Sources County-level data from the 2015-2016 Health Resources and Services Administration's (HRSA's) Area Health Resources Files (AHRF) were used to estimate Veteran populations in HRSA-designated health professional shortage areas (HPSAs). This information was then linked to 2015 VA health facility information from the Department of Veterans Affairs. Study Design Potential Veteran populations living in Shortage Area Counties with no VHA facilities were estimated, and the composition of these populations was explored by Census division and state. Principal Findings Nationwide, approximately 24 percent of all Veterans and 23 percent of Veterans enrolled in VHA health care live in Shortage Area Counties. These estimates mask considerable variation across states. Conclusions An examination of Veterans residing in Shortage Area Counties suggests extensive maldistribution of health services across the United States and the continued need to find ways to improve health care access for all Veterans. Effective avenues for doing so may include increasing health workforce flexibility through expansion of nurse practitioner scopes of practice. JF - Health Services Research AU - Doyle, Jamie Mihoko AU - Streeter, Robin A AD - Office of Extramural Research, Office of the Director, National Institutes of Health, Bethesda, MD; National Center for Health Workforce Analysis, Health Resources and Services Administration, Rockville, MD ; National Center for Health Workforce Analysis, Health Resources and Services Administration, Rockville, MD ; Office of Extramural Research, Office of the Director, National Institutes of Health, Bethesda, MD; National Center for Health Workforce Analysis, Health Resources and Services Administration, Rockville, MD Y1 - 2017/02// PY - 2017 DA - Feb 2017 SP - 459 EP - 480 CY - Chicago PB - Wiley Subscription Services, Inc. VL - 52 IS - S1 SN - 0017-9124 KW - Medical Sciences KW - Veterans KW - Labour force KW - Composition KW - Service provision KW - Flexibility KW - Census KW - Health services KW - Occupational health and safety KW - Health professionals KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1862136670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Services+Research&rft.atitle=Veterans%27+Location+in+Health+Professional+Shortage+Areas%3A+Implications+for+Access+to+Care+and+Workforce+Supply&rft.au=Doyle%2C+Jamie+Mihoko%3BStreeter%2C+Robin+A&rft.aulast=Doyle&rft.aufirst=Jamie&rft.date=2017-02-01&rft.volume=52&rft.issue=S1&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Health+Services+Research&rft.issn=00179124&rft_id=info:doi/10.1111%2F1475-6773.12633 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © Health Research and Educational Trust N1 - Last updated - 2017-01-27 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1111/1475-6773.12633 ER - TY - JOUR T1 - Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations. AN - 1859715278; 27517672 AB - The current single-chemical-as-carcinogen risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that may be affecting crucial cancer hallmark mechanisms that serve to enable carcinogenesis. Could ongoing low-dose exposures to a mixture of commonly encountered environmental chemicals produce effects in concert that lead to carcinogenesis? A workshop held at the NIEHS in August 2015 evaluated the scientific support for the low-dose mixture hypothesis of carcinogenesis and developed a research agenda. Here we describe the science that supports this novel theory, identify knowledge gaps, recommend future methodologies, and explore preventative risk assessment and policy decision-making that incorporates cancer biology, environmental health science, translational toxicology, and clinical epidemiology. The theoretical merits of the low-dose carcinogenesis hypothesis are well founded with clear biological relevance, and therefore, the premise warrants further investigation. Expert recommendations include the need for better insights into the ways in which noncarcinogenic constituents might combine to uniquely affect the process of cellular transformation (in vitro) and environmental carcinogenesis (in vivo), including investigations of the role of key defense mechanisms in maintaining transformed cells in a dormant state. The scientific community will need to acknowledge limitations of animal-based models in predicting human responses; evaluate biological events leading to carcinogenesis both spatially and temporally; examine the overlap between measurable cancer hallmarks and characteristics of carcinogens; incorporate epigenetic biomarkers, in silico modelling, high-performance computing and high-resolution imaging, microbiome, metabolomics, and transcriptomics into future research efforts; and build molecular annotations of network perturbations. The restructuring of many existing regulatory frameworks will require adequate testing of relevant environmental mixtures to build a critical mass of evidence on which to base policy decisions. Citation: Miller MF, Goodson WH III, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L. 2017. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: scientific underpinnings and research recommendations. Environ Health Perspect 125:163-169; http://dx.doi.org/10.1289/EHP411. JF - Environmental health perspectives AU - Miller, Mark F AU - Goodson, William H AU - Manjili, Masoud H AU - Kleinstreuer, Nicole AU - Bisson, William H AU - Lowe, Leroy AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 163 EP - 169 VL - 125 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859715278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Low-Dose+Mixture+Hypothesis+of+Carcinogenesis+Workshop%3A+Scientific+Underpinnings+and+Research+Recommendations.&rft.au=Miller%2C+Mark+F%3BGoodson%2C+William+H%3BManjili%2C+Masoud+H%3BKleinstreuer%2C+Nicole%3BBisson%2C+William+H%3BLowe%2C+Leroy&rft.aulast=Miller&rft.aufirst=Mark&rft.date=2017-02-01&rft.volume=125&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP411 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-12 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1289/EHP411 ER - TY - JOUR T1 - Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study AN - 1859498030; PQ0004014291 AB - Purpose Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. Materials and Methods Five radiologists (n=2 prostate dedicated, n=3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy whole-mount histopathology produced with patient-specific three-dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. Results Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS greater than or equal to 3 and 90% for PIRADS greater than or equal to 4. Specialists performed better only for PIRADS greater than or equal to 4 with sensitivity 90% versus 79% (P=0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. Conclusion By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. Level of Evidence: 1 J. Magn. Reson. Imaging 2017; 45:579-585. JF - Journal of Magnetic Resonance Imaging AU - Greer, Matthew D AU - Brown, Anna M AU - Shih, Joanna H AU - Summers, Ronald M AU - Marko, Jamie AU - Law, Yan Mee AU - Sankineni, Sandeep AU - George, Arvin K AU - Merino, Maria J AU - Pinto, Peter A AU - Choyke, Peter L AU - Turkbey, Baris AD - Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 579 EP - 585 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 45 IS - 2 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859498030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Magnetic+Resonance+Imaging&rft.atitle=Accuracy+and+agreement+of+PIRADSv2+for+prostate+cancer+mpMRI%3A+A+multireader+study&rft.au=Greer%2C+Matthew+D%3BBrown%2C+Anna+M%3BShih%2C+Joanna+H%3BSummers%2C+Ronald+M%3BMarko%2C+Jamie%3BLaw%2C+Yan+Mee%3BSankineni%2C+Sandeep%3BGeorge%2C+Arvin+K%3BMerino%2C+Maria+J%3BPinto%2C+Peter+A%3BChoyke%2C+Peter+L%3BTurkbey%2C+Baris&rft.aulast=Greer&rft.aufirst=Matthew&rft.date=2017-02-01&rft.volume=45&rft.issue=2&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.25372 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/jmri.25372 ER - TY - JOUR T1 - Undernutrition as independent predictor of early mortality in elderly cancer patients AN - 1859484149; PQ0004015752 AB - Objectives The aim of this study was to evaluate the 1-y survival of elderly patients with cancer and the association between undernutrition and mortality. Methods This was a cohort study with elderly patients ages greater than or equal to 65 y admitted between September and October 2014. A nutritionist performed a Mini Nutritional Assessment-Short Form (MNA-SF) assessment during 48 h of hospital admission and collected data about potential confounding variables (comorbidities, stage of cancer, treatment in the previous 3 mo, and reason for hospitalization). Vital status was determined from the medical records or public records office. Overall survival was estimated using the Kaplan-Meier method. Cox regression was performed to estimate unadjusted hazard ratios. Variables with P < 0.20 by univariate analysis were selected for multivariate analysis. P < 0.05 was considered statistically significant. Results Of the 136 patients (mean age, 73.1 y; 52.2% men), 29.4%, 41.2%, and 29.4% were classified as normal, at risk for undernutrition, and undernutrition, respectively, according to the MNA-SF. The mortality rate was 31.6% after 12 mo. One-year mortality was higher among the undernourished patients, followed by patients at risk for undernutrition. After adjustment for confounding variables, the multivariate regression Cox model showed that being undernourished according to the MNA-SF increased the risk for death at 1 y (hazard ratio, 5.59; 95% confidence interval, 1.8-17.3; P < 0.001). Conclusion The results showed that the MNA-SF can be a useful tool in identifying elderly patients at higher risk for 1-y mortality. JF - Nutrition AU - Martucci, Renata B AU - Barbosa, Mariana V AU - D'Almeida, Cristiane A AU - Rodrigues, Viviane D AU - Bergmann, Anke AU - de Pinho, Nivaldo B AU - Thuler, Luiz Claudio S AD - Nutrition and Dietetic Service, Cancer Hospital Unit I, National Cancer Institute Jose Alencar Gomes da Silva, Rio de Janeiro, Brazil Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 65 EP - 70 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 34 SN - 0899-9007, 0899-9007 KW - Toxicology Abstracts KW - Cancer KW - Aging KW - Survival KW - Nutrition assessment KW - Undernutrition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859484149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition&rft.atitle=Undernutrition+as+independent+predictor+of+early+mortality+in+elderly+cancer+patients&rft.au=Martucci%2C+Renata+B%3BBarbosa%2C+Mariana+V%3BD%27Almeida%2C+Cristiane+A%3BRodrigues%2C+Viviane+D%3BBergmann%2C+Anke%3Bde+Pinho%2C+Nivaldo+B%3BThuler%2C+Luiz+Claudio+S&rft.aulast=Martucci&rft.aufirst=Renata&rft.date=2017-02-01&rft.volume=34&rft.issue=&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Nutrition&rft.issn=08999007&rft_id=info:doi/10.1016%2Fj.nut.2016.09.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 21 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1016/j.nut.2016.09.011 ER - TY - JOUR T1 - CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit. AN - 1858107709; 27534267 AB - Because of unavoidable confounding variables in the direct study of human subjects, it has been difficult to unravel the effects of prenatal cocaine exposure on the human fetal brain, as well as the cellular and biochemical mechanisms involved. Here, we propose a novel approach using a human pluripotent stem cell (hPSC)-based 3D neocortical organoid model. This model retains essential features of human neocortical development by encompassing a single self-organized neocortical structure, without including an animal-derived gelatinous matrix. We reported previously that prenatal cocaine exposure to rats during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex. We also identified a role of CYP450 and consequent oxidative ER stress signaling in these effects. However, because of differences between humans and rodents in neocorticogenesis and brain CYP metabolism, translation of the research findings from the rodent model to human brain development is uncertain. Using hPSC 3D neocortical organoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation of reactive oxygen species, inhibition of neocortical progenitor cell proliferation, induction of premature neuronal differentiation, and interruption of neural tissue development. Furthermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3A5 as a therapeutic target to mitigate the deleterious neurodevelopmental effects of prenatal cocaine exposure in humans. Moreover, 3D organoid methodology provides an innovative platform for identifying adverse effects of abused psychostimulants and pharmaceutical agents, and can be adapted for use in neurodevelopmental disorders with genetic etiologies. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Lee, Chun-Ting AU - Chen, Jia AU - Kindberg, Abigail A AU - Bendriem, Raphael M AU - Spivak, Charles E AU - Williams, Melanie P AU - Richie, Christopher T AU - Handreck, Annelie AU - Mallon, Barbara S AU - Lupica, Carl R AU - Lin, Da-Ting AU - Harvey, Brandon K AU - Mash, Deborah C AU - Freed, William J AD - Intramural Research Program (IRP), National Institute on Drug Abuse, National Institutes of Health (NIH), Baltimore, MD, USA. ; Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany. ; NIH Stem Cell Unit, IRP, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. ; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 774 EP - 784 VL - 42 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858107709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=CYP3A5+Mediates+Effects+of+Cocaine+on+Human+Neocorticogenesis%3A+Studies+using+an+In+Vitro+3D+Self-Organized+hPSC+Model+with+a+Single+Cortex-Like+Unit.&rft.au=Lee%2C+Chun-Ting%3BChen%2C+Jia%3BKindberg%2C+Abigail+A%3BBendriem%2C+Raphael+M%3BSpivak%2C+Charles+E%3BWilliams%2C+Melanie+P%3BRichie%2C+Christopher+T%3BHandreck%2C+Annelie%3BMallon%2C+Barbara+S%3BLupica%2C+Carl+R%3BLin%2C+Da-Ting%3BHarvey%2C+Brandon+K%3BMash%2C+Deborah+C%3BFreed%2C+William+J&rft.aulast=Lee&rft.aufirst=Chun-Ting&rft.date=2017-02-01&rft.volume=42&rft.issue=3&rft.spage=774&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=1740-634X&rft_id=info:doi/10.1038%2Fnpp.2016.156 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/npp.2016.156 ER - TY - JOUR T1 - CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction. AN - 1858106672; 27534265 AB - Agonist-replacement therapies have been successfully used for treatment of opiate and nicotine addiction, but not for cocaine addiction. One of the major obstacles is the cocaine-like addictive potential of the agonists themselves. We report here an atypical dopamine (DA) transporter (DAT) inhibitor, CTDP-32476, that may have translational potential for treating cocaine addiction. In vitro ligand-binding assays suggest that CTDP-32476 is a potent and selective DAT inhibitor and a competitive inhibitor of cocaine binding to the DAT. Systemic administration of CTDP-32476 alone produced a slow-onset, long-lasting increase in extracellular nucleus accumbens DA, locomotion, and brain-stimulation reward. Drug-naive rats did not self-administer CTDP-32476. In a substitution test, cocaine self-administration rats displayed a progressive reduction in CTDP-32476 self-administration with an extinction pattern of drug-taking behavior, suggesting significantly lower addictive potential than cocaine. Pretreatment with CTDP-32476 inhibited cocaine self-administration, cocaine-associated cue-induced relapse to drug seeking, and cocaine-enhanced extracellular DA in the nucleus accumbens. These findings suggest that CTDP-32476 is a unique DAT inhibitor that not only could satisfy 'drug hunger' through its slow-onset long-lasting DAT inhibitor action, but also render subsequent administration of cocaine ineffectual-thus constituting a novel and unique compound with translational potential as an agonist therapy for treatment of cocaine addiction. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Xi, Zheng-Xiong AU - Song, Rui AU - Li, Xia AU - Lu, Guan-Yi AU - Peng, Xiao-Qing AU - He, Yi AU - Bi, Guo-Hua AU - Sheng, Siyuan Peter AU - Yang, Hong-Ju AU - Zhang, Haiying AU - Li, Jin AU - Froimowitz, Mark AU - Gardner, Eliot L AD - Neuropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA. ; State Key Laboratory of Toxicology and Medical Countermeasures and Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China. ; Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA. ; Department of Behavioral Health, Saint Elizabeth's Hospital, Washington, DC, USA. ; Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 682 EP - 694 VL - 42 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858106672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=CTDP-32476%3A+A+Promising+Agonist+Therapy+for+Treatment+of+Cocaine+Addiction.&rft.au=Xi%2C+Zheng-Xiong%3BSong%2C+Rui%3BLi%2C+Xia%3BLu%2C+Guan-Yi%3BPeng%2C+Xiao-Qing%3BHe%2C+Yi%3BBi%2C+Guo-Hua%3BSheng%2C+Siyuan+Peter%3BYang%2C+Hong-Ju%3BZhang%2C+Haiying%3BLi%2C+Jin%3BFroimowitz%2C+Mark%3BGardner%2C+Eliot+L&rft.aulast=Xi&rft.aufirst=Zheng-Xiong&rft.date=2017-02-01&rft.volume=42&rft.issue=3&rft.spage=682&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=1740-634X&rft_id=info:doi/10.1038%2Fnpp.2016.155 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/npp.2016.155 ER - TY - JOUR T1 - Sample size calculations for prevalent cohort designs AN - 1856453265 AB - Cross-sectional prevalent cohort design has drawn considerable interests in the studies of association between risk factors and time-to-event outcome. The sampling scheme in such design gives rise to length-biased data that require specialized analysis strategy but can improve study efficiency. The power and sample size calculation methods are however lacking for studies with prevalent cohort design, and using the formula developed for traditional survival data may overestimate sample size. We derive the sample size formulas that are appropriate for the design of cross-sectional prevalent cohort studies, under the assumptions of exponentially distributed event time and uniform follow-up for cross-sectional prevalent cohort design. We perform numerical and simulation studies to compare the sample size requirements for achieving the same power between prevalent cohort and incident cohort designs. We also use a large prospective prevalent cohort study to demonstrate the procedure. Using rigorous designs and proper analysis tools, the prospective prevalent cohort design can be more efficient than the incident cohort design with the same total sample sizes and study durations. JF - Statistical Methods in Medical Research AU - Liu, Hao AU - Shen, Yu AU - Ning, Jing AU - Qin, Jing AD - Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA ; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA ; Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA Y1 - 2017/02// PY - 2017 DA - Feb 2017 SP - 280 EP - 291 CY - London PB - Sage Publications Ltd. VL - 26 IS - 1 SN - 0962-2802 KW - Medical Sciences KW - incident cohort design KW - length-biased data KW - prevalent cohort design KW - sample size determination KW - survival data KW - Power KW - Cohort analysis KW - Uniforms KW - Risk factors KW - Sampling KW - Simulation KW - Bias UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856453265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistical+Methods+in+Medical+Research&rft.atitle=Sample+size+calculations+for+prevalent+cohort+designs&rft.au=Liu%2C+Hao%3BShen%2C+Yu%3BNing%2C+Jing%3BQin%2C+Jing&rft.aulast=Liu&rft.aufirst=Hao&rft.date=2017-02-01&rft.volume=26&rft.issue=1&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Statistical+Methods+in+Medical+Research&rft.issn=09622802&rft_id=info:doi/10.1177%2F0962280214544730 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2014 N1 - Last updated - 2017-01-16 DO - http://dx.doi.org/10.1177/0962280214544730 ER - TY - JOUR T1 - Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening AN - 1855077795; PQ0003949716 AB - More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Three human neuronal cell lines were evaluated as high throughput screening models for neuronal cytotoxicity: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells. After 7 days of differentiation, LUHMES expressed the highest levels of neuronal markers. Differentiated LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than differentiated SH-SY5Y or NSCs, and greater cytotoxic sensitivity to 11 compounds compared to undifferentiated LUHMES cells. JF - Journal of Applied Toxicology AU - Tong, Zhi-Bin AU - Hogberg, Helena AU - Kuo, David AU - Sakamuru, Srilatha AU - Xia, Menghang AU - Smirnova, Lena AU - Hartung, Thomas AU - Gerhold, David AD - National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 167 EP - 180 PB - Wiley Subscription Services, Inc., 1105 N Market St Wilmington DE 19801 VL - 37 IS - 2 SN - 0260-437X, 0260-437X KW - CSA Neurosciences Abstracts; Environment Abstracts; Toxicology Abstracts KW - Apoptosis KW - survivin KW - Parkinson's disease KW - Brain KW - Vincristine KW - Cell culture KW - Fetuses KW - Neurodegenerative diseases KW - Differentiation KW - Cytotoxicity KW - Movement disorders KW - Dopamine KW - Neurons KW - Neurotoxicity KW - Neuroblastoma cells KW - high-throughput screening KW - Colchicine KW - Neural stem cells KW - X 24310:Pharmaceuticals KW - N3 11028:Neuropharmacology & toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855077795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Toxicology&rft.atitle=Characterization+of+three+human+cell+line+models+for+high-throughput+neuronal+cytotoxicity+screening&rft.au=Tong%2C+Zhi-Bin%3BHogberg%2C+Helena%3BKuo%2C+David%3BSakamuru%2C+Srilatha%3BXia%2C+Menghang%3BSmirnova%2C+Lena%3BHartung%2C+Thomas%3BGerhold%2C+David&rft.aulast=Tong&rft.aufirst=Zhi-Bin&rft.date=2017-02-01&rft.volume=37&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Toxicology&rft.issn=0260437X&rft_id=info:doi/10.1002%2Fjat.3334 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Apoptosis; survivin; Parkinson's disease; Brain; Vincristine; Cell culture; Fetuses; Differentiation; Neurodegenerative diseases; Cytotoxicity; Dopamine; Movement disorders; Neurons; Neurotoxicity; Neuroblastoma cells; Colchicine; high-throughput screening; Neural stem cells DO - http://dx.doi.org/10.1002/jat.3334 ER - TY - JOUR T1 - Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions. AN - 1851290265; 27992790 AB - Human papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis. Our study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis. Women with normal cervix who were high-risk HPV-negative (N=104) and HPV-positive (N=105); women with CIN 1 (N=106) and CIN 2/CIN 3 (N=62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N=106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women. HPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp. The higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology AU - Ghosh, Ishita AU - Muwonge, Richard AU - Mittal, Srabani AU - Banerjee, Dipanwita AU - Kundu, Pratip AU - Mandal, Ranajit AU - Biswas, Jaydip AU - Basu, Partha AD - Chittaranjan National Cancer Institute, Kolkata, West Bengal, India. ; Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France. ; Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France. Electronic address: BasuP@iarc.fr. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 43 EP - 48 VL - 87 KW - Trichomonas vaginalis KW - Cervical intraepithelial neoplasia KW - Candida KW - Human papillomavirus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851290265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+virology+%3A+the+official+publication+of+the+Pan+American+Society+for+Clinical+Virology&rft.atitle=Association+between+high+risk+human+papillomavirus+infection+and+co-infection+with+Candida+spp.+and+Trichomonas+vaginalis+in+women+with+cervical+premalignant+and+malignant+lesions.&rft.au=Ghosh%2C+Ishita%3BMuwonge%2C+Richard%3BMittal%2C+Srabani%3BBanerjee%2C+Dipanwita%3BKundu%2C+Pratip%3BMandal%2C+Ranajit%3BBiswas%2C+Jaydip%3BBasu%2C+Partha&rft.aulast=Ghosh&rft.aufirst=Ishita&rft.date=2017-02-01&rft.volume=87&rft.issue=&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+virology+%3A+the+official+publication+of+the+Pan+American+Society+for+Clinical+Virology&rft.issn=1873-5967&rft_id=info:doi/10.1016%2Fj.jcv.2016.12.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-19 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.jcv.2016.12.007 ER - TY - JOUR T1 - Estimating population exposure to ambient polycyclic aromatic hydrocarbon in the United States - Part I: Model development and evaluation. AN - 1851288211; 27988136 AB - PAHs (polycyclic aromatic hydrocarbons) in the environment are of significant concern due to their negative impact on human health. PAH measurements at the air toxics monitoring network stations alone are not sufficient to provide a complete picture of ambient PAH levels or to allow accurate assessment of public exposure in the United States. In this study, speciation profiles for PAHs were prepared using data assembled from existing emission profile data bases, and the Sparse Matrix Operator Kernel Emissions (SMOKE) model was used to generate the gridded national emissions of 16 priority PAHs in the US. The estimated emissions were applied to simulate ambient concentration of PAHs for January, April, July and October 2011, using a modified Community Multiscale Air Quality (CMAQ) model (v5.0.1) that treats the gas and particle phase partitioning of PAHs and their reactions in the gas phase and on particle surface. Predicted daily PAH concentrations at 61 air toxics monitoring sites generally agreed with observations, and averaging the predictions over a month reduced the overall error. The best model performance was obtained at rural sites, with an average mean fractional bias (MFB) of -0.03 and mean fractional error (MFE) of 0.70. Concentrations at suburban and urban sites were underestimated with overall MFB=-0.57 and MFE=0.89. Predicted PAH concentrations were highest in January with better model performance (MFB=0.12, MFE=0.69; including all sites), and lowest in July with worse model performance (MFB=-0.90, MFE=1.08). Including heterogeneous reactions of several PAHs with O3 on particle surface reduced the over-prediction bias in winter, although significant uncertainties were expected due to relative simple treatment of the heterogeneous reactions in the current model. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Environment international AU - Zhang, Jie AU - Li, Jingyi AU - Wang, Peng AU - Chen, Gang AU - Mendola, Pauline AU - Sherman, Seth AU - Ying, Qi AD - Zachary Depart of Civil Engineering, Texas A&M University, College Station, TX 77845, United States. ; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD 20852, United States. ; The Emmes Corporation, Rockville, MD 20850, United States. ; Zachary Depart of Civil Engineering, Texas A&M University, College Station, TX 77845, United States. Electronic address: qying@civil.tamu.edu. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 263 EP - 274 VL - 99 KW - United States KW - Model performance KW - CMAQ KW - Speciation profiles KW - Exposure KW - SMOKE KW - PAH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851288211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+international&rft.atitle=Estimating+population+exposure+to+ambient+polycyclic+aromatic+hydrocarbon+in+the+United+States+-+Part+I%3A+Model+development+and+evaluation.&rft.au=Zhang%2C+Jie%3BLi%2C+Jingyi%3BWang%2C+Peng%3BChen%2C+Gang%3BMendola%2C+Pauline%3BSherman%2C+Seth%3BYing%2C+Qi&rft.aulast=Zhang&rft.aufirst=Jie&rft.date=2017-02-01&rft.volume=99&rft.issue=&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Environment+international&rft.issn=1873-6750&rft_id=info:doi/10.1016%2Fj.envint.2016.12.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-18 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1016/j.envint.2016.12.002 ER - TY - JOUR T1 - Harnessing molecular motors for nanoscale pulldown in live cells. AN - 1847889681; 27932498 AB - Protein-protein interactions (PPIs) regulate assembly of macromolecular complexes, yet remain challenging to study within the native cytoplasm where they normally exert their biological effect. Here we miniaturize the concept of affinity pulldown, a gold-standard in vitro PPI interrogation technique, to perform nanoscale pulldowns (NanoSPDs) within living cells. NanoSPD hijacks the normal process of intracellular trafficking by myosin motors to forcibly pull fluorescently tagged protein complexes along filopodial actin filaments. Using dual-color total internal reflection fluorescence microscopy, we demonstrate complex formation by showing that bait and prey molecules are simultaneously trafficked and actively concentrated into a nanoscopic volume at the tips of filopodia. The resulting molecular traffic jams at filopodial tips amplify fluorescence intensities and allow PPIs to be interrogated using standard epifluorescence microscopy. A rigorous quantification framework and software tool are provided to statistically evaluate NanoSPD data sets. We demonstrate the capabilities of NanoSPD for a range of nuclear and cytoplasmic PPIs implicated in human deafness, in addition to dissecting these interactions using domain mapping and mutagenesis experiments. The NanoSPD methodology is extensible for use with other fluorescent molecules, in addition to proteins, and the platform can be easily scaled for high-throughput applications. © 2017 Bird, Barzik, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). JF - Molecular biology of the cell AU - Bird, Jonathan E AU - Barzik, Melanie AU - Drummond, Meghan C AU - Sutton, Daniel C AU - Goodman, Spencer M AU - Morozko, Eva L AU - Cole, Stacey M AU - Boukhvalova, Alexandra K AU - Skidmore, Jennifer AU - Syam, Diana AU - Wilson, Elizabeth A AU - Fitzgerald, Tracy AU - Rehman, Atteeq U AU - Martin, Donna M AU - Boger, Erich T AU - Belyantseva, Inna A AU - Friedman, Thomas B AD - Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20814 jonathan.bird@nih.gov. ; Laboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20814. ; Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109. ; Mouse Auditory Testing Core Facility, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20814. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 SP - 463 EP - 475 VL - 28 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847889681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Harnessing+molecular+motors+for+nanoscale+pulldown+in+live+cells.&rft.au=Bird%2C+Jonathan+E%3BBarzik%2C+Melanie%3BDrummond%2C+Meghan+C%3BSutton%2C+Daniel+C%3BGoodman%2C+Spencer+M%3BMorozko%2C+Eva+L%3BCole%2C+Stacey+M%3BBoukhvalova%2C+Alexandra+K%3BSkidmore%2C+Jennifer%3BSyam%2C+Diana%3BWilson%2C+Elizabeth+A%3BFitzgerald%2C+Tracy%3BRehman%2C+Atteeq+U%3BMartin%2C+Donna+M%3BBoger%2C+Erich+T%3BBelyantseva%2C+Inna+A%3BFriedman%2C+Thomas+B&rft.aulast=Bird&rft.aufirst=Jonathan&rft.date=2017-02-01&rft.volume=28&rft.issue=3&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=1939-4586&rft_id=info:doi/10.1091%2Fmbc.E16-08-0583 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1091/mbc.E16-08-0583 ER - TY - JOUR T1 - Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons. AN - 1847889279; 27932496 AB - Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense, as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid β-peptide, hydrogen peroxide, and high levels of glutamate. Collectively our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons. © 2017 Yao et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). JF - Molecular biology of the cell AU - Yao, Pamela J AU - Manor, Uri AU - Petralia, Ronald S AU - Brose, Rebecca D AU - Wu, Ryan T Y AU - Ott, Carolyn AU - Wang, Ya-Xian AU - Charnoff, Ari AU - Lippincott-Schwartz, Jennifer AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. ; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. ; Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 SP - 387 EP - 395 VL - 28 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847889279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Sonic+hedgehog+pathway+activation+increases+mitochondrial+abundance+and+activity+in+hippocampal+neurons.&rft.au=Yao%2C+Pamela+J%3BManor%2C+Uri%3BPetralia%2C+Ronald+S%3BBrose%2C+Rebecca+D%3BWu%2C+Ryan+T+Y%3BOtt%2C+Carolyn%3BWang%2C+Ya-Xian%3BCharnoff%2C+Ari%3BLippincott-Schwartz%2C+Jennifer%3BMattson%2C+Mark+P&rft.aulast=Yao&rft.aufirst=Pamela&rft.date=2017-02-01&rft.volume=28&rft.issue=3&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=1939-4586&rft_id=info:doi/10.1091%2Fmbc.E16-07-0553 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1091/mbc.E16-07-0553 ER - TY - JOUR T1 - Effect of anxiety on behavioural pattern separation in humans AN - 1845245991 AB - Behavioural pattern separation (BPS), the ability to distinguish among similar stimuli based on subtle physical differences, has been used to study the mechanism underlying stimulus generalisation. Fear overgeneralisation is often observed in individuals with posttraumatic stress disorder and other anxiety disorders. However, the relationship between anxiety and BPS remains unclear. The purpose of this study was to determine the effect of anxiety (threat of shock) on BPS, which was assessed across separate encoding and retrieval sessions. Images were encoded/retrieved during blocks of threat or safety in a 2 × 2 factorial design. During retrieval, participants indicated whether images were new, old, or altered. Better accuracy was observed for altered images encoded during periods of threat compared to safety, but only if those images were also retrieved during periods of safety. These results suggest that overgeneralisation in anxiety may be due to altered pattern separation. JF - Cognition & Emotion AU - Balderston, Nicholas L AU - Mathur, Ambika AU - Adu-Brimpong, Joel AU - Hale, Elizabeth A AU - Ernst, Monique AU - Grillon, Christian AD - Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA ; Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Y1 - 2017/02// PY - 2017 DA - Feb 2017 SP - 238 EP - 248 CY - Hove PB - Taylor & Francis Ltd. VL - 31 IS - 2 SN - 0269-9931 KW - Psychology KW - Pattern separation KW - threat of shock KW - anxiety KW - startle KW - generalisation KW - Retrieval KW - Fear KW - Accuracy KW - Stimulus KW - Anxiety disorders KW - Encoding KW - Posttraumatic stress disorder KW - Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845245991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cognition+%26+Emotion&rft.atitle=Effect+of+anxiety+on+behavioural+pattern+separation+in+humans&rft.au=Balderston%2C+Nicholas+L%3BMathur%2C+Ambika%3BAdu-Brimpong%2C+Joel%3BHale%2C+Elizabeth+A%3BErnst%2C+Monique%3BGrillon%2C+Christian&rft.aulast=Balderston&rft.aufirst=Nicholas&rft.date=2017-02-01&rft.volume=31&rft.issue=2&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=Cognition+%26+Emotion&rft.issn=02699931&rft_id=info:doi/10.1080%2F02699931.2015.1096235 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1080/02699931.2015.1096235 ER - TY - JOUR T1 - Identification of Human Anti-HIV gp160 Monoclonal Antibodies That Make Effective Immunotoxins. AN - 1841137569; 27852851 AB - The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on the surface of both virions and infected cells. Env is the target of neutralizing antibodies (Abs) and has been the subject of intense study in efforts to produce HIV vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such as immunotoxins (ITs). In the course of screening monoclonal antibodies (MAbs) for their ability to deliver cytotoxic agents to infected or Env-transfected cells, we noted disparities in their functional activities. Different MAbs showed diverse functions that did not correlate with each other. For example, MAbs against the external loop region of gp41 made the most effective ITs against infected cells but did not neutralize virus and bound only moderately to the same cells that they killed so effectively when they were used in ITs. There were also differences in IT-mediated killing among transfected and infected cell lines that were unrelated to the binding of the MAb to the target cells. Our studies of a well-characterized antigen demonstrate that MAbs against different epitopes have different functional activities and that the binding of one MAb can influence the interaction of other MAbs that bind elsewhere on the antigen. These results have implications for the use of MAbs and ITs to kill HIV-infected cells and eradicate persistent reservoirs of HIV infection. There is increased interest in using antibodies to treat and cure HIV infection. Antibodies can neutralize free virus and kill cells already carrying the virus. The virus envelope (Env) is the only HIV protein expressed on the surfaces of virions and infected cells. In this study, we examined a panel of human anti-Env antibodies for their ability to deliver cell-killing toxins to HIV-infected cells and to perform other antiviral functions. The ability of an antibody to make an effective immunotoxin could not be predicted from its other functional characteristics, such as its neutralizing activity. Anti-HIV immunotoxins could be used to eliminate virus reservoirs that persist despite effective antiretroviral therapy. Copyright © 2017 American Society for Microbiology. JF - Journal of virology AU - Pincus, Seth H AU - Song, Kejing AU - Maresh, Grace A AU - Hamer, Dean H AU - Dimitrov, Dimiter S AU - Chen, Weizao AU - Zhang, Mei-Yun AU - Ghetie, Victor F AU - Chan-Hui, Po-Ying AU - Robinson, James E AU - Vitetta, Ellen S AD - Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA spincu@lsuhsc.edu. ; Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA. ; Laboratory of Biochemistry, Center for Cancer Research, NCI, Bethesda, Maryland, USA. ; Cancer and Inflammation Program, Center for Cancer Research, NCI, Frederick, Maryland, USA. ; Departments of Immunology and Microbiology, UT Southwestern Medical Center, Dallas, Texas, USA. ; Theraclone Sciences, Seattle, Washington, USA. ; Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 VL - 91 IS - 3 KW - epitope KW - gp160 KW - HIV envelope KW - immunotoxin KW - monoclonal antibody UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841137569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+of+Human+Anti-HIV+gp160+Monoclonal+Antibodies+That+Make+Effective+Immunotoxins.&rft.au=Pincus%2C+Seth+H%3BSong%2C+Kejing%3BMaresh%2C+Grace+A%3BHamer%2C+Dean+H%3BDimitrov%2C+Dimiter+S%3BChen%2C+Weizao%3BZhang%2C+Mei-Yun%3BGhetie%2C+Victor+F%3BChan-Hui%2C+Po-Ying%3BRobinson%2C+James+E%3BVitetta%2C+Ellen+S&rft.aulast=Pincus&rft.aufirst=Seth&rft.date=2017-02-01&rft.volume=91&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/10.1128%2FJVI.01955-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-17 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1128/JVI.01955-16 ER - TY - JOUR T1 - Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study. AN - 1839108531; 27829682 AB - To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had <100 polyps and 51.8% had CRC. A total of 36 different MUTYH variants were identified: 13 (36.1%) were classified as pathogenetic, whereas 23 (63.9%) were variants of unknown significance (VUS). Two pathogenetic variants were observed in 78 patients (26.1%). A large homozygous deletion of exon 15 was found in one patient (<1.0%). MAP patients were younger than those with negative MUTYH testing at polyps diagnosis (P<0.0001) and at first cancer diagnosis (P=0.007). MAP patients carrying the p.Glu480del variant presented with a younger age at polyp diagnosis as compared to patients carrying p.Gly396Asp and p.Tyr179Cys variants. A high heterogeneity of MUTYH variants and a high rate of VUS were identified in a cohort of Italian patients with suspected MAP. Genotype-phenotype analysis suggests that the p.Glu480del variant is associated with a severe phenotype. JF - Journal of human genetics AU - Ricci, Maria Teresa AU - Miccoli, Sara AU - Turchetti, Daniela AU - Bondavalli, Davide AU - Viel, Alessandra AU - Quaia, Michele AU - Giacomini, Elisa AU - Gismondi, Viviana AU - Sanchez-Mete, Lupe AU - Stigliano, Vittoria AU - Martayan, Aline AU - Mazzei, Filomena AU - Bignami, Margherita AU - Bonelli, Luigina AU - Varesco, Liliana AD - Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy. ; Research Center on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. ; Funcional Onco-genomics and Genetics, CRO Aviano National Cancer Institute, Aviano (PN), Italy. ; Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute-IRCCS, Rome, Italy. ; Clinical Pathology Unit, Regina Elena National Cancer Institute-IRCCS, Rome, Italy. ; Unit of Experimental and Computational Carcinogenesis, Istituto Superiore di Sanità, Rome, Italy. ; Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genoa, Italy. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 309 EP - 315 VL - 62 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839108531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+human+genetics&rft.atitle=Type+and+frequency+of+MUTYH+variants+in+Italian+patients+with+suspected+MAP%3A+a+retrospective+multicenter+study.&rft.au=Ricci%2C+Maria+Teresa%3BMiccoli%2C+Sara%3BTurchetti%2C+Daniela%3BBondavalli%2C+Davide%3BViel%2C+Alessandra%3BQuaia%2C+Michele%3BGiacomini%2C+Elisa%3BGismondi%2C+Viviana%3BSanchez-Mete%2C+Lupe%3BStigliano%2C+Vittoria%3BMartayan%2C+Aline%3BMazzei%2C+Filomena%3BBignami%2C+Margherita%3BBonelli%2C+Luigina%3BVaresco%2C+Liliana&rft.aulast=Ricci&rft.aufirst=Maria&rft.date=2017-02-01&rft.volume=62&rft.issue=2&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+genetics&rft.issn=1435-232X&rft_id=info:doi/10.1038%2Fjhg.2016.132 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-10 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1038/jhg.2016.132 ER - TY - JOUR T1 - Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. AN - 1835672048; 27658484 AB - 3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance and the β-keto analog of 3,4-methylenedioxy-N-methylamphetamine (MDMA). It is well established that MDMA metabolism produces bioactive metabolites. Here we tested the hypothesis that methylone metabolism in rats can form bioactive metabolites. First, we examined the pharmacokinetics (PKs) of methylone and its metabolites after subcutaneous (sc) methylone administration (3, 6, 12 mg/kg) to male rats fitted with intravenous (iv) catheters for repeated blood sampling. Plasma specimens were assayed by liquid chromatography tandem mass spectrometry to quantify methylone and its phase I metabolites: 3,4-methylenedioxycathinone (MDC), 3,4-dihydroxy-N-methylcathinone (HHMC), and 4-hydroxy-3-methoxy-N-methylcathinone (HMMC). The biological activity of methylone and its metabolites was then compared using in vitro transporter assays and in vivo microdialysis in rat nucleus accumbens. For the PK study, we found that methylone and MDC peaked early (Tmax=15-45 min) and were short lived (t1/2=60-90 min), while HHMC and HMMC peaked later (Tmax=60-120 min) and persisted (t1/2=120-180 min). Area-under-the-curve values for methylone and MDC were greater than dose-proportional, suggesting non-linear accumulation. Methylone produced significant locomotor activation, which was correlated with plasma methylone, MDC, and HHMC concentrations. Methylone, MDC, and HHMC were substrate-type releasers at monoamine transporters as determined in vitro, but only methylone and MDC (1, 3 mg/kg, iv) produced significant elevations in brain extracellular dopamine and 5-HT in vivo. Our findings demonstrate that methylone is extensively metabolized in rats, but MDC is the only centrally active metabolite that could contribute to overall effects of the drug in vivo. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Elmore, Joshua S AU - Dillon-Carter, Ora AU - Partilla, John S AU - Ellefsen, Kayla N AU - Concheiro, Marta AU - Suzuki, Masaki AU - Rice, Kenner C AU - Huestis, Marilyn A AU - Baumann, Michael H AD - Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. ; Chemistry & Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. ; Drug Design and Synthesis Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 649 EP - 660 VL - 42 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835672048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Pharmacokinetic+Profiles+and+Pharmacodynamic+Effects+for+Methylone+and+Its+Metabolites+in+Rats.&rft.au=Elmore%2C+Joshua+S%3BDillon-Carter%2C+Ora%3BPartilla%2C+John+S%3BEllefsen%2C+Kayla+N%3BConcheiro%2C+Marta%3BSuzuki%2C+Masaki%3BRice%2C+Kenner+C%3BHuestis%2C+Marilyn+A%3BBaumann%2C+Michael+H&rft.aulast=Elmore&rft.aufirst=Joshua&rft.date=2017-02-01&rft.volume=42&rft.issue=3&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=1740-634X&rft_id=info:doi/10.1038%2Fnpp.2016.213 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/npp.2016.213 ER - TY - JOUR T1 - Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury. AN - 1835515348; 27775817 AB - Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Goldring, Christopher AU - Antoine, Daniel J AU - Bonner, Frank AU - Crozier, Jonathan AU - Denning, Chris AU - Fontana, Robert J AU - Hanley, Neil A AU - Hay, David C AU - Ingelman-Sundberg, Magnus AU - Juhila, Satu AU - Kitteringham, Neil AU - Silva-Lima, Beatriz AU - Norris, Alan AU - Pridgeon, Chris AU - Ross, James A AU - Young, Rowena Sison AU - Tagle, Danilo AU - Tornesi, Belen AU - van de Water, Bob AU - Weaver, Richard J AU - Zhang, Fang AU - Park, B Kevin AD - MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. ; Stem Cells for Safer Medicines, London, UK. ; European Partnership for Alternative Approaches to Animal Testing, Brussels, Belgium. ; Department of Stem Cell Biology, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK. ; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. ; Centre for Endocrinology & Diabetes, University of Manchester, and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. ; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK. ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. ; R&D, In Vitro Biology, Orion Pharma, Espoo, Finland. ; Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. ; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD. ; Abbvie Global Pharmaceutical Research and Development, North Chicago, IL. ; Faculty of Science, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, University of Leiden, Leiden, The Netherlands. ; Institut de Recherches Internationales Servier, Suresnes, France. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 710 EP - 721 VL - 65 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835515348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Stem+cell-derived+models+to+improve+mechanistic+understanding+and+prediction+of+human+drug-induced+liver+injury.&rft.au=Goldring%2C+Christopher%3BAntoine%2C+Daniel+J%3BBonner%2C+Frank%3BCrozier%2C+Jonathan%3BDenning%2C+Chris%3BFontana%2C+Robert+J%3BHanley%2C+Neil+A%3BHay%2C+David+C%3BIngelman-Sundberg%2C+Magnus%3BJuhila%2C+Satu%3BKitteringham%2C+Neil%3BSilva-Lima%2C+Beatriz%3BNorris%2C+Alan%3BPridgeon%2C+Chris%3BRoss%2C+James+A%3BYoung%2C+Rowena+Sison%3BTagle%2C+Danilo%3BTornesi%2C+Belen%3Bvan+de+Water%2C+Bob%3BWeaver%2C+Richard+J%3BZhang%2C+Fang%3BPark%2C+B+Kevin&rft.aulast=Goldring&rft.aufirst=Christopher&rft.date=2017-02-01&rft.volume=65&rft.issue=2&rft.spage=710&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28886 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1002/hep.28886 ER - TY - JOUR T1 - Modulation of serotonin transporter function by kappa-opioid receptor ligands. AN - 1835447202; 27743931 AB - Kappa opioid receptor (KOR) agonists produce dysphoria and psychotomimesis. While KOR agonists produce pro-depressant-like effects, KOR antagonists produce anti-depressant-like effects in rodent models. The cellular mechanisms and downstream effector(s) by which KOR ligands produce these effects are not clear. KOR agonists modulate serotonin (5-HT) transmission in the brain regions implicated in mood and motivation regulation. Presynaptic serotonin transporter (SERT) activity is critical in the modulation of synaptic 5-HT and, subsequently, in mood disorders. Detailing the molecular events of KOR-linked SERT regulation is important for examining the postulated role of this protein in mood disorders. In this study, we used heterologous expression systems and native tissue preparations to determine the cellular signaling cascades linked to KOR-mediated SERT regulation. KOR agonists U69,593 and U50,488 produced a time and concentration dependent KOR antagonist-reversible decrease in SERT function. KOR-mediated functional down-regulation of SERT is sensitive to CaMKII and Akt inhibition. The U69,593-evoked decrease in SERT activity is associated with a decreased transport Vmax, reduced SERT cell surface expression, and increased SERT phosphorylation. Furthermore, KOR activation enhanced SERT internalization and decreased SERT delivery to the membrane. These data demonstrate that KOR activation decreases 5-HT uptake by altering SERT trafficking mechanisms and phosphorylation status to reduce the functional availability of surface SERT. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Neuropharmacology AU - Sundaramurthy, Santhanalakshmi AU - Annamalai, Balasubramaniam AU - Samuvel, Devadoss J AU - Shippenberg, Toni S AU - Jayanthi, Lankupalle D AU - Ramamoorthy, Sammanda AD - Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. ; Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. ; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. ; Integrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA. ; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: sammanda.ramamoorthy@vcuhealth.org. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 281 EP - 292 VL - 113 KW - Phosphorylation KW - Serotonin transporter KW - Kappa opioid receptor KW - Clearance KW - Serotonin KW - Trafficking UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835447202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Modulation+of+serotonin+transporter+function+by+kappa-opioid+receptor+ligands.&rft.au=Sundaramurthy%2C+Santhanalakshmi%3BAnnamalai%2C+Balasubramaniam%3BSamuvel%2C+Devadoss+J%3BShippenberg%2C+Toni+S%3BJayanthi%2C+Lankupalle+D%3BRamamoorthy%2C+Sammanda&rft.aulast=Sundaramurthy&rft.aufirst=Santhanalakshmi&rft.date=2017-02-01&rft.volume=113&rft.issue=&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2016.10.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuropharm.2016.10.011 ER - TY - JOUR T1 - Design and In Vivo Characterization of Immunoconjugates Targeting HIV gp160. AN - 1834994363; 27795412 AB - The envelope (Env) glycoprotein of HIV is expressed on the surface of productively infected cells and can be used as a target for cytotoxic immunoconjugates (ICs), in which cell-killing moieties, including toxins, drugs, or radionuclides, are chemically or genetically linked to monoclonal antibodies (MAbs) or other targeting ligands. Such ICs could be used to eliminate persistent reservoirs of HIV infection. We have found that MAbs which bind to the external loop of gp41, e.g., MAb 7B2, make highly effective ICs, particularly when used in combination with soluble CD4. We evaluated the toxicity, immunogenicity, and efficacy of the ICs targeted with 7B2 in mice and in simian-human immunodeficiency virus-infected macaques. In the macaques, we tested immunotoxins (ITs), consisting of protein toxins bound to the targeting agent. ITs were well tolerated and initially efficacious but were ultimately limited by their immunogenicity. In an effort to decrease immunogenicity, we tested different toxic moieties, including recombinant toxins, cytotoxic drugs, and tubulin inhibitors. ICs containing deglycosylated ricin A chain prepared from ricin toxin extracted from castor beans were the most effective in killing HIV-infected cells. Having identified immunogenicity as a major concern, we show that conjugation of IT to polyethylene glycol limits immunogenicity. These studies demonstrate that cytotoxic ICs can target virus-infected cells in vivo but also highlight potential problems to be addressed. It is not yet possible to cure HIV infection. Even after years of fully effective antiviral therapy, a persistent reservoir of virus-infected cells remains. Here we propose that a targeted conjugate consisting of an anti-HIV antibody bound to a toxic moiety could function to kill the HIV-infected cells that constitute this reservoir. We tested this approach in HIV-infected cells grown in the lab and in animal infections. Our studies demonstrated that these immunoconjugates are effective both in vitro and in test animals. In particular, ITs constructed with the deglycosylated A chain prepared from native ricin were the most effective in killing cells, but their utility was blunted because they provoked immune reactions that interfered with the therapeutic effects. We then demonstrated that coating of the ITs with polyethylene glycol minimized the immunogenicity, as has been demonstrated with other protein therapies. Copyright © 2017 American Society for Microbiology. JF - Journal of virology AU - Pincus, Seth H AU - Song, Kejing AU - Maresh, Grace A AU - Frank, Anderson AU - Worthylake, David AU - Chung, Hye-Kyung AU - Polacino, Patricia AU - Hamer, Dean H AU - Coyne, Cody P AU - Rosenblum, Michael G AU - Marks, John W AU - Chen, Gang AU - Weiss, Deborah AU - Ghetie, Victor AU - Vitetta, Ellen S AU - Robinson, James E AU - Hu, Shiu-Lok AD - Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA spincu@lsuhsc.edu. ; Research Institute for Children, Children's Hospital, New Orleans, Louisiana, USA. ; Department of Pediatrics and Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. ; Advanced Biosciences Laboratories, Inc., Rockville, Maryland, USA. ; Washington National Primate Research Center, University of Washington, Seattle, Washington, USA. ; Laboratory of Biochemistry, Center for Cancer Research, NCI, Bethesda, Maryland, USA. ; Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA. ; Department of Experimental Therapeutics, M. D. Anderson Cancer Center, Houston, Texas, USA. ; Concortis Biosystems, San Diego, California, USA. ; Departments of Immunology and Microbiology, UT Southwestern Medical Center, Dallas, Texas, USA. ; Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA. Y1 - 2017/02/01/ PY - 2017 DA - 2017 Feb 01 VL - 91 IS - 3 KW - immunoglobulins KW - human immunodeficiency virus KW - antibody drug conjugate KW - monoclonal antibodies KW - immunotoxins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834994363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Design+and+In+Vivo+Characterization+of+Immunoconjugates+Targeting+HIV+gp160.&rft.au=Pincus%2C+Seth+H%3BSong%2C+Kejing%3BMaresh%2C+Grace+A%3BFrank%2C+Anderson%3BWorthylake%2C+David%3BChung%2C+Hye-Kyung%3BPolacino%2C+Patricia%3BHamer%2C+Dean+H%3BCoyne%2C+Cody+P%3BRosenblum%2C+Michael+G%3BMarks%2C+John+W%3BChen%2C+Gang%3BWeiss%2C+Deborah%3BGhetie%2C+Victor%3BVitetta%2C+Ellen+S%3BRobinson%2C+James+E%3BHu%2C+Shiu-Lok&rft.aulast=Pincus&rft.aufirst=Seth&rft.date=2017-02-01&rft.volume=91&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/10.1128%2FJVI.01360-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-31 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1128/JVI.01360-16 ER - TY - JOUR T1 - Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on Hexavalent Chromium. AN - 1826741944; 27483499 AB - Evaluating the impact of federally funded research with a broad, methodical, and objective approach is important to ensure that public funds advance the mission of federal agencies. We aimed to develop a methodical approach that would yield a broad assessment of National Toxicology Program's (NTP's) effectiveness across multiple sectors and demonstrate the utility of the approach through a case study. A conceptual model was developed with defined activities, outputs (products), and outcomes (proximal, intermediate, distal) and applied retrospectively to NTP's research on hexavalent chromium (CrVI). Proximal outcomes were measured by counting views of and requests for NTP's products by external stakeholders. Intermediate outcomes were measured by bibliometric analysis. Distal outcomes were assessed through Web and LexisNexis searches for documents related to legislation or regulation changes. The approach identified awareness of NTP's work on CrVI by external stakeholders (proximal outcome) and citations of NTP's research in scientific publications, reports, congressional testimonies, and legal and policy documents (intermediate outcome). NTP's research was key to the nation's first-ever drinking water standard for CrVI adopted by California in 2014 (distal outcome). By applying this approach to a case study, the utility and limitations of the approach were identified, including challenges to evaluating the outcomes of a research program. This study identified a broad and objective approach for assessing NTP's effectiveness, including methodological needs for more thorough and efficient impact assessments in the future. Citation: Xie Y, Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S. National Toxicology Program: a case study on hexavalent chromium. Environ Health Perspect 125:181-188; http://dx.doi.org/10.1289/EHP21. JF - Environmental health perspectives AU - Xie, Yun AU - Holmgren, Stephanie AU - Andrews, Danica M K AU - Wolfe, Mary S AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 181 EP - 188 VL - 125 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826741944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Evaluating+the+Impact+of+the+U.S.+National+Toxicology+Program%3A+A+Case+Study+on+Hexavalent+Chromium.&rft.au=Xie%2C+Yun%3BHolmgren%2C+Stephanie%3BAndrews%2C+Danica+M+K%3BWolfe%2C+Mary+S&rft.aulast=Xie&rft.aufirst=Yun&rft.date=2016-03-01&rft.volume=44&rft.issue=1&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Law%2C+Medicine+%26+Ethics&rft.issn=10731105&rft_id=info:doi/10.1177%2F1073110516644211 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-02 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1289/EHP21 ER - TY - JOUR T1 - Using natural products to promote caspase-8-dependent cancer cell death. AN - 1826702537; 27286684 AB - The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patients) are highly resistant to TRAIL-mediated cell death. Therefore, there is an underlying interest in identifying agents that can be combined with TRAIL to improve its efficacy. There are numerous reports in which combination of TRAIL with standard antineoplastic drugs has resulted in enhanced cancer cell death in vitro. However, many of these chemotherapeutic drugs are nonspecific and associated with adverse effects, which raise serious concerns for cancer therapy in patients. By contrast, natural products have been shown to be safer and efficacious alternatives. Recently, a number of studies have suggested that certain natural products when combined with TRAIL can enhance cancer cell death. In this review, we highlight molecular pathways that might be targeted by various natural products to promote cell death, and focus on our recent work with withanolides as TRAIL sensitizers. Finally, we will suggest synergistic approaches for combining active withanolides with various forms of immunotherapy to promote cancer cell death and an effective antitumor immune response. JF - Cancer immunology, immunotherapy : CII AU - Tewary, Poonam AU - Gunatilaka, A A Leslie AU - Sayers, Thomas J AD - Cancer and Inflammation Program, National Cancer Institute, Frederick, Frederick, MD, 21702, USA. tewaryp@mail.nih.gov. ; Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ, USA. ; Cancer and Inflammation Program, National Cancer Institute, Frederick, Frederick, MD, 21702, USA. sayerst@mail.nih.gov. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 223 EP - 231 VL - 66 IS - 2 KW - TRAIL KW - Poly (I:C) KW - Apoptosis KW - PIVAC15 KW - Necroptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826702537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.atitle=Using+natural+products+to+promote+caspase-8-dependent+cancer+cell+death.&rft.au=Tewary%2C+Poonam%3BGunatilaka%2C+A+A+Leslie%3BSayers%2C+Thomas+J&rft.aulast=Tewary&rft.aufirst=Poonam&rft.date=2017-02-01&rft.volume=66&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=1432-0851&rft_id=info:doi/10.1007%2Fs00262-016-1855-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1007/s00262-016-1855-0 ER - TY - JOUR T1 - Male Breast Cancer Incidence and Mortality Risk in the Japanese Atomic Bomb Survivors - Differences in Excess Relative and Absolute Risk from Female Breast Cancer. AN - 1826698125; 27286002 AB - There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the United Kingdom, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. We compare radiation-associated excess relative and absolute risks of male and female breast cancers. Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. We observed significant (p ≤ 0.01) dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are elevations by factors of approximately 15 and 5, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data, there are elevations by factors of approximately 20 and 10, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least a factor of 5 that of many other malignancies. There is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding. Citation: Little MP, McElvenny DM. 2017. Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors - differences in excess relative and absolute risk from female breast cancer. Environ Health Perspect 125:223-229; http://dx.doi.org/10.1289/EHP151. JF - Environmental health perspectives AU - Little, Mark P AU - McElvenny, Damien M AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 223 EP - 229 VL - 125 IS - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826698125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Male+Breast+Cancer+Incidence+and+Mortality+Risk+in+the+Japanese+Atomic+Bomb+Survivors+-+Differences+in+Excess+Relative+and+Absolute+Risk+from+Female+Breast+Cancer.&rft.au=Little%2C+Mark+P%3BMcElvenny%2C+Damien+M&rft.aulast=Little&rft.aufirst=Mark&rft.date=2017-02-01&rft.volume=125&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP151 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1289/EHP151 ER - TY - JOUR T1 - Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin. AN - 1826648599; 26503631 AB - A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy. We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints. At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention. We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice. NCT00468910. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. JF - Gut AU - Roy, Hemant K AU - Turzhitsky, Vladimir AU - Wali, Ramesh AU - Radosevich, Andrew J AU - Jovanovic, Borko AU - Della'Zanna, Gary AU - Umar, Asad AU - Rubin, David T AU - Goldberg, Michael J AU - Bianchi, Laura AU - De La Cruz, Mart AU - Bogojevic, Andrej AU - Helenowski, Irene B AU - Rodriguez, Luz AU - Chatterton, Robert AU - Skripkauskas, Silvia AU - Page, Katherine AU - Weber, Christopher R AU - Huang, Xiaoke AU - Richmond, Ellen AU - Bergan, Raymond C AU - Backman, Vadim AD - Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA. ; Department of Biomedical Engineering, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Department of Preventive Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. ; Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA. ; Department of Medicine, NorthShore University Health Systems, Evanston, Illinois, USA. ; Department of Obstetrics and Gynecology, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA. ; Department of Pathology, The University of Chicago Medical Center, Chicago, Illinois, USA. Y1 - 2017/02// PY - 2017 DA - February 2017 SP - 285 EP - 292 VL - 66 IS - 2 KW - COLORECTAL NEOPLASIA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826648599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=Spectral+biomarkers+for+chemoprevention+of+colonic+neoplasia%3A+a+placebo-controlled+double-blinded+trial+with+aspirin.&rft.au=Roy%2C+Hemant+K%3BTurzhitsky%2C+Vladimir%3BWali%2C+Ramesh%3BRadosevich%2C+Andrew+J%3BJovanovic%2C+Borko%3BDella%27Zanna%2C+Gary%3BUmar%2C+Asad%3BRubin%2C+David+T%3BGoldberg%2C+Michael+J%3BBianchi%2C+Laura%3BDe+La+Cruz%2C+Mart%3BBogojevic%2C+Andrej%3BHelenowski%2C+Irene+B%3BRodriguez%2C+Luz%3BChatterton%2C+Robert%3BSkripkauskas%2C+Silvia%3BPage%2C+Katherine%3BWeber%2C+Christopher+R%3BHuang%2C+Xiaoke%3BRichmond%2C+Ellen%3BBergan%2C+Raymond+C%3BBackman%2C+Vadim&rft.aulast=Roy&rft.aufirst=Hemant&rft.date=2017-02-01&rft.volume=66&rft.issue=2&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2015-309996 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2015-10-27 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1136/gutjnl-2015-309996 ER - TY - JOUR T1 - Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration. AN - 1863220785; 28138971 AB - Establishing science-based driving per se blood Δ9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. JF - Journal of applied toxicology : JAT AU - Newmeyer, Matthew N AU - Swortwood, Madeleine J AU - Taylor, Megan E AU - Abulseoud, Osama A AU - Woodward, Thomas H AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, Baltimore, MD, USA. ; Maryland Drug Recognition Expert Coordinator, Maryland State Police, Pikesville, MD, USA. Y1 - 2017/01/31/ PY - 2017 DA - 2017 Jan 31 KW - cannabis KW - pupil size KW - modified Romberg balance KW - walk and turn KW - edibles KW - performance KW - one leg stand KW - Drug Evaluation and Classification Program UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1863220785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+toxicology+%3A+JAT&rft.atitle=Evaluation+of+divided+attention+psychophysical+task+performance+and+effects+on+pupil+sizes+following+smoked%2C+vaporized+and+oral+cannabis+administration.&rft.au=Newmeyer%2C+Matthew+N%3BSwortwood%2C+Madeleine+J%3BTaylor%2C+Megan+E%3BAbulseoud%2C+Osama+A%3BWoodward%2C+Thomas+H%3BHuestis%2C+Marilyn+A&rft.aulast=Newmeyer&rft.aufirst=Matthew&rft.date=2017-01-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=1099-1263&rft_id=info:doi/10.1002%2Fjat.3440 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-31 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1002/jat.3440 ER - TY - JOUR T1 - The Human Longevity Gene Homolog INDY and Interleukin-6 Interact in Hepatic Lipid Metabolism. AN - 1862947196; 28133767 AB - Reduced expression of the Indy ('I am Not Dead, Yet') gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane associated citrate transporter expressed highly in the liver, protects mice from high-fat diet and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We aimed to study a possible role of mIndy in human hepatic fat metabolism. In obese, insulin resistant patients with NAFLD, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In non-human primates, a two year high fat, high sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription via the IL-6-receptor (IL-6R) and activation of the transcription factor Stat3 and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-Stat3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and non-human primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 via mINDY. Targeting human mINDY may have therapeutic potential in obese patients with NAFLD. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - von Loeffelholz, Christian AU - Lieske, Stefanie AU - Neuschäfer-Rube, Frank AU - Willmes, Diana M AU - Raschzok, Nathanael AU - Sauer, Igor M AU - König, Jörg AU - Fromm, Martin AU - Horn, Paul AU - Chatzigeorgiou, Antonis AU - Pathe-Neuschäfer-Rube, Andrea AU - Jordan, Jens AU - Pfeiffer, Andreas F H AU - Mingrone, Geltrude AU - Bornstein, Stefan R AU - Stroehle, Peter AU - Harms, Christoph AU - Wunderlich, F Thomas AU - Helfand, Stephen L AU - Bernier, Michel AU - de Cabo, Rafael AU - Shulman, Gerald I AU - Chavakis, Triantafyllos AU - Püschel, Gerhard P AU - Birkenfeld, Andreas L AD - Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Friedrich Schiller University, and Department of Anesthesiology and Intensive Care, Jena University Hospital, Jena, 01774, Germany. ; Section of Metabolic Vascular Medicine, Medical Clinic III, Dresden University School of Medicine, Paul Langerhans Institute Dresden (PLID), TU Dresden, 01307, Germany. ; Lehrstuhl für Biochemie der Ernährung, Universität Potsdam, Potsdam, 14558, Germany. ; General, Visceral, and Transplantation Surgery, Charité - University School of Medicine, Berlin, 10117, Germany. ; Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität, Erlangen-Nürnberg, 91054, Germany. ; Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Dresden, TUD, Germany. ; Institute for Clinical Pharmacology, Hannover Medical School, 30625, Hannover, Germany. ; Department of Endocrinology, Diabetes and Nutrition, Charité - University School of Medicine, Berlin, 10117, Germany. ; Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 8WA, UK. ; Max Planck Institute for Metabolism Research, Excellence cluster on cellular stress responses in aging associated diseases (CECAD), Cologne, 5093, Germany. ; Department of Experimental Neurology, Charité-Universitätsmedizin Berlin, Center for Stroke Research, Charitéplatz 1, 10117, Berlin, Germany. ; Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912, USA. ; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA. ; Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520, USA. Y1 - 2017/01/30/ PY - 2017 DA - 2017 Jan 30 KW - NAFLD KW - Liver KW - IL-6 KW - Insulin Resistance KW - Indy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1862947196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=The+Human+Longevity+Gene+Homolog+INDY+and+Interleukin-6+Interact+in+Hepatic+Lipid+Metabolism.&rft.au=von+Loeffelholz%2C+Christian%3BLieske%2C+Stefanie%3BNeusch%C3%A4fer-Rube%2C+Frank%3BWillmes%2C+Diana+M%3BRaschzok%2C+Nathanael%3BSauer%2C+Igor+M%3BK%C3%B6nig%2C+J%C3%B6rg%3BFromm%2C+Martin%3BHorn%2C+Paul%3BChatzigeorgiou%2C+Antonis%3BPathe-Neusch%C3%A4fer-Rube%2C+Andrea%3BJordan%2C+Jens%3BPfeiffer%2C+Andreas+F+H%3BMingrone%2C+Geltrude%3BBornstein%2C+Stefan+R%3BStroehle%2C+Peter%3BHarms%2C+Christoph%3BWunderlich%2C+F+Thomas%3BHelfand%2C+Stephen+L%3BBernier%2C+Michel%3Bde+Cabo%2C+Rafael%3BShulman%2C+Gerald+I%3BChavakis%2C+Triantafyllos%3BP%C3%BCschel%2C+Gerhard+P%3BBirkenfeld%2C+Andreas+L&rft.aulast=von+Loeffelholz&rft.aufirst=Christian&rft.date=2017-01-30&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.29089 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-30 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1002/hep.29089 ER - TY - JOUR T1 - Associations among personal care product use patterns and exogenous hormone use in the NIEHS Sister Study. AN - 1861861964; 28120835 AB - It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N=47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 January 2017; doi:10.1038/jes.2016.82. JF - Journal of exposure science & environmental epidemiology AU - Taylor, Kyla W AU - Baird, Donna D AU - Herring, Amy H AU - Engel, Lawrence S AU - Nichols, Hazel B AU - Sandler, Dale P AU - Troester, Melissa A AD - Office of Health Assessment and Translation, National Toxicology Program, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina 27709 USA. ; Epidemiology Department, National Institute of Environmental Health Sciences, Chapel Hill, North Carolina, USA. ; Biostatistics Deptartment, University of North Carolina, Chapel Hill, North Carolina, USA. ; Epidemiology Deptartment, University of North Carolina, Chapel Hill, North Carolina, USA. Y1 - 2017/01/25/ PY - 2017 DA - 2017 Jan 25 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861861964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+exposure+science+%26+environmental+epidemiology&rft.atitle=Associations+among+personal+care+product+use+patterns+and+exogenous+hormone+use+in+the+NIEHS+Sister+Study.&rft.au=Taylor%2C+Kyla+W%3BBaird%2C+Donna+D%3BHerring%2C+Amy+H%3BEngel%2C+Lawrence+S%3BNichols%2C+Hazel+B%3BSandler%2C+Dale+P%3BTroester%2C+Melissa+A&rft.aulast=Taylor&rft.aufirst=Kyla&rft.date=2017-01-25&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+exposure+science+%26+environmental+epidemiology&rft.issn=1559-064X&rft_id=info:doi/10.1038%2Fjes.2016.82 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-25 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1038/jes.2016.82 ER - TY - JOUR T1 - Engineering Phototheranostic Nanoscale Metal-Organic Frameworks for Multimodal Imaging-Guided Cancer Therapy. AN - 1854106990; 28032505 AB - Many photoresponsive dyes have been utilized as imaging and photodynamic/photothermal therapy agents. Indocyanine green (ICG) is the only near-infrared region (NIR) organic dye for clinical applications approved by the United States Food and Drug Administration; however, the clinical application of ICG is limited by its poor aqueous solubility, low cancer specificity, and low sensitivity in cancer theranostics. To overcome these issues, a multifunctional nanoplatform based on hyaluronic acid (HA) and ICG-engineered metal-organic framework MIL-100(Fe) nanoparticles (MOF@HA@ICG NPs) was successfully developed for imaging-guided, anticancer photothermal therapy (PTT). The synthesized NPs showed a high loading content of ICG (40%), strong NIR absorbance, and photostability. The in vitro and in vivo imaging showed that the MOF@HA@ICG NPs exhibited greater cellular uptake in CD44-positive MCF-7 cells and enhanced tumor accumulation in xenograft tumors due to their targeting capability, compared to MOF@ICG NPs (non-HA-targeted) and free ICG. The in vitro photothermal toxicity and in vivo PTT treatments demonstrated that MOF@HA@ICG NPs could effectively inhibit the growth of MCF-7 cells/xenograft tumors. These results suggest that MOF@HA@ICG NPs could be served as a new promising theranostic nanoplatform for improved anticancer PTT through cancer-specific and image-guided drug delivery. JF - ACS applied materials & interfaces AU - Cai, Wen AU - Gao, Haiyan AU - Chu, Chengchao AU - Wang, Xiaoyong AU - Wang, Junqing AU - Zhang, Pengfei AU - Lin, Gan AU - Li, Wengang AU - Liu, Gang AU - Chen, Xiaoyuan AD - Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi 710061, China. ; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen, Fujian 361102, China. ; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda, Maryland 20892, United States. Y1 - 2017/01/25/ PY - 2017 DA - 2017 Jan 25 SP - 2040 EP - 2051 VL - 9 IS - 3 KW - photothermal therapy KW - bioimaging KW - metal−organic frameworks (MOFs) KW - indocyanine green KW - theranostic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854106990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+applied+materials+%26+interfaces&rft.atitle=Engineering+Phototheranostic+Nanoscale+Metal-Organic+Frameworks+for+Multimodal+Imaging-Guided+Cancer+Therapy.&rft.au=Cai%2C+Wen%3BGao%2C+Haiyan%3BChu%2C+Chengchao%3BWang%2C+Xiaoyong%3BWang%2C+Junqing%3BZhang%2C+Pengfei%3BLin%2C+Gan%3BLi%2C+Wengang%3BLiu%2C+Gang%3BChen%2C+Xiaoyuan&rft.aulast=Cai&rft.aufirst=Wen&rft.date=2017-01-25&rft.volume=9&rft.issue=3&rft.spage=2040&rft.isbn=&rft.btitle=&rft.title=ACS+applied+materials+%26+interfaces&rft.issn=1944-8252&rft_id=info:doi/10.1021%2Facsami.6b11579 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-29 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1021/acsami.6b11579 ER - TY - JOUR T1 - Mechanisms and Barriers in Cancer Nanomedicine: Addressing Challenges, Looking for Solutions. AN - 1857376725; 28068099 AB - Remarkable progress has recently been made in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in several promising candidates in clinical trials. Despite these advances, clinical applications of nanoparticle-based therapeutic/imaging agents remain limited by biological, immunological, and translational barriers. In order to overcome the existing status quo in drug delivery, there is a need for open and frank discussion in the nanomedicine community on what is needed to make qualitative leaps toward translation. In this Nano Focus, we present the main discussion topics and conclusions from a recent workshop: "Mechanisms and Barriers in Nanomedicine". The focus of this informal meeting was on biological, toxicological, immunological, and translational aspects of nanomedicine and approaches to move the field forward productively. We believe that these topics reflect the most important issues in cancer nanomedicine. JF - ACS nano AU - Anchordoquy, Thomas J AU - Barenholz, Yechezkel AU - Boraschi, Diana AU - Chorny, Michael AU - Decuzzi, Paolo AU - Dobrovolskaia, Marina A AU - Farhangrazi, Z Shadi AU - Farrell, Dorothy AU - Gabizon, Alberto AU - Ghandehari, Hamidreza AU - Godin, Biana AU - La-Beck, Ninh M AU - Ljubimova, Julia AU - Moghimi, S Moein AU - Pagliaro, Len AU - Park, Ji-Ho AU - Peer, Dan AU - Ruoslahti, Erkki AU - Serkova, Natalie J AU - Simberg, Dmitri AD - Laboratory of Membrane and Liposome Research, IMRIC, The Hebrew University-Hadassah Medical School , Jerusalem 91120, Israel. ; Institute of Protein Biochemistry, National Research Council , 80131 Napoli, Italy. ; Department of Pediatrics, Perelman School of Medicine and the Children's Hospital of Philadelphia , Philadelphia, Pennsylvania 19104, United States. ; Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia , 16163 Genoa, Italy. ; Nanotechnology Characterization Lab, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702, United States. ; Biotrends International, Denver Technological Center , Greenwood Village, Colorado 80111, United States. ; Office of Cancer Nanotechnology Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. ; Oncology Institute, Shaare Zedek Medical Center, and Hebrew University-School of Medicine , Jerusalem 9103102, Israel. ; Departments of Pharmaceutics, Pharmaceutical Chemistry and of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States. ; Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States. ; Departments of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center , Abilene, Texas 79601, United States. ; Nanomedicine Research Center, Departments of Neurosurgery and of Biomedical Sciences, Comprehensive Cancer Center, Cedars-Sinai Medical Center , Los Angeles, California 90048, United States. ; School of Medicine, Pharmacy and Health, Durham University , Queen's Campus, Stockton-On-Tees TS17 6BH, United Kingdom. ; Siva Therapeutics Inc., Austin, Texas 78759, United States. ; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology , Daejeon 34141, Republic of Korea. ; Departments of Cell Research and Immunology and of Materials Sciences and Engineering, Tel Aviv University , Tel Aviv 69978, Israel. ; Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California 92037, United States. Y1 - 2017/01/24/ PY - 2017 DA - 2017 Jan 24 SP - 12 EP - 18 VL - 11 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857376725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+nano&rft.atitle=Mechanisms+and+Barriers+in+Cancer+Nanomedicine%3A+Addressing+Challenges%2C+Looking+for+Solutions.&rft.au=Anchordoquy%2C+Thomas+J%3BBarenholz%2C+Yechezkel%3BBoraschi%2C+Diana%3BChorny%2C+Michael%3BDecuzzi%2C+Paolo%3BDobrovolskaia%2C+Marina+A%3BFarhangrazi%2C+Z+Shadi%3BFarrell%2C+Dorothy%3BGabizon%2C+Alberto%3BGhandehari%2C+Hamidreza%3BGodin%2C+Biana%3BLa-Beck%2C+Ninh+M%3BLjubimova%2C+Julia%3BMoghimi%2C+S+Moein%3BPagliaro%2C+Len%3BPark%2C+Ji-Ho%3BPeer%2C+Dan%3BRuoslahti%2C+Erkki%3BSerkova%2C+Natalie+J%3BSimberg%2C+Dmitri&rft.aulast=Anchordoquy&rft.aufirst=Thomas&rft.date=2017-01-24&rft.volume=11&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=ACS+nano&rft.issn=1936-086X&rft_id=info:doi/10.1021%2Facsnano.6b08244 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-09 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1021/acsnano.6b08244 ER - TY - JOUR T1 - Glucose-Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy. AN - 1852658839; 27936311 AB - Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)-assisted conversion of glucose into gluconic acid and toxic H2 O2 , a novel treatment paradigm of starving-like therapy is developed for significant tumor-killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2 O2 can oxidize l-Arginine (l-Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l-Arg, a novel glucose-responsive nanomedicine (l-Arg-HMON-GOx) has been for the first time constructed for synergistic cancer starving-like/gas therapy without the need of external excitation, which yields a remarkable H2 O2 -NO cooperative anticancer effect with minimal adverse effect. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. JF - Angewandte Chemie (International ed. in English) AU - Fan, Wenpei AU - Lu, Nan AU - Huang, Peng AU - Liu, Yi AU - Yang, Zhen AU - Wang, Sheng AU - Yu, Guocan AU - Liu, Yijing AU - Hu, Junkai AU - He, Qianjun AU - Qu, Junle AU - Wang, Tianfu AU - Chen, Xiaoyuan AD - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China. ; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA. ; Department of Chemistry & Biochemistry, University of Maryland, College Park, MD, 20742, USA. ; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China. Y1 - 2017/01/24/ PY - 2017 DA - 2017 Jan 24 SP - 1229 EP - 1233 VL - 56 IS - 5 KW - ultrasound imaging KW - nitric oxide KW - hydrogen peroxide KW - mesoporous nanomaterials KW - synergistic therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852658839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Angewandte+Chemie+%28International+ed.+in+English%29&rft.atitle=Glucose-Responsive+Sequential+Generation+of+Hydrogen+Peroxide+and+Nitric+Oxide+for+Synergistic+Cancer+Starving-Like%2FGas+Therapy.&rft.au=Fan%2C+Wenpei%3BLu%2C+Nan%3BHuang%2C+Peng%3BLiu%2C+Yi%3BYang%2C+Zhen%3BWang%2C+Sheng%3BYu%2C+Guocan%3BLiu%2C+Yijing%3BHu%2C+Junkai%3BHe%2C+Qianjun%3BQu%2C+Junle%3BWang%2C+Tianfu%3BChen%2C+Xiaoyuan&rft.aulast=Fan&rft.aufirst=Wenpei&rft.date=2017-01-24&rft.volume=56&rft.issue=5&rft.spage=1229&rft.isbn=&rft.btitle=&rft.title=Angewandte+Chemie+%28International+ed.+in+English%29&rft.issn=1521-3773&rft_id=info:doi/10.1002%2Fanie.201610682 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/anie.201610682 ER - TY - JOUR T1 - Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior. AN - 1861613100; 28114294 AB - Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch-clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABAB receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially modulated and activated separate receptor populations in dopamine neurons. Genetic deletion of GABAB receptors from dopamine neurons in adult mice did not affect general or morphine-induced locomotor activity, but markedly increased cocaine-induced locomotion. Collectively, our findings demonstrate notable selectivity in the inhibitory architecture of the VTA and suggest that long-range GABAergic inputs to dopamine neurons fundamentally regulate behavioral responses to cocaine. JF - Nature neuroscience AU - Edwards, Nicholas J AU - Tejeda, Hugo A AU - Pignatelli, Marco AU - Zhang, Shiliang AU - McDevitt, Ross A AU - Wu, Jocelyn AU - Bass, Caroline E AU - Bettler, Bernhard AU - Morales, Marisela AU - Bonci, Antonello AD - Intramural Research Program, National Institute on Drug Abuse, US National Institutes of Health, Baltimore, Maryland, USA. ; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA. ; Department of Biomedicine, Pharmazentrum, University of Basel, Basel, Switzerland. Y1 - 2017/01/23/ PY - 2017 DA - 2017 Jan 23 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861613100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+neuroscience&rft.atitle=Circuit+specificity+in+the+inhibitory+architecture+of+the+VTA+regulates+cocaine-induced+behavior.&rft.au=Edwards%2C+Nicholas+J%3BTejeda%2C+Hugo+A%3BPignatelli%2C+Marco%3BZhang%2C+Shiliang%3BMcDevitt%2C+Ross+A%3BWu%2C+Jocelyn%3BBass%2C+Caroline+E%3BBettler%2C+Bernhard%3BMorales%2C+Marisela%3BBonci%2C+Antonello&rft.aulast=Edwards&rft.aufirst=Nicholas&rft.date=2017-01-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Nature+neuroscience&rft.issn=1546-1726&rft_id=info:doi/10.1038%2Fnn.4482 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-23 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1038/nn.4482 ER - TY - JOUR T1 - In Silico Prediction of Physicochemical Properties of Environmental Chemicals Using Molecular Fingerprints and Machine Learning. AN - 1852780265; 28006899 AB - There are little available toxicity data on the vast majority of chemicals in commerce. High-throughput screening (HTS) studies, such as those being carried out by the U.S. Environmental Protection Agency (EPA) ToxCast program in partnership with the federal Tox21 research program, can generate biological data to inform models for predicting potential toxicity. However, physicochemical properties are also needed to model environmental fate and transport, as well as exposure potential. The purpose of the present study was to generate an open-source quantitative structure-property relationship (QSPR) workflow to predict a variety of physicochemical properties that would have cross-platform compatibility to integrate into existing cheminformatics workflows. In this effort, decades-old experimental property data sets available within the EPA EPI Suite were reanalyzed using modern cheminformatics workflows to develop updated QSPR models capable of supplying computationally efficient, open, and transparent HTS property predictions in support of environmental modeling efforts. Models were built using updated EPI Suite data sets for the prediction of six physicochemical properties: octanol-water partition coefficient (logP), water solubility (logS), boiling point (BP), melting point (MP), vapor pressure (logVP), and bioconcentration factor (logBCF). The coefficient of determination (R2) between the estimated values and experimental data for the six predicted properties ranged from 0.826 (MP) to 0.965 (BP), with model performance for five of the six properties exceeding those from the original EPI Suite models. The newly derived models can be employed for rapid estimation of physicochemical properties within an open-source HTS workflow to inform fate and toxicity prediction models of environmental chemicals. JF - Journal of chemical information and modeling AU - Zang, Qingda AU - Mansouri, Kamel AU - Williams, Antony J AU - Judson, Richard S AU - Allen, David G AU - Casey, Warren M AU - Kleinstreuer, Nicole C AD - Integrated Laboratory Systems, Inc. , Research Triangle Park, North Carolina 27709, United States. ; National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711, United States. ; National Toxicology Program, National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709, United States. Y1 - 2017/01/23/ PY - 2017 DA - 2017 Jan 23 SP - 36 EP - 49 VL - 57 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852780265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chemical+information+and+modeling&rft.atitle=In+Silico+Prediction+of+Physicochemical+Properties+of+Environmental+Chemicals+Using+Molecular+Fingerprints+and+Machine+Learning.&rft.au=Zang%2C+Qingda%3BMansouri%2C+Kamel%3BWilliams%2C+Antony+J%3BJudson%2C+Richard+S%3BAllen%2C+David+G%3BCasey%2C+Warren+M%3BKleinstreuer%2C+Nicole+C&rft.aulast=Zang&rft.aufirst=Qingda&rft.date=2017-01-23&rft.volume=57&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemical+information+and+modeling&rft.issn=1549-960X&rft_id=info:doi/10.1021%2Facs.jcim.6b00625 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-23 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1021/acs.jcim.6b00625 ER - TY - JOUR T1 - Effects of perfluorinated chemicals on thyroid function, markers of ovarian reserve, and natural fertility. AN - 1861594042; 28111093 AB - Perfluorinated chemicals (PFCs) can act as endocrine-disrupting chemicals, but there has been limited study of their effects on ovarian reserve or fecundability. 99 women, 30-44 years old, without infertility were followed until pregnancy. Initially, serum was evaluated for Antimullerian hormone (AMH), thyroid hormones: thyroid stimulating hormone (TSH), thyroxine (T4), free thyroxine (fT4), and triiodothyronine (T3), and PFCs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS). Bivariate analyses assessed the relationship between thyroid hormones, AMH, and PFCs. Fecundability ratios (FR) were determined for each PFC using a discrete time-varying Cox model and a day-specific probability model. PFC levels were positively correlated with each other (r 0.24 to 0.90), but there was no correlation with TSH (r 0.02 to 0.15) or AMH (r -0.01 to -0.15). FR point estimates for each PFC were neither strong nor statistically significant. Although increased exposure to PFCs correlates with thyroid hormone levels, there is no significant association with fecundability or ovarian reserve. Copyright © 2017 Elsevier Inc. All rights reserved. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Crawford, Natalie M AU - Fenton, Suzanne E AU - Strynar, Mark AU - Hines, Erin P AU - Pritchard, David A AU - Steiner, Anne Z AD - Department of Obstetrics and Gynecology, University of North Carolina, 4001 Old Campus Building, CB 7570, Chapel Hill, NC 27599, USA. Electronic address: nmcraw@gmail.com. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. ; The National Exposure Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC 27709, USA. ; National Center for Environmental Assessment, United States Environmental Protection Agency, Research Triangle Park, NC 27709, USA. ; Department of Biostatistics, University of North Carolina, 3101 McGavran-Greenberg Hall, CB 7420, Chapel Hill, NC 27599, USA. ; Department of Obstetrics and Gynecology, University of North Carolina, 4001 Old Campus Building, CB 7570, Chapel Hill, NC 27599, USA. Electronic address: anne_steiner@med.unc.edu. Y1 - 2017/01/19/ PY - 2017 DA - 2017 Jan 19 KW - fecundability KW - perfluorinated chemicals KW - ovarian reserve KW - thyroid hormones KW - endocrine disrupting chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861594042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Effects+of+perfluorinated+chemicals+on+thyroid+function%2C+markers+of+ovarian+reserve%2C+and+natural+fertility.&rft.au=Crawford%2C+Natalie+M%3BFenton%2C+Suzanne+E%3BStrynar%2C+Mark%3BHines%2C+Erin+P%3BPritchard%2C+David+A%3BSteiner%2C+Anne+Z&rft.aulast=Crawford&rft.aufirst=Natalie&rft.date=2017-01-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=1873-1708&rft_id=info:doi/10.1016%2Fj.reprotox.2017.01.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-23 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.reprotox.2017.01.006 ER - TY - JOUR T1 - Cholinergic signaling in myelination. AN - 1861576527; 28101995 AB - There is a long history of research on acetylcholine (ACh) function in myelinating glia, but a resurgence of interest recently as a result of the therapeutic potential of manipulating ACh signaling to promote remyelination, and the broader interest in neurotransmitter signaling in activity-dependent myelination. Myelinating glia express all the major types of muscarinic and nicotinic ACh receptors at different stages of development, and acetylcholinesterase and butyrylcholinesterase are highly expressed in white matter. This review traces the history of research on ACh signaling in Schwann cells, oligodendrocytes, and in the myelin sheath, and summarizes current knowledge on the intracellular signaling and functional consequences of ACh signaling in myelinating glia. Implications of ACh in diseases, such as Alzheimer's disease, multiple sclerosis, and white matter toxicity caused by pesticides are considered, together with an outline of major questions for future research. GLIA 2017. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. JF - Glia AU - Fields, R Douglas AU - Dutta, Dipankar J AU - Belgrad, Jillian AU - Robnett, Maya AD - Nervous System Development and Plasticity Section, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland. Y1 - 2017/01/19/ PY - 2017 DA - 2017 Jan 19 KW - acetylcholine (ACh) KW - muscarinic receptors KW - acetylcholinesterase (AChE) KW - nicotinic receptors KW - organophosphates KW - butyrylcholinesterase (BChE) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861576527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glia&rft.atitle=Cholinergic+signaling+in+myelination.&rft.au=Fields%2C+R+Douglas%3BDutta%2C+Dipankar+J%3BBelgrad%2C+Jillian%3BRobnett%2C+Maya&rft.aulast=Fields&rft.aufirst=R&rft.date=2017-01-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Glia&rft.issn=1098-1136&rft_id=info:doi/10.1002%2Fglia.23101 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-19 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/glia.23101 ER - TY - JOUR T1 - Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. AN - 1861587896; 28108358 AB - The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties. Studies in those suffering from an AUD have revealed significant alterations in dopamine (DA), GABA, cannabinoids, opioid and serotonin neurotransmission and in brain energy utilization (glucose and acetate metabolism) that are likely to contribute to compulsive alcohol taking, dysphoria/depression, and to alcohol-associated neurotoxicity. Studies have also evaluated the effects of abstinence on recovery of brain metabolism and neurotransmitter function and the potential value of some of these measures to predict clinical outcomes. Finally, PET studies have started to provide insights about the neuronal mechanisms by which certain genes contribute to the vulnerability to AUD. These findings have helped identify new strategies for prevention and treatment of AUD. Published by Elsevier Ltd. JF - Neuropharmacology AU - Volkow, Nora D AU - Wiers, Corinde E AU - Shokri-Kojori, Ehsan AU - Tomasi, Dardo AU - Wang, Gene-Jack AU - Baler, Ruben AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, United States; National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: nvolkow@nida.nih.gov. ; National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, United States. ; National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD 20892, United States. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 KW - Dopamine D2 receptors KW - Frontal activity KW - Alcoholism KW - Brain metabolism KW - Brain imaging KW - Striatum UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861587896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Neurochemical+and+metabolic+effects+of+acute+and+chronic+alcohol+in+the+human+brain%3A+Studies+with+positron+emission+tomography.&rft.au=Volkow%2C+Nora+D%3BWiers%2C+Corinde+E%3BShokri-Kojori%2C+Ehsan%3BTomasi%2C+Dardo%3BWang%2C+Gene-Jack%3BBaler%2C+Ruben&rft.aulast=Volkow&rft.aufirst=Nora&rft.date=2017-01-18&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2017.01.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-21 N1 - Date revised - 2017-01-31 N1 - Last updated - 2017-01-31 DO - http://dx.doi.org/10.1016/j.neuropharm.2017.01.012 ER - TY - JOUR T1 - Hydrogen sulfide reduces RAGE toxicity through inhibition of its dimer formation. AN - 1861587344; 28108276 AB - RAGE is important in the development of neurodegenerative diseases. The present study was designed to investigate the effect of hydrogen sulfide (H2S, an endogenous gaseous mediator) on the cytotoxicity caused by RAGE activation during the chronic oxidative stress. Aβ1-42 decreased cell viability and induced cell senescence in SH-SY5Y cells. Treatment with advanced glycation end products (AGEs) induced cell injury in HEK293 cells stably expressing RAGE (HEK293-RAGE) and stimulated inflammatory responses in SH-SY5Y cells. Pretreatment of SH-SY5Y cells with an H2S donor, NaHS, significantly attenuated the above harmful effects caused by Aβ1-42 or AGEs. Western blotting analysis shows that oxidative stress enhanced RAGE protein expression which was attenuated by either NaHS or over-expression of cystathionine β-synthase (CBS), a critical enzyme for producing H2S in brain cells. Both Western blots and split GFP complementation analysis demonstrate that NaHS reduced H2O2-enhanced RAGE dimerization. Immunofluorescence analysis shows that H2O2 up-regulated the membrane expression of wild-type RAGE. However, H2O2-enhanced expression of the RAGE harboring C259S/C310S double mutation (DM-RAGE) was observed in the endoplasmic reticulum. Treatment with NaHS attenuated the effects of H2O2 on the protein expression of WT-RAGE, but not that of DM-RAGE. Cycloheximide chase and ubiquitination assays show that NaHS reduced the half-life of WT-RAGE to a similar level of DM-RAGE. S-sulfhydration assay with the tag-switch technique demonstrate that H2S may directly S-sulfhydrate the C259/C301 residues. Our data suggest that H2S reduces RAGE dimer formation and impairs its membrane stability. The lowered plasma membrane abundance of RAGE therefore helps to protect cells against various RAGE mediated pathological effects. Copyright © 2017 Elsevier Inc. All rights reserved. JF - Free radical biology & medicine AU - Zhou, Hong AU - Ding, Lei AU - Wu, Zhiyuan AU - Cao, Xu AU - Zhang, Qichun AU - Lin, Li AU - Bian, Jin-Song AD - Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore. ; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore; Life Science Institute, National University of Singapore, Singapore. ; Laboratory of Cardiovascular Sciences, National Institute on Aging, Baltimore, MD 21224, USA. ; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600 Singapore, Singapore; Life Science Institute, National University of Singapore, Singapore. Electronic address: phcbjs@nus.edu.sg. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 SP - 262 EP - 271 VL - 104 KW - Pharmacology KW - Free radicals KW - Aging KW - Hydrogen sulfide KW - Neurodegeneration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861587344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Hydrogen+sulfide+reduces+RAGE+toxicity+through+inhibition+of+its+dimer+formation.&rft.au=Zhou%2C+Hong%3BDing%2C+Lei%3BWu%2C+Zhiyuan%3BCao%2C+Xu%3BZhang%2C+Qichun%3BLin%2C+Li%3BBian%2C+Jin-Song&rft.aulast=Zhou&rft.aufirst=Hong&rft.date=2017-01-18&rft.volume=104&rft.issue=&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=1873-4596&rft_id=info:doi/10.1016%2Fj.freeradbiomed.2017.01.026 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-21 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1016/j.freeradbiomed.2017.01.026 ER - TY - JOUR T1 - Clinical and pathological characteristics of HIV- and HHV8- negative Castleman disease. AN - 1861575370; 28100459 AB - Castleman disease (CD) comprises three poorly-understood lymphoproliferative variants that share several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation, and involves multiple lymph node regions. Human herpes virus-8 causes MCD (HHV-8-associated MCD) in immunocompromised individuals, such as HIV infected patients. However, greater than 50% MCD cases are HIV and HHV-8 negative, defined as idiopathic (iMCD). The clinical and biological behavior of CD remain poorly elucidated. In this study, we analyzed the clinicopathologic features of 74 patients (43 UCD and 31 iMCD) and therapeutic response of 96 patients (43 UCD and 53 iMCD) in HIV/HHV8-negative CD compared with 51 HIV/HHV8-positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3-30.4% of marrow cells. In the lymph nodes, higher numbers of CD3+ lymphocytes (median, 58.88±20.57) and lower frequency of CD19+/CD5+ (median, 5.88±6.52) were observed in iMCD patients compared to UCD (median CD3+ cells, 43.19±17.37; median CD19+/CD5+ cells, 17.37±15.80). Complete surgical resection is better option for patients with UCD. Siltuximab had greater proportion of complete responses and longer progression-free survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals CD a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response. Copyright © 2017 American Society of Hematology. JF - Blood AU - Yu, Li AU - Tu, Meifeng AU - Cortes, Jorge AU - Xu-Monette, Zijun Y AU - Miranda, Roberto N AU - Zhang, Jun AU - Orlowski, Robert Z AU - Neelapu, Sattva AU - Boddu, Prajwal C AU - Akosile, Mary A AU - Uldrick, Thomas S AU - Yarchoan, Robert AU - Medeiros, L Jeffrey AU - Li, Yong AU - Fajgenbaum, David C AU - Young, Ken H AD - Department of Hematology, The Second Affiliate Hospital of Nanchang University, China. ; 3Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China. ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. ; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. ; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States. ; HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, United States. ; Department of Cancer Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, United States. ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. ; Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX, United States khyoung@mdanderson.org. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861575370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Clinical+and+pathological+characteristics+of+HIV-+and+HHV8-+negative+Castleman+disease.&rft.au=Yu%2C+Li%3BTu%2C+Meifeng%3BCortes%2C+Jorge%3BXu-Monette%2C+Zijun+Y%3BMiranda%2C+Roberto+N%3BZhang%2C+Jun%3BOrlowski%2C+Robert+Z%3BNeelapu%2C+Sattva%3BBoddu%2C+Prajwal+C%3BAkosile%2C+Mary+A%3BUldrick%2C+Thomas+S%3BYarchoan%2C+Robert%3BMedeiros%2C+L+Jeffrey%3BLi%2C+Yong%3BFajgenbaum%2C+David+C%3BYoung%2C+Ken+H&rft.aulast=Yu&rft.aufirst=Li&rft.date=2017-01-18&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=1528-0020&rft_id=info:doi/10.1182%2Fblood-2016-11-748855 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-19 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1182/blood-2016-11-748855 ER - TY - JOUR T1 - Amphiphilic-Polymer-Guided Plasmonic Assemblies and Their Biomedical Applications. AN - 1861568860; 28095685 AB - Plasmonic nanostructures with unique physical and biological properties have attracted increased attention for potential biomedical applications. Polymers grafted on metal nanoparticle surface can be used as assembly regulating molecules to guide nanoparticles organize into ordered or hierarchical structures in solution, within condensed phases, or at interfaces. In this Topical Review, we will highlight recent efforts on self-assembly of gold nanoparticles coated with polymer brushes. How and what kind of polymer graft can be used to adjust nanoparticle interactions, to dictate interparticle orientation, and to determine assembled nanostructures will be discussed. Furthermore, the Topical Review will shed light on the physicochemical properties, including self-assembly behavior and kinetics, tunable localized surface plasmon resonance effect, enhanced surface enhanced Raman scattering, and other optical and thermal properties. The potential of self-assembled nanostructures for applications in different fields, especially in biomedicine, will also be elaborated. JF - Bioconjugate chemistry AU - Song, Jibin AU - Niu, Gang AU - Chen, Xiaoyuan AD - Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health , Bethesda, Maryland 20892, United States. Y1 - 2017/01/18/ PY - 2017 DA - 2017 Jan 18 SP - 105 EP - 114 VL - 28 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861568860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Amphiphilic-Polymer-Guided+Plasmonic+Assemblies+and+Their+Biomedical+Applications.&rft.au=Song%2C+Jibin%3BNiu%2C+Gang%3BChen%2C+Xiaoyuan&rft.aulast=Song&rft.aufirst=Jibin&rft.date=2017-01-18&rft.volume=28&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=1520-4812&rft_id=info:doi/10.1021%2Facs.bioconjchem.6b00521 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-18 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1021/acs.bioconjchem.6b00521 ER - TY - JOUR T1 - Association of Osteopontin Gene Polymorphisms with Colorectal Cancer. AN - 1861572517; 28095066 AB - We investigated the association of the Osteopontin (OPN) (rs9138 and rs1126616) polymorphisms with colorectal cancer (CRC). One hundred CRC patients and 112 healthy individuals were subjected to OPN (rs9138 and rs1126616) genotyping and measurement of OPN protein plasma level. The C allele of OPN rs1126616 and the CC haplotype were significantly higher in CRC patient (p = 0.036, 0.003, respectively). In females, the C allele of OPN rs9318 (A/C) polymorphism was significantly associated with increased CRC risk (p = 0.036). The plasma OPN level >104.35 ng/mL was significantly associated with CRC. Our findings suggest a significant role played by OPN (rs9138 and rs1126616) in colorectal carcinogenesis. JF - Cancer investigation AU - Kamal, Asmaa AU - Darwish, Rania Kamal AU - Saad, Samar AU - Salama, Mohamed AU - El-Baradie, Tarek S AU - Mahmoud, Heba G M AU - Elshiwy, Yasmine AD - a Department of Clinical & Chemical Pathology, Faculty of Medicine , Cairo University , Cairo , Egypt. ; b Department of Surgical Oncology, National Cancer Institute , Cairo Univeristy , Cairo , Egypt. Y1 - 2017/01/17/ PY - 2017 DA - 2017 Jan 17 SP - 1 EP - 7 KW - OPN rs9138 KW - OPN rs1126616 KW - Gene polymorphism KW - Osteopontin KW - Colorectal cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861572517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+investigation&rft.atitle=Association+of+Osteopontin+Gene+Polymorphisms+with+Colorectal+Cancer.&rft.au=Kamal%2C+Asmaa%3BDarwish%2C+Rania+Kamal%3BSaad%2C+Samar%3BSalama%2C+Mohamed%3BEl-Baradie%2C+Tarek+S%3BMahmoud%2C+Heba+G+M%3BElshiwy%2C+Yasmine&rft.aulast=Kamal&rft.aufirst=Asmaa&rft.date=2017-01-17&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=1532-4192&rft_id=info:doi/10.1080%2F07357907.2016.1247454 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-17 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1080/07357907.2016.1247454 ER - TY - JOUR T1 - A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. AN - 1861562993; 28096355 AB - The self-assembly of α-synuclein is closely associated with Parkinson's disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson's disease and related conditions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Perni, Michele AU - Galvagnion, Céline AU - Maltsev, Alexander AU - Meisl, Georg AU - Müller, Martin B D AU - Challa, Pavan K AU - Kirkegaard, Julius B AU - Flagmeier, Patrick AU - Cohen, Samuel I A AU - Cascella, Roberta AU - Chen, Serene W AU - Limboker, Ryan AU - Sormanni, Pietro AU - Heller, Gabriella T AU - Aprile, Francesco A AU - Cremades, Nunilo AU - Cecchi, Cristina AU - Chiti, Fabrizio AU - Nollen, Ellen A A AU - Knowles, Tuomas P J AU - Vendruscolo, Michele AU - Bax, Adriaan AU - Zasloff, Michael AU - Dobson, Christopher M AD - Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. ; Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, United Kingdom. ; Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence 50134, Italy. ; Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC), University of Zaragoza, 50018 Zaragoza, Spain. ; University Medical Centre Groningen, European Research Institute for the Biology of Aging, University of Groningen, Groningen 9713 AV, The Netherlands. ; Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; mv245@cam.ac.uk bax@nih.gov maz5@georgetown.edu cmd44@cam.ac.uk. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; mv245@cam.ac.uk bax@nih.gov maz5@georgetown.edu cmd44@cam.ac.uk. ; MedStar-Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC 20010 mv245@cam.ac.uk bax@nih.gov maz5@georgetown.edu cmd44@cam.ac.uk. Y1 - 2017/01/17/ PY - 2017 DA - 2017 Jan 17 KW - Parkinson’s disease KW - amyloid formation KW - toxic oligomers KW - drug development KW - protein aggregation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861562993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+natural+product+inhibits+the+initiation+of+%CE%B1-synuclein+aggregation+and+suppresses+its+toxicity.&rft.au=Perni%2C+Michele%3BGalvagnion%2C+C%C3%A9line%3BMaltsev%2C+Alexander%3BMeisl%2C+Georg%3BM%C3%BCller%2C+Martin+B+D%3BChalla%2C+Pavan+K%3BKirkegaard%2C+Julius+B%3BFlagmeier%2C+Patrick%3BCohen%2C+Samuel+I+A%3BCascella%2C+Roberta%3BChen%2C+Serene+W%3BLimboker%2C+Ryan%3BSormanni%2C+Pietro%3BHeller%2C+Gabriella+T%3BAprile%2C+Francesco+A%3BCremades%2C+Nunilo%3BCecchi%2C+Cristina%3BChiti%2C+Fabrizio%3BNollen%2C+Ellen+A+A%3BKnowles%2C+Tuomas+P+J%3BVendruscolo%2C+Michele%3BBax%2C+Adriaan%3BZasloff%2C+Michael%3BDobson%2C+Christopher+M&rft.aulast=Perni&rft.aufirst=Michele&rft.date=2017-01-17&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=1091-6490&rft_id=info:doi/10.1073%2Fpnas.1610586114 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-18 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1073/pnas.1610586114 ER - TY - JOUR T1 - Unconventional oil and gas development and risk of childhood leukemia: Assessing the evidence. AN - 1835678718; 27783932 AB - The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into the relationship between UO&G development and risk of cancer in general and childhood leukemia in particular. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. JF - The Science of the total environment AU - Elliott, Elise G AU - Trinh, Pauline AU - Ma, Xiaomei AU - Leaderer, Brian P AU - Ward, Mary H AU - Deziel, Nicole C AD - Yale School of Public Health, Yale University, 60 College St., New Haven, CT 06520, USA. ; National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD 20850, USA. ; Yale School of Public Health, Yale University, 60 College St., New Haven, CT 06520, USA.. Electronic address: nicole.deziel@yale.edu. Y1 - 2017/01/15/ PY - 2017 DA - 2017 Jan 15 SP - 138 EP - 147 VL - 576 KW - Air pollution KW - Water contamination KW - Carcinogens KW - Shale KW - Wastewater KW - Hydraulic fracturing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835678718?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Science+of+the+total+environment&rft.atitle=Unconventional+oil+and+gas+development+and+risk+of+childhood+leukemia%3A+Assessing+the+evidence.&rft.au=Elliott%2C+Elise+G%3BTrinh%2C+Pauline%3BMa%2C+Xiaomei%3BLeaderer%2C+Brian+P%3BWard%2C+Mary+H%3BDeziel%2C+Nicole+C&rft.aulast=Elliott&rft.aufirst=Elise&rft.date=2017-01-15&rft.volume=576&rft.issue=&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2016.10.072 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.scitotenv.2016.10.072 ER - TY - JOUR T1 - Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats. AN - 1861512564; 28086769 AB - Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-β), type I TGF-β receptor (TβR-1), type II TGF-β receptor (TβR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR. Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CCl4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-β, TβR-I, TβR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. ginseng extract had an anti-fibrosis effect via the regulation of the TGF-β1/Smad signaling pathway in the CCl4-induced liver fibrosis model. The major target was the inhibition of the expression of TGF-β1, Smad2, and Smad3. JF - BMC complementary and alternative medicine AU - Hafez, Mohamed M AU - Hamed, Sherifa S AU - El-Khadragy, Manal F AU - Hassan, Zeinab K AU - Al Rejaie, Salim S AU - Sayed-Ahmed, Mohamed M AU - Al-Harbi, Naif O AU - Al-Hosaini, Khalid A AU - Al-Harbi, Mohamed M AU - Alhoshani, Ali R AU - Al-Shabanah, Othman A AU - Alsharari, Shakir Dekhal AD - Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. ; Department of Zoology, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. ; National Cancer Institute, Virology and Immunology Unit, Cancer Biology Department, Cairo University, Cairo, Egypt. ; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. shabanah@ksu.edu.sa. Y1 - 2017/01/13/ PY - 2017 DA - 2017 Jan 13 SP - 45 VL - 17 IS - 1 KW - Interleukin-8 KW - 0 KW - Plant Extracts KW - Receptors, Transforming Growth Factor beta KW - Smad Proteins KW - Transforming Growth Factor beta1 KW - Interleukin-10 KW - 130068-27-8 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Gene expression KW - Carbon tetrachloride KW - Ginseng extract KW - Real time PCR KW - Smad Proteins -- genetics KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Carbon Tetrachloride -- adverse effects KW - Rats KW - Smad Proteins -- metabolism KW - Interleukin-10 -- metabolism KW - Signal Transduction -- drug effects KW - Rats, Wistar KW - Interleukin-8 -- genetics KW - Interleukin-10 -- genetics KW - Interleukin-8 -- metabolism KW - Male KW - Liver Cirrhosis -- chemically induced KW - Panax -- chemistry KW - Transforming Growth Factor beta1 -- metabolism KW - Liver Cirrhosis -- drug therapy KW - Liver Cirrhosis -- metabolism KW - Transforming Growth Factor beta1 -- genetics KW - Liver Cirrhosis -- genetics KW - Plant Extracts -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861512564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+complementary+and+alternative+medicine&rft.atitle=Effect+of+ginseng+extract+on+the+TGF-%CE%B21+signaling+pathway+in+CCl4-induced+liver+fibrosis+in+rats.&rft.au=Hafez%2C+Mohamed+M%3BHamed%2C+Sherifa+S%3BEl-Khadragy%2C+Manal+F%3BHassan%2C+Zeinab+K%3BAl+Rejaie%2C+Salim+S%3BSayed-Ahmed%2C+Mohamed+M%3BAl-Harbi%2C+Naif+O%3BAl-Hosaini%2C+Khalid+A%3BAl-Harbi%2C+Mohamed+M%3BAlhoshani%2C+Ali+R%3BAl-Shabanah%2C+Othman+A%3BAlsharari%2C+Shakir+Dekhal&rft.aulast=Hafez&rft.aufirst=Mohamed&rft.date=2017-01-13&rft.volume=17&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=BMC+complementary+and+alternative+medicine&rft.issn=1472-6882&rft_id=info:doi/10.1186%2Fs12906-016-1507-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-25 N1 - Date created - 2017-01-14 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1186/s12906-016-1507-0 ER - TY - JOUR T1 - Vibrio cholerae Cholix toxin-induced HepG2 cell death is enhanced by tumor necrosis factor-alpha through ROS and intracellular signal-regulated kinases. AN - 1861495899; 28087840 AB - Cholix toxin (Cholix) from Vibrio cholerae is a potent virulence factor exhibiting ADP-ribosyltransferase activity on eukaryotic elongation factor 2 (eEF2) of host cells, resulting in inhibition of protein synthesis. Administration of Cholix or its homologue Pseudomonas exotoxin A (PEA) to mice causes lethal hepatocyte damage. In this study, we demonstrate cytotoxicity of Cholix on immortalized human hepatocytes in the presence of tumor necrosis factor α (TNF-α), which has been reported to play a fatal role in PEA administered to mice. Compared to incubating HepG2 cells with Cholix alone, co-treatment with TNF-α and Cholix (TNF-α/Cholix) significantly enhanced activation of caspases, cytochrome c release from mitochondria into cytoplasm, and poly-ADP-ribose polymerase (PARP) cleavage, while incubation with TNF-α alone or co-treatment with TNF-α/χαταλyτιχαλlψ inactive Cholix did not. In the early stage of cell death, Cholix increased phosphorylation of mitogen-activated protein kinases (e.g., p38, ERK, JNK) and Akt, which was not affected by TNF-α alone. MAPK inhibitors (SP600125, SB20852, U0126) suppressed PARP cleavage induced by TNF-α/Cholix. Protein kinase inhibitor Go6976 suppressed JNK phosphorylation and PARP cleavage by TNF-α/Cholix. In contrast, PKC activator PMA in the absence of TNF-α promoted Cholix-induced PARP cleavage. Reactive oxygen species (ROS) inhibitor, N-acetyl cysteine (NAC), suppressed TNF-α/Χhoλιξ-induced JNK and ERK phosphorylation, resulting in inhibition of PARP cleavage. These data suggest that ROS and JNK pathways are important mediators of TNF-α/Cholix-induced HepG2 cell death. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Ogura, Kohei AU - Terasaki, Yasuhiro AU - Miyoshi-Akiyama, Tohru AU - Terasaki, Mika AU - Moss, Joel AU - Noda, Masatoshi AU - Yahiro, Kinnosuke AD - Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan. ; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan. ; Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. ; Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA. ; Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan; yahirok@faculty.chiba-u.jp. Y1 - 2017/01/13/ PY - 2017 DA - 2017 Jan 13 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861495899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Vibrio+cholerae+Cholix+toxin-induced+HepG2+cell+death+is+enhanced+by+tumor+necrosis+factor-alpha+through+ROS+and+intracellular+signal-regulated+kinases.&rft.au=Ogura%2C+Kohei%3BTerasaki%2C+Yasuhiro%3BMiyoshi-Akiyama%2C+Tohru%3BTerasaki%2C+Mika%3BMoss%2C+Joel%3BNoda%2C+Masatoshi%3BYahiro%2C+Kinnosuke&rft.aulast=Ogura&rft.aufirst=Kohei&rft.date=2017-01-13&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfx009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-14 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1093/toxsci/kfx009 ER - TY - JOUR T1 - Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity. AN - 1857753264; 28074935 AB - The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context. JF - Scientific reports AU - Maiorani, Orlando AU - Pivetta, Eliana AU - Capuano, Alessandra AU - Modica, Teresa Maria Elisa AU - Wassermann, Bruna AU - Bucciotti, Francesco AU - Colombatti, Alfonso AU - Doliana, Roberto AU - Spessotto, Paola AD - Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute, Aviano 33081, Italy. Y1 - 2017/01/11/ PY - 2017 DA - 2017 Jan 11 SP - 39974 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857753264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Neutrophil+elastase+cleavage+of+the+gC1q+domain+impairs+the+EMILIN1-%CE%B14%CE%B21+integrin+interaction%2C+cell+adhesion+and+anti-proliferative+activity.&rft.au=Maiorani%2C+Orlando%3BPivetta%2C+Eliana%3BCapuano%2C+Alessandra%3BModica%2C+Teresa+Maria+Elisa%3BWassermann%2C+Bruna%3BBucciotti%2C+Francesco%3BColombatti%2C+Alfonso%3BDoliana%2C+Roberto%3BSpessotto%2C+Paola&rft.aulast=Maiorani&rft.aufirst=Orlando&rft.date=2017-01-11&rft.volume=7&rft.issue=&rft.spage=39974&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep39974 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-11 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/srep39974 ER - TY - JOUR T1 - Cost evaluation of irinotecan-related toxicities associated with the UGT1A1*28 patient genotype. AN - 1857751914; 28074472 AB - The adoption of a pre-emptive UGT1A1*28 genotyping to increase irinotecan safety in clinical practice is still limited. This is the first actual study of costs associated to the management of irinotecan-related toxicity, and their association with UGT1A1*28 genotype. A retrospective analysis of the cost of toxicity management was conducted on 243 metastatic colorectal cancer patients enrolled in a clinical trial and treated with standard of care FOLFIRI. The mean predicted cost per patient was higher for *28/*28 (4,886€), versus *1/*1 (812€), (regression coefficient 1.79, 95%CI=1.31-2.28; P<0.001) and for *1/*28 (1,119€) versus *1/*1 (regression coefficient 0.32, 95%CI=0.04-0.60; P=0.024). This is consistent with a different grade 4 toxicity profile among the three genotypes, and a higher frequency of costly interventions like hospitalization among patients with the *28 allele. A differential toxicity management cost by *28 genotype is herein demonstrated, representing a first step towards a demonstration of the test clinical utility. This article is protected by copyright. All rights reserved. © 2017 American Society for Clinical Pharmacology and Therapeutics. JF - Clinical pharmacology and therapeutics AU - Roncato, R AU - Cecchin, E AU - Montico, M AU - De Mattia, E AU - Giodini, L AU - Buonadonna, A AU - Solfrini, V AU - Innocenti, F AU - Toffoli, G AD - Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico- National Cancer Institute, 2-33081, Aviano, Italy. ; Medical Oncology Unit B, Centro Di Riferimento Oncologico- National Cancer Institute, 2-33081, Aviano, Italy. ; Sanitary Direction, Centro Di Riferimento Oncologico- National Cancer Institute, 2-33081, Aviano, Italy. ; Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. Y1 - 2017/01/11/ PY - 2017 DA - 2017 Jan 11 KW - direct medical costs KW - irinotecan KW - cost of toxicity management KW - UGT1A1*28 KW - pharmacogenetics KW - colorectal cancer KW - Italy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857751914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Epidemiology&rft.atitle=Circulatory+disease+mortality+in+the+Massachusetts+tuberculosis+fluoroscopy+cohort+study&rft.au=Little%2C+Mark+P%3BZablotska%2C+Lydia+B%3BBrenner%2C+Alina+V%3BLipshultz%2C+Steven+E&rft.aulast=Little&rft.aufirst=Mark&rft.date=2016-03-01&rft.volume=31&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Epidemiology&rft.issn=03932990&rft_id=info:doi/10.1007%2Fs10654-015-0075-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cpt.615 ER - TY - JOUR T1 - Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo. AN - 1857374964; 28071703 AB - Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo. JF - Scientific reports AU - Bruno, Robert D AU - Fleming, Jodie M AU - George, Andrea L AU - Boulanger, Corinne A AU - Schedin, Pepper AU - Smith, Gilbert H AD - School of Medical Diagnostic &Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA 23529, USA. ; Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC, 27707, USA. ; Mammary Stem Cell Biology Section, Basic Research Laboratory, CCR, NCI/NIH, Bethesda MD, 20892, USA. ; Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Y1 - 2017/01/10/ PY - 2017 DA - 2017 Jan 10 SP - 40196 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1857374964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Mammary+extracellular+matrix+directs+differentiation+of+testicular+and+embryonic+stem+cells+to+form+functional+mammary+glands+in+vivo.&rft.au=Bruno%2C+Robert+D%3BFleming%2C+Jodie+M%3BGeorge%2C+Andrea+L%3BBoulanger%2C+Corinne+A%3BSchedin%2C+Pepper%3BSmith%2C+Gilbert+H&rft.aulast=Bruno&rft.aufirst=Robert&rft.date=2017-01-10&rft.volume=7&rft.issue=&rft.spage=40196&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep40196 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-10 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/srep40196 ER - TY - JOUR T1 - Oxidized nucleotide insertion by pol β confounds ligation during base excision repair. AN - 1856864860; 28067232 AB - Oxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase β (pol β) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol β insertion of oxidized purine nucleotides into the BER intermediate in vitro. These results suggest the possibility that BER mediated toxic strand breaks are produced in cells under oxidative stress conditions. We observe enhanced cytotoxicity in oxidizing-agent treated pol β expressing mouse fibroblasts, suggesting formation of DNA strand breaks under these treatment conditions. Increased cytotoxicity following MTH1 knockout or treatment with MTH1 inhibitor suggests the oxidation of precursor nucleotides. JF - Nature communications AU - Çağlayan, Melike AU - Horton, Julie K AU - Dai, Da-Peng AU - Stefanick, Donna F AU - Wilson, Samuel H AD - Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2017/01/09/ PY - 2017 DA - 2017 Jan 09 SP - 14045 VL - 8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856864860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Oxidized+nucleotide+insertion+by+pol+%CE%B2+confounds+ligation+during+base+excision+repair.&rft.au=%C3%87a%C4%9Flayan%2C+Melike%3BHorton%2C+Julie+K%3BDai%2C+Da-Peng%3BStefanick%2C+Donna+F%3BWilson%2C+Samuel+H&rft.aulast=%C3%87a%C4%9Flayan&rft.aufirst=Melike&rft.date=2017-01-09&rft.volume=8&rft.issue=&rft.spage=14045&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms14045 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms14045 ER - TY - JOUR T1 - Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl. AN - 1852676393; 27966365 AB - Occupational exposures to the diketone flavoring agent, diacetyl, have been associated with bronchiolitis obliterans, a rare condition of airway fibrosis. Model studies in rodents have suggested that the airway epithelium is a major site of diacetyl toxicity, but the effects of diacetyl exposure upon the human airway epithelium are poorly characterized. Here we performed quantitative LC-MS/MS-based proteomics to study the effects of repeated diacetyl vapor exposures on 3D organotypic cultures of human primary tracheobronchial epithelial cells. Using a label-free approach, we quantified approximately 3400 proteins and 5700 phosphopeptides in cell lysates across four independent donors. Altered expression of proteins and phosphopeptides were suggestive of loss of cilia and increased squamous differentiation in diacetyl-exposed cells. These phenomena were confirmed by immunofluorescence staining of culture cross sections. Hyperphosphorylation and cross-linking of basal cell keratins were also observed in diacetyl-treated cells, and we used parallel reaction monitoring to confidently localize and quantify previously uncharacterized sites of phosphorylation in keratin 6. Collectively, these data identify numerous molecular changes in the epithelium that may be important to the pathogenesis of flavoring-induced bronchiolitis obliterans. More generally, this study highlights the utility of quantitative proteomics for the study of in vitro models of airway injury and disease. JF - Journal of proteome research AU - Foster, Matthew W AU - Gwinn, William M AU - Kelly, Francine L AU - Brass, David M AU - Valente, Ashlee M AU - Moseley, M Arthur AU - Thompson, J Will AU - Morgan, Daniel L AU - Palmer, Scott M AD - National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709, United States. Y1 - 2017/01/09/ PY - 2017 DA - 2017 Jan 09 KW - squamous metaplasia KW - repetin KW - butter flavoring KW - RSPH4A KW - TGM1 KW - butanedione KW - BO KW - cornified envelope KW - PRM KW - pentanedione UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852676393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+proteome+research&rft.atitle=Proteomic+Analysis+of+Primary+Human+Airway+Epithelial+Cells+Exposed+to+the+Respiratory+Toxicant+Diacetyl.&rft.au=Foster%2C+Matthew+W%3BGwinn%2C+William+M%3BKelly%2C+Francine+L%3BBrass%2C+David+M%3BValente%2C+Ashlee+M%3BMoseley%2C+M+Arthur%3BThompson%2C+J+Will%3BMorgan%2C+Daniel+L%3BPalmer%2C+Scott+M&rft.aulast=Foster&rft.aufirst=Matthew&rft.date=2017-01-09&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+proteome+research&rft.issn=1535-3907&rft_id=info:doi/10.1021%2Facs.jproteome.6b00672 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jproteome.6b00672 ER - TY - JOUR T1 - Renal Toxicities of Novel Agents Used for Treatment of Multiple Myeloma. AN - 1856594646; 27654928 AB - Survival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma. Copyright © 2016 by the American Society of Nephrology. JF - Clinical journal of the American Society of Nephrology : CJASN AU - Wanchoo, Rimda AU - Abudayyeh, Ala AU - Doshi, Mona AU - Edeani, Amaka AU - Glezerman, Ilya G AU - Monga, Divya AU - Rosner, Mitchell AU - Jhaveri, Kenar D AD - Division of Nephrology, Hofstra Northwell School of Medicine, Great Neck, New York. ; Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ; Division of Nephrology, Wayne State University School of Medicine, Detroit, Michigan. ; Kidney Diseases Branch, National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland. ; Department of Medicine, Renal Service, Memorial Sloan Kettering Cancer Center and Department of Medicine, Weill Cornell Medical Center, New York, New York. ; Nephrology Division, University of Mississippi Medical Center, Jackson, Mississippi; and. ; Division of Nephrology, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia. ; Division of Nephrology, Hofstra Northwell School of Medicine, Great Neck, New York; kjhaveri@northwell.edu. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 176 EP - 189 VL - 12 IS - 1 KW - Proteasome Inhibitors KW - multiple myeloma KW - Coal Tar KW - electrolytes KW - humans KW - chronic kidney disease KW - Antibodies, Monoclonal KW - drug nephrotoxicity KW - Acute Kidney Injury KW - acute renal failure KW - Water-Electrolyte Imbalance KW - kidney KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856594646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+journal+of+the+American+Society+of+Nephrology+%3A+CJASN&rft.atitle=Renal+Toxicities+of+Novel+Agents+Used+for+Treatment+of+Multiple+Myeloma.&rft.au=Wanchoo%2C+Rimda%3BAbudayyeh%2C+Ala%3BDoshi%2C+Mona%3BEdeani%2C+Amaka%3BGlezerman%2C+Ilya+G%3BMonga%2C+Divya%3BRosner%2C+Mitchell%3BJhaveri%2C+Kenar+D&rft.aulast=Wanchoo&rft.aufirst=Rimda&rft.date=2017-01-06&rft.volume=12&rft.issue=1&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Clinical+journal+of+the+American+Society+of+Nephrology+%3A+CJASN&rft.issn=1555-905X&rft_id=info:doi/10.2215%2FCJN.06100616 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-22 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.2215/CJN.06100616 ER - TY - JOUR T1 - Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward. AN - 1856593194; 27618739 AB - Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions. JF - Annual review of pharmacology and toxicology AU - Volkow, Nora D AU - Hampson, Aidan J AU - Baler, Ruben D AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892; email: nvolkow@nida.nih.gov. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 285 EP - 308 VL - 57 KW - endocannabinoids KW - cannabis KW - reward KW - THC KW - stress KW - marijuana UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856593194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Don%27t+Worry%2C+Be+Happy%3A+Endocannabinoids+and+Cannabis+at+the+Intersection+of+Stress+and+Reward.&rft.au=Volkow%2C+Nora+D%3BHampson%2C+Aidan+J%3BBaler%2C+Ruben+D&rft.aulast=Volkow&rft.aufirst=Nora&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-010716-104615 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-010716-104615 ER - TY - JOUR T1 - CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism? AN - 1856593185; 27575715 AB - There are many challenges along the path to the approval of new drugs to treat CNS disorders, one of the greatest areas of unmet medical need with a large societal burden and health-care impact. Unfortunately, over the past two decades, few CNS drug approvals have succeeded, leading many pharmaceutical companies to deprioritize this therapeutic area. The reasons for the failures in CNS drug discovery are likely to be multifactorial. However, selecting the most biologically plausible molecular targets that are relevant to the disorder is a critical first step to improve the probability of success. In this review, we outline previous methods for identifying and validating novel targets for CNS drug discovery, and, cognizant of previous failures, we discuss potential new strategies that may improve the probability of success of developing novel treatments for CNS disorders. JF - Annual review of pharmacology and toxicology AU - Hutson, P H AU - Clark, J A AU - Cross, A J AD - Neurobiology, CNS Discovery, Teva Pharmaceuticals, West Chester, Pennsylvania 19380; email: peter.hutson@tevapharm.com. ; Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20892; email: Janet.Clark@nih.gov. ; Neuroscience Innovative Medicines, AstraZeneca, Cambridge, Massachusetts 01239; email: alan.cross@azneuro.com. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 171 EP - 187 VL - 57 KW - drug development KW - psychiatry KW - neurology KW - drug discovery KW - translational research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856593185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=CNS+Target+Identification+and+Validation%3A+Avoiding+the+Valley+of+Death+or+Naive+Optimism%3F&rft.au=Hutson%2C+P+H%3BClark%2C+J+A%3BCross%2C+A+J&rft.aulast=Hutson&rft.aufirst=P&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-010716-104624 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-010716-104624 ER - TY - JOUR T1 - Harnessing Big Data for Systems Pharmacology. AN - 1836728054; 27814027 AB - Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable. JF - Annual review of pharmacology and toxicology AU - Xie, Lei AU - Draizen, Eli J AU - Bourne, Philip E AD - Department of Computer Science, Hunter College, The City University of New York, New York, NY 10065; email: lei.xie@hunter.cuny.edu. ; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894; email: philip.bourne@nih.gov. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 245 EP - 262 VL - 57 KW - data science KW - systems pharmacology modeling KW - NIH Commons KW - systems biology KW - computational modeling KW - machine learning KW - cloud computing KW - semantic web UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836728054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Harnessing+Big+Data+for+Systems+Pharmacology.&rft.au=Xie%2C+Lei%3BDraizen%2C+Eli+J%3BBourne%2C+Philip+E&rft.aulast=Xie&rft.aufirst=Lei&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-010716-104659 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-010716-104659 ER - TY - JOUR T1 - Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology". AN - 1835420354; 27732830 AB - Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care. JF - Annual review of pharmacology and toxicology AU - Insel, Paul A AU - Amara, Susan G AU - Blaschke, Terrence F AU - Meyer, Urs A AD - Department of Pharmacology, University of California, San Diego, La Jolla, California 92093. ; National Institute of Mental Health, Bethesda, Maryland 20892. ; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305. ; Biozentrum, University of Basel, CH-4056 Basel, Switzerland. Y1 - 2017/01/06/ PY - 2017 DA - 2017 Jan 06 SP - 13 EP - 17 VL - 57 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835420354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+pharmacology+and+toxicology&rft.atitle=Introduction+to+the+Theme+%22New+Methods+and+Novel+Therapeutic+Approaches+in+Pharmacology+and+Toxicology%22.&rft.au=Insel%2C+Paul+A%3BAmara%2C+Susan+G%3BBlaschke%2C+Terrence+F%3BMeyer%2C+Urs+A&rft.aulast=Insel&rft.aufirst=Paul&rft.date=2017-01-06&rft.volume=57&rft.issue=&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+pharmacology+and+toxicology&rft.issn=1545-4304&rft_id=info:doi/10.1146%2Fannurev-pharmtox-091616-023708 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1146/annurev-pharmtox-091616-023708 ER - TY - JOUR T1 - Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18. AN - 1855788136; 28052328 AB - Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log10 -transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted  = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted  = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted  = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log10 -unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association. © 2017 UICC. JF - International journal of cancer AU - Fu Xi, Long AU - Schiffman, Mark AU - Ke, Yang AU - Hughes, James P AU - Galloway, Denise A AU - He, Zhonghu AU - Hulbert, Ayaka AU - Winer, Rachel L AU - Koutsky, Laura A AU - Kiviat, Nancy B AD - Department of Pathology, School of Medicine, University of Washington, Seattle, WA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. ; Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing, People's Republic of China. ; Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA. ; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA. ; Department of Epidemiology, University of Washington, Seattle, WA. Y1 - 2017/01/04/ PY - 2017 DA - 2017 Jan 04 KW - risk association KW - human papillomavirus KW - cervical intraepithelial neoplasia KW - viral load UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855788136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Type-dependent+association+between+risk+of+cervical+intraepithelial+neoplasia+and+viral+load+of+oncogenic+human+papillomavirus+types+other+than+types+16+and+18.&rft.au=Fu+Xi%2C+Long%3BSchiffman%2C+Mark%3BKe%2C+Yang%3BHughes%2C+James+P%3BGalloway%2C+Denise+A%3BHe%2C+Zhonghu%3BHulbert%2C+Ayaka%3BWiner%2C+Rachel+L%3BKoutsky%2C+Laura+A%3BKiviat%2C+Nancy+B&rft.aulast=Fu+Xi&rft.aufirst=Long&rft.date=2017-01-04&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.30594 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-04 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1002/ijc.30594 ER - TY - JOUR T1 - Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. AN - 1855331799; 28051126 AB - Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes non-alcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-α, PPAR-γ, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE. JF - Scientific reports AU - Abdelmegeed, Mohamed A AU - Choi, Youngshim AU - Godlewski, Grzegorz AU - Ha, Seung-Kwon AU - Banerjee, Atrayee AU - Jang, Sehwan AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA. ; Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20982, USA. Y1 - 2017/01/04/ PY - 2017 DA - 2017 Jan 04 SP - 39764 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855331799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Cytochrome+P450-2E1+promotes+fast+food-mediated+hepatic+fibrosis.&rft.au=Abdelmegeed%2C+Mohamed+A%3BChoi%2C+Youngshim%3BGodlewski%2C+Grzegorz%3BHa%2C+Seung-Kwon%3BBanerjee%2C+Atrayee%3BJang%2C+Sehwan%3BSong%2C+Byoung-Joon&rft.aulast=Abdelmegeed&rft.aufirst=Mohamed&rft.date=2017-01-04&rft.volume=7&rft.issue=&rft.spage=39764&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep39764 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep39764 ER - TY - JOUR T1 - Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity. AN - 1855066304; 28045021 AB - The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB2R agonists to study the role of CB2R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research. JF - Nature communications AU - Soethoudt, Marjolein AU - Grether, Uwe AU - Fingerle, Jürgen AU - Grim, Travis W AU - Fezza, Filomena AU - de Petrocellis, Luciano AU - Ullmer, Christoph AU - Rothenhäusler, Benno AU - Perret, Camille AU - van Gils, Noortje AU - Finlay, David AU - MacDonald, Christa AU - Chicca, Andrea AU - Gens, Marianela Dalghi AU - Stuart, Jordyn AU - de Vries, Henk AU - Mastrangelo, Nicolina AU - Xia, Lizi AU - Alachouzos, Georgios AU - Baggelaar, Marc P AU - Martella, Andrea AU - Mock, Elliot D AU - Deng, Hui AU - Heitman, Laura H AU - Connor, Mark AU - Di Marzo, Vincenzo AU - Gertsch, Jürg AU - Lichtman, Aron H AU - Maccarrone, Mauro AU - Pacher, Pal AU - Glass, Michelle AU - van der Stelt, Mario AD - Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. ; Roche Innovation Center Basel, F. Hoffman-La Roche Ltd., Grenzachterstrasse 124, Basel 4070, Switzerland. ; Department of Biochemistry, NMI, University Tübingen, Markwiesenstrasse 55, Reutlingen 72770, Germany. ; Department of Pharmacology and Toxicology, 1220 East Broad Street, PO Box 980613, Richmond, Virginia 23298-0613, USA. ; Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, Via Montpellier 1, Rome 00133, Italy. ; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R., Via Campi Flegrei 34, Comprensorio Olivetti, Pozzuoli 80078, Italy. ; Department of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. ; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park road, Grafton, Auckland 1023, New Zealand. ; Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, Bern CH-3012, Switzerland. ; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, New South Wales 2109, Australia. ; Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, Rome 00128, Italy. ; European Center for Brain Research/IRCCS Santa Lucia Foundation, via del Fosso del Fiorano 65, Rome 00143, Italy. ; Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute of Health/NIAAA, 5625 Fishers Lane, Rockville, Maryland 20852, USA. Y1 - 2017/01/03/ PY - 2017 DA - 2017 Jan 03 SP - 13958 VL - 8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855066304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Cannabinoid+CB2+receptor+ligand+profiling+reveals+biased+signalling+and+off-target+activity.&rft.au=Soethoudt%2C+Marjolein%3BGrether%2C+Uwe%3BFingerle%2C+J%C3%BCrgen%3BGrim%2C+Travis+W%3BFezza%2C+Filomena%3Bde+Petrocellis%2C+Luciano%3BUllmer%2C+Christoph%3BRothenh%C3%A4usler%2C+Benno%3BPerret%2C+Camille%3Bvan+Gils%2C+Noortje%3BFinlay%2C+David%3BMacDonald%2C+Christa%3BChicca%2C+Andrea%3BGens%2C+Marianela+Dalghi%3BStuart%2C+Jordyn%3Bde+Vries%2C+Henk%3BMastrangelo%2C+Nicolina%3BXia%2C+Lizi%3BAlachouzos%2C+Georgios%3BBaggelaar%2C+Marc+P%3BMartella%2C+Andrea%3BMock%2C+Elliot+D%3BDeng%2C+Hui%3BHeitman%2C+Laura+H%3BConnor%2C+Mark%3BDi+Marzo%2C+Vincenzo%3BGertsch%2C+J%C3%BCrg%3BLichtman%2C+Aron+H%3BMaccarrone%2C+Mauro%3BPacher%2C+Pal%3BGlass%2C+Michelle%3Bvan+der+Stelt%2C+Mario&rft.aulast=Soethoudt&rft.aufirst=Marjolein&rft.date=2017-01-03&rft.volume=8&rft.issue=&rft.spage=13958&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms13958 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms13958 ER - TY - JOUR T1 - Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China. AN - 1852658684; 27936627 AB - Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin (HSA) in 29 nonsmoking Xuanwei and Fuyuan females who used smoky coal, smokeless coal, or wood and 10 local controls who used electricity or gas fuel. Our untargeted "adductomics" method detected 50 tryptic peptides of HSA, containing Cys34 and prominent post-translational modifications. Putative adducts included Cys34 oxidation products, mixed disulfides, rearrangements, and truncations. The most significant differences in adduct levels across fuel types were observed for S-glutathione (S-GSH) and S-γ-glutamylcysteine (S-γ-GluCys), both of which were present at lower levels in subjects exposed to combustion products than in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene, the largest reductions in levels of S-GSH and S-γ-GluCys relative to controls were observed for users of smoky coal, compared to users of smokeless coal and wood. These results point to possible depletion of GSH, an essential antioxidant, and its precursor γ-GluCys in nonsmoking females exposed to indoor-combustion products in Xuanwei and Fuyuan, China. JF - Environmental science & technology AU - Lu, Sixin S AU - Grigoryan, Hasmik AU - Edmands, William M B AU - Hu, Wei AU - Iavarone, Anthony T AU - Hubbard, Alan AU - Rothman, Nathaniel AU - Vermeulen, Roel AU - Lan, Qing AU - Rappaport, Stephen M AD - Department of Nutritional Sciences and Toxicology, College of Natural Resources, University of California , Berkeley, California 94720, United States. ; Division of Environmental Health Sciences, School of Public Health, University of California , Berkeley, California 94720, United States. ; Department of Health and Human Service, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville, Maryland 20850, United States. ; California Institute for Quantitative Biosciences, University of California , Berkeley, California 94720, United States. ; Division of Biostatistics, School of Public Health, University of California , Berkeley, California 94720, United States. ; Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University , 3508 TD Utrecht, The Netherlands. Y1 - 2017/01/03/ PY - 2017 DA - 2017 Jan 03 SP - 46 EP - 57 VL - 51 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852658684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+science+%26+technology&rft.atitle=Profiling+the+Serum+Albumin+Cys34+Adductome+of+Solid+Fuel+Users+in+Xuanwei+and+Fuyuan%2C+China.&rft.au=Lu%2C+Sixin+S%3BGrigoryan%2C+Hasmik%3BEdmands%2C+William+M+B%3BHu%2C+Wei%3BIavarone%2C+Anthony+T%3BHubbard%2C+Alan%3BRothman%2C+Nathaniel%3BVermeulen%2C+Roel%3BLan%2C+Qing%3BRappaport%2C+Stephen+M&rft.aulast=Lu&rft.aufirst=Sixin&rft.date=2017-01-03&rft.volume=51&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Environmental+science+%26+technology&rft.issn=1520-5851&rft_id=info:doi/10.1021%2Facs.est.6b03955 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.est.6b03955 ER - TY - JOUR T1 - An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity. AN - 1852786764; 28011845 AB - Ceramides are key intermediates in sphingolipid biosynthesis and potent signaling molecules. However, excess ceramide is toxic, causing growth arrest and apoptosis. In this study, we identify a novel mechanism by which cells prevent the toxic accumulation of ceramides; they facilitate nonvesicular ceramide transfer from the endoplasmic reticulum (ER) to the Golgi complex, where ceramides are converted to complex sphingolipids. We find that the yeast protein Nvj2p promotes the nonvesicular transfer of ceramides from the ER to the Golgi complex. The protein is a tether that generates close contacts between these compartments and may directly transport ceramide. Nvj2p normally resides at contacts between the ER and other organelles, but during ER stress, it relocalizes to and increases ER-Golgi contacts. ER-Golgi contacts fail to form during ER stress in cells lacking Nvj2p. Our findings demonstrate that cells regulate ER-Golgi contacts in response to stress and reveal that nonvesicular ceramide transfer out of the ER prevents the buildup of toxic amounts of ceramides. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. JF - The Journal of cell biology AU - Liu, Li-Ka AU - Choudhary, Vineet AU - Toulmay, Alexandre AU - Prinz, William A AD - Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. ; Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 toulmayal@niddk.nih.gov prinzw@helix.nih.gov. Y1 - 2017/01/02/ PY - 2017 DA - 2017 Jan 02 SP - 131 EP - 147 VL - 216 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852786764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=An+inducible+ER-Golgi+tether+facilitates+ceramide+transport+to+alleviate+lipotoxicity.&rft.au=Liu%2C+Li-Ka%3BChoudhary%2C+Vineet%3BToulmay%2C+Alexandre%3BPrinz%2C+William+A&rft.aulast=Liu&rft.aufirst=Li-Ka&rft.date=2017-01-02&rft.volume=216&rft.issue=1&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=1540-8140&rft_id=info:doi/10.1083%2Fjcb.201606059 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-24 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1083/jcb.201606059 ER - TY - JOUR T1 - Caught between two proteins: a mycobacterial inhibitor challenges the mold AN - 1863210602; PQ0003986939 AB - Elucidating the target or mechanism of action of potential drugs in the discovery pipeline is an integral component of most programs. For antibacterial compounds, generation of resistant mutants followed by whole genome sequencing has often been successful in uncovering the proteins involved in regulating compound activation, uptake, efflux and importantly, target processes. When this process succeeds, we are quick to declare a target. In a study reported by Sing and Dhar et al. (in press), the combination of resistant mutant generation, whole genome sequencing and recombineering to identify the target of a Mycobacterium tuberculosis growth inhibitor, pointed to a mechanism involving a scaffolding protein, Wag31, involved in polar elongation of mycobacterial cells. Time-lapse microscopy and electron microscopy confirmed the view that this inhibitor resulted in interruption of nascent cell wall biosynthesis. However, co-expression as well as regulated titration of the putative Wag31 target demonstrated that the wild-type allele was dominant and showed no synergy with the inhibitor. The most plausible explanation from their results was that this inhibitor interfered with the interaction of Wag31 with one of its interacting partners in the elongation complex. JF - Molecular Microbiology AU - Boshoff, Helena I AD - Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892-3206, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 2 EP - 6 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 103 IS - 1 SN - 0950-382X, 0950-382X KW - Microbiology Abstracts B: Bacteriology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1863210602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Caught+between+two+proteins%3A+a+mycobacterial+inhibitor+challenges+the+mold&rft.au=Boshoff%2C+Helena+I&rft.aulast=Boshoff&rft.aufirst=Helena&rft.date=2017-01-01&rft.volume=103&rft.issue=1&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fmmi.13570 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1111/mmi.13570 ER - TY - JOUR T1 - Neuronal Cell Death and Degeneration through Increased Nitroxidative Stress and Tau Phosphorylation in HIV-1 Transgenic Rats. AN - 1861587464; 28107387 AB - The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT. Mechanistic studies revealed that increased levels of nitroxidative stress marker proteins such as NADPH-oxidase, cytochrome P450-2E1 (CYP2E1), inducible nitric oxide synthase (iNOS), the stress-activated mitogen-activated protein kinases such as JNK and p38K, activated cell-cycle dependent CDK5, hypoxia-inducible protein-1α, nitrated proteins, hyperphosphorylated tau, and amyloid plaques in HIV-Tg rats were consistently observed in HIV-1 Tg rats. Confocal microscopy and cell viability analyses showed that treatment with an antioxidant N-acetylcysteine or a specific inhibitor of iNOS 1400W significantly prevented the increased apoptosis of neuro-2A cells by HIV-1 Tat or gp120 protein, demonstrating the causal role of HIV-1 mediated nitroxidative stress and protein nitration in promoting neuronal cell death. Immunoprecipitation and immunoblot analysis confirmed nitration of Hsp90, evaluated as an example of nitrated proteins, suggesting possible involvement of nitrated proteins in neuronal damage. Further, activated p-JNK directly binds tau and phosphorylates multiple amino acids, suggesting an important role of p-JNK in tau hyperphosphorylation and tauopathy. These changes were accompanied with elevated levels of many apoptosis-related proteins Bax and cleaved (activated) caspase-3 as well as proinflammatory cytokines including TNF-α, IL-6 and MCP-1. Collectively, these results indicate that raised nitroxidative stress accompanied by elevated inflammation, cell death signaling pathway including activated p-JNK, C-terminal C99 amyloid fragment formation and tau hyperphosphorylation are responsible for increased apoptosis of neuronal cells and neurodegeneration in 5-month old HIV-Tg rats. JF - PloS one AU - Cho, Young-Eun AU - Lee, Myoung-Hwa AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, United States of America. ; Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, United States of America. Y1 - 2017 PY - 2017 DA - 2017 SP - 1 VL - 12 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861587464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PloS+one&rft.atitle=Neuronal+Cell+Death+and+Degeneration+through+Increased+Nitroxidative+Stress+and+Tau+Phosphorylation+in+HIV-1+Transgenic+Rats.&rft.au=Cho%2C+Young-Eun%3BLee%2C+Myoung-Hwa%3BSong%2C+Byoung-Joon&rft.aulast=Cho&rft.aufirst=Young-Eun&rft.date=2017-01-01&rft.volume=12&rft.issue=1&rft.spage=e0169945&rft.isbn=&rft.btitle=&rft.title=PloS+one&rft.issn=1932-6203&rft_id=info:doi/10.1371%2Fjournal.pone.0169945 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-20 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1371/journal.pone.0169945 ER - TY - JOUR T1 - Tetrabromobisphenol A activates the hepatic interferon pathway in rats AN - 1859502039; PQ0004015269 AB - Tetrabromobisphenol A (TBBPA) is a widely used flame retardant in printed circuit boards, paper, and textiles. In a two-year study, TBBPA showed evidence of uterine tumors in female Wistar-Han rats and liver and colon tumors in B6C3F1 mice. In order to gain further insight into early gene and pathway changes leading to cancer, we exposed female Wistar Han rats to TBBPA at 0, 25, 250, or 1000mg/kg (oral gavage in corn oil, 5/week) for 13 weeks. Because at the end of the TBBPA exposure period, there were no treatment-related effects on body weights, liver or uterus lesions, and liver and uterine organ weights were within 10% of controls, only the high dose animals were analyzed. Analysis of the hepatic and uterine transcriptomes showed TBBPA-induced changes primarily in the liver (1000mg/kg), with 159 transcripts corresponding to 132 genes differentially expressed compared to controls (FDR=0.05). Pathway analysis showed activation of interferon (IFN) and metabolic networks. TBBPA induced few molecular changes in the uterus. Activation of the interferon pathway in the liver occurred after 13-weeks of TBBPA exposure, and with longer term TBBPA exposure this may lead to immunomodulatory changes that contribute to carcinogenic processes. JF - Toxicology Letters AU - Dunnick, J K AU - Morgan, D L AU - Elmore, SA AU - Gerrish, K AU - Pandiri, A AU - Ton, T V AU - Shockley, K R AU - Merrick, BA AD - Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 32 EP - 41 PB - Elsevier B.V., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland VL - 266 SN - 0378-4274, 0378-4274 KW - Toxicology Abstracts KW - Tetrabromobisphenol A KW - Toxicogenomics KW - Microarray KW - Interferon response transcripts KW - Pathway analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859502039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Tetrabromobisphenol+A+activates+the+hepatic+interferon+pathway+in+rats&rft.au=Dunnick%2C+J+K%3BMorgan%2C+D+L%3BElmore%2C+SA%3BGerrish%2C+K%3BPandiri%2C+A%3BTon%2C+T+V%3BShockley%2C+K+R%3BMerrick%2C+BA&rft.aulast=Dunnick&rft.aufirst=J&rft.date=2017-01-01&rft.volume=266&rft.issue=&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/10.1016%2Fj.toxlet.2016.11.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1016/j.toxlet.2016.11.019 ER - TY - JOUR T1 - Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year AN - 1859501011; PQ0004015398 AB - Background Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. Conclusions This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD. JF - Journal of Allergy and Clinical Immunology AU - Kennedy, Elizabeth A AU - Connolly, Jennifer AU - Hourihane, Jonathan O'B AU - Fallon, Padraic G AU - McLean, WHIrwin AU - Murray, Deirdre AU - Jo, Jay-Hyun AU - Segre, Julia A AU - Kong, Heidi H AU - Irvine, Alan D AD - Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 166 EP - 172 PB - Elsevier Science Ltd., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 139 IS - 1 SN - 0091-6749, 0091-6749 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Staphylococcus aureus KW - atopic dermatitis KW - skin KW - microbiome KW - longitudinal birth cohort KW - 16S sequencing KW - AD Atopic dermatitis KW - Af Antecubital fossa KW - AMOVA Analysis of molecular variance KW - BASELINE Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints KW - FLG Filaggrin KW - Nt Nasal tip KW - OTU Operational taxonomic unit KW - Pf Popliteal fossa UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859501011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Allergy+and+Clinical+Immunology&rft.atitle=Skin+microbiome+before+development+of+atopic+dermatitis%3A+Early+colonization+with+commensal+staphylococci+at+2+months+is+associated+with+a+lower+risk+of+atopic+dermatitis+at+1+year&rft.au=Kennedy%2C+Elizabeth+A%3BConnolly%2C+Jennifer%3BHourihane%2C+Jonathan+O%27B%3BFallon%2C+Padraic+G%3BMcLean%2C+WHIrwin%3BMurray%2C+Deirdre%3BJo%2C+Jay-Hyun%3BSegre%2C+Julia+A%3BKong%2C+Heidi+H%3BIrvine%2C+Alan+D&rft.aulast=Kennedy&rft.aufirst=Elizabeth&rft.date=2017-01-01&rft.volume=139&rft.issue=1&rft.spage=166&rft.isbn=&rft.btitle=&rft.title=Journal+of+Allergy+and+Clinical+Immunology&rft.issn=00916749&rft_id=info:doi/10.1016%2Fj.jaci.2016.07.029 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 43 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1016/j.jaci.2016.07.029 ER - TY - JOUR T1 - Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone AN - 1859499069; PQ0003966527 AB - Purpose To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. Materials and Methods Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm super(2)) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm super(2) were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm super(2)) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. Results The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm super(2) (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm super(2). The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm super(2). There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. Conclusion The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm super(2). The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm super(2). Level of Evidence: 4 J. Magn. Reson. Imaging 2017; 45:125-131. JF - Journal of Magnetic Resonance Imaging AU - Agarwal, Harsh K AU - Mertan, Francesca V AU - Sankineni, Sandeep AU - Bernardo, Marcelino AU - Senegas, Julien AU - Keupp, Jochen AU - Daar, Dagane AU - Merino, Maria AU - Wood, Bradford J AU - Pinto, Peter A AU - Choyke, Peter L AU - Turkbey, Baris AD - Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 125 EP - 131 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 45 IS - 1 SN - 1053-1807, 1053-1807 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859499069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Magnetic+Resonance+Imaging&rft.atitle=Optimal+high+b-value+for+diffusion+weighted+MRI+in+diagnosing+high+risk+prostate+cancers+in+the+peripheral+zone&rft.au=Agarwal%2C+Harsh+K%3BMertan%2C+Francesca+V%3BSankineni%2C+Sandeep%3BBernardo%2C+Marcelino%3BSenegas%2C+Julien%3BKeupp%2C+Jochen%3BDaar%2C+Dagane%3BMerino%2C+Maria%3BWood%2C+Bradford+J%3BPinto%2C+Peter+A%3BChoyke%2C+Peter+L%3BTurkbey%2C+Baris&rft.aulast=Agarwal&rft.aufirst=Harsh&rft.date=2017-01-01&rft.volume=45&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance+Imaging&rft.issn=10531807&rft_id=info:doi/10.1002%2Fjmri.25353 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/jmri.25353 ER - TY - JOUR T1 - Quadruple-Negative GIST Is a Sentinel for Unrecognized Neurofibromatosis Type 1 Syndrome AN - 1859496720; PQ0004016226 AB - Purpose: The majority of gastrointestinal stromal tumors (GIST) are driven by KIT, PDGFRA, or, less commonly, BRAF mutations, and SDH gene inactivation is involved in a limited fraction of gastric lesions. However, about 10% of GISTs are devoid of any of such alterations and are poorly responsive to standard treatments. This study aims to shed light on the molecular drivers of quadruple-negative GISTs.Experimental Design: Twenty-two sporadic quadruple-negative GISTs with no prior association with Neurofibromatosis Type 1 syndrome were molecularly profiled for a panel of genes belonging to tyrosine kinase pathways or previously implicated in GISTs. For comparison purposes, 24 GISTs carrying KIT, PDGFRA, or SDH gene mutations were also analyzed. Molecular findings were correlated to clinicopathologic features.Results: Most quadruple-negative GISTs featured intestinal localization, with a female predilection. About 60% (13/22) of quadruple-negative tumors carried NF1 pathogenic mutations, often associated with biallelic inactivation. The analysis of normal tissues, available in 11 cases, indicated the constitutional nature of the NF1 mutation in 7 of 11 cases, unveiling an unrecognized Neurofibromatosis Type 1 syndromic condition. Multifocality and a multinodular pattern of growth were common findings in NF1-mutated quadruple-negative GISTs.Conclusions: NF1 gene mutations are frequent in quadruple-negative GISTs and are often constitutional, indicating that a significant fraction of patients with apparently sporadic quadruple-negative GISTs are affected by unrecognized Neurofibromatosis Type 1 syndrome. Hence, a diagnosis of quadruple-negative GIST, especially if multifocal or with a multinodular growth pattern and a nongastric location, should alert the clinician to a possible Neurofibromatosis Type 1 syndromic condition. Clin Cancer Res; 23(1); 273-82. [copy2016 AACR. JF - Clinical Cancer Research AU - Gasparotto, Daniela AU - Rossi, Sabrina AU - Polano, Maurizio AU - Tamborini, Elena AU - Lorenzetto, Erica AU - Sbaraglia, Marta AU - Mondello, Alessia AU - Massani, Marco AU - Lamon, Stefano AU - Bracci, Raffaella AU - Mandolesi, Alessandra AU - Frate, Elisabetta AU - Stanzial, Franco AU - Agaj, Jerin AU - Mazzoleni, Guido AU - Pilotti, Silvana AU - Gronchi, Alessandro AU - Dei Tos, Angelo Paolo AU - Maestro, Roberta AD - Experimental Oncology 1, CRO Aviano National Cancer Institute, Aviano, Italy, maestro@cro.it Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 273 EP - 282 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 23 IS - 1 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Quadruple-Negative+GIST+Is+a+Sentinel+for+Unrecognized+Neurofibromatosis+Type+1+Syndrome&rft.au=Gasparotto%2C+Daniela%3BRossi%2C+Sabrina%3BPolano%2C+Maurizio%3BTamborini%2C+Elena%3BLorenzetto%2C+Erica%3BSbaraglia%2C+Marta%3BMondello%2C+Alessia%3BMassani%2C+Marco%3BLamon%2C+Stefano%3BBracci%2C+Raffaella%3BMandolesi%2C+Alessandra%3BFrate%2C+Elisabetta%3BStanzial%2C+Franco%3BAgaj%2C+Jerin%3BMazzoleni%2C+Guido%3BPilotti%2C+Silvana%3BGronchi%2C+Alessandro%3BDei+Tos%2C+Angelo+Paolo%3BMaestro%2C+Roberta&rft.aulast=Gasparotto&rft.aufirst=Daniela&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0152 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0152 ER - TY - JOUR T1 - Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer AN - 1859496177; PQ0004016230 AB - Purpose: Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential.Experimental Design: Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum.Results: Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P < 0.05) AUC (range, 0.66-0.75) or pAUC (range, 0.007-0.009). The biomarkers that improved discrimination of patients with metastatic-lethal prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P <0.05).Conclusions: Eight differentially methylated CpGs that distinguish patients with metastatic-lethal from nonrecurrent tumors were validated. These novel epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. [copy2016 AACR. JF - Clinical Cancer Research AU - Zhao, Shanshan AU - Geybels, Milan S AU - Leonardson, Amy AU - Rubicz, Rohina AU - Kolb, Suzanne AU - Yan, Qingxiang AU - Klotzle, Brandy AU - Bibikova, Marina AU - Hurtado-Coll, Antonio AU - Troyer, Dean AU - Lance, Raymond AU - Lin, Daniel W AU - Wright, Jonathan L AU - Ostrander, Elaine A AU - Fan, Jian-Bing AU - Feng, Ziding AU - Stanford, Janet L AD - National Institute of Environmental Health Sciences, Biostatistics and Computational Biology Branch, Research Triangle Park, Durham, North Carolina, jstanfor@fredhutch.org Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 311 EP - 319 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 23 IS - 1 SN - 1078-0432, 1078-0432 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Epigenome-Wide+Tumor+DNA+Methylation+Profiling+Identifies+Novel+Prognostic+Biomarkers+of+Metastatic-Lethal+Progression+in+Men+Diagnosed+with+Clinically+Localized+Prostate+Cancer&rft.au=Zhao%2C+Shanshan%3BGeybels%2C+Milan+S%3BLeonardson%2C+Amy%3BRubicz%2C+Rohina%3BKolb%2C+Suzanne%3BYan%2C+Qingxiang%3BKlotzle%2C+Brandy%3BBibikova%2C+Marina%3BHurtado-Coll%2C+Antonio%3BTroyer%2C+Dean%3BLance%2C+Raymond%3BLin%2C+Daniel+W%3BWright%2C+Jonathan+L%3BOstrander%2C+Elaine+A%3BFan%2C+Jian-Bing%3BFeng%2C+Ziding%3BStanford%2C+Janet+L&rft.aulast=Zhao&rft.aufirst=Shanshan&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0549 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0549 ER - TY - JOUR T1 - ISMRM Raw data format: A proposed standard for MRI raw datasets AN - 1859496027; PQ0003987633 AB - Purpose This work proposes the ISMRM Raw Data format as a common MR raw data format, which promotes algorithm and data sharing. Methods A file format consisting of a flexible header and tagged frames of k-space data was designed. Application Programming Interfaces were implemented in C/C++, MATLAB, and Python. Converters for Bruker, General Electric, Philips, and Siemens proprietary file formats were implemented in C++. Raw data were collected using magnetic resonance imaging scanners from four vendors, converted to ISMRM Raw Data format, and reconstructed using software implemented in three programming languages (C++, MATLAB, Python). Results Images were obtained by reconstructing the raw data from all vendors. The source code, raw data, and images comprising this work are shared online, serving as an example of an image reconstruction project following a paradigm of reproducible research. Conclusion The proposed raw data format solves a practical problem for the magnetic resonance imaging community. It may serve as a foundation for reproducible research and collaborations. The ISMRM Raw Data format is a completely open and community-driven format, and the scientific community is invited (including commercial vendors) to participate either as users or developers. Magn Reson Med 77:411-421, 2017. JF - Magnetic Resonance in Medicine AU - Inati, Souheil J AU - Naegele, Joseph D AU - Zwart, Nicholas R AU - Roopchansingh, Vinai AU - Lizak, Martin J AU - Hansen, David C AU - Liu, Chia-Ying AU - Atkinson, David AU - Kellman, Peter AU - Kozerke, Sebastian AU - Xue, Hui AU - Campbell-Washburn, Adrienne E AU - Soerensen, Thomas S AU - Hansen, Michael S AD - National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 411 EP - 421 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 77 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=ISMRM+Raw+data+format%3A+A+proposed+standard+for+MRI+raw+datasets&rft.au=Inati%2C+Souheil+J%3BNaegele%2C+Joseph+D%3BZwart%2C+Nicholas+R%3BRoopchansingh%2C+Vinai%3BLizak%2C+Martin+J%3BHansen%2C+David+C%3BLiu%2C+Chia-Ying%3BAtkinson%2C+David%3BKellman%2C+Peter%3BKozerke%2C+Sebastian%3BXue%2C+Hui%3BCampbell-Washburn%2C+Adrienne+E%3BSoerensen%2C+Thomas+S%3BHansen%2C+Michael+S&rft.aulast=Inati&rft.aufirst=Souheil&rft.date=2017-01-01&rft.volume=77&rft.issue=1&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.26089 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1002/mrm.26089 ER - TY - JOUR T1 - Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1-Associated Adult T-cell Leukemia/lymphoma AN - 1859495761; PQ0004016195 AB - Purpose: Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression-free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated ATL.Experimental Design: Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a single-institution, nonrandomized, open-label phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks.Results: Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 of 29 patients [95% confidence interval (CI), 32.5%-70.6%]. The 15 patients who responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression-free survival was 2.0 months. Median overall survival was 5.9 months. The most common adverse events were 2 with vasovagal episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%) grade 3 and (17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia (24%), and thrombocytopenia (10%). All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14%) of patients.Conclusions: Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multidrug therapies for ATL. Clin Cancer Res; 23(1); 35-42. [copy2016 AACR. JF - Clinical Cancer Research AU - Sharma, Kamal AU - Janik, John E AU - O'Mahony, Deirdre AU - Stewart, Donn AU - Pittaluga, Stefania AU - Stetler-Stevenson, Maryalice AU - Jaffe, Elaine S AU - Raffeld, Mark AU - Fleisher, Thomas A AU - Lee, Cathryn C AU - Steinberg, Seth M AU - Waldmann, Thomas A AU - Morris, John C AD - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, tawald@helix.nih.gov Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 35 EP - 42 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 23 IS - 1 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859495761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Phase+II+Study+of+Alemtuzumab+%28CAMPATH-1%29+in+Patients+with+HTLV-1-Associated+Adult+T-cell+Leukemia%2Flymphoma&rft.au=Sharma%2C+Kamal%3BJanik%2C+John+E%3BO%27Mahony%2C+Deirdre%3BStewart%2C+Donn%3BPittaluga%2C+Stefania%3BStetler-Stevenson%2C+Maryalice%3BJaffe%2C+Elaine+S%3BRaffeld%2C+Mark%3BFleisher%2C+Thomas+A%3BLee%2C+Cathryn+C%3BSteinberg%2C+Seth+M%3BWaldmann%2C+Thomas+A%3BMorris%2C+John+C&rft.aulast=Sharma&rft.aufirst=Kamal&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-1022 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-1022 ER - TY - JOUR T1 - Endometriosis diagnosis and staging by operating surgeon and expert review using multiple diagnostic tools: an inter-rater agreement study AN - 1859487784; PQ0003986525 AB - Objective To determine agreement on endometriosis diagnosis between real-time laparoscopy and subsequent expert review of digital images, operative reports, magnetic resonance imaging (MRI), and histopathology, viewed sequentially. Design Inter-rater agreement study. Setting Five urban surgical centres. Population Women, aged 18-44 years, who underwent a laparoscopy regardless of clinical indication. A random sample of 105 women with and 43 women without a postoperative endometriosis diagnosis was obtained from the ENDO study. Methods Laparoscopies were diagnosed, digitally recorded, and reassessed. Main outcome measures Inter-observer agreement of endometriosis diagnosis and staging according to the revised American Society for Reproductive Medicine criteria. Prevalence and bias-adjusted kappa values ( Kappa ) were calculated for diagnosis, and weighted Kappa values were calculated for staging. Results Surgeons and expert reviewers had substantial agreement on diagnosis and staging after viewing digital images (n = 148; mean Kappa = 0.67, range 0.61-0.69; mean Kappa = 0.64, range 0.53-0.78, respectively) and after additionally viewing operative reports (n = 148; mean Kappa = 0.88, range 0.85-0.89; mean Kappa = 0.85, range 0.84-0.86, respectively). Although additionally viewing MRI findings (n = 36) did not greatly impact agreement, agreement substantially decreased after viewing histological findings (n = 67), with expert reviewers changing their assessment from a positive to a negative diagnosis in up to 20% of cases. Conclusion Although these findings suggest that misclassification bias in the diagnosis or staging of endometriosis via visualised disease is minimal, they should alert gynaecologists who review operative images in order to make decisions on endometriosis treatment that operative reports/drawings and histopathology, but not necessarily MRI, will improve their ability to make sound judgments. JF - BJOG AU - Schliep, K C AU - Chen, Z AU - Stanford, J B AU - Xie, Y AU - Mumford, S L AU - Hammoud, A O AU - Boiman Johnstone, E AU - Dorais, J K AU - Varner, M W AU - Buck Louis, GM AU - Peterson, C M AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 220 EP - 229 PB - Wiley Subscription Services, Inc., 1105 N Market St Wilmington DE 19801 VL - 124 IS - 2 SN - 1470-0328, 1470-0328 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859487784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BJOG&rft.atitle=Endometriosis+diagnosis+and+staging+by+operating+surgeon+and+expert+review+using+multiple+diagnostic+tools%3A+an+inter-rater+agreement+study&rft.au=Schliep%2C+K+C%3BChen%2C+Z%3BStanford%2C+J+B%3BXie%2C+Y%3BMumford%2C+S+L%3BHammoud%2C+A+O%3BBoiman+Johnstone%2C+E%3BDorais%2C+J+K%3BVarner%2C+M+W%3BBuck+Louis%2C+GM%3BPeterson%2C+C+M&rft.aulast=Schliep&rft.aufirst=K&rft.date=2017-01-01&rft.volume=124&rft.issue=2&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=BJOG&rft.issn=14700328&rft_id=info:doi/10.1111%2F1471-0528.13711 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1111/1471-0528.13711 ER - TY - JOUR T1 - Characterization of aqueous formulations of tetra- and pentavalent forms of vanadium in support of test article selection in toxicology studies AN - 1859487637; PQ0004018525 AB - Tetravalent (V super(IV)) and pentavalent (V super(V)) forms of vanadium were selected for testing by the National Toxicology Program via drinking water exposure due to potential human exposure. To aid in the test article selection, drinking water formulations (125-2000 mg/L) of vanadyl sulfate (V super(IV)), sodium orthovanadate, and sodium metavanadate (V super(V)) were characterized by ultraviolet/visible (UV/VIS) spectroscopy, mass spectrometry (MS), or super(51)V nuclear magnetic resonance (NMR) spectroscopy. Aqueous formulations of orthovanadate, metavanadate, and vanadyl sulfate in general were basic, neutral, and acidic, respectively. Changes in vanadium speciation were investigated by adjusting formulation pH to acidic, neutral, or basic. There was no visible difference in UV/VIS spectra of pentavalent forms. NMR and MS analyses showed that the predominant oxidovanadate species in both ortho- and metavanadate formulations at basic and acidic pH, respectively, were the monomer and decamer, while, a mixture of oxidovanadates were present at neutral pH. Oxidovanadate species were not observed in vanadyl sulfate formulations at acidic pH but were observed at basic pH suggesting conversion of V super(IV) to V super(V). These data suggest that formulations of both ortho- and metavanadate form similar oxidovanadate species in acidic, neutral and basic pH and exist mainly in the V super(V) form while vanadyl sulfate exists mainly as V super(IV) in acidic pH. Therefore, the formulation stability overtime was investigated only for sodium metavanadate and vanadyl sulfate. Drinking water formulations (50 and 2000 mg/L) of metavanadate (~pH 7) and vanadyl sulfate (~pH 3.5) were greater than or equal to 92 % of target concentration up to 42 days at ~5 degree C and ambient temperature demonstrating the utility in toxicology studies. JF - Environmental Science and Pollution Research International AU - Mutlu, Esra AU - Cristy, Tim AU - Graves, Steven W AU - Hooth, Michelle J AU - Waidyanatha, Suramya AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop K2-07, Research Triangle Park, NC, 27709, USA, waidyanathas@niehs.nih.gov Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 405 EP - 416 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 24 IS - 1 SN - 0944-1344, 0944-1344 KW - Pollution Abstracts; Ecology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859487637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Science+and+Pollution+Research+International&rft.atitle=Characterization+of+aqueous+formulations+of+tetra-+and+pentavalent+forms+of+vanadium+in+support+of+test+article+selection+in+toxicology+studies&rft.au=Mutlu%2C+Esra%3BCristy%2C+Tim%3BGraves%2C+Steven+W%3BHooth%2C+Michelle+J%3BWaidyanatha%2C+Suramya&rft.aulast=Mutlu&rft.aufirst=Esra&rft.date=2017-01-01&rft.volume=24&rft.issue=1&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Environmental+Science+and+Pollution+Research+International&rft.issn=09441344&rft_id=info:doi/10.1007%2Fs11356-016-7803-x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 57 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1007/s11356-016-7803-x ER - TY - JOUR T1 - Trends in published meta-analyses in cancer research, 2008-2013 AN - 1859483147; PQ0004019499 AB - In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials. JF - Cancer Causes & Control AU - Qadir, Ximena V AU - Clyne, Mindy AU - Lam, Tram Kim AU - Khoury, Muin J AU - Schully, Sheri D AD - Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, 6100 Executive Boulevard, Suite 2B03, Bethesda, MD, USA, schullys@mail.nih.gov Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 5 EP - 12 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 28 IS - 1 SN - 0957-5243, 0957-5243 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859483147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Trends+in+published+meta-analyses+in+cancer+research%2C+2008-2013&rft.au=Qadir%2C+Ximena+V%3BClyne%2C+Mindy%3BLam%2C+Tram+Kim%3BKhoury%2C+Muin+J%3BSchully%2C+Sheri+D&rft.aulast=Qadir&rft.aufirst=Ximena&rft.date=2017-01-01&rft.volume=28&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1007%2Fs10552-016-0830-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 14 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1007/s10552-016-0830-6 ER - TY - JOUR T1 - An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort AN - 1859481620; PQ0003999300 AB - Background/ Objectives: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study.Subjects/ Methods: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing. Results: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases. Conclusions: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease. JF - International Journal of Obesity AU - Wilson, L E AU - Harlid, S AU - Xu, Z AU - Sandler, D P AU - Taylor, J A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 194 EP - 199 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 1 SN - 0307-0565, 0307-0565 KW - Biochemistry Abstracts 2: Nucleic Acids; Health & Safety Science Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859481620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=An+epigenome-wide+study+of+body+mass+index+and+DNA+methylation+in+blood+using+participants+from+the+Sister+Study+cohort&rft.au=Wilson%2C+L+E%3BHarlid%2C+S%3BXu%2C+Z%3BSandler%2C+D+P%3BTaylor%2C+J+A&rft.aulast=Wilson&rft.aufirst=L&rft.date=2017-01-01&rft.volume=41&rft.issue=1&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.184 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-02-01 DO - http://dx.doi.org/10.1038/ijo.2016.184 ER - TY - JOUR T1 - Disease Centered Around Calcified Taenia solium Granuloma AN - 1859479823; PQ0004008865 AB - Taenia solium (the pork tapeworm) is present in most developing countries, where it is a frequent cause of seizures and other neurological disease. Parasitic larvae invade the human brain, establish, and eventually resolve, leaving a calcified scar. While these lesions are common in endemic regions, and most of these are clinically silent, a proportion of individuals with calcified cysticerci develop seizures from these lesions, and 30-65% of these cases are associated with perilesional edema (PE), likely due to host inflammation. This manuscript summarizes the importance, characteristics, natural history, and potential prevention and treatments of symptomatic calcified neurocysticercosis (NCC). JF - Trends in Parasitology AU - Nash, Theodore E AU - Bustos, Javier A AU - Garcia, Hector H AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 65 EP - 73 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 33 IS - 1 SN - 1471-4922, 1471-4922 KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - neurocysticercosis KW - calcified granuloma KW - perilesional edema KW - epilepsy KW - seizures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859479823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Parasitology&rft.atitle=Disease+Centered+Around+Calcified+Taenia+solium+Granuloma&rft.au=Nash%2C+Theodore+E%3BBustos%2C+Javier+A%3BGarcia%2C+Hector+H&rft.aulast=Nash&rft.aufirst=Theodore&rft.date=2017-01-01&rft.volume=33&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Trends+in+Parasitology&rft.issn=14714922&rft_id=info:doi/10.1016%2Fj.pt.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1016/j.pt.2016.09.003 ER - TY - JOUR T1 - Impact of parental obesity on neonatal markers of inflammation and immune response AN - 1859479412; PQ0003999303 AB - Background/ Objectives: Maternal obesity may influence neonatal and childhood morbidities through increased inflammation and/or altered immune response. Less is known about paternal obesity. We hypothesized that excessive parental weight contributes to elevated inflammation and altered immunoglobulin (Ig) profiles in neonates.Subjects/ Methods: In the Upstate KIDS Study maternal pre-pregnancy body mass index (BMI) was obtained from vital records and paternal BMI from maternal report. Biomarkers were measured from newborn dried blood spots (DBS) among neonates whose parents provided consent. Inflammatory scores were calculated by assigning one point for each of five pro-inflammatory biomarkers above the median and one point for an anti-inflammatory cytokine below the median. Linear regression models and generalized estimating equations were used to estimate mean differences ( beta ) and 95% confidence intervals (CI) in the inflammatory score and Ig levels by parental overweight/obesity status compared with normal weight. Results: Among 2974 pregnancies, 51% were complicated by excessive maternal weight (BMI>25), 73% by excessive paternal weight and 28% by excessive gestational weight gain. Maternal BMI categories of overweight (BMI 25.0-29.9) and obese class II/III (BMI greater than or equal to 35) were associated with increased neonatal inflammation scores ( beta =0.12, 95% CI: 0.02, 0.21; P=0.02 and beta =0.13, CI: -0.002, 0.26; P=0.05, respectively) but no increase was observed in the obese class I group (BMI 30-34.9). Mothers with class I and class II/III obesity had newborns with increased IgM levels ( beta =0.11, CI: 0.04, 0.17; P=0.001 and beta =0.12, CI: 0.05, 0.19); P<0.001, respectively). Paternal groups of overweight, obese class I and obese class II/III had decreased neonatal IgM levels ( beta =-0.08, CI: -0.13,-0.03, P=0.001; beta =-0.07, CI: -0.13, -0.01, P=0.029 and beta =-0.11, CI:-0.19,-0.04, P=0.003, respectively). Conclusions: Excessive maternal weight was generally associated with increased inflammation and IgM supporting previous observations of maternal obesity and immune dysregulation in offspring. The role of paternal obesity requires further study. JF - International Journal of Obesity AU - Broadney, M M AU - Chahal, N AU - Michels, K A AU - McLain, A C AU - Ghassabian, A AU - Lawrence, D A AU - Yeung, E H AD - Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 30 EP - 37 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 1 SN - 0307-0565, 0307-0565 KW - Health & Safety Science Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859479412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=Impact+of+parental+obesity+on+neonatal+markers+of+inflammation+and+immune+response&rft.au=Broadney%2C+M+M%3BChahal%2C+N%3BMichels%2C+K+A%3BMcLain%2C+A+C%3BGhassabian%2C+A%3BLawrence%2C+D+A%3BYeung%2C+E+H&rft.aulast=Broadney&rft.aufirst=M&rft.date=2017-01-01&rft.volume=41&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.187 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1038/ijo.2016.187 ER - TY - JOUR T1 - A longitudinal study of serum insulin and insulin resistance as predictors of weight and body fat gain in African American and Caucasian children AN - 1859479258; PQ0003999283 AB - Background: The influence of insulin and insulin resistance (IR) on children's weight and fat gain is unclear. Objective: To evaluate insulin and IR as predictors of weight and body fat gain in children at high risk for adult obesity. We hypothesized that baseline IR would be positively associated with follow-up body mass index (BMI) and fat mass.Subjects/ Methods: Two hundred and forty-nine healthy African American and Caucasian children aged 6-12 years at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were followed for up to 15 years with repeated BMI and fat mass measurements. We examined baseline serum insulin and homeostasis model of assessment-IR (HOMA-IR) as predictors of follow-up BMI Z-score and fat mass by dual-energy X-ray absorptiometry in mixed model longitudinal analyses accounting for baseline body composition, pubertal stage, sociodemographic factors and follow-up interval. Results: At baseline, 39% were obese (BMI[egs]95th percentile for age/sex). Data from 1335 annual visits were examined. Children were followed for an average of 7.2 plus or minus 4.3 years, with a maximum follow-up of 15 years. After accounting for covariates, neither baseline insulin nor HOMA-IR was significantly associated with follow-up BMI (Ps>0.26), BMIz score (Ps>0.22), fat mass (Ps>0.78) or fat mass percentage (Ps>0.71). In all models, baseline BMI (P<0.0001), body fat mass (P<0.0001) and percentage of fat (P<0.001) were strong positive predictors for change in BMI and fat mass. In models restricted to children without obesity at baseline, some but not all models had significant interaction terms between body adiposity and insulinemia/HOMA-IR that suggested less gain in mass among those with greater insulin or IR. The opposite was found in some models restricted to children with obesity at baseline. Conclusions: In middle childhood, BMI and fat mass, but not insulin or IR, are strong predictors of children's gains in BMI and fat mass during adolescence. JF - International Journal of Obesity AU - Sedaka, N M AU - Olsen, C H AU - Yannai, L E AU - Stutzman, W E AU - Krause, A J AU - Sherafat-Kazemzadeh, R AU - Condarco, T A AU - Brady, S M AU - Demidowich, A P AU - Reynolds, J C AU - Yanovski, S Z AU - Hubbard, V S AU - Yanovski, J A AD - Section on Growth and Obesity (SGO), Program in Developmental Endocrinology and Genetics (PDEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 61 EP - 70 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 1 SN - 0307-0565, 0307-0565 KW - Health & Safety Science Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859479258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=A+longitudinal+study+of+serum+insulin+and+insulin+resistance+as+predictors+of+weight+and+body+fat+gain+in+African+American+and+Caucasian+children&rft.au=Sedaka%2C+N+M%3BOlsen%2C+C+H%3BYannai%2C+L+E%3BStutzman%2C+W+E%3BKrause%2C+A+J%3BSherafat-Kazemzadeh%2C+R%3BCondarco%2C+T+A%3BBrady%2C+S+M%3BDemidowich%2C+A+P%3BReynolds%2C+J+C%3BYanovski%2C+S+Z%3BHubbard%2C+V+S%3BYanovski%2C+J+A&rft.aulast=Sedaka&rft.aufirst=N&rft.date=2017-01-01&rft.volume=41&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.145 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1038/ijo.2016.145 ER - TY - JOUR T1 - Association of N-Methyl-D-Aspartate receptor 2B Subunit (GRIN2B) polymorphism with earlier age at onset of withdrawal symptoms in Indian alcohol dependent subjects AN - 1859473537 AB - The associations of GRIN2B polymorphism (rs1806201) with alcohol withdrawal and related clinical parameters in alcohol dependent subjects were investigated. Cases were assessed using a semi-structured clinical pro forma for alcohol abuse and a questionnaire for family history of alcohol dependence and psychiatric disorders after obtaining informed consent. The study included alcohol dependent male cases (n = 220, age at onset of alcohol withdrawal symptoms = 32.4 ± 8.8 y) recruited at the Center for Addiction Medicine, National Institute of Mental Health and Neurosciences, Bangalore, India. The controls comprised of healthy unrelated males (n = 183) who were ethnically matched and selected randomly. The polymorphism rs1806201 was analyzed by polymerase chain reaction and restriction fragment length polymorphism. The presence of T allele at this locus was significantly associated with lower age at onset of alcohol withdrawal symptoms (p = .005) among the cases. Mean age at onset of alcohol withdrawal symptoms in subjects who were T carriers was 31.4 ± 8.5 y (n = 160) and non-T carriers was 35.2 ± 9.0 y (n = 60). The SNP rs1806201 in GRIN2B may play an important role in genetic susceptibility to earlier age of withdrawal in alcohol dependent patients. JF - Journal of Addictive Diseases AU - Paul, Pradip, MSc AU - Dahale, Ajit, MD AU - Kishore, Brij, MD AU - Chand, Prabhat, MD AU - Benegal, Vivek, MD AU - Jain, Sanjeev, MD AU - Murthy, Pratima, MD AU - Purushottam, Meera, PhD AD - Molecular Genetics Laboratory, Neurobiology Research Centre, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India ; Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India ; Mid-West Area Mental Health Service, North Western Mental Health, Melbourne Health, Victoria, Australia ; Center for Addiction Medicine, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India ; Molecular Genetics Laboratory, Neurobiology Research Centre, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India Y1 - 2017///Jan/Mar PY - 2017 DA - Jan/Mar 2017 SP - 48 EP - 52 CY - Binghamton PB - Taylor & Francis Ltd. VL - 36 IS - 1 SN - 1055-0887 KW - Drug Abuse And Alcoholism KW - Alcohol dependence KW - withdrawal KW - glutamate KW - N-Methyl-D-Aspartate receptor (GRIN2B) KW - polymorphism KW - rs1806201 KW - Men KW - Symptoms KW - Neurosciences KW - Susceptibility KW - Psychiatric disorders KW - Genetic family histories KW - Addiction KW - Informed consent KW - Genetic susceptibility KW - Age of onset KW - Questionnaires KW - Parameters KW - Chemical analysis KW - Withdrawal symptoms KW - Alcohol abuse KW - Mental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859473537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Addictive+Diseases&rft.atitle=Association+of+N-Methyl-D-Aspartate+receptor+2B+Subunit+%28GRIN2B%29+polymorphism+with+earlier+age+at+onset+of+withdrawal+symptoms+in+Indian+alcohol+dependent+subjects&rft.au=Paul%2C+Pradip%2C+MSc%3BDahale%2C+Ajit%2C+MD%3BKishore%2C+Brij%2C+MD%3BChand%2C+Prabhat%2C+MD%3BBenegal%2C+Vivek%2C+MD%3BJain%2C+Sanjeev%2C+MD%3BMurthy%2C+Pratima%2C+MD%3BPurushottam%2C+Meera%2C+PhD&rft.aulast=Paul&rft.aufirst=Pradip&rft.date=2017-01-01&rft.volume=36&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Journal+of+Addictive+Diseases&rft.issn=10550887&rft_id=info:doi/10.1080%2F10550887.2016.1140434 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2017 Taylor & Francis Group, LLC N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1080/10550887.2016.1140434 ER - TY - JOUR T1 - Patient's lung cancer diagnosis as a cue for relatives' smoking cessation: evaluating the constructs of the teachable moment AN - 1858560688 AB - Background To understand whether patient-reported experiences with lung cancer may create teachable moments (TM) for their relatives as evidenced by shifts in their risk perceptions, affective response, and self-image and in turn, motivation to quit smoking. Methods Patients at a comprehensive cancer center (n=152) completed a survey within 6 months of lung cancer diagnosis to assess their cancer-related symptoms and openness and enumerated relatives who were smokers. Relative smokers (n=218) then completed a survey assessing their risk perceptions, affective response, and self-image as a smoker related to the patient's diagnosis (TM mechanisms), and their motivation to quit smoking. Cross-sectional mediation and moderation analyses were conducted to explore the links between patient-reported experiences, and relatives' TM mechanisms, and motivation to quit smoking. Results Relative-reported affect was a significant mediator of the association between patient-reported symptoms and relative smoker's desire to quit. Relatives' self-image was a significant moderator of the association between patient-reported symptoms and relative smoker's desire to quit, such that patients' reported symptoms were associated with relatives' desire to quit only when the relative smoker reported a generally positive self-image as a smoker. No evidence was found for moderated mediation. However, the link between symptoms and negative affect was moderated by perceptions of risk. Conclusion Whether smokers experience a family member's lung cancer as a TM is influenced by multiple interrelated cognitive and affective factors that warrant further exploration. Clearer understanding of these factors could inform how to re-invigorate and sustain this motivation to promote concrete actions toward smoking cessation. Copyright © 2015 John Wiley & Sons, Ltd. JF - Psycho-Oncology AU - McBride, Colleen M AU - Blocklin, Michelle AU - Lipkus, Isaac M AU - Klein, William M P AU - Brandon, Thomas H AD - Department of Behavioral Sciences and Health Education, Emory Rollins School of Public Health, Atlanta, GA, USA ; Abt Associates, Boston, MA, USA ; Duke University, Durham, NC, USA ; National Cancer Institute, Rockville, MD, USA; National Institutes of Health, Bethesda, MD, USA ; Tobacco Research and Intervention Program, Moffitt Cancer Center, Tampa, FL, USA ; Department of Behavioral Sciences and Health Education, Emory Rollins School of Public Health, Atlanta, GA, USA Y1 - 2017/01// PY - 2017 DA - Jan 2017 SP - 88 EP - 95 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 26 IS - 1 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Smokers KW - Risk perception KW - Smoking KW - Negative affect KW - Motivation KW - Relatives KW - Openness KW - Cessation KW - Perceptions KW - Lung cancer KW - Risk assessment KW - Affective responses KW - Mediation KW - Negative affectivity KW - Surveys KW - Selfimage KW - Desire KW - Diagnosis KW - Moderation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858560688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=Patient%27s+lung+cancer+diagnosis+as+a+cue+for+relatives%27+smoking+cessation%3A+evaluating+the+constructs+of+the+teachable+moment&rft.au=McBride%2C+Colleen+M%3BBlocklin%2C+Michelle%3BLipkus%2C+Isaac+M%3BKlein%2C+William+M+P%3BBrandon%2C+Thomas+H&rft.aulast=McBride&rft.aufirst=Colleen&rft.date=2017-01-01&rft.volume=26&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.4011 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2017 John Wiley & Sons, Ltd. N1 - Last updated - 2017-01-16 DO - http://dx.doi.org/10.1002/pon.4011 ER - TY - JOUR T1 - Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. AN - 1858109610; 28076415 AB - A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design. JF - PLoS pathogens AU - Wibmer, Constantinos Kurt AU - Gorman, Jason AU - Ozorowski, Gabriel AU - Bhiman, Jinal N AU - Sheward, Daniel J AU - Elliott, Debra H AU - Rouelle, Julie AU - Smira, Ashley AU - Joyce, M Gordon AU - Ndabambi, Nonkululeko AU - Druz, Aliaksandr AU - Asokan, Mangai AU - Burton, Dennis R AU - Connors, Mark AU - Abdool Karim, Salim S AU - Mascola, John R AU - Robinson, James E AU - Ward, Andrew B AU - Williamson, Carolyn AU - Kwong, Peter D AU - Morris, Lynn AU - Moore, Penny L AD - Centre for HIV and STIs, National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. ; Department of Integrative Structural and Computational Biology, CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, California, United States of America. ; Institute of Infectious Disease and Molecular Medicine (IDM) and Division of Medical Virology, University of Cape Town and NHLS, Cape Town, South Africa. ; Department of Pediatrics, Tulane University Medical Center, New Orleans, Louisiana, United States of America. ; Department of Immunology and Microbial Science, CHAVI-ID and IAVI Neutralizing Antibody Centre, The Scripps Research Institute, La Jolla, California, United States of America. ; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. ; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 1 VL - 13 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1858109610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+pathogens&rft.atitle=Structure+and+Recognition+of+a+Novel+HIV-1+gp120-gp41+Interface+Antibody+that+Caused+MPER+Exposure+through+Viral+Escape.&rft.au=Wibmer%2C+Constantinos+Kurt%3BGorman%2C+Jason%3BOzorowski%2C+Gabriel%3BBhiman%2C+Jinal+N%3BSheward%2C+Daniel+J%3BElliott%2C+Debra+H%3BRouelle%2C+Julie%3BSmira%2C+Ashley%3BJoyce%2C+M+Gordon%3BNdabambi%2C+Nonkululeko%3BDruz%2C+Aliaksandr%3BAsokan%2C+Mangai%3BBurton%2C+Dennis+R%3BConnors%2C+Mark%3BAbdool+Karim%2C+Salim+S%3BMascola%2C+John+R%3BRobinson%2C+James+E%3BWard%2C+Andrew+B%3BWilliamson%2C+Carolyn%3BKwong%2C+Peter+D%3BMorris%2C+Lynn%3BMoore%2C+Penny+L&rft.aulast=Wibmer&rft.aufirst=Constantinos&rft.date=2017-01-01&rft.volume=13&rft.issue=1&rft.spage=e1006074&rft.isbn=&rft.btitle=&rft.title=PLoS+pathogens&rft.issn=1553-7374&rft_id=info:doi/10.1371%2Fjournal.ppat.1006074 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2017-01-11 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1371/journal.ppat.1006074 ER - TY - JOUR T1 - Neuroserpin Attenuates H2O2-Induced Oxidative Stress in Hippocampal Neurons via AKT and BCL-2 Signaling Pathways. AN - 1856868286; 27510267 AB - Oxidative stress plays a critical role in neuronal injury and is associated with various neurological diseases. Here, we explored the potential protective effect of neuroserpin against oxidative stress in primary cultured hippocampal neurons. Our results show that neuroserpin inhibits H2O2-induced neurotoxicity in hippocampal cultures as measured by WST, LDH release, and TUNEL assays. We found that neuroserpin enhanced the activation of AKT in cultures subjected to oxidative stress and that the AKT inhibitor Ly294002 blocked this neuroprotective effect. Neuroserpin increased the expression of the anti-apoptotic protein BCL-2 and blocked the activation of caspase-3. Neuroserpin did not increase the level of neuroprotection over levels seen in neurons transduced with a BCL-2 expression vector, and an inhibitor of Trk receptors, K252a, did not block neuroserpin's effect. Taken together, our study demonstrates that neuroserpin protects against oxidative stress-induced dysfunction and death of primary cultured hippocampal neurons through the AKT-BCL-2 signaling pathway through a mechanism that does not involve the Trk receptors and leads to inhibition of caspase-3 activation. JF - Journal of molecular neuroscience : MN AU - Cheng, Yong AU - Loh, Y Peng AU - Birch, Nigel P AD - Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA. ; School of Biological Sciences, Centre for Brain Research and Brain Research New Zealand, Rangahau Roro Aotearoa, University of Auckland, 3a Symonds Street 92019, Auckland, 1142, New Zealand. n.birch@auckland.ac.nz. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 123 EP - 131 VL - 61 IS - 1 KW - Hippocampal neurons KW - Reactive oxygen species KW - Protease inhibitor KW - Oxidative stress KW - Neuroprotection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856868286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+neuroscience+%3A+MN&rft.atitle=Neuroserpin+Attenuates+H2O2-Induced+Oxidative+Stress+in+Hippocampal+Neurons+via+AKT+and+BCL-2+Signaling+Pathways.&rft.au=Cheng%2C+Yong%3BLoh%2C+Y+Peng%3BBirch%2C+Nigel+P&rft.aulast=Cheng&rft.aufirst=Yong&rft.date=2017-01-01&rft.volume=61&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=1559-1166&rft_id=info:doi/10.1007%2Fs12031-016-0807-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s12031-016-0807-7 ER - TY - JOUR T1 - Variability in measures of health and health behavior among emerging adults 1 year after high school according to college status AN - 1856379130 AB - Objective: To examine changes in health behaviors among US emerging adults 1 year after high school. Participants: The national sample of participants (N = 1,927), including those attending 4-year college/university (n = 884), 2-year colleges/technical schools (n = 588), and no college (n = 455), participated in annual spring surveys 2013-2014. Methods: Health behaviors were assessed the last year of high school and first year of college; differences by college status controlling for previous-year values were estimated using regression analyses. Results: Relative to 4-year college attendees, those attending technical school/community college were less likely to binge drink (odds ratio [OR] = 0.57, confidence interval [CI] = 0.38-0.86) but more likely to speed (OR = 1.26, CI = 1.0-2.84), consume sodas (OR = 1.57, CI = 1.0-2.47), and report lower family satisfaction (p < .01), with marginally more physical and depressive symptoms. College nonattendees reported more DWI (driving while intoxicated; OR = 1.60, CI = 1.05-2.47), soda drinking (OR = 2.51, CI = 1.76-3.59), oversleeping (OR = 4.78, CI = 3.65-8.63), and less family satisfaction (p < .04). Conclusions: Health risk behaviors among emerging adults varied by college status. JF - Journal of American College Health AU - Simons-Morton, Bruce, EdD, MPH AU - Haynie, Denise, PhD, MPH AU - O'Brien, Fearghal, PhD AU - Lipsky, Leah, PhD AU - Bible, Joe, PhD AU - Liu, Danping, PhD AD - Health Behavior Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA ; Biostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA ; Health Behavior Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA Y1 - 2017/01// PY - 2017 DA - Jan 2017 SP - 58 EP - 66 CY - Washington PB - Taylor & Francis Ltd. VL - 65 IS - 1 SN - 0744-8481 KW - Education--Higher Education KW - College health KW - college students KW - diet KW - driving KW - exercise KW - mental health KW - physical health KW - substance use KW - Confidence intervals KW - Adults KW - First year KW - Health behaviour KW - Depression KW - Behavioural changes KW - Family satisfaction KW - Physical symptoms KW - Carbonated beverages KW - Risk behaviour KW - Variability UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856379130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+American+College+Health&rft.atitle=Variability+in+measures+of+health+and+health+behavior+among+emerging+adults+1+year+after+high+school+according+to+college+status&rft.au=Simons-Morton%2C+Bruce%2C+EdD%2C+MPH%3BHaynie%2C+Denise%2C+PhD%2C+MPH%3BO%27Brien%2C+Fearghal%2C+PhD%3BLipsky%2C+Leah%2C+PhD%3BBible%2C+Joe%2C+PhD%3BLiu%2C+Danping%2C+PhD&rft.aulast=Simons-Morton&rft.aufirst=Bruce&rft.date=2017-01-01&rft.volume=65&rft.issue=1&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Journal+of+American+College+Health&rft.issn=07448481&rft_id=info:doi/10.1080%2F07448481.2016.1238384 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - This article not subject to US copyright law N1 - Last updated - 2017-01-08 DO - http://dx.doi.org/10.1080/07448481.2016.1238384 ER - TY - JOUR T1 - Developmental Relations Among Behavioral Inhibition, Anxiety, and Attention Biases to Threat and Positive Information AN - 1855652820 AB - This study examined relations between behavioral inhibition (BI) assessed in toddlerhood (n = 268) and attention biases (AB) to threat and positive faces and maternal-reported anxiety assessed when children were 5- and 7-year-old. Results revealed that BI predicted anxiety at age 7 in children with AB toward threat, away from positive, or with no bias, at age 7; BI did not predict anxiety for children displaying AB away from threat or toward positive. Five-year AB did not moderate the link between BI and 7-year anxiety. No direct association between AB and BI or anxiety was detected; moreover, children did not show stable AB across development. These findings extend our understanding of the developmental links among BI, AB, and anxiety. JF - Child Development AU - White, Lauren K AU - Degnan, Kathryn A AU - Henderson, Heather A AU - Perez-Edgar, Koraly AU - Walker, Olga L AU - Shechner, Tomer AU - Leibenluft, Ellen AU - Bar-Haim, Yair AU - Pine, Daniel S AU - Fox, Nathan A AD - Children's Hospital of Philadelphia ; Catholic University ; University of Waterloo ; The Pennsylvania State University ; University of Maryland, College Park ; University of Haifa ; National Institute of Mental Health ; Tel Aviv University ; Children's Hospital of Philadelphia Y1 - 2017///Jan/Feb PY - 2017 DA - Jan/Feb 2017 SP - 141 EP - 155 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 88 IS - 1 SN - 0009-3920 KW - Psychology KW - Attentional bias KW - Anxiety KW - Children KW - Inhibition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855652820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Developmental+Relations+Among+Behavioral+Inhibition%2C+Anxiety%2C+and+Attention+Biases+to+Threat+and+Positive+Information&rft.au=White%2C+Lauren+K%3BDegnan%2C+Kathryn+A%3BHenderson%2C+Heather+A%3BPerez-Edgar%2C+Koraly%3BWalker%2C+Olga+L%3BShechner%2C+Tomer%3BLeibenluft%2C+Ellen%3BBar-Haim%2C+Yair%3BPine%2C+Daniel+S%3BFox%2C+Nathan+A&rft.aulast=White&rft.aufirst=Lauren&rft.date=2017-01-01&rft.volume=88&rft.issue=1&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fcdev.12696 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development © 2017 The Society for Research in Child Development, Inc. N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1111/cdev.12696 ER - TY - JOUR T1 - Face Detection and the Development of Own-Species Bias in Infant Macaques AN - 1854601982 AB - In visually complex environments, numerous items compete for attention. Infants may exhibit attentional efficiency--privileged detection, attention capture, and holding--for face-like stimuli. However, it remains unknown when these biases develop and what role, if any, experience plays in this emerging skill. Here, nursery-reared infant macaques' (Macaca mulatta;n = 10) attention to faces in 10-item arrays of nonfaces was measured using eye tracking. With limited face experience, 3-week-old monkeys were more likely to detect faces and looked longer at faces compared to nonfaces, suggesting a robust face detection system. By 3 months, after peer exposure, infants looked faster to conspecific faces but not heterospecific faces, suggesting an own-species bias in face attention capture, consistent with perceptual attunement. JF - Child Development AU - Simpson, Elizabeth A AU - Jakobsen, Krisztina V AU - Damon, Fabrice AU - Suomi, Stephen J AU - Ferrari, Pier F AU - Paukner, Annika AD - University of Miami ; James Madison University ; Université Grenoble Alpes ; National Institutes of Health ; Università di Parma ; University of Miami Y1 - 2017///Jan/Feb PY - 2017 DA - Jan/Feb 2017 SP - 103 EP - 113 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 88 IS - 1 SN - 0009-3920 KW - Psychology KW - Detection KW - Tracking KW - Eye tracking KW - Infants KW - Holding KW - Bias KW - Attention KW - Monkeys UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854601982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Face+Detection+and+the+Development+of+Own-Species+Bias+in+Infant+Macaques&rft.au=Simpson%2C+Elizabeth+A%3BJakobsen%2C+Krisztina+V%3BDamon%2C+Fabrice%3BSuomi%2C+Stephen+J%3BFerrari%2C+Pier+F%3BPaukner%2C+Annika&rft.aulast=Simpson&rft.aufirst=Elizabeth&rft.date=2017-01-01&rft.volume=88&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fcdev.12565 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development © 2017 The Society for Research in Child Development, Inc. N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1111/cdev.12565 ER - TY - JOUR T1 - Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences AN - 1854601976 AB - Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood. JF - Child Development AU - Schneider, Mary L AU - Moore, Colleen F AU - Adkins, Miriam AU - Barr, Christina S AU - Larson, Julie A AU - Resch, Leslie M AU - Roberts, Andrew AD - Department of Kinesiology, University of Wisconsin-Madison; Harlow Center for Biological Psychology, University of Wisconsin-Madison; Department of Psychology, University of Wisconsin-Madison ; Department of Psychology, University of Wisconsin-Madison; Department of Psychology, Montana State University-Bozeman ; Department of Kinesiology, University of Wisconsin-Madison ; National Institutes of Health ; Department of Kinesiology, University of Wisconsin-Madison; Harlow Center for Biological Psychology, University of Wisconsin-Madison ; Minnesota State University-Mankato ; Department of Kinesiology, University of Wisconsin-Madison; Harlow Center for Biological Psychology, University of Wisconsin-Madison; Department of Psychology, University of Wisconsin-Madison Y1 - 2017///Jan/Feb PY - 2017 DA - Jan/Feb 2017 SP - 183 EP - 197 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 88 IS - 1 SN - 0009-3920 KW - Psychology KW - Dopamine KW - Genetic factors KW - Alleles KW - Sensory processes KW - Adulthood KW - Emission KW - Tomography KW - Fetal exposure KW - Animals KW - Positron emission tomography KW - Antenatal KW - Monkeys UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854601976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Sensory+Processing+in+Rhesus+Monkeys%3A+Developmental+Continuity%2C+Prenatal+Treatment%2C+and+Genetic+Influences&rft.au=Schneider%2C+Mary+L%3BMoore%2C+Colleen+F%3BAdkins%2C+Miriam%3BBarr%2C+Christina+S%3BLarson%2C+Julie+A%3BResch%2C+Leslie+M%3BRoberts%2C+Andrew&rft.aulast=Schneider&rft.aufirst=Mary&rft.date=2017-01-01&rft.volume=88&rft.issue=1&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fcdev.12572 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development © 2017 The Society for Research in Child Development, Inc. N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1111/cdev.12572 ER - TY - JOUR T1 - The histopathological evaluation of drug-induced liver injury. AN - 1852677738; 27960237 AB - Drug-induced liver injury (DILI) presents unique challenges to the pathologist. It is not only an uncommon reason for liver biopsy, but the pathology of DILI is spread across the entire spectrum of hepatic injury patterns. It is important for the pathologist to suspect DILI when the histological changes are unusual or out of synchronicity with the patient's history. A systematic evaluation approach will yield the most information. It begins with the characterization of the general pattern of injury which, for most cases, will be found in a handful of necroinflammatory and cholestatic patterns. A careful assessment of the severity of injury across the various anatomic compartments will provide information on the probable natural history of the injury. Correlation of liver injury with the patient's medication history and clinical findings will help to narrow the differential diagnosis, particularly when it is recognized that most drugs have a limited range of histological findings and vary in their propensity to cause injury. This review provides an overview of the assessment of the liver biopsy and its use to confirm or exclude particular drugs as contributing to the patient's liver injury. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Histopathology AU - Kleiner, David E AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 81 EP - 93 VL - 70 IS - 1 KW - cholestasis KW - acute hepatitis KW - acute liver failure KW - hepatic necrosis KW - hepatotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852677738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Histopathology&rft.atitle=The+histopathological+evaluation+of+drug-induced+liver+injury.&rft.au=Kleiner%2C+David+E&rft.aulast=Kleiner&rft.aufirst=David&rft.date=2017-01-01&rft.volume=70&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Histopathology&rft.issn=1365-2559&rft_id=info:doi/10.1111%2Fhis.13082 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/his.13082 ER - TY - JOUR T1 - Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes. AN - 1852656862; 27648552 AB - The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis. JF - Journal of clinical gastroenterology AU - Björnsson, Einar S AU - Gu, Jiezhun AU - Kleiner, David E AU - Chalasani, Naga AU - Hayashi, Paul H AU - Hoofnagle, Jay H AU - DILIN Investigators AD - *Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institutes of Health, Bethesda, MD †The Faculty of Medicine, University of Iceland ‡National University Hospital of Iceland, Reykjavik, Iceland §Duke Clinical Research Institute, Durham, NC ∥Laboratory of Pathology, National Cancer Institute, National Institutes of Health ¶Indiana University School of Medicine, Indianapolis, IN #University of North Carolina, Chapel Hill, NC. ; DILIN Investigators Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 63 EP - 69 VL - 51 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852656862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+gastroenterology&rft.atitle=Azathioprine+and+6-Mercaptopurine-induced+Liver+Injury%3A+Clinical+Features+and+Outcomes.&rft.au=Bj%C3%B6rnsson%2C+Einar+S%3BGu%2C+Jiezhun%3BKleiner%2C+David+E%3BChalasani%2C+Naga%3BHayashi%2C+Paul+H%3BHoofnagle%2C+Jay+H%3BDILIN+Investigators&rft.aulast=Bj%C3%B6rnsson&rft.aufirst=Einar&rft.date=2017-01-01&rft.volume=51&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=1539-2031&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mechanism of O2 diffusion and reduction in FeFe hydrogenases. AN - 1851299047; 27995927 AB - FeFe hydrogenases are the most efficient H2-producing enzymes. However, inactivation by O2 remains an obstacle that prevents them being used in many biotechnological devices. Here, we combine electrochemistry, site-directed mutagenesis, molecular dynamics and quantum chemical calculations to uncover the molecular mechanism of O2 diffusion within the enzyme and its reactions at the active site. We propose that the partial reversibility of the reaction with O2 results from the four-electron reduction of O2 to water. The third electron/proton transfer step is the bottleneck for water production, competing with formation of a highly reactive OH radical and hydroxylated cysteine. The rapid delivery of electrons and protons to the active site is therefore crucial to prevent the accumulation of these aggressive species during prolonged O2 exposure. These findings should provide important clues for the design of hydrogenase mutants with increased resistance to oxidative damage. JF - Nature chemistry AU - Kubas, Adam AU - Orain, Christophe AU - De Sancho, David AU - Saujet, Laure AU - Sensi, Matteo AU - Gauquelin, Charles AU - Meynial-Salles, Isabelle AU - Soucaille, Philippe AU - Bottin, Hervé AU - Baffert, Carole AU - Fourmond, Vincent AU - Best, Robert B AU - Blumberger, Jochen AU - Léger, Christophe AD - Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT, UK. ; Aix Marseille Univ, CNRS, Laboratoire de Bioénergétique et Ingénierie des Protéines, Institut de Microbiologie de la Méditerranée, Marseille, France. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Institut de Biologie et de Technologies de Saclay IBITECS, SB2SM, F-91191 Gif sur Yvette, France. ; Université de Toulouse, INSA, UPS, INP, LISBP, INRA:UMR792, CNRS:UMR 5504, 135 avenue de Rangueil, Toulouse 31077 Cedex 04, France. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 88 EP - 95 VL - 9 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851299047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+chemistry&rft.atitle=Mechanism+of+O2+diffusion+and+reduction+in+FeFe+hydrogenases.&rft.au=Kubas%2C+Adam%3BOrain%2C+Christophe%3BDe+Sancho%2C+David%3BSaujet%2C+Laure%3BSensi%2C+Matteo%3BGauquelin%2C+Charles%3BMeynial-Salles%2C+Isabelle%3BSoucaille%2C+Philippe%3BBottin%2C+Herv%C3%A9%3BBaffert%2C+Carole%3BFourmond%2C+Vincent%3BBest%2C+Robert+B%3BBlumberger%2C+Jochen%3BL%C3%A9ger%2C+Christophe&rft.aulast=Kubas&rft.aufirst=Adam&rft.date=2017-01-01&rft.volume=9&rft.issue=1&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Nature+chemistry&rft.issn=1755-4349&rft_id=info:doi/10.1038%2Fnchem.2592 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nchem.2592 ER - TY - JOUR T1 - High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study. AN - 1851297150; 27996157 AB - Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P 59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction 59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Environmental and molecular mutagenesis AU - Rusiecki, Jennifer A AU - Beane Freeman, Laura E AU - Bonner, Matthew R AU - Alexander, Melannie AU - Chen, Ligong AU - Andreotti, Gabriella AU - Barry, Kathryn H AU - Moore, Lee E AU - Byun, Hyang-Min AU - Kamel, Freya AU - Alavanja, Michael AU - Hoppin, Jane A AU - Baccarelli, Andrea AD - Department of Preventive Medicine, Uniformed Services University, Bethesda, Maryland. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. ; Department of Epidemiology and Environmental Health, State University of New York, Buffalo, New York. ; Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom. ; Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. ; Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina. ; Harvard School of Public Health, Harvard University, Boston, Massachusetts. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 19 EP - 29 VL - 58 IS - 1 KW - exposure KW - Agricultural Health Study KW - epigenetics KW - DNA methylation KW - pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851297150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=High+pesticide+exposure+events+and+DNA+methylation+among+pesticide+applicators+in+the+agricultural+health+study.&rft.au=Rusiecki%2C+Jennifer+A%3BBeane+Freeman%2C+Laura+E%3BBonner%2C+Matthew+R%3BAlexander%2C+Melannie%3BChen%2C+Ligong%3BAndreotti%2C+Gabriella%3BBarry%2C+Kathryn+H%3BMoore%2C+Lee+E%3BByun%2C+Hyang-Min%3BKamel%2C+Freya%3BAlavanja%2C+Michael%3BHoppin%2C+Jane+A%3BBaccarelli%2C+Andrea&rft.aulast=Rusiecki&rft.aufirst=Jennifer&rft.date=2017-01-01&rft.volume=58&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=1098-2280&rft_id=info:doi/10.1002%2Fem.22067 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/em.22067 ER - TY - JOUR T1 - Pharmacokinetics of lenalidomide during high cut-off dialysis in a patient with multiple myeloma and renal failure. AN - 1851294783; 27988790 AB - High cut-off dialysis, increasingly used in multiple myeloma patients, is susceptible to influence anticancer drug elimination. We report about lenalidomide disposition in a patient on high cut-off dialysis for renal failure secondary to myeloma cast nephropathy. The patient received a higher dosage of lenalidomide (5 mg b.i.d.), owing to concerns about a potential decrease in lenalidomide exposure during dialysis sessions. A set of blood samples was taken in order to develop a pharmacokinetic model accounting for lenalidomide concentrations in this setting. According to our model, the area under the curve was 3273 µg h/L, i.e., 60% higher than expected under usual dosage (25 mg q.d.) with normal renal function. Despite this, the patient did not develop major hematological toxicity. Lenalidomide doses of 5 mg b.i.d. led to high exposure in a patient with renal failure undergoing high cut-off dialysis. Yet, the dosage of 5 mg q.d. recommended in conventional dialysis would probably be adequate in such patients. JF - Cancer chemotherapy and pharmacology AU - Dao, Kim AU - Lu, Yimin AU - Peer, Cody J AU - Figg, William D AU - Stadelmann, Raphael AU - Burnier, Michel AU - Buclin, Thierry AU - Kissling, Sebastien AD - Division of Clinical Pharmacology, Biomedicine, Department of Laboratories, CHUV, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 17, 1011, Lausanne, Switzerland. kim.dao@chuv.ch. ; Service of Nephrology, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. ; Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; Division of Hematology, Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. ; Division of Clinical Pharmacology, Biomedicine, Department of Laboratories, CHUV, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 17, 1011, Lausanne, Switzerland. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 215 EP - 218 VL - 79 IS - 1 KW - High cut-off membrane KW - Lenalidomide KW - High-flux dialysis KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851294783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Pharmacokinetics+of+lenalidomide+during+high+cut-off+dialysis+in+a+patient+with+multiple+myeloma+and+renal+failure.&rft.au=Dao%2C+Kim%3BLu%2C+Yimin%3BPeer%2C+Cody+J%3BFigg%2C+William+D%3BStadelmann%2C+Raphael%3BBurnier%2C+Michel%3BBuclin%2C+Thierry%3BKissling%2C+Sebastien&rft.aulast=Dao&rft.aufirst=Kim&rft.date=2017-01-01&rft.volume=79&rft.issue=1&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=1432-0843&rft_id=info:doi/10.1007%2Fs00280-016-3219-z LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00280-016-3219-z ER - TY - JOUR T1 - Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant. AN - 1851272957; 27618144 AB - We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment. © 2016 S. Karger AG, Basel. JF - Chemotherapy AU - Renzi, Daniela AU - Marchesi, Francesco AU - De Angelis, Gottardo AU - Elia, Loredana AU - Salvatorelli, Emanuela AU - Gumenyuk, Svitlana AU - Palombi, Francesca AU - Pisani, Francesco AU - Romano, Atelda AU - Spadea, Antonio AU - Papa, Elena AU - Canfora, Marco AU - Arcese, William AU - Mengarelli, Andrea AU - Rome Transplant Network AD - Hematology and Stem Cell Transplant Unit, Regina Elena National Cancer Institute, Rome, Italy. ; Rome Transplant Network Y1 - 2017 PY - 2017 DA - 2017 SP - 58 EP - 61 VL - 62 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851272957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemotherapy&rft.atitle=Ponatinib+Induces+a+Persistent+Molecular+Response+and+Graft-versus-Host+Disease%2FGraft-versus-Leukemia+Effect+in+a+Patient+with+Philadelphia-Positive+Acute+Lymphoblastic+Leukemia+with+a+T315I+Mutation+following+Early+Relapse+after+Allogeneic+Transplant.&rft.au=Renzi%2C+Daniela%3BMarchesi%2C+Francesco%3BDe+Angelis%2C+Gottardo%3BElia%2C+Loredana%3BSalvatorelli%2C+Emanuela%3BGumenyuk%2C+Svitlana%3BPalombi%2C+Francesca%3BPisani%2C+Francesco%3BRomano%2C+Atelda%3BSpadea%2C+Antonio%3BPapa%2C+Elena%3BCanfora%2C+Marco%3BArcese%2C+William%3BMengarelli%2C+Andrea%3BRome+Transplant+Network&rft.aulast=Renzi&rft.aufirst=Daniela&rft.date=2017-01-01&rft.volume=62&rft.issue=1&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=Chemotherapy&rft.issn=1421-9794&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials. AN - 1847895497; 27935336 AB - According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future. JF - Expert opinion on investigational drugs AU - Oronsky, Bryan AU - Paulmurugan, Ramasamy AU - Foygel, Kira AU - Scicinski, Jan AU - Knox, Susan J AU - Peehl, Donna AU - Zhao, Hongjuan AU - Ning, Shoucheng AU - Cabrales, Pedro AU - Summers, Thomas A AU - Reid, Tony R AU - Fitch, William L AU - Kim, Michelle M AU - Trepel, Jane B AU - Lee, Min-Jung AU - Kesari, Santosh AU - Abrouk, Nacer D AU - Day, Regina M AU - Oronsky, Arnold AU - Ray, Carolyn M AU - Carterg, Corey A AD - a EpicentRx (no department). ; b Department of Radiology , Stanford University , Palo Alto , CA , USA. ; c Department of Radiation Oncology , Stanford University , Palo Alto , CA , USA. ; d Department of Urology , Stanford University , Palo Alto , CA , USA. ; f Department of Bioengineering , University of California at San Diego (UCSD ) , La Jolla , CA , USA. ; g Murtha Cancer Center , Walter Reed National Military Medical Center ; Bethesda , MD , USA. ; h Moores Cancer Center , University of California at San Diego (UCSD) , CA , USA. ; e Department of Anesthesia , Stanford University , Palo Alto , CA , USA. ; k Innovexe. ; i National Cancer Institute , National Institutes of Health , Bethesda , MD , USA. ; j John Wayne Cancer Institute, Providence Saint John's Health Center , CA , USA. ; l Department of pharmacology , Uniformed Services University , Bethesda , MD , USA. ; m InterWest Partners. ; n Cancer Center, St. Francis Hospital , Hartford , CT , USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 109 EP - 119 VL - 26 IS - 1 KW - RRx-001 KW - cancer stem cells KW - cancer therapy KW - Tumor associated macrophages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847895497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=RRx-001%3A+a+systemically+non-toxic+M2-to-M1+macrophage+stimulating+and+prosensitizing+agent+in+Phase+II+clinical+trials.&rft.au=Oronsky%2C+Bryan%3BPaulmurugan%2C+Ramasamy%3BFoygel%2C+Kira%3BScicinski%2C+Jan%3BKnox%2C+Susan+J%3BPeehl%2C+Donna%3BZhao%2C+Hongjuan%3BNing%2C+Shoucheng%3BCabrales%2C+Pedro%3BSummers%2C+Thomas+A%3BReid%2C+Tony+R%3BFitch%2C+William+L%3BKim%2C+Michelle+M%3BTrepel%2C+Jane+B%3BLee%2C+Min-Jung%3BKesari%2C+Santosh%3BAbrouk%2C+Nacer+D%3BDay%2C+Regina+M%3BOronsky%2C+Arnold%3BRay%2C+Carolyn+M%3BCarterg%2C+Corey+A&rft.aulast=Oronsky&rft.aufirst=Bryan&rft.date=2017-01-01&rft.volume=26&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/10.1080%2F13543784.2017.1268600 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/13543784.2017.1268600 ER - TY - JOUR T1 - Phase I clinical and pharmacokinetic study of S-1 plus oral leucovorin in patients with metastatic colorectal cancer. AN - 1847893675; 27933371 AB - S-1 has shown a response rate of 35% in chemonaïve patients with metastatic colorectal cancer (mCRC). Leucovorin enhances the antitumor activity of 5-fluorouracil, and concurrent oral administration of S-1 and leucovorin may represent a more active treatment option for mCRC. S-1 (35 mg/m2) and leucovorin (25 mg/body) were orally administered twice daily to chemonaïve patients with mCRC. Predefined dose (schedule)-limiting toxicities (DLTs) during the first course and treatment continuity during the first two courses were evaluated during three periods of treatment with S-1 plus leucovorin (level 0, 2 weeks; level 1, 3 weeks; and level 2, 4 weeks), each followed by a 2-week rest. The pharmacokinetics (PK) of S-1 and leucovorin were studied on days 1 and 14 of the first course. Fifteen patients were enrolled. All three patients had DLTs at level 2, and this level was considered the maximum tolerated schedule. Level 0 was designated as the recommended schedule based on the incidences of DLTs and treatment continuity. The main toxic effects were gastrointestinal, such as diarrhea and stomatitis. There was no grade 4 adverse event or treatment-related death. The overall response rate was 67% (95% confidence interval, 38-88%). The PK profiles of S-1 plus leucovorin were similar to those in previous studies. The recommended schedule was 2 weeks of S-1 plus leucovorin followed by a 2-week rest. The increased response and gastrointestinal toxicities of S-1 plus leucovorin as compared with S-1 monotherapy suggest that co-administration of leucovorin enhanced the activity of S-1. JF - Cancer chemotherapy and pharmacology AU - Yoshino, Takayuki AU - Hyodo, Ichinosuke AU - Nishina, Tomohiro AU - Narahara, Hiroyuki AU - Sugimoto, Naotoshi AU - Yoshisue, Kunihiro AU - Boku, Narikazu AD - Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. tyoshino@east.ncc.go.jp. ; Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan. ; Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. ; Division of Clinical Research Center, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan. ; Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. ; Pharmacokinetics Research Laboratories, Tsukuba Research Center, Taiho Pharmaceutical Co., Ltd, Tsukuba, Japan. ; Department of Gastrointestinal Oncology, National Cancer Institute Hospital, Tokyo, Japan. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 107 EP - 116 VL - 79 IS - 1 KW - Colorectal cancer KW - Leucovorin KW - S-1 KW - Pharmacokinetics KW - Recommended schedule KW - Phase I study UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847893675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Phase+I+clinical+and+pharmacokinetic+study+of+S-1+plus+oral+leucovorin+in+patients+with+metastatic+colorectal+cancer.&rft.au=Yoshino%2C+Takayuki%3BHyodo%2C+Ichinosuke%3BNishina%2C+Tomohiro%3BNarahara%2C+Hiroyuki%3BSugimoto%2C+Naotoshi%3BYoshisue%2C+Kunihiro%3BBoku%2C+Narikazu&rft.aulast=Yoshino&rft.aufirst=Takayuki&rft.date=2017-01-01&rft.volume=79&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=1432-0843&rft_id=info:doi/10.1007%2Fs00280-016-3212-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00280-016-3212-6 ER - TY - JOUR T1 - Computational Tools for Allosteric Drug Discovery: Site Identification and Focus Library Design. AN - 1845831980; 27914066 AB - Allostery is an intrinsic phenomenon of biological macromolecules involving regulation and/or signal transduction induced by a ligand binding to an allosteric site distinct from a molecule's active site. Allosteric drugs are currently receiving increased attention in drug discovery because drugs that target allosteric sites can provide important advantages over the corresponding orthosteric drugs including specific subtype selectivity within receptor families. Consequently, targeting allosteric sites, instead of orthosteric sites, can reduce drug-related side effects and toxicity. On the down side, allosteric drug discovery can be more challenging than traditional orthosteric drug discovery due to difficulties associated with determining the locations of allosteric sites and designing drugs based on these sites and the need for the allosteric effects to propagate through the structure, reach the ligand binding site and elicit a conformational change. In this study, we present computational tools ranging from the identification of potential allosteric sites to the design of "allosteric-like" modulator libraries. These tools may be particularly useful for allosteric drug discovery. JF - Methods in molecular biology (Clifton, N.J.) AU - Huang, Wenkang AU - Nussinov, Ruth AU - Zhang, Jian AD - Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine (SJTU-SM), Shanghai, 200025, China. ; Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, National Cancer Institute, Frederick, MD, 21702, USA. NussinoR@helix.nih.gov. ; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine (SJTU-SM), Shanghai, 200025, China. jian.zhang@sjtu.edu.cn. Y1 - 2017 PY - 2017 DA - 2017 SP - 439 EP - 446 VL - 1529 KW - Allosteric drug discovery KW - Allosteric drug design KW - Allostery KW - Allosteric site KW - Allosteric modulator UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845831980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Computational+Tools+for+Allosteric+Drug+Discovery%3A+Site+Identification+and+Focus+Library+Design.&rft.au=Huang%2C+Wenkang%3BNussinov%2C+Ruth%3BZhang%2C+Jian&rft.aulast=Huang&rft.aufirst=Wenkang&rft.date=2017-01-01&rft.volume=1529&rft.issue=&rft.spage=439&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=1940-6029&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Predictive Comprehensive Geriatric Assessment in elderly prostate cancer patients: the prospective observational scoop trial results. AN - 1845255749; 27579728 AB - The Comprehensive Geriatric Assessment (CGA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. Most patients receiving docetaxel for metastatic castration-resistant prostate cancer are in their seventies or older. We explored the efficacy of the CGA in predicting chemotherapy feasibility and response to docetaxel in a cohort of 24 patients aged at least 70. This was an observational, prospective study involving 24 patients who were 70 years of age or older and about to start chemotherapy with docetaxel for metastatic castration-resistant prostate cancer; we performed a CGA including five domains and divided our patients into 'healthy' and 'frail'; the relations between general condition and (i) early chemotherapy discontinuation and (ii) response to docetaxel were explored. We found a statistically significant relationship between frailty assessed by CGA and early docetaxel discontinuation; we also found an association between frailty and response to chemotherapy, but this did not reach statistical significance. A geriatric assessment before starting chemotherapy may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. Further analyses are required to simplify the CGA tools and to facilitate its incorporation into routine clinical practice. JF - Anti-cancer drugs AU - Della Pepa, Chiara AU - Cavaliere, Carla AU - Rossetti, Sabrina AU - Di Napoli, Marilena AU - Cecere, Sabrina C AU - Crispo, Anna AU - De Sangro, Carlo AU - Rossi, Emanuela AU - Turitto, Dino AU - Germano, Domenico AU - Iovane, Gelsomina AU - Berretta, Massimiliano AU - D'Aniello, Carmine AU - Pisconti, Salvatore AU - Maiorino, Luigi AU - Daniele, Bruno AU - Gridelli, Cesare AU - Pignata, Sandro AU - Facchini, Gaetano AD - aDivision of Medical Oncology, Department of Uro-Gynaecological Oncology 'Istituto Nazionale Tumori' 'Fondazione G. Pascale'-IRCCS bUnit of Epidemiology, 'Istituto Nazionale Tumori' 'Fondazione G. Pascale' - IRCCS cDivision of Medical Oncology, 'San Gennaro dei Poveri' Hospital, Naples dDepartment of Onco-Ematology and Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto eDivision of Medical Oncology, 'San Giuseppe Moscati' Hospital, Avellino fDivision of Medical Oncology, 'Gaetano Rummo' Hospital, Benevento gDepartment of Medical Oncology, National Cancer Institute, Aviano, Italy. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 104 EP - 109 VL - 28 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845255749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Predictive+Comprehensive+Geriatric+Assessment+in+elderly+prostate+cancer+patients%3A+the+prospective+observational+scoop+trial+results.&rft.au=Della+Pepa%2C+Chiara%3BCavaliere%2C+Carla%3BRossetti%2C+Sabrina%3BDi+Napoli%2C+Marilena%3BCecere%2C+Sabrina+C%3BCrispo%2C+Anna%3BDe+Sangro%2C+Carlo%3BRossi%2C+Emanuela%3BTuritto%2C+Dino%3BGermano%2C+Domenico%3BIovane%2C+Gelsomina%3BBerretta%2C+Massimiliano%3BD%27Aniello%2C+Carmine%3BPisconti%2C+Salvatore%3BMaiorino%2C+Luigi%3BDaniele%2C+Bruno%3BGridelli%2C+Cesare%3BPignata%2C+Sandro%3BFacchini%2C+Gaetano&rft.aulast=Della+Pepa&rft.aufirst=Chiara&rft.date=2017-01-01&rft.volume=28&rft.issue=1&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=1473-5741&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in locally advanced cervical cancer. AN - 1844354140; 27888705 AB - To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT). Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models. Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001). Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - European journal of obstetrics, gynecology, and reproductive biology AU - Bogani, Giorgio AU - Sabatucci, Ilaria AU - Maltese, Giuseppa AU - Lecce, Francesca AU - Signorelli, Mauro AU - Martinelli, Fabio AU - Chiappa, Valentina AU - Indini, Alice AU - Leone Roberti Maggiore, Umberto AU - Borghi, Chiara AU - Fucà, Giovanni AU - Ditto, Antonino AU - Raspagliesi, Francesco AU - Lorusso, Domenica AD - Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy. Electronic address: giorgiobogani@yahoo.it. ; Department of Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy. ; Academic Unit of Obstetrics and Gynecology, IRCCS AOU San-Martino-IST, Genoa, Italy. ; Department of Morphology, Surgery and Experimental Medicine, Ferrara, Italy. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 41 EP - 45 VL - 208 KW - Neoadjuvant chemotherapy KW - Cervical cancer KW - Survival KW - Leukopenia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844354140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+obstetrics%2C+gynecology%2C+and+reproductive+biology&rft.atitle=Chemotherapy-related+leukopenia+as+a+biomarker+predicting+survival+outcomes+in+locally+advanced+cervical+cancer.&rft.au=Bogani%2C+Giorgio%3BSabatucci%2C+Ilaria%3BMaltese%2C+Giuseppa%3BLecce%2C+Francesca%3BSignorelli%2C+Mauro%3BMartinelli%2C+Fabio%3BChiappa%2C+Valentina%3BIndini%2C+Alice%3BLeone+Roberti+Maggiore%2C+Umberto%3BBorghi%2C+Chiara%3BFuc%C3%A0%2C+Giovanni%3BDitto%2C+Antonino%3BRaspagliesi%2C+Francesco%3BLorusso%2C+Domenica&rft.aulast=Bogani&rft.aufirst=Giorgio&rft.date=2017-01-01&rft.volume=208&rft.issue=&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=European+journal+of+obstetrics%2C+gynecology%2C+and+reproductive+biology&rft.issn=1872-7654&rft_id=info:doi/10.1016%2Fj.ejogrb.2016.11.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ejogrb.2016.11.017 ER - TY - JOUR T1 - Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study. AN - 1842600255; 27871980 AB - Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW. Published by Elsevier Ltd. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Von Tungeln, Linda S AU - Walker, Nigel J AU - Olson, Greg R AU - Mendoza, Maria C B AU - Felton, Robert P AU - Thorn, Brett T AU - Marques, M Matilde AU - Pogribny, Igor P AU - Doerge, Daniel R AU - Beland, Frederick A AD - Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States. ; Toxicologic Pathology Associates, Jefferson, AR 72079, United States. ; Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, United States. ; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal. ; Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. Electronic address: frederick.beland@fda.hhs.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 170 EP - 181 VL - 99 KW - Rats KW - Cholangiocarcinoma KW - Cholangiofibrosis KW - Furan KW - Tumorigenicity KW - Bioassay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842600255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Low+dose+assessment+of+the+carcinogenicity+of+furan+in+male+F344%2FN+Nctr+rats+in+a+2-year+gavage+study.&rft.au=Von+Tungeln%2C+Linda+S%3BWalker%2C+Nigel+J%3BOlson%2C+Greg+R%3BMendoza%2C+Maria+C+B%3BFelton%2C+Robert+P%3BThorn%2C+Brett+T%3BMarques%2C+M+Matilde%3BPogribny%2C+Igor+P%3BDoerge%2C+Daniel+R%3BBeland%2C+Frederick+A&rft.aulast=Von+Tungeln&rft.aufirst=Linda&rft.date=2017-01-01&rft.volume=99&rft.issue=&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.11.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.11.015 ER - TY - JOUR T1 - Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS). AN - 1842599471; 27873235 AB - An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here. Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity. Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids. These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients. Molteni Farmaceutici, Italy. JF - Advances in therapy AU - Mercadante, Sebastiano AU - Marchetti, Paolo AU - Cuomo, Arturo AU - Caraceni, Augusto AU - Mediati, Rocco Domenico AU - Mammucari, Massimo AU - Natoli, Silvia AU - Lazzari, Marzia AU - Dauri, Mario AU - Airoldi, Mario AU - Azzarello, Giuseppe AU - Bandera, Mauro AU - Blasi, Livio AU - Cartenì, Giacomo AU - Chiurazzi, Bruno AU - Costanzo, Benedetta Veruska Pierpaola AU - Degiovanni, Daniela AU - Fusco, Flavio AU - Guardamagna, Vittorio AU - Iaffaioli, Vincenzo AU - Liguori, Simeone AU - Lorusso, Vito AU - Mameli, Sergio AU - Mattioli, Rodolfo AU - Mazzei, Teresita AU - Melotti, Rita Maria AU - Menardo, Valentino AU - Miotti, Danilo AU - Moroso, Stefano AU - De Santis, Stefano AU - Orsetti, Remo AU - Papa, Alfonso AU - Ricci, Sergio AU - Sabato, Alessandro Fabrizio AU - Scelzi, Elvira AU - Sofia, Michele AU - Tonini, Giuseppe AU - Aielli, Federica AU - Valle, Alessandro AU - IOPS MS study group AD - Anesthesia and Intensive Care and Pain Relief and Supportive Care, La Maddalena Cancer Center, Via San Lorenzo 312, 90146, Palermo, Italy. terapiadeldolore@lamaddalenanet.it. ; Molecular and Clinical Medicine, Medical Oncology, La Sapienza University of Rome, Rome, Italy. ; Anesthesiology, Resuscitation, and Pain Therapy Department, National Cancer Institute, IRCCS Foundation Pascale, Naples, Italy. ; Palliative Care, Pain Therapy and Rehabilitation, National Cancer Institute IRCCS Foundation, Milan, Italy. ; Palliative Care and Pain Therapy Unit, Careggi Hospital, Florence, Italy. ; Primary Care Unit, ASL RM1, Rome, Italy. ; Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, Rome, Italy. ; 2nd Medical Oncology Division, Città della Salute e della Scienza Hospital of Turin, Turin, Italy. ; Medical Specialties Department, Oncology and Oncologic Hematology, ASL 13 Mirano, Venice, Italy. ; Medical Oncology Unit, Ospedale di Circolo e Fondazione Macchi Hospital, Varese, Italy. ; Medical Oncology Unit, ARNAS Ospedale Civico, Di Cristina, Benfratelli, Palermo, Italy. ; Medical Oncology, A.O.R.N. Cardarelli, Naples, Italy. ; Palliative Care Unit, SAMO ONLUS, Catania, Italy. ; Palliative Care Unit, ASLAL, Casale Monferrato, Italy. ; Palliative Care Unit, Department of Primary and Community Care, ASL3 Genovese, Genoa, Italy. ; Palliative Care and Pain Therapy Unit, European Oncology Institute IRCCS, Milan, Italy. ; Abdominal Medical Oncology, National Cancer Institute, IRCCS Foundation Pascale, Naples, Italy. ; Palliative Care and Pain Therapy Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy. ; Medical Oncology Unit, National Cancer Research Centre "Giovanni Paolo II", Bari, Italy. ; Pain Therapy Unit, "A. Businco" Hospital, ASL 8, Cagliari, Italy. ; Medical Oncology Unit, S. Croce Hospital, Fano, Pesaro, Italy. ; Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy. ; Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy. ; Pain Therapy, S. Croce e Carle, Hospital Cuneo, Cuneo, Italy. ; Palliative Care Unit, Salvatore Maugeri-IRCCS Foundation, Pavia, Italy. ; Medical Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. ; Palliative Care and Oncologic Pain Service, S. Camillo-Forlanini Hospital, Rome, Italy. ; Pain Medicine Unit, S. Camillo-Forlanini Hospital, Rome, Italy. ; Pain Relief, A.O. Dei Colli, Monaldi Hospital, Naples, Italy. ; Division of Medical Oncology, Department of Oncology, S. Chiara University Hospital, Pisa, Italy. ; Medical Oncology, Castelfranco Veneto Hospital, Treviso, Italy. ; Department of Palliative Care with Hospice and Pain Therapy Unit, "G.Salvini" Hospital, Garbagnate Milanese, Milan, Italy. ; Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy. ; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. ; Palliative Care, FARO Foundation, Turin, Italy. ; IOPS MS study group Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 120 EP - 135 VL - 34 IS - 1 KW - Pain assessment KW - Rapid-onset opioid KW - Breakthrough pain KW - Cancer pain UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842599471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+therapy&rft.atitle=Breakthrough+Cancer+Pain%3A+Preliminary+Data+of+The+Italian+Oncologic+Pain+Multisetting+Multicentric+Survey+%28IOPS-MS%29.&rft.au=Mercadante%2C+Sebastiano%3BMarchetti%2C+Paolo%3BCuomo%2C+Arturo%3BCaraceni%2C+Augusto%3BMediati%2C+Rocco+Domenico%3BMammucari%2C+Massimo%3BNatoli%2C+Silvia%3BLazzari%2C+Marzia%3BDauri%2C+Mario%3BAiroldi%2C+Mario%3BAzzarello%2C+Giuseppe%3BBandera%2C+Mauro%3BBlasi%2C+Livio%3BCarten%C3%AC%2C+Giacomo%3BChiurazzi%2C+Bruno%3BCostanzo%2C+Benedetta+Veruska+Pierpaola%3BDegiovanni%2C+Daniela%3BFusco%2C+Flavio%3BGuardamagna%2C+Vittorio%3BIaffaioli%2C+Vincenzo%3BLiguori%2C+Simeone%3BLorusso%2C+Vito%3BMameli%2C+Sergio%3BMattioli%2C+Rodolfo%3BMazzei%2C+Teresita%3BMelotti%2C+Rita+Maria%3BMenardo%2C+Valentino%3BMiotti%2C+Danilo%3BMoroso%2C+Stefano%3BDe+Santis%2C+Stefano%3BOrsetti%2C+Remo%3BPapa%2C+Alfonso%3BRicci%2C+Sergio%3BSabato%2C+Alessandro+Fabrizio%3BScelzi%2C+Elvira%3BSofia%2C+Michele%3BTonini%2C+Giuseppe%3BAielli%2C+Federica%3BValle%2C+Alessandro%3BIOPS+MS+study+group&rft.aulast=Mercadante&rft.aufirst=Sebastiano&rft.date=2017-01-01&rft.volume=34&rft.issue=1&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Advances+in+therapy&rft.issn=1865-8652&rft_id=info:doi/10.1007%2Fs12325-016-0440-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-22 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1007/s12325-016-0440-4 ER - TY - JOUR T1 - Avoiding phagocytosis-related artifact in myeloid derived suppressor cell T-lymphocyte suppression assays. AN - 1841797780; 27856191 AB - Myeloid-derived suppressor cells (MDSCs) have garnered much attention in recent years as a potential target for altering the immunosuppressive tumor microenvironment in a variety of solid tumor types. The ability to accurately assess the immunosuppressive capacity of MDSCs is fundamental to the development of therapeutic approaches aimed at disabling these immunosuppressive functions. In this article we provide evidence that the use of CD3/28 coated microbeads leads to artefactual T-lymphocyte suppression due to sequestration of beads by MDSCs isolated from the spleens of wild-type mice bearing subcutaneous syngeneic, carcinogen-induced oral cavity carcinomas. Mechanisms of this finding may include early MDSC death and acquisition of phagocytic capacity. These artefactual findings were avoided by eliminating the use of microbeads and instead using plate bound CD3/28 antibody as the T-lymphocyte stimulus. We propose model-specific validation of microbead-based MDSC assays, or use of an alternative stimulation approach such as plate bound CD3/28 antibodies. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of immunological methods AU - Davis, Ruth J AU - Silvin, Christopher AU - Allen, Clint T AD - Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States. ; Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, United States; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: clint.allen@nih.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 12 EP - 18 VL - 440 KW - MDSC KW - Artifact KW - Myeloid-derived suppressor cells KW - T-cell suppression assay KW - Phagocytosis KW - CD3/28 microbeads UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841797780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunological+methods&rft.atitle=Avoiding+phagocytosis-related+artifact+in+myeloid+derived+suppressor+cell+T-lymphocyte+suppression+assays.&rft.au=Davis%2C+Ruth+J%3BSilvin%2C+Christopher%3BAllen%2C+Clint+T&rft.aulast=Davis&rft.aufirst=Ruth&rft.date=2017-01-01&rft.volume=440&rft.issue=&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=1872-7905&rft_id=info:doi/10.1016%2Fj.jim.2016.11.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jim.2016.11.006 ER - TY - JOUR T1 - Liver injury from herbal and dietary supplements. AN - 1841795830; 27677775 AB - Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide, and HDS-induced liver injury in the United States has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements. Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute hepatitis-like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges in diagnosis, identification of the responsible constituents, treatment, and prevention. Also important are improvements in regulatory oversight of nonprescription products to guarantee their constituents and ensure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. (Hepatology 2017;65:363-373). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Navarro, Victor J AU - Khan, Ikhlas AU - Björnsson, Einar AU - Seeff, Leonard B AU - Serrano, Jose AU - Hoofnagle, Jay H AD - Division of Hepatology, Einstein Healthcare Network, Philadelphia, PA. ; Department of Pharmacognosy, School of Pharmacy, University of Mississippi, Jackson, MS. ; National University Hospital of Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. ; Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 363 EP - 373 VL - 65 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841795830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Liver+injury+from+herbal+and+dietary+supplements.&rft.au=Navarro%2C+Victor+J%3BKhan%2C+Ikhlas%3BBj%C3%B6rnsson%2C+Einar%3BSeeff%2C+Leonard+B%3BSerrano%2C+Jose%3BHoofnagle%2C+Jay+H&rft.aulast=Navarro&rft.aufirst=Victor&rft.date=2017-01-01&rft.volume=65&rft.issue=1&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28813 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28813 ER - TY - JOUR T1 - Psychological health in long-term cancer survivorship: an Italian survey on depression and anxiety AN - 1837058569 AB - Since long-term survivorship is now a reality for an increasingly number of people with a history of cancer, understanding their psychological health can inform health care policy as well as help supporting individual patients. This study was aimed to describe depression and anxiety (i.e. two of the most common psychological symptoms reported in oncology) in a sample of Italian long-term cancer survivors (LTCSs) defined as people who have been free from cancer and cancer treatments for at least five years. Four hundred and four Italian adult LTCSs completed a battery of questionnaires including the Zung Self-rating Depression Scale and the State Anxiety sub-scale of the State-Trait Anxiety Inventory respectively for depression and anxiety assessment. 16.5% of the sample displayed mild depression, 11.1% moderate depression, and 7.1% severe depression. depression was negatively associated with education (p = .017), perceived social support as provided by the family (p = .028), and perceived social support provided by friends (p = .008), and it was positively associated with occupational status (p = .023), presence of health issues (p = .010), and anxiety (p < .001). 8.7 and 15.8% of the sample were respectively possible and probable cases of anxiety. Anxiety was negatively associated with occupational status (p = .038) and it was positively associated with depression (p < .001). These data support ongoing assessment and monitoring of depression and anxiety in LTCSs, and stimulate the development and testing of psychological interventions for such individuals. In addition, they encourage further study on the psychological health of this specific population. JF - Psychology, Health & Medicine AU - Muzzatti, Barbara AU - Giovannini, Lorena AU - Romito, Francesca AU - Cormio, Claudia AU - Barberio, Daniela AU - Abate, Valentina AU - De Falco, Francesco AU - Annunziata, Maria Antonietta AD - Centro di Riferimento Oncologico - National Cancer Institute, Aviano, Italy ; Istituto Tumori "G. Paolo II" - National Cancer Institute, Bari, Italy ; Istituto Tumori "G. Pascale" - National Cancer Institute, Napoli, Italy ; Centro di Riferimento Oncologico - National Cancer Institute, Aviano, Italy Y1 - 2017/01// PY - 2017 DA - Jan 2017 SP - 12 EP - 18 CY - Abingdon PB - Taylor & Francis Ltd. VL - 22 IS - 1 SN - 1354-8506 KW - Psychology KW - Anxiety KW - cancer survivorship KW - depression KW - oncology KW - psychological health KW - Health care KW - Friends KW - Anxiety-Depression KW - Mental health KW - Psychological wellbeing KW - Survivors KW - Oncology KW - Occupational status KW - Genetic family histories KW - Perceived social support KW - Questionnaires KW - Psychological development KW - Psychological problems KW - Trait anxiety KW - Cancer KW - Social support UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837058569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychology%2C+Health+%26+Medicine&rft.atitle=Psychological+health+in+long-term+cancer+survivorship%3A+an+Italian+survey+on+depression+and+anxiety&rft.au=Muzzatti%2C+Barbara%3BGiovannini%2C+Lorena%3BRomito%2C+Francesca%3BCormio%2C+Claudia%3BBarberio%2C+Daniela%3BAbate%2C+Valentina%3BDe+Falco%2C+Francesco%3BAnnunziata%2C+Maria+Antonietta&rft.aulast=Muzzatti&rft.aufirst=Barbara&rft.date=2017-01-01&rft.volume=22&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Psychology%2C+Health+%26+Medicine&rft.issn=13548506&rft_id=info:doi/10.1080%2F13548506.2016.1164874 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 Informa UK Limited, trading as Taylor & Francis Group N1 - Last updated - 2016-11-08 DO - http://dx.doi.org/10.1080/13548506.2016.1164874 ER - TY - JOUR T1 - A Brief Overview of the STP 35th Annual Symposium on the Basis and Relevance of Variation in Toxicologic Responses. AN - 1836736439; 27815490 AB - The title of the 2016 Society of Toxicologic Pathology (STP) Symposium was the "Basis and Relevance of Variation in Toxicologic Responses." Many factors may contribute to variation in toxicologic responses and can confound results, complicate interpretation of data, interfere with reproducibility, and make extrapolation to humans problematic. This brief overview summarizes speaker presentations from each session which describes important factors that may impact the interpretation of nonclinical discovery and developmental toxicity studies. In addition, summaries of the Continuing Education (CE) courses and other educational events that occurred during the Symposium are highlighted. JF - Toxicologic pathology AU - Irizarry, Armando R AU - Gropp, Kathryn E AU - Dixon, Darlene AD - 1 Eli Lilly & Company, Indianapolis, Indiana, USA. ; 2 Pfizer Inc., Groton, Connecticut, USA. ; 3 National Institute of Environmental Health Sciences and the National Toxicology Program, National Institutes of Health (NIH), U.S. Department of Health and Human Services (HHS), Research Triangle Park, North Carolina, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 52 EP - 56 VL - 45 IS - 1 KW - Toxicologic Pathology KW - clinical pathology KW - variation KW - nonclinical toxicity studies KW - toxicology KW - toxicologic responses KW - annual symposium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836736439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=A+Brief+Overview+of+the+STP+35th+Annual+Symposium+on+the+Basis+and+Relevance+of+Variation+in+Toxicologic+Responses.&rft.au=Irizarry%2C+Armando+R%3BGropp%2C+Kathryn+E%3BDixon%2C+Darlene&rft.aulast=Irizarry&rft.aufirst=Armando&rft.date=2017-01-01&rft.volume=45&rft.issue=1&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=1533-1601&rft_id=info:doi/10.1177%2F0192623316675765 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0192623316675765 ER - TY - JOUR T1 - The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study. AN - 1836733204; 27810988 AB - Little is known about arsenic and diabetes in youth. We examined the association of arsenic with type 1 and type 2 diabetes in the SEARCH for Diabetes in Youth Case-Control (SEARCH-CC) study. Because one-carbon metabolism can influence arsenic metabolism, we also evaluated the potential interaction of folate and vitamin B12 with arsenic metabolism on the odds of diabetes. Six hundred eighty-eight participants <22 years of age (429 with type 1 diabetes, 85 with type 2 diabetes, and 174 control participants) were evaluated. Arsenic species (inorganic arsenic [iAs], monomethylated arsenic [MMA], dimethylated arsenic [DMA]), and one-carbon metabolism biomarkers (folate and vitamin B12) were measured in plasma. We used the sum of iAs, MMA, and DMA (∑As) and the individual species as biomarkers of arsenic concentrations and the relative proportions of the species over their sum (iAs%, MMA%, DMA%) as biomarkers of arsenic metabolism. Median ∑As, iAs%, MMA%, and DMA% were 83.1 ng/L, 63.4%, 10.3%, and 25.2%, respectively. ∑As was not associated with either type of diabetes. The fully adjusted odds ratios (95% CI), rescaled to compare a difference in levels corresponding to the interquartile range of iAs%, MMA%, and DMA%, were 0.68 (0.50-0.91), 1.33 (1.02-1.74), and 1.28 (1.01-1.63), respectively, for type 1 diabetes and 0.82 (0.48-1.39), 1.09 (0.65-1.82), and 1.17 (0.77-1.77), respectively, for type 2 diabetes. In interaction analysis, the odds ratio of type 1 diabetes by MMA% was 1.80 (1.25-2.58) and 0.98 (0.70-1.38) for participants with plasma folate levels above and below the median (P for interaction = 0.02), respectively. Low iAs% versus high MMA% and DMA% was associated with a higher odds of type 1 diabetes, with a potential interaction by folate levels. These data support further research on the role of arsenic metabolism in type 1 diabetes, including the interplay with one-carbon metabolism biomarkers. © 2017 by the American Diabetes Association. JF - Diabetes care AU - Grau-Pérez, Maria AU - Kuo, Chin-Chi AU - Spratlen, Miranda AU - Thayer, Kristina A AU - Mendez, Michelle A AU - Hamman, Richard F AU - Dabelea, Dana AU - Adgate, John L AU - Knowler, William C AU - Bell, Ronny A AU - Miller, Frederick W AU - Liese, Angela D AU - Zhang, Chongben AU - Douillet, Christelle AU - Drobná, Zuzana AU - Mayer-Davis, Elizabeth J AU - Styblo, Miroslav AU - Navas-Acien, Ana AD - Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD mgraupe1@jhu.edu anavasa1@jhu.edu. ; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC. ; Department of Nutrition, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC. ; Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO. ; Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Denver, Aurora, CO. ; Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ. ; Wake Forest School of Medicine, Winston-Salem, NC. ; National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD. ; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 46 EP - 53 VL - 40 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836733204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes+care&rft.atitle=The+Association+of+Arsenic+Exposure+and+Metabolism+With+Type+1+and+Type+2+Diabetes+in+Youth%3A+The+SEARCH+Case-Control+Study.&rft.au=Grau-P%C3%A9rez%2C+Maria%3BKuo%2C+Chin-Chi%3BSpratlen%2C+Miranda%3BThayer%2C+Kristina+A%3BMendez%2C+Michelle+A%3BHamman%2C+Richard+F%3BDabelea%2C+Dana%3BAdgate%2C+John+L%3BKnowler%2C+William+C%3BBell%2C+Ronny+A%3BMiller%2C+Frederick+W%3BLiese%2C+Angela+D%3BZhang%2C+Chongben%3BDouillet%2C+Christelle%3BDrobn%C3%A1%2C+Zuzana%3BMayer-Davis%2C+Elizabeth+J%3BStyblo%2C+Miroslav%3BNavas-Acien%2C+Ana&rft.aulast=Grau-P%C3%A9rez&rft.aufirst=Maria&rft.date=2017-01-01&rft.volume=40&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Diabetes+care&rft.issn=1935-5548&rft_id=info:doi/10.2337%2Fdc16-0810 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.2337/dc16-0810 ER - TY - JOUR T1 - Experimental and Study Design Considerations for Uncovering Oncometabolites. AN - 1836732291; 27807829 AB - Metabolomics as a field has gained attention due to its potential for biomarker discovery, namely because it directly reflects disease phenotype and is the downstream effect of posttranslational modifications. The field provides a "top-down," integrated view of biochemistry in complex organisms, as opposed to the traditional "bottom-up" approach that aims to analyze networks of interactions between genes, proteins and metabolites. It also allows for the detection of thousands of endogenous metabolites in various clinical biospecimens in a high-throughput manner, including tissue and biofluids such as blood and urine. Of note, because biological fluid samples can be collected relatively easily, the time-dependent fluctuations of metabolites can be readily studied in detail.In this chapter, we aim to provide an overview of (1) analytical methods that are currently employed in the field, and (2) study design concepts that should be considered prior to conducting high-throughput metabolomics studies. While widely applicable, the concepts presented here are namely applicable to high-throughput untargeted studies that aim to search for metabolite biomarkers that are associated with a particular human disease. JF - Methods in molecular biology (Clifton, N.J.) AU - Haznadar, Majda AU - Mathé, Ewy A AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA. ; Biomedical Informatics Department, College of Medicine, Ohio State University, Columbus, OH, 43210, USA. Ewy.Mathe@osumc.edu. Y1 - 2017 PY - 2017 DA - 2017 SP - 37 EP - 47 VL - 1513 KW - Biomarker discovery KW - Oncometabolites KW - Analytical techniques KW - Mass spectrometry KW - Metabolomics KW - Study design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836732291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Experimental+and+Study+Design+Considerations+for+Uncovering+Oncometabolites.&rft.au=Haznadar%2C+Majda%3BMath%C3%A9%2C+Ewy+A&rft.aulast=Haznadar&rft.aufirst=Majda&rft.date=2017-01-01&rft.volume=1513&rft.issue=&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=1940-6029&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury. AN - 1835689316; 27634590 AB - Overdose of acetaminophen (APAP) is a major cause of acute liver failure. This study was aimed to identify pathways related to hepatotoxicity and potential biomarkers of liver injury. Rats were treated with low (100 mg/kg) and high (1250 mg/kg) doses of APAP, and liver tissues at 6 and 24 h post-treatment were analyzed using a proteomic approach of 16O/18O labeling and 2D-LC-MS/MS. Molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner upon APAP treatment. Imbalanced expression of hemeoxygenase 1 (HMOX1) and biliverdin reductase A (BLVRA) was associated with hepatotoxicity. Protein abundance changes of a total of 31 proteins were uniquely correlated to liver damage, among which a dramatic increase of HMOX1 levels in plasma was observed. Liver injury-associated significant elevation of plasma HMOX1 was further validated in mice treated with APAP. This study unveiled molecular changes associated with APAP-induced liver toxicity at the pathway levels and identified HMOX1 as a potential plasma biomarker of liver injury. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Proteomics. Clinical applications AU - Gao, Yuan AU - Cao, Zhijun AU - Yang, Xi AU - Abdelmegeed, Mohamed A AU - Sun, Jinchun AU - Chen, Si AU - Beger, Richard D AU - Davis, Kelly AU - Salminen, William F AU - Song, Byoung-Joon AU - Mendrick, Donna L AU - Yu, Li-Rong AD - Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. ; Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. ; Toxicologic Pathology Associates, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 VL - 11 IS - 1-2 KW - Heme oxygenase 1 (HMOX1) KW - Hepatotoxicity KW - Acetaminophen KW - MS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835689316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics.+Clinical+applications&rft.atitle=Proteomic+analysis+of+acetaminophen-induced+hepatotoxicity+and+identification+of+heme+oxygenase+1+as+a+potential+plasma+biomarker+of+liver+injury.&rft.au=Gao%2C+Yuan%3BCao%2C+Zhijun%3BYang%2C+Xi%3BAbdelmegeed%2C+Mohamed+A%3BSun%2C+Jinchun%3BChen%2C+Si%3BBeger%2C+Richard+D%3BDavis%2C+Kelly%3BSalminen%2C+William+F%3BSong%2C+Byoung-Joon%3BMendrick%2C+Donna+L%3BYu%2C+Li-Rong&rft.aulast=Gao&rft.aufirst=Yuan&rft.date=2017-01-01&rft.volume=11&rft.issue=1-2&rft.spage=360&rft.isbn=&rft.btitle=&rft.title=Addiction+biology&rft.issn=1369-1600&rft_id=info:doi/10.1111%2Fadb.12206 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/prca.201600123 ER - TY - JOUR T1 - FutureTox III: Bridges for Translation. AN - 1835685355; 27780885 AB - Future Tox III, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2015. Building upon Future Tox I and II, Future Tox III was focused on developing the high throughput risk assessment paradigm and taking the science of in vitro data and in silico models forward to explore the question-what progress is being made to address challenges in implementing the emerging big-data toolbox for risk assessment and regulatory decision-making. This article reports on the outcome of the workshop including 2 examples of where advancements in predictive toxicology approaches are being applied within Federal agencies, where opportunities remain within the exposome and AOP domains, and how collectively the toxicology community across multiple sectors can continue to bridge the translation from historical approaches to Tox21 implementation relative to risk assessment and regulatory decision-making. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Juberg, Daland R AU - Knudsen, Thomas B AU - Sander, Miriam AU - Beck, Nancy B AU - Faustman, Elaine M AU - Mendrick, Donna L AU - Fowle, John R AU - Hartung, Thomas AU - Tice, Raymond R AU - Lemazurier, Emmanuel AU - Becker, Richard A AU - Fitzpatrick, Suzanne Compton AU - Daston, George P AU - Harrill, Alison AU - Hines, Ronald N AU - Keller, Douglas A AU - Lipscomb, John C AU - Watson, David AU - Bahadori, Tina AU - Crofton, Kevin M AD - Dow AgroSciences, Indianapolis, Indiana; drjuberg@dow.com. ; US Environmental Protection Agency, Research Triangle Park, North Carolina. ; Page One Editorial Services, Boulder, Colorado. ; American Chemistry Council, Washington, The District of Columbia. ; University of Washington, Seattle, Washington. ; US Food and Drug Administration, Silver Spring, Maryland. ; Science to Inform, LLC, Pittsboro, North Carolina. ; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. ; National Toxicology Program/National Institute of Environmental Health Sciences, Durham, North Carolina. ; INERIS-Chronic Risk Division, Verneeuil-en-Halatte, France. ; US Food and Drug Administration, College Park, Maryland. ; Procter & Gamble Company, Cincinnati, Ohio. ; University of Arkansas for Medical Sciences, Little Rock, Arkansas. ; Sanofi, Bridgewater, New Jersey. ; US Environmental Protection Agency, Cincinnati, Ohio. ; Lhasa Limited, Leeds, United Kingdom. ; US Environmental Protection Agency, Washington, The District of Columbia. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 22 EP - 31 VL - 155 IS - 1 KW - predictive toxicology KW - testing alternatives. KW - in vitro and alternatives KW - regulatory/policy KW - risk assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835685355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=FutureTox+III%3A+Bridges+for+Translation.&rft.au=Juberg%2C+Daland+R%3BKnudsen%2C+Thomas+B%3BSander%2C+Miriam%3BBeck%2C+Nancy+B%3BFaustman%2C+Elaine+M%3BMendrick%2C+Donna+L%3BFowle%2C+John+R%3BHartung%2C+Thomas%3BTice%2C+Raymond+R%3BLemazurier%2C+Emmanuel%3BBecker%2C+Richard+A%3BFitzpatrick%2C+Suzanne+Compton%3BDaston%2C+George+P%3BHarrill%2C+Alison%3BHines%2C+Ronald+N%3BKeller%2C+Douglas+A%3BLipscomb%2C+John+C%3BWatson%2C+David%3BBahadori%2C+Tina%3BCrofton%2C+Kevin+M&rft.aulast=Juberg&rft.aufirst=Daland&rft.date=2017-01-01&rft.volume=155&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfw194 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/toxsci/kfw194 ER - TY - JOUR T1 - An Interaction between Arsenic-Induced Epigenetic Modification and Inflammatory Promotion in a Skin Equivalent during Arsenic Carcinogenesis. AN - 1835519759; 27592797 AB - Animal studies have shown that chemical carcinogenesis consists of a three-stage process: initiation, promotion, and progression. However, because of the lack of a suitable tissue model, the molecular mechanisms of cell-cell interactions involved in those processes remain unclear. We have established a human intraepidermal carcinoma skin equivalent with organotypic culture-consisting of keratinocytes, fibroblasts, and peripheral blood mononuclear cells - induced by arsenic treatment. This SE shows the pathognomonic characteristics of arsenic-induced Bowen's disease, including acanthosis, dysplasia, and dyskeratosis. Using this SE model, we showed that arsenic initiated SUV39H2-mediated epigenetic modification of E2F1, which induced centrosome amplification in keratinocytes in 2 days; this, however, led to caspase-8-mediated apoptosis in 10 days. In parallel, arsenic stimulated tumor necrosis factor-α release mainly from peripheral blood mononuclear cells. Tumor necrosis factor-α triggered anti-apoptotic signals via FLIP-associated caspase-8 inactivation in arsenic-treated keratinocytes, which in turn contributed to cell survival and aneuploidy. The interaction between arsenic-induced epigenetic modification and inflammatory promotion resulted in the development of the pathognomonic features of arsenic-induced Bowen's disease in this model. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. JF - The Journal of investigative dermatology AU - Liao, Wei-Ting AU - Lu, Jian-He AU - Lee, Chih-Hung AU - Lan, Cheng-Che E AU - Chang, Jan-Gowth AU - Chai, Chee-Yin AU - Yu, Hsin-Su AD - Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. ; Graduate Institute of Medical Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. ; Department of Dermatology, Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. ; Department of Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. ; College of Medicine, China Medical University, Taichung 404, Taiwan. ; Department of Pathology, Kaohsiung Medical University and Hospital, Kaohsiung 807, Taiwan. ; Department of Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan 350, Taiwan. Electronic address: dermyu@nhri.org.tw. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 187 EP - 196 VL - 137 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835519759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=An+Interaction+between+Arsenic-Induced+Epigenetic+Modification+and+Inflammatory+Promotion+in+a+Skin+Equivalent+during+Arsenic+Carcinogenesis.&rft.au=Liao%2C+Wei-Ting%3BLu%2C+Jian-He%3BLee%2C+Chih-Hung%3BLan%2C+Cheng-Che+E%3BChang%2C+Jan-Gowth%3BChai%2C+Chee-Yin%3BYu%2C+Hsin-Su&rft.aulast=Liao&rft.aufirst=Wei-Ting&rft.date=2017-01-01&rft.volume=137&rft.issue=1&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=1523-1747&rft_id=info:doi/10.1016%2Fj.jid.2016.08.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jid.2016.08.017 ER - TY - JOUR T1 - Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity. AN - 1835514661; 27775880 AB - Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site-directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking OCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactivate tyrosinase and result in OCA1B albinism. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. JF - Pigment cell & melanoma research AU - Dolinska, Monika B AU - Kus, Nicole J AU - Farney, S Katie AU - Wingfield, Paul T AU - Brooks, Brian P AU - Sergeev, Yuri V AD - National Eye Institute, National Institutes of Health, Bethesda, MD, USA. ; National Institute of Artritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 41 EP - 52 VL - 30 IS - 1 KW - protein stability KW - genetic mutations KW - protein unfolding KW - protein structure KW - oculocutaneous albinism KW - tyrosinase KW - protein purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835514661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pigment+cell+%26+melanoma+research&rft.atitle=Oculocutaneous+albinism+type+1%3A+link+between+mutations%2C+tyrosinase+conformational+stability%2C+and+enzymatic+activity.&rft.au=Dolinska%2C+Monika+B%3BKus%2C+Nicole+J%3BFarney%2C+S+Katie%3BWingfield%2C+Paul+T%3BBrooks%2C+Brian+P%3BSergeev%2C+Yuri+V&rft.aulast=Dolinska&rft.aufirst=Monika&rft.date=2017-01-01&rft.volume=30&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Pigment+cell+%26+melanoma+research&rft.issn=1755-148X&rft_id=info:doi/10.1111%2Fpcmr.12546 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-31 N1 - Last updated - 2017-01-31 DO - http://dx.doi.org/10.1111/pcmr.12546 ER - TY - JOUR T1 - Serum polybrominated diphenyl ether (PBDE) concentrations in relation to biomarkers of oxidative stress and inflammation: The National Health and Nutrition Examination Survey 2003-2004. AN - 1835450348; 27750136 AB - Exposure to polybrominated diphenyl ethers (PBDEs) has been associated with various adverse health outcomes related to liver, neural and endocrine systems. Some of these may be the result of PBDE-induced oxidative stress or inflammation, but these associations have been explored minimally in humans. In the present study we examined the relationship between PBDE concentrations and biomarkers of oxidative stress and inflammation measured in blood samples among a representative US sample from the National Health and Nutrition Examination Survey. Oxidative stress biomarkers showed no significant associations with PBDEs in adjusted regression models. For inflammation biomarkers, we observed small but statistically significant positive associations between BDE-153 and alkaline phosphatase (percent change with an interquartile range [IQR] increase in BDE-153=0.82, 95% confidence interval [CI]=0.01, 1.65) and absolute neutrophil count (percent change with IQR increase in BDE-153=0.53%, 95% CI=0.03, 1.04). Associations with other PBDE congeners and inflammation markers were generally positive but did not reach statistical significance. These results are consistent with human research of oxidative stress and inflammation in response to PBDE congeners and mixtures, and support previous reports of inflammation in response to PBDE treatment in animal and in vitro studies. More detailed toxicological and epidemiologic research in humans is needed to confirm the present results, and to determine the potential clinical and public health significance of these findings. Published by Elsevier B.V. JF - The Science of the total environment AU - Yuan, Ye AU - Meeker, John D AU - Ferguson, Kelly K AD - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. ; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. ; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA; Epidemiology Branch, National Institute of Environmental Health Sciences, USA. Electronic address: kelly.ferguson2@nih.gov. Y1 - 2017/01/01/ PY - 2017 DA - 2017 Jan 01 SP - 400 EP - 405 VL - 575 KW - Blood biomarkers KW - Reactive oxygen species KW - Flame retardants KW - National Health and Nutrition Examination Survey KW - C-reactive protein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835450348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Science+of+the+total+environment&rft.atitle=Serum+polybrominated+diphenyl+ether+%28PBDE%29+concentrations+in+relation+to+biomarkers+of+oxidative+stress+and+inflammation%3A+The+National+Health+and+Nutrition+Examination+Survey+2003-2004.&rft.au=Yuan%2C+Ye%3BMeeker%2C+John+D%3BFerguson%2C+Kelly+K&rft.aulast=Yuan&rft.aufirst=Ye&rft.date=2017-01-01&rft.volume=575&rft.issue=&rft.spage=400&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2016.10.028 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.scitotenv.2016.10.028 ER - TY - JOUR T1 - Safety and Efficacy of Atorvastatin in Human Immunodeficiency Virus-infected Children, Adolescents and Young Adults With Hyperlipidemia. AN - 1835443990; 27749649 AB - Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy. Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin. Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children. JF - The Pediatric infectious disease journal AU - Melvin, Ann J AU - Montepiedra, Grace AU - Aaron, Lisa AU - Meyer, William A AU - Spiegel, Hans M AU - Borkowsky, William AU - Abzug, Mark J AU - Best, Brookie M AU - Crain, Marilyn J AU - Borum, Peggy R AU - Graham, Bobbie AU - Anthony, Patricia AU - Shin, Katherine AU - Siberry, George K AU - P1063 Study Team AD - From the *Division of Pediatric Infectious Disease, Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Washington; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts; ‡Quest Diagnostics, Baltimore, Maryland; §HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Contractor to National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; ¶Department of Pediatrics, New York University School of Medicine, New York City, New York; ‖Department of Pediatrics (Infectious Diseases), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado; **UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, University of California San Diego, San Diego, California; ††Department of Pediatrics and Microbiology, University of Alabama at Birmingham Pediatric Infectious Diseases, Birmingham, Alabama; ‡‡Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida; §§Frontier Science Inc., Buffalo, New York; ¶¶University of Southern California Maternal Child Adolescent Virology Research Lab, Los Angeles, California; ‖‖Pharmaceutical Affairs Branch Division of AIDS, NIAID, NIH, Bethesda, Maryland; and ***Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. ; P1063 Study Team Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 53 EP - 60 VL - 36 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835443990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Safety+and+Efficacy+of+Atorvastatin+in+Human+Immunodeficiency+Virus-infected+Children%2C+Adolescents+and+Young+Adults+With+Hyperlipidemia.&rft.au=Melvin%2C+Ann+J%3BMontepiedra%2C+Grace%3BAaron%2C+Lisa%3BMeyer%2C+William+A%3BSpiegel%2C+Hans+M%3BBorkowsky%2C+William%3BAbzug%2C+Mark+J%3BBest%2C+Brookie+M%3BCrain%2C+Marilyn+J%3BBorum%2C+Peggy+R%3BGraham%2C+Bobbie%3BAnthony%2C+Patricia%3BShin%2C+Katherine%3BSiberry%2C+George+K%3BP1063+Study+Team&rft.aulast=Melvin&rft.aufirst=Ann&rft.date=2017-01-01&rft.volume=36&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=1532-0987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The Second Pediatric Blood and Marrow Transplant Consortium International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Defining the Unique Late Effects of Children Undergoing Hematopoietic Cell Transplantation for Immune Deficiencies, Inherited Marrow Failure Disorders, and Hemoglobinopathies. AN - 1835411720; 27737772 AB - An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant consortium entitled "Late Effects Screening and Recommendations Following Allogeneic Hematopoietic Cell Transplant for Immune Deficiency and Nonmalignant Hematologic Disease" was held in Minneapolis, Minnesota on May 10, 2016 and May 11, 2016. The purpose of the conference was to address the unmet need for greater understanding of and the screening for long-term complications in the growing population of survivors of transplantation for nonmalignant disorders. The conference focused on transplantation for hemoglobinopathy, immune deficiency, and inherited bone marrow syndromes. A multidisciplinary group of experts in the disease areas and transplantation late effects presented the current state of understanding of how the underlying disease, pretransplantation therapies, and transplantation-related factors uniquely interact to influence the development of late toxicities. Recommendations were put forth by the group for the late effects screening of survivors of transplantation for these nonmalignant disorders. The findings and recommendations that came from this conference will be presented in a series of 6 additional manuscripts in the upcoming months. In this manuscript, we explore the need for screening practices specific to the survivors of transplantation for nonmalignant diseases and the methodologic challenges associated with the study of these patients. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved. JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Dietz, Andrew C AU - Duncan, Christine N AU - Alter, Blanche P AU - Bresters, Dorine AU - Cowan, Morton J AU - Notarangelo, Luigi AU - Rosenberg, Philip S AU - Shenoy, Shalini AU - Skinner, Roderick AU - Walters, Mark C AU - Wagner, John AU - Baker, K Scott AU - Pulsipher, Michael A AD - Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California. ; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts. ; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; Willem-Alexander Children's Hospital, SCT Unit, Leiden University Medical Center, Leiden, The Netherlands. ; University of California San Francisco, Department of Pediatrics, Allergy, Immunology, and Blood and Marrow Transplant Division, San Francisco, California. ; Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. ; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; St. Louis Children's Hospital, Washington University, St. Louis, Missouri. ; Great North Children's Hospital and Northern Institute of Cancer Research, Newcastle upon Tyne, United Kingdom. ; UCSF Benioff Children's Hospital Oakland, Oakland, California. ; Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota. ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. ; Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California. Electronic address: mpulsipher@chla.usc.edu. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 24 EP - 29 VL - 23 IS - 1 KW - Late effects KW - Immune deficiencies KW - Hemoglobinopathies KW - Marrow failure disorders KW - Pediatric allogeneic bone marrow transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835411720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=The+Second+Pediatric+Blood+and+Marrow+Transplant+Consortium+International+Consensus+Conference+on+Late+Effects+after+Pediatric+Hematopoietic+Cell+Transplantation%3A+Defining+the+Unique+Late+Effects+of+Children+Undergoing+Hematopoietic+Cell+Transplantation+for+Immune+Deficiencies%2C+Inherited+Marrow+Failure+Disorders%2C+and+Hemoglobinopathies.&rft.au=Dietz%2C+Andrew+C%3BDuncan%2C+Christine+N%3BAlter%2C+Blanche+P%3BBresters%2C+Dorine%3BCowan%2C+Morton+J%3BNotarangelo%2C+Luigi%3BRosenberg%2C+Philip+S%3BShenoy%2C+Shalini%3BSkinner%2C+Roderick%3BWalters%2C+Mark+C%3BWagner%2C+John%3BBaker%2C+K+Scott%3BPulsipher%2C+Michael+A&rft.aulast=Dietz&rft.aufirst=Andrew&rft.date=2017-01-01&rft.volume=23&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=1523-6536&rft_id=info:doi/10.1016%2Fj.bbmt.2016.10.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-14 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1016/j.bbmt.2016.10.004 ER - TY - JOUR T1 - Polycyclic aromatic hydrocarbons and postmenopausal breast cancer: An evaluation of effect measure modification by body mass index and weight change. AN - 1835409894; 27741445 AB - Polycyclic aromatic hydrocarbons (PAHs) have been linked to breast cancer in many, but not all, previous studies. PAHs are lipophilic and stored in fat tissue, which we hypothesized may result in constant low-dose exposure to these carcinogens. No previous studies have evaluated whether obesity modifies associations between multiple measures of PAHs and breast cancer incidence. This population-based study included 1,006 postmenopausal women with first primary in situ or invasive breast cancer and 990 age-frequency matched controls. To evaluate effect modification by obesity (adult body mass index (BMI, kg/m2) and weight change) on multiple PAH measures (the biomarker PAH-DNA adducts, and long-term sources active cigarette smoking, living with a smoking spouse, grilled/smoked meat intake, residential synthetic log burning, and vehicular traffic), interaction contrast ratios (ICRs) for the additive scale, and ratio of odds ratios (RORs) with log-likelihood ratio tests (LRT) for the multiplicative scale, were determined using unconditional logistic regression. BMI modified the PAH-DNA adduct and postmenopausal breast cancer association on the additive (ICR: 0.49; 95% CI: 0.01, 0.96) and multiplicative (ROR: 1.56; 95% CI: 0.91, 2.68) scales. The odds ratio for detectable vs. non-detectable adducts was increased among women with BMI ≥25 (OR=1.34; 95% CI: 0.94, 1.92), but not in those with BMI <25 (OR=0.86; 95% CI: 0.57, 1.28) (LRT p=0.1). For most other PAH measures, the pattern of modification by BMI/weight gain was similar, but estimates were imprecise. The association between PAH-DNA adducts and breast cancer incidence may be elevated among overweight/obese women. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Environmental research AU - Niehoff, Nicole AU - White, Alexandra J AU - McCullough, Lauren E AU - Steck, Susan E AU - Beyea, Jan AU - Mordukhovich, Irina AU - Shen, Jing AU - Neugut, Alfred I AU - Conway, Kathleen AU - Santella, Regina M AU - Gammon, Marilie D AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: nicolen@live.unc.edu. ; Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Department of Epidemiology, Emory University, Atlanta, GA, USA. ; Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA. ; Department of Consulting in the Public Interest (CIPI), Lambertville, NJ, USA. ; Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. ; Department of Environmental Health Sciences, Columbia University, New York, NY, USA. ; Department of Epidemiology, Columbia University, New York, NY, USA; Departments of Medicine, Columbia University, New York, NY, USA. ; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 17 EP - 25 VL - 152 KW - Obesity KW - Polycyclic aromatic hydrocarbons KW - Weight gain KW - Adducts KW - Breast cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835409894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Polycyclic+aromatic+hydrocarbons+and+postmenopausal+breast+cancer%3A+An+evaluation+of+effect+measure+modification+by+body+mass+index+and+weight+change.&rft.au=Niehoff%2C+Nicole%3BWhite%2C+Alexandra+J%3BMcCullough%2C+Lauren+E%3BSteck%2C+Susan+E%3BBeyea%2C+Jan%3BMordukhovich%2C+Irina%3BShen%2C+Jing%3BNeugut%2C+Alfred+I%3BConway%2C+Kathleen%3BSantella%2C+Regina+M%3BGammon%2C+Marilie+D&rft.aulast=Niehoff&rft.aufirst=Nicole&rft.date=2017-01-01&rft.volume=152&rft.issue=&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=1096-0953&rft_id=info:doi/10.1016%2Fj.envres.2016.09.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.envres.2016.09.022 ER - TY - JOUR T1 - A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts. AN - 1835399000; 27613525 AB - There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC. The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors. Associations with survival were evaluated by Cox regression and Kaplan-Meier survival analyses in two independent cohorts of 121 and 91 patients with SCC, respectively. A classifier score based on multivariable Cox regression was derived and examined in six additional publicly available data sets of stage I/II lung SCC expression profiles (n = 358). The prognostic value of this classifier was evaluated in meta-analysis of patients with stage I/II (n = 479) and stage I (n = 326) lung SCC. Dual specificity phosphatase 6 gene (DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome in two independent patient cohorts. Their expression values were utilized to develop a classifier that identified patients with stage I/II lung SCC at high risk for recurrence (hazard ratio [HR] = 4.7, p = 0.018) or cancer-specific mortality (HR = 3.5, p = 0.016). This classifier also identified patients at high risk for recurrence (HR = 2.7, p = 0.008) or death (HR = 2.2, p = 0.001) in publicly available data sets of stage I/II and in meta-analysis of stage I patients. We have established and validated a prognostic classifier to inform clinical management of patients with lung SCC after surgical resection. Published by Elsevier Inc. JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer AU - Noro, Rintaro AU - Ishigame, Teruhide AU - Walsh, Naomi AU - Shiraishi, Kouya AU - Robles, Ana I AU - Ryan, Bríd M AU - Schetter, Aaron J AU - Bowman, Elise D AU - Welsh, Judith A AU - Seike, Masahiro AU - Gemma, Akihiko AU - Skaug, Vidar AU - Mollerup, Steen AU - Haugen, Aage AU - Yokota, Jun AU - Kohno, Takashi AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Laboratory of Human Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland. ; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. ; Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. ; Department of Chemical and Biological Working Environment, National Institute of Occupational Health, Oslo, Norway. ; Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer, Barcelona, Spain. ; Laboratory of Human Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. Electronic address: curtis_harris@nih.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 65 EP - 76 VL - 12 IS - 1 KW - Gene expression KW - Microarray KW - Biomarker KW - Prognostic classifier KW - Lung squamous cell carcinoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835399000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+thoracic+oncology+%3A+official+publication+of+the+International+Association+for+the+Study+of+Lung+Cancer&rft.atitle=A+Two-Gene+Prognostic+Classifier+for+Early-Stage+Lung+Squamous+Cell+Carcinoma+in+Multiple+Large-Scale+and+Geographically+Diverse+Cohorts.&rft.au=Noro%2C+Rintaro%3BIshigame%2C+Teruhide%3BWalsh%2C+Naomi%3BShiraishi%2C+Kouya%3BRobles%2C+Ana+I%3BRyan%2C+Br%C3%ADd+M%3BSchetter%2C+Aaron+J%3BBowman%2C+Elise+D%3BWelsh%2C+Judith+A%3BSeike%2C+Masahiro%3BGemma%2C+Akihiko%3BSkaug%2C+Vidar%3BMollerup%2C+Steen%3BHaugen%2C+Aage%3BYokota%2C+Jun%3BKohno%2C+Takashi%3BHarris%2C+Curtis+C&rft.aulast=Noro&rft.aufirst=Rintaro&rft.date=2017-01-01&rft.volume=12&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Journal+of+thoracic+oncology+%3A+official+publication+of+the+International+Association+for+the+Study+of+Lung+Cancer&rft.issn=1556-1380&rft_id=info:doi/10.1016%2Fj.jtho.2016.08.141 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jtho.2016.08.141 ER - TY - JOUR T1 - Drug interactions in HIV treatment: complementary & alternative medicines and over-the-counter products. AN - 1835397569; 27715369 AB - Use of complementary and alternative medicines (CAMs) and over-the-counter (OTC) medications are very common among HIV-infected patients. These products can cause clinically significant drug-drug interactions (DDIs) with antiretroviral (ARV) medications, thereby increasing risk for negative outcomes such as toxicity or loss of virologic control. Areas covered: This article provides an updated review of the different mechanisms by which CAM and OTC products are implicated in DDIs with ARV medications. Expert commentary: Much of the literature published to date involves studies of CAMs interacting with older ARV agents via the cytochrome P450 (CYP450) system. However, the HIV treatment and prevention arsenal is continually evolving. Furthermore, our elucidation of the role of non-CYP450 mediated DDIs with ARV medications is greatly increasing. Therefore, clinicians are well served to understand the various mechanisms and extent by which new ARV therapies may be involved in drug interactions with CAMs and OTC medications. JF - Expert review of clinical pharmacology AU - Brooks, Kristina M AU - George, Jomy M AU - Kumar, Parag AD - a Clinical Pharmacokinetics Research Unit, Clinical Center Pharmacy Department , National Institutes of Health , Bethesda , MD , USA. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 59 EP - 79 VL - 10 IS - 1 KW - herbals KW - Antiretrovirals KW - drug interactions KW - over-the-counter (OTC) KW - HIV KW - pharmacokinetics KW - supplements KW - complementary and alternative medicines (CAMs) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835397569?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+review+of+clinical+pharmacology&rft.atitle=Drug+interactions+in+HIV+treatment%3A+complementary+%26amp%3B+alternative+medicines+and+over-the-counter+products.&rft.au=Brooks%2C+Kristina+M%3BGeorge%2C+Jomy+M%3BKumar%2C+Parag&rft.aulast=Brooks&rft.aufirst=Kristina&rft.date=2017-01-01&rft.volume=10&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+clinical+pharmacology&rft.issn=1751-2441&rft_id=info:doi/10.1080%2F17512433.2017.1246180 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/17512433.2017.1246180 ER - TY - JOUR T1 - A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin. AN - 1826715975; 27392538 AB - Valproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer. An open-label Simon two-stage phase II trial. Valproic acid was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid-stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake. Thirteen patients with a median age of 66 years (50-78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hürthle cell carcinoma. None of the 10 patients who completed the 10-week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression. Valproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin. © 2016 John Wiley & Sons Ltd. JF - Clinical endocrinology AU - Nilubol, Naris AU - Merkel, Roxanne AU - Yang, Lily AU - Patel, Dhaval AU - Reynolds, James C AU - Sadowski, Samira M AU - Neychev, Vladimir AU - Kebebew, Electron AD - Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Nuclear Medicine Department, Clinical Research Center, National Institutes of Health, Bethesda, MD, USA. ; Thoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland. ; Department of Surgery, University Multiprofile Hospital for Active Treatment 'Alexandrovska', Medical University, Sofia, Bulgaria. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 128 EP - 133 VL - 86 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826715975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+endocrinology&rft.atitle=A+phase+II+trial+of+valproic+acid+in+patients+with+advanced%2C+radioiodine-resistant+thyroid+cancers+of+follicular+cell+origin.&rft.au=Nilubol%2C+Naris%3BMerkel%2C+Roxanne%3BYang%2C+Lily%3BPatel%2C+Dhaval%3BReynolds%2C+James+C%3BSadowski%2C+Samira+M%3BNeychev%2C+Vladimir%3BKebebew%2C+Electron&rft.aulast=Nilubol&rft.aufirst=Naris&rft.date=2017-01-01&rft.volume=86&rft.issue=1&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Clinical+endocrinology&rft.issn=1365-2265&rft_id=info:doi/10.1111%2Fcen.13154 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cen.13154 ER - TY - JOUR T1 - Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury. AN - 1826699152; 27311619 AB - Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine. We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls). Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively). In analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved. JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association AU - de Boer, Ynto S AU - Kosinski, Andrzej S AU - Urban, Thomas J AU - Zhao, Zhen AU - Long, Nanye AU - Chalasani, Naga AU - Kleiner, David E AU - Hoofnagle, Jay H AU - Drug-Induced Liver Injury Network AD - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: y.deboer@vumc.nl. ; Duke Clinical Research Institute, Durham, North Carolina. ; Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, North Carolina. ; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland. ; Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana. ; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. ; Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Electronic address: hoofnaglej@extra.niddk.nih.gov. ; Drug-Induced Liver Injury Network Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 103 EP - 112.e2 VL - 15 IS - 1 KW - Immune Response KW - Immunoglobulin KW - Database Analysis KW - Toxicity KW - Hepatotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826699152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.atitle=Features+of+Autoimmune+Hepatitis+in+Patients+With+Drug-induced+Liver+Injury.&rft.au=de+Boer%2C+Ynto+S%3BKosinski%2C+Andrzej+S%3BUrban%2C+Thomas+J%3BZhao%2C+Zhen%3BLong%2C+Nanye%3BChalasani%2C+Naga%3BKleiner%2C+David+E%3BHoofnagle%2C+Jay+H%3BDrug-Induced+Liver%C2%A0Injury%C2%A0Network&rft.aulast=de+Boer&rft.aufirst=Ynto&rft.date=2017-01-01&rft.volume=15&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.issn=1542-7714&rft_id=info:doi/10.1016%2Fj.cgh.2016.05.043 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cgh.2016.05.043 ER - TY - JOUR T1 - Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases. AN - 1826679270; 27143693 AB - As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mitochondrial dysfunction, such as decreased electron transport chain (ETC) enzyme activity and impaired cellular respiration. We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases. Additionally, interventions to improve mitochondrial function and attenuate the symptoms of aging are examined. Published by Elsevier B.V. JF - Ageing research reviews AU - DeBalsi, Karen L AU - Hoff, Kirsten E AU - Copeland, William C AD - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. ; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: copelan1@niehs.nih.gov. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 89 EP - 104 VL - 33 KW - POLG KW - Mitochondrial DNA mutations KW - Aging KW - Age-related diseases KW - MtDNA replication KW - DNA polymerase gamma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826679270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ageing+research+reviews&rft.atitle=Role+of+the+mitochondrial+DNA+replication+machinery+in+mitochondrial+DNA+mutagenesis%2C+aging+and+age-related+diseases.&rft.au=DeBalsi%2C+Karen+L%3BHoff%2C+Kirsten+E%3BCopeland%2C+William+C&rft.aulast=DeBalsi&rft.aufirst=Karen&rft.date=2017-01-01&rft.volume=33&rft.issue=&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Ageing+research+reviews&rft.issn=1872-9649&rft_id=info:doi/10.1016%2Fj.arr.2016.04.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.arr.2016.04.006 ER - TY - JOUR T1 - Dibenzo[def,p]chrysene transplacental carcinogenesis in wild-type, Cyp1b1 knockout, and CYP1B1 humanized mice. AN - 1826660414; 26990437 AB - The cytochrome P450 (CYP) 1 family is active toward numerous environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs). Utilizing a mouse model, null for Cyp1b1 and expressing human CYP1B1, we tested the hypothesis that hCYP1B1 is important for dibenzo[def,p]chrysene (DBC) transplacental carcinogenesis. Wild-type mCyp1b1, transgenic hCYP1B1 (mCyp1b1 null background), and mCyp1b1 null mice were assessed. Each litter had an equal number of siblings with Ahrb-1/d and Ahrd/d alleles. Pregnant mice were dosed (gavage) on gestation day 17 with 6.5 or 12 mg/kg of DBC or corn oil. At 10 months of age, mortality, general health, lymphoid disease and lung tumor incidence, and multiplicity were assessed. hCYP1B1 genotype did not impact lung tumor multiplicity, but tended to enhance incidence compared to Cyp1b1 wild-type mice (P = 0.07). As with Cyp1b1 in wild-type mice, constitutive hCYP1B1 protein is non-detectable in liver but was induced with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Wild-type mice were 59% more likely to succumb to T-cell Acute Lymphoblastic Leukemia (T-ALL). Unlike an earlier examination of the Ahr genotype in this model (Yu et al., Cancer Res, 2006;66:755-762), but in agreement with a more recent study (Shorey et al., Toxicol Appl Pharmacol, 2013;270:60-69), this genotype was not associated with lung tumor incidence, multiplicity, or mortality. Sex was not significant with respect to lung tumor incidence or mortality but males exhibited significantly greater multiplicity. Lung tumor incidence was greater in mCyp1b1 nulls compared to wild-type mice. To our knowledge, this is the first application of a humanized mouse model in transplacental carcinogenesis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Molecular carcinogenesis AU - Madeen, Erin P AU - Löhr, Christiane V AU - You, Hannah AU - Siddens, Lisbeth K AU - Krueger, Sharon K AU - Dashwood, Roderick H AU - Gonzalez, Frank J AU - Baird, William M AU - Ho, Emily AU - Bramer, Lisa AU - Waters, Katrina M AU - Williams, David E AD - Department of Molecular and Environmental Toxicology, Oregon State University, Corvallis, Oregon. ; Cancer Prevention and Intervention Program, Linus Pauling Institute, Oregon State University, Corvallis, Oregon. ; Center for Epigenetics and Disease Prevention, M.D. Anderson Cancer Center, Houston, Texas. ; Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. ; Superfund Research Program, Oregon State University, Corvallis, Oregon. Y1 - 2017/01// PY - 2017 DA - January 2017 SP - 163 EP - 171 VL - 56 IS - 1 KW - transplacental cancer KW - PAH carcinogenesis KW - cytochrome P450 1B1 KW - CYP1B1 humanized mice UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826660414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Dibenzo%5Bdef%2Cp%5Dchrysene+transplacental+carcinogenesis+in+wild-type%2C+Cyp1b1+knockout%2C+and+CYP1B1+humanized+mice.&rft.au=Madeen%2C+Erin+P%3BL%C3%B6hr%2C+Christiane+V%3BYou%2C+Hannah%3BSiddens%2C+Lisbeth+K%3BKrueger%2C+Sharon+K%3BDashwood%2C+Roderick+H%3BGonzalez%2C+Frank+J%3BBaird%2C+William+M%3BHo%2C+Emily%3BBramer%2C+Lisa%3BWaters%2C+Katrina+M%3BWilliams%2C+David+E&rft.aulast=Madeen&rft.aufirst=Erin&rft.date=2017-01-01&rft.volume=56&rft.issue=1&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=1098-2744&rft_id=info:doi/10.1002%2Fmc.22480 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-03-18 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1002/mc.22480 ER - TY - JOUR T1 - The landscape of new drugs in lymphoma. AN - 1854107024; 28031560 AB - The landscape of drugs for the treatment of lymphoma has become crowded in light of the plethora of new agents, necessitating the efficient prioritization of drugs for expedited development. The number of drugs available, and the fact that many can be given for an extended period of time, has resulted in the emergence of new challenges; these include determining the optimal duration of therapy, and the need to balance costs, benefits, and the risk of late-onset toxicities. Moreover, with the increase in the number of available investigational drugs, the number of possible combinations is becoming overwhelming, which necessitates prioritization plans for the selective development of novel combination regimens. In this Review, we describe the most-promising agents in clinical development for the treatment of lymphoma, and provide expert opinion on new strategies that might enable more streamlined drug development. We also address new approaches for patient selection and for incorporating new end points into clinical trials. JF - Nature reviews. Clinical oncology AU - Younes, Anas AU - Ansell, Stephen AU - Fowler, Nathan AU - Wilson, Wyndham AU - de Vos, Sven AU - Seymour, John AU - Advani, Ranjana AU - Forero, Andres AU - Morschhauser, Franck AU - Kersten, Marie Jose AU - Tobinai, Kensei AU - Zinzani, Pier Luigi AU - Zucca, Emanuele AU - Abramson, Jeremy AU - Vose, Julie AD - Lymphoma Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. ; Division of Haematology, Mayo Clinic, 200 1st St Sw, Rochester, Minnesota 55905, USA. ; Department of Lymphoma and Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. ; Lymphoid Malignancies Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA. ; Department of Medicine, Ronald Reagan UCLA Medical Center, Santa Monica, California 90404, USA. ; Department of Haematology, Peter MacCallum Cancer Centre, A'Beckett Street, East Melbourne, Victoria 8006, Australia. ; Division of Oncology, Stanford University Cancer Center, 875 Blake Wilbur Drive, Stanford, California 94305, USA. ; Division of Haematology and Oncology, University of Alabama School of Medicine, 1720 2nd Avenue South, NP2540, Birmingham, Alabama 35294-3300, USA. ; Department of Haematology, Hôpital Claude Huriez, F-59037 Lille, France. ; Department of Haematology, Academic Medical Center and LYMMCARE, Amsterdam, Netherlands. ; Haematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ; Institute of Haematology "L. e A. Seràgnoli," University of Bologna, Via Massarenti, 9-40138 Bologna, Italy. ; Oncology Institute of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland. ; Massachusetts General Hospital Cancer Center, Yawkey Center for Outpatient Care, Mailstop: Yawkey 9A, 32 Fruit Street, Boston, Massachusetts 02114, USA. ; UNMC Oncology/Haematology Division, 987680 Nebraska Medical Center, Omaha, Nebraska 681980-7680, USA. Y1 - 2016/12/29/ PY - 2016 DA - 2016 Dec 29 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854107024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Clinical+oncology&rft.atitle=The+landscape+of+new+drugs+in+lymphoma.&rft.au=Younes%2C+Anas%3BAnsell%2C+Stephen%3BFowler%2C+Nathan%3BWilson%2C+Wyndham%3Bde+Vos%2C+Sven%3BSeymour%2C+John%3BAdvani%2C+Ranjana%3BForero%2C+Andres%3BMorschhauser%2C+Franck%3BKersten%2C+Marie+Jose%3BTobinai%2C+Kensei%3BZinzani%2C+Pier+Luigi%3BZucca%2C+Emanuele%3BAbramson%2C+Jeremy%3BVose%2C+Julie&rft.aulast=Younes&rft.aufirst=Anas&rft.date=2016-12-29&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Clinical+oncology&rft.issn=1759-4782&rft_id=info:doi/10.1038%2Fnrclinonc.2016.205 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-29 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/nrclinonc.2016.205 ER - TY - JOUR T1 - Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. AN - 1854104478; 28029918 AB - Background Effective medical therapies are lacking for the treatment of neurofibromatosis type 1-related plexiform neurofibromas, which are characterized by elevated RAS-mitogen-activated protein kinase (MAPK) signaling. Methods We conducted a phase 1 trial of selumetinib (AZD6244 or ARRY-142886), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics. Selumetinib was administered twice daily at a dose of 20 to 30 mg per square meter of body-surface area on a continuous dosing schedule (in 28-day cycles). We also tested selumetinib using a mouse model of neurofibromatosis type 1-related neurofibroma. Response to treatment (i.e., an increase or decrease from baseline in the volume of plexiform neurofibromas) was monitored by using volumetric magnetic resonance imaging analysis to measure the change in size of the plexiform neurofibroma. Results A total of 24 children (median age, 10.9 years; range, 3.0 to 18.5) with a median tumor volume of 1205 ml (range, 29 to 8744) received selumetinib. Patients were able to receive selumetinib on a long-term basis; the median number of cycles was 30 (range, 6 to 56). The maximum tolerated dose was 25 mg per square meter (approximately 60% of the recommended adult dose). The most common toxic effects associated with selumetinib included acneiform rash, gastrointestinal effects, and asymptomatic creatine kinase elevation. The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults. Treatment with selumetinib resulted in confirmed partial responses (tumor volume decreases from baseline of ≥20%) in 17 of the 24 children (71%) and decreases from baseline in neurofibroma volume in 12 of 18 mice (67%). Disease progression (tumor volume increase from baseline of ≥20%) has not been observed to date. Anecdotal evidence of decreases in tumor-related pain, disfigurement, and functional impairment was observed. Conclusions Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803 .). JF - The New England journal of medicine AU - Dombi, Eva AU - Baldwin, Andrea AU - Marcus, Leigh J AU - Fisher, Michael J AU - Weiss, Brian AU - Kim, AeRang AU - Whitcomb, Patricia AU - Martin, Staci AU - Aschbacher-Smith, Lindsey E AU - Rizvi, Tilat A AU - Wu, Jianqiang AU - Ershler, Rachel AU - Wolters, Pamela AU - Therrien, Janet AU - Glod, John AU - Belasco, Jean B AU - Schorry, Elizabeth AU - Brofferio, Alessandra AU - Starosta, Amy J AU - Gillespie, Andrea AU - Doyle, Austin L AU - Ratner, Nancy AU - Widemann, Brigitte C AD - From the Center for Cancer Research, Pediatric Oncology Branch, Bethesda (E.D., A. Baldwin, L.J.M., P. Whitcomb, S.M., R.E., P. Wolters, J.T., J.G., A.J.S., A.G., B.C.W.) and the Cancer Therapy Evaluation Program, Shady Grove (A.L.D.), National Cancer Institute, and the National Heart, Lung, and Blood Institute (A. Brofferio), Bethesda, National Institutes of Health, and the Food and Drug Administration, Silver Spring (L.J.M., R.E.) - all in Maryland; the Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.J.F., J.B.B.); Children's National Health System, Washington, DC (A.K.); and Cincinnati Children's Hospital, Cincinnati (B.W., L.E.A.-S., T.A.R., J.W., E.S., N.R.). Y1 - 2016/12/29/ PY - 2016 DA - 2016 Dec 29 SP - 2550 EP - 2560 VL - 375 IS - 26 KW - AZD 6244 KW - 0 KW - Benzimidazoles KW - Protein Kinase Inhibitors KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Humans KW - Disease Progression KW - Disease Models, Animal KW - Mice KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Neurofibromatosis 1 -- drug therapy KW - Protein Kinase Inhibitors -- adverse effects KW - Neurofibroma, Plexiform -- drug therapy KW - Benzimidazoles -- adverse effects KW - Benzimidazoles -- administration & dosage KW - Protein Kinase Inhibitors -- administration & dosage KW - Protein Kinase Inhibitors -- pharmacokinetics KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - Benzimidazoles -- pharmacokinetics KW - Neurofibroma, Plexiform -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854104478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Activity+of+Selumetinib+in+Neurofibromatosis+Type+1-Related+Plexiform+Neurofibromas.&rft.au=Dombi%2C+Eva%3BBaldwin%2C+Andrea%3BMarcus%2C+Leigh+J%3BFisher%2C+Michael+J%3BWeiss%2C+Brian%3BKim%2C+AeRang%3BWhitcomb%2C+Patricia%3BMartin%2C+Staci%3BAschbacher-Smith%2C+Lindsey+E%3BRizvi%2C+Tilat+A%3BWu%2C+Jianqiang%3BErshler%2C+Rachel%3BWolters%2C+Pamela%3BTherrien%2C+Janet%3BGlod%2C+John%3BBelasco%2C+Jean+B%3BSchorry%2C+Elizabeth%3BBrofferio%2C+Alessandra%3BStarosta%2C+Amy+J%3BGillespie%2C+Andrea%3BDoyle%2C+Austin+L%3BRatner%2C+Nancy%3BWidemann%2C+Brigitte+C&rft.aulast=Dombi&rft.aufirst=Eva&rft.date=2016-12-29&rft.volume=375&rft.issue=26&rft.spage=2550&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/10.1056%2FNEJMoa1605943 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-10 N1 - Date created - 2016-12-28 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT01362803; ClinicalTrials.gov N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1056/NEJMoa1605943 ER - TY - JOUR T1 - Exome sequencing provides additional evidence for the involvement of ARHGAP29 in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate. AN - 1853741387; 28029220 AB - Recent advances in genomics methodologies, in particular the availability of next-generation sequencing approaches have made it possible to identify risk loci throughout the genome, in particular the exome. In the current study, we present findings from an exome study conducted in five affected individuals of a multiplex family with cleft palate only. The GEnome MINIng (GEMINI) pipeline was used to functionally annotate the single nucleotide polymorphisms, insertions and deletions. Filtering methods were applied to identify variants that are clinically relevant and present in affected individuals at minor allele frequencies (≤1%) in the 1000 Genomes Project single nucleotide polymorphism database, Exome Aggregation Consortium, and Exome Variant Server databases. The bioinformatics tool Systems Tool for Craniofacial Expression-Based Gene Discovery was used to prioritize cleft candidates in our list of variants, and Sanger sequencing was used to validate the presence of identified variants in affected and unaffected relatives. Our analyses approach narrowed the candidates down to the novel missense variant in ARHGAP29 (GenBank: NM_004815.3, NP_004806.3;c.1654T>C [p.Ser552Pro]. A functional assay in zebrafish embryos showed that the encoded protein lacks the activity possessed by its wild-type counterpart, and migration assays revealed that keratinocytes transfected with wild-type ARHGAP29 migrated faster than counterparts transfected with the p.Ser552Pro ARHGAP29 variant or empty vector (control). These findings reveal ARHGAP29 to be a regulatory protein essential for proper development of the face, identifies an amino acid that is key for this, and provides a potential new diagnostic tool.Birth Defects Research (Part A) 00:000-000, 2016.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Birth defects research. Part A, Clinical and molecular teratology AU - Liu, Huan AU - Busch, Tamara AU - Eliason, Steven AU - Anand, Deepti AU - Bullard, Steven AU - Gowans, Lord J J AU - Nidey, Nichole AU - Petrin, Aline AU - Augustine-Akpan, Eno-Abasi AU - Saadi, Irfan AU - Dunnwald, Martine AU - Lachke, Salil A AU - Zhu, Ying AU - Adeyemo, Adebowale AU - Amendt, Brad AU - Roscioli, Tony AU - Cornell, Robert AU - Murray, Jeffrey AU - Butali, Azeez AD - Department of Anatomy and Cell Biology, Iowa City, Iowa. ; Department of Pediatrics, University of Iowa, Iowa City, Iowa. ; Department of Biological Sciences, University of Delaware, Newark, Deleware. ; Department of Internal Medicine, University of Iowa, Iowa City, Iowa. ; Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, Iowa. ; Department of Anatomy and Cell Biology, University of Kansas Medical Center Kansas City, Kansas. ; Newcastle GOLD Service, Hunter Genetics, Waratah, NSW, Australia. ; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. ; Department of Medical Genetics, Sydney Children's Hospital, Sydney, Australia. Y1 - 2016/12/28/ PY - 2016 DA - 2016 Dec 28 KW - exome KW - cleft palate KW - missense mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1853741387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.atitle=Exome+sequencing+provides+additional+evidence+for+the+involvement+of+ARHGAP29+in+Mendelian+orofacial+clefting+and+extends+the+phenotypic+spectrum+to+isolated+cleft+palate.&rft.au=Liu%2C+Huan%3BBusch%2C+Tamara%3BEliason%2C+Steven%3BAnand%2C+Deepti%3BBullard%2C+Steven%3BGowans%2C+Lord+J+J%3BNidey%2C+Nichole%3BPetrin%2C+Aline%3BAugustine-Akpan%2C+Eno-Abasi%3BSaadi%2C+Irfan%3BDunnwald%2C+Martine%3BLachke%2C+Salil+A%3BZhu%2C+Ying%3BAdeyemo%2C+Adebowale%3BAmendt%2C+Brad%3BRoscioli%2C+Tony%3BCornell%2C+Robert%3BMurray%2C+Jeffrey%3BButali%2C+Azeez&rft.aulast=Liu&rft.aufirst=Huan&rft.date=2016-12-28&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.issn=1542-0760&rft_id=info:doi/10.1002%2Fbdra.23596 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/bdra.23596 ER - TY - JOUR T1 - Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium. AN - 1853745274; 28027596 AB - Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programmes have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics Consortium (U-PGx), which has been funded by the European Commission's Horizon-2020 programme, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREPARE), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multi-center, multi-gene, multi-drug, multi-ethnic, and multi-healthcare system approach. This article is protected by copyright. All rights reserved. © 2016 American Society for Clinical Pharmacology and Therapeutics. JF - Clinical pharmacology and therapeutics AU - van der Wouden, Cathelijne H AU - Cambon-Thomsen, Anne AU - Cecchin, Erika AU - Cheung, Ka-Chun AU - Lucía Dávila-Fajardo, Cristina AU - Deneer, Vera H AU - Dolžan, Vita AU - Ingelman-Sundberg, Magnus AU - Jönsson, Siv AU - Karlsson, Mats O AU - Kriek, Marjolein AU - Mitropoulou, Christina AU - Patrinos, George P AU - Pirmohamed, Munir AU - Samwald, Matthias AU - Schaeffeler, Elke AU - Schwab, Matthias AU - Steinberger, Daniela AU - Stingl, Julia AU - Sunder-Plassmann, Gere AU - Toffoli, Giuseppe AU - Turner, Richard M AU - van Rhenen, Mandy H AU - Swen, Jesse J AU - Guchelaar, Henk-Jan AU - Ubiquitous Pharmacogenomics Consortium AD - Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands. ; UMR Inserm U1027 and Université de Toulouse III Paul Sabatier, Toulouse, France. ; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. ; Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands. ; Department of Clinical Pharmacy, Granada University Hospital, Institute for Biomedical Research, Granada, Spain. ; Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands. ; Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia. ; Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden. ; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. ; Center for Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. ; The Golden Helix Foundation, London, United Kingdom. ; University of Patras, School of Health Sciences, Department of Pharmacy, University Campus, Rion, Patras, Greece. ; Department of Molecular & Clinical Pharmacology, Royal Liverpool University Hospital and University of Liverpool, Liverpool, United Kingdom. ; Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. ; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Tübingen, Germany. ; bio.logis Center for Human Genetics, Frankfurt am Main, Germany. ; Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany. ; Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. ; Ubiquitous Pharmacogenomics Consortium Y1 - 2016/12/27/ PY - 2016 DA - 2016 Dec 27 KW - Pre-emptive KW - Clinical Trial KW - Pharmacogenomics KW - Adverse Drug Reactions KW - Genotyping KW - Next-Generation Sequencing KW - Clinical Implementation KW - Pharmacogenetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1853745274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Implementing+Pharmacogenomics+in+Europe%3A+Design+and+Implementation+Strategy+of+the+Ubiquitous+Pharmacogenomics+Consortium.&rft.au=van+der+Wouden%2C+Cathelijne+H%3BCambon-Thomsen%2C+Anne%3BCecchin%2C+Erika%3BCheung%2C+Ka-Chun%3BLuc%C3%ADa+D%C3%A1vila-Fajardo%2C+Cristina%3BDeneer%2C+Vera+H%3BDol%C5%BEan%2C+Vita%3BIngelman-Sundberg%2C+Magnus%3BJ%C3%B6nsson%2C+Siv%3BKarlsson%2C+Mats+O%3BKriek%2C+Marjolein%3BMitropoulou%2C+Christina%3BPatrinos%2C+George+P%3BPirmohamed%2C+Munir%3BSamwald%2C+Matthias%3BSchaeffeler%2C+Elke%3BSchwab%2C+Matthias%3BSteinberger%2C+Daniela%3BStingl%2C+Julia%3BSunder-Plassmann%2C+Gere%3BToffoli%2C+Giuseppe%3BTurner%2C+Richard+M%3Bvan+Rhenen%2C+Mandy+H%3BSwen%2C+Jesse+J%3BGuchelaar%2C+Henk-Jan%3BUbiquitous+Pharmacogenomics+Consortium&rft.aulast=van+der+Wouden&rft.aufirst=Cathelijne&rft.date=2016-12-27&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=1532-6535&rft_id=info:doi/10.1002%2Fcpt.602 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cpt.602 ER - TY - JOUR T1 - Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations. AN - 1853363032; 28025329 AB - To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US. JF - Human molecular genetics AU - Seow, Wei Jie AU - Matsuo, Keitaro AU - Hsiung, Chao Agnes AU - Shiraishi, Kouya AU - Song, Minsun AU - Kim, Hee Nam AU - Wong, Maria Pik AU - Hong, Yun-Chul AU - Hosgood, H Dean AU - Wang, Zhaoming AU - Chang, I-Shou AU - Wang, Jiu-Cun AU - Chatterjee, Nilanjan AU - Tucker, Margaret AU - Wei, Hu AU - Mitsudomi, Tetsuya AU - Zheng, Wei AU - Kim, Jin Hee AU - Zhou, Baosen AU - Caporaso, Neil E AU - Albanes, Demetrius AU - Shin, Min-Ho AU - Chung, Lap Ping AU - An, She-Juan AU - Wang, Ping AU - Zheng, Hong AU - Yatabe, Yasushi AU - Zhang, Xu-Chao AU - Kim, Young Tae AU - Shu, Xiao-Ou AU - Kim, Young-Chul AU - Bassig, Bryan A AU - Chang, Jiang AU - Ho, James Chung Man AU - Ji, Bu-Tian AU - Kubo, Michiaki AU - Daigo, Yataro AU - Ito, Hidemi AU - Momozawa, Yukihide AU - Ashikawa, Kyota AU - Kamatani, Yoichiro AU - Honda, Takayuki AU - Sakamoto, Hiromi AU - Kunitoh, Hideo AU - Tsuta, Koji AU - Watanabe, Shun-Ichi AU - Nokihara, Hiroshi AU - Miyagi, Yohei AU - Nakayama, Haruhiko AU - Matsumoto, Shingo AU - Tsuboi, Masahiro AU - Goto, Koichi AU - Yin, Zhihua AU - Shi, Jianxin AU - Takahashi, Atsushi AU - Goto, Akiteru AU - Minamiya, Yoshihiro AU - Shimizu, Kimihiro AU - Tanaka, Kazumi AU - Wu, Tangchun AU - Wei, Fusheng AU - Wong, Jason Y Y AU - Matsuda, Fumihiko AU - Su, Jian AU - Kim, Yeul Hong AU - Oh, In-Jae AU - Song, Fengju AU - Lee, Victor Ho Fun AU - Su, Wu-Chou AU - Chen, Yuh-Min AU - Chang, Gee-Chen AU - Chen, Kuan-Yu AU - Huang, Ming-Shyan AU - Yang, Pan-Chyr AU - Lin, Hsien-Chih AU - Xiang, Yong-Bing AU - Seow, Adeline AU - Park, Jae Yong AU - Kweon, Sun-Seog AU - Chen, Chien-Jen AU - Li, Haixin AU - Gao, Yu-Tang AU - Wu, Chen AU - Qian, Biyun AU - Lu, Daru AU - Liu, Jianjun AU - Jeon, Hyo-Sung AU - Hsiao, Chin-Fu AU - Sung, Jae Sook AU - Tsai, Ying-Huang AU - Jung, Yoo Jin AU - Guo, Huan AU - Hu, Zhibin AU - Wang, Wen-Chang AU - Chung, Charles C AU - Lawrence, Charles AU - Burdett, Laurie AU - Yeager, Meredith AU - Jacobs, Kevin B AU - Hutchinson, Amy AU - Berndt, Sonja I AU - He, Xingzhou AU - Wu, Wei AU - Wang, Junwen AU - Li, Yuqing AU - Choi, Jin Eun AU - Park, Kyong Hwa AU - Sung, Sook Whan AU - Liu, Li AU - Kang, Chang Hyun AU - Hu, Lingmin AU - Chen, Chung-Hsing AU - Yang, Tsung-Ying AU - Xu, Jun AU - Guan, Peng AU - Tan, Wen AU - Wang, Chih-Liang AU - Sihoe, Alan Dart Loon AU - Chen, Ying AU - Choi, Yi Young AU - Hung, Jen-Yu AU - Kim, Jun Suk AU - Yoon, Ho-Il AU - Cai, Qiuyin AU - Lin, Chien-Chung AU - Park, In Kyu AU - Xu, Ping AU - Dong, Jing AU - Kim, Christopher AU - He, Qincheng AU - Perng, Reury-Perng AU - Chen, Chih-Yi AU - Vermeulen, Roel AU - Wu, Junjie AU - Lim, Wei-Yen AU - Chen, Kun-Chieh AU - Chan, John K C AU - Chu, Minjie AU - Li, Yao-Jen AU - Li, Jihua AU - Chen, Hongyan AU - Yu, Chong-Jen AU - Jin, Li AU - Lo, Yen-Li AU - Chen, Ying-Hsiang AU - Fraumeni, Joseph F AU - Liu, Jie AU - Yamaji, Taiki AU - Yang, Yang AU - Hicks, Belynda AU - Wyatt, Kathleen AU - Li, Shengchao A AU - Dai, Juncheng AU - Ma, Hongxia AU - Jin, Guangfu AU - Song, Bao AU - Wang, Zhehai AU - Cheng, Sensen AU - Li, Xuelian AU - Ren, Yangwu AU - Cui, Ping AU - Iwasaki, Motoki AU - Shimazu, Taichi AU - Tsugane, Shoichiro AU - Zhu, Junjie AU - Jiang, Gening AU - Fei, Ke AU - Wu, Guoping AU - Chien, Li-Hsin AU - Chen, Hui-Ling AU - Su, Yu-Chun AU - Tsai, Fang-Yu AU - Chen, Yi-Song AU - Yu, Jinming AU - Stevens, Victoria L AU - Laird-Offringa, Ite A AU - Marconett, Crystal N AU - Lin, Dongxin AU - Chen, Kexin AU - Wu, Yi-Long AU - Landi, Maria Teresa AU - Shen, Hongbing AU - Rothman, Nathaniel AU - Kohno, Takashi AU - Chanock, Stephen J AU - Lan, Qing AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA ephswj@nus.edu.sg. ; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. ; Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. ; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. ; Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea. ; Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong. ; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. ; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. ; Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, People's Republic of China. ; Division of Thoracic Surgery, Kinki University School of Medicine, Sayama, Japan. ; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. ; Department of Integrative Bioscience & Biotechnology, Sejong University, Seoul, Republic of Korea. ; Department of Epidemiology, School of Public Health, China Medical University, Shenyang, People's Republic of China. ; Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. ; Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China. ; Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. ; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan. ; Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ; Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea. ; Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. ; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong. ; Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan. ; Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Division of Epidemiology & Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. ; Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan. ; Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan. ; Department of Pathology, National Cancer Center Hospital, Tokyo, Japan. ; Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. ; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. ; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa, Japan. ; Department of Thoracic Surgery, Kanagawa Cancer Center, Kanagawa, Japan. ; Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Chiba, Japan. ; Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan. ; Department of Thoracic Oncology, National Cancer Center Hospital East, Japan. ; Department of Cellular and Organ Pathology. ; Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita City, Japan. ; Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan. ; Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. ; China National Environmental Monitoring Center, Beijing, People's Republic of China. ; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. ; Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea. ; Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong. ; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ; Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. ; School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. ; Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. ; Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. ; Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China. ; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. ; Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. ; Genomic Research Center, Academia Sinica, Taipei, Taiwan. ; Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. ; Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. ; Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan. ; Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. ; The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. ; Westat, Rockville, MD, USA. ; Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China. ; Department of Health Sciences Research. ; Cancer Prevention Institute of California, Fremont, CA, USA. ; Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Republic of Korea. ; Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China. ; Ministry of Education Key Laboratory of Modern Toxicology. ; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. ; School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. ; Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan. ; Department of Surgery, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. ; Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. ; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. ; Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, People's Republic of China. ; Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan. ; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. ; Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. ; Agency for Integrated Care, Singapore. ; Department of Pathology, Queen Elizabeth Hospital, Hong Kong, People's Republic of China. ; Qujing Center for Diseases Control and Prevention, Qujing, People's Republic of China. ; Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People's Republic of China. ; Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. ; Shanghai Pulmonary Hospital, Shanghai, People's Republic of China. ; Laboratory Services, American Cancer Society, Atlanta, GA, USA. ; Department of Surgery, Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Y1 - 2016/12/26/ PY - 2016 DA - 2016 Dec 26 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1853363032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Association+between+GWAS-identified+lung+adenocarcinoma+susceptibility+loci+and+EGFR+mutations+in+never-smoking+Asian+women%2C+and+comparison+with+findings+from+Western+populations.&rft.au=Seow%2C+Wei+Jie%3BMatsuo%2C+Keitaro%3BHsiung%2C+Chao+Agnes%3BShiraishi%2C+Kouya%3BSong%2C+Minsun%3BKim%2C+Hee+Nam%3BWong%2C+Maria+Pik%3BHong%2C+Yun-Chul%3BHosgood%2C+H+Dean%3BWang%2C+Zhaoming%3BChang%2C+I-Shou%3BWang%2C+Jiu-Cun%3BChatterjee%2C+Nilanjan%3BTucker%2C+Margaret%3BWei%2C+Hu%3BMitsudomi%2C+Tetsuya%3BZheng%2C+Wei%3BKim%2C+Jin+Hee%3BZhou%2C+Baosen%3BCaporaso%2C+Neil+E%3BAlbanes%2C+Demetrius%3BShin%2C+Min-Ho%3BChung%2C+Lap+Ping%3BAn%2C+She-Juan%3BWang%2C+Ping%3BZheng%2C+Hong%3BYatabe%2C+Yasushi%3BZhang%2C+Xu-Chao%3BKim%2C+Young+Tae%3BShu%2C+Xiao-Ou%3BKim%2C+Young-Chul%3BBassig%2C+Bryan+A%3BChang%2C+Jiang%3BHo%2C+James+Chung+Man%3BJi%2C+Bu-Tian%3BKubo%2C+Michiaki%3BDaigo%2C+Yataro%3BIto%2C+Hidemi%3BMomozawa%2C+Yukihide%3BAshikawa%2C+Kyota%3BKamatani%2C+Yoichiro%3BHonda%2C+Takayuki%3BSakamoto%2C+Hiromi%3BKunitoh%2C+Hideo%3BTsuta%2C+Koji%3BWatanabe%2C+Shun-Ichi%3BNokihara%2C+Hiroshi%3BMiyagi%2C+Yohei%3BNakayama%2C+Haruhiko%3BMatsumoto%2C+Shingo%3BTsuboi%2C+Masahiro%3BGoto%2C+Koichi%3BYin%2C+Zhihua%3BShi%2C+Jianxin%3BTakahashi%2C+Atsushi%3BGoto%2C+Akiteru%3BMinamiya%2C+Yoshihiro%3BShimizu%2C+Kimihiro%3BTanaka%2C+Kazumi%3BWu%2C+Tangchun%3BWei%2C+Fusheng%3BWong%2C+Jason+Y+Y%3BMatsuda%2C+Fumihiko%3BSu%2C+Jian%3BKim%2C+Yeul+Hong%3BOh%2C+In-Jae%3BSong%2C+Fengju%3BLee%2C+Victor+Ho+Fun%3BSu%2C+Wu-Chou%3BChen%2C+Yuh-Min%3BChang%2C+Gee-Chen%3BChen%2C+Kuan-Yu%3BHuang%2C+Ming-Shyan%3BYang%2C+Pan-Chyr%3BLin%2C+Hsien-Chih%3BXiang%2C+Yong-Bing%3BSeow%2C+Adeline%3BPark%2C+Jae+Yong%3BKweon%2C+Sun-Seog%3BChen%2C+Chien-Jen%3BLi%2C+Haixin%3BGao%2C+Yu-Tang%3BWu%2C+Chen%3BQian%2C+Biyun%3BLu%2C+Daru%3BLiu%2C+Jianjun%3BJeon%2C+Hyo-Sung%3BHsiao%2C+Chin-Fu%3BSung%2C+Jae+Sook%3BTsai%2C+Ying-Huang%3BJung%2C+Yoo+Jin%3BGuo%2C+Huan%3BHu%2C+Zhibin%3BWang%2C+Wen-Chang%3BChung%2C+Charles+C%3BLawrence%2C+Charles%3BBurdett%2C+Laurie%3BYeager%2C+Meredith%3BJacobs%2C+Kevin+B%3BHutchinson%2C+Amy%3BBerndt%2C+Sonja+I%3BHe%2C+Xingzhou%3BWu%2C+Wei%3BWang%2C+Junwen%3BLi%2C+Yuqing%3BChoi%2C+Jin+Eun%3BPark%2C+Kyong+Hwa%3BSung%2C+Sook+Whan%3BLiu%2C+Li%3BKang%2C+Chang+Hyun%3BHu%2C+Lingmin%3BChen%2C+Chung-Hsing%3BYang%2C+Tsung-Ying%3BXu%2C+Jun%3BGuan%2C+Peng%3BTan%2C+Wen%3BWang%2C+Chih-Liang%3BSihoe%2C+Alan+Dart+Loon%3BChen%2C+Ying%3BChoi%2C+Yi+Young%3BHung%2C+Jen-Yu%3BKim%2C+Jun+Suk%3BYoon%2C+Ho-Il%3BCai%2C+Qiuyin%3BLin%2C+Chien-Chung%3BPark%2C+In+Kyu%3BXu%2C+Ping%3BDong%2C+Jing%3BKim%2C+Christopher%3BHe%2C+Qincheng%3BPerng%2C+Reury-Perng%3BChen%2C+Chih-Yi%3BVermeulen%2C+Roel%3BWu%2C+Junjie%3BLim%2C+Wei-Yen%3BChen%2C+Kun-Chieh%3BChan%2C+John+K+C%3BChu%2C+Minjie%3BLi%2C+Yao-Jen%3BLi%2C+Jihua%3BChen%2C+Hongyan%3BYu%2C+Chong-Jen%3BJin%2C+Li%3BLo%2C+Yen-Li%3BChen%2C+Ying-Hsiang%3BFraumeni%2C+Joseph+F%3BLiu%2C+Jie%3BYamaji%2C+Taiki%3BYang%2C+Yang%3BHicks%2C+Belynda%3BWyatt%2C+Kathleen%3BLi%2C+Shengchao+A%3BDai%2C+Juncheng%3BMa%2C+Hongxia%3BJin%2C+Guangfu%3BSong%2C+Bao%3BWang%2C+Zhehai%3BCheng%2C+Sensen%3BLi%2C+Xuelian%3BRen%2C+Yangwu%3BCui%2C+Ping%3BIwasaki%2C+Motoki%3BShimazu%2C+Taichi%3BTsugane%2C+Shoichiro%3BZhu%2C+Junjie%3BJiang%2C+Gening%3BFei%2C+Ke%3BWu%2C+Guoping%3BChien%2C+Li-Hsin%3BChen%2C+Hui-Ling%3BSu%2C+Yu-Chun%3BTsai%2C+Fang-Yu%3BChen%2C+Yi-Song%3BYu%2C+Jinming%3BStevens%2C+Victoria+L%3BLaird-Offringa%2C+Ite+A%3BMarconett%2C+Crystal+N%3BLin%2C+Dongxin%3BChen%2C+Kexin%3BWu%2C+Yi-Long%3BLandi%2C+Maria+Teresa%3BShen%2C+Hongbing%3BRothman%2C+Nathaniel%3BKohno%2C+Takashi%3BChanock%2C+Stephen+J%3BLan%2C+Qing&rft.aulast=Seow&rft.aufirst=Wei&rft.date=2016-12-26&rft.volume=&rft.issue=&rft.spage=e20&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/10.1093%2Fnar%2Fgkv907 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-27 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1093/hmg/ddw414 ER - TY - JOUR T1 - Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. AN - 1859755533; 28013405 AB - D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initial pre-clinical testing demonstrated the anti-tumor efficacy of D2C7-IT against orthotopic glioblastoma xenograft models expressing EGFRwt, EGFRvIII, or both EGFRwt and EGFRvIII. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a phase I/II clinical trial. D2C7-IT was expressed under the control of the T7 promoter in Escherichia coli BLR (λ DE3). D2C7-IT was produced by a 10-L batch fermentation process and was then purified from inclusion bodies using anion exchange, size exclusion, and an endotoxin removal process that achieved a yield of over 300 mg of purified protein. The final vialed batch of D2C7-IT for clinical testing was at a concentration of 0.12 ± 0.1 mg/mL, the pH was at 7.4 ± 0.4, and endotoxin levels were below the detection limit of 10 EU/mL (1.26 EU/mL). The stability of the vialed D2C7-IT has been monitored over a period of 42 months through protein concentration, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing, size exclusion chromatography, cytotoxicity, sterility, and pH measurements. The vialed D2C7-IT is currently being tested in a phase I/II clinical trial by intratumoral convection-enhanced delivery for 72 h in patients with recurrent glioblastoma (NCT02303678, D2C7 for Adult Patients with Recurrent Malignant Glioma; clinicaltrials.gov ). JF - Applied microbiology and biotechnology AU - Chandramohan, Vidyalakshmi AU - Pegram, Charles N AU - Piao, Hailan AU - Szafranski, Scott E AU - Kuan, Chien-Tsun AU - Pastan, Ira H AU - Bigner, Darell D AD - Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC, USA. vidyalakshmi.chandramohan@duke.edu. ; Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC, USA. ; Center for Cancer Research, National Cancer Institute, Building 37, Room 5106, Bethesda, MD, 20892, USA. Y1 - 2016/12/24/ PY - 2016 DA - 2016 Dec 24 KW - Recombinant immunotoxin KW - Malignant glioma KW - Epidermal growth factor receptor KW - Mutant EGFR variant III KW - Good laboratory practice UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859755533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+microbiology+and+biotechnology&rft.atitle=Production+and+quality+control+assessment+of+a+GLP-grade+immunotoxin%2C+D2C7-%28scdsFv%29-PE38KDEL%2C+for+a+phase+I%2FII+clinical+trial.&rft.au=Chandramohan%2C+Vidyalakshmi%3BPegram%2C+Charles+N%3BPiao%2C+Hailan%3BSzafranski%2C+Scott+E%3BKuan%2C+Chien-Tsun%3BPastan%2C+Ira+H%3BBigner%2C+Darell+D&rft.aulast=Chandramohan&rft.aufirst=Vidyalakshmi&rft.date=2016-12-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Applied+microbiology+and+biotechnology&rft.issn=1432-0614&rft_id=info:doi/10.1007%2Fs00253-016-8063-x LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00253-016-8063-x ER - TY - JOUR T1 - TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice. AN - 1852786578; 28012173 AB - Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy. JF - Epilepsia AU - Phelan, Kevin D AU - Shwe, U Thaung AU - Cozart, Michael A AU - Wu, Hong AU - Mock, Matthew M AU - Abramowitz, Joel AU - Birnbaumer, Lutz AU - Zheng, Fang AD - Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. ; Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. ; Neurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, U.S.A. Y1 - 2016/12/24/ PY - 2016 DA - 2016 Dec 24 KW - Beta rhythm KW - Transient receptor potential channels KW - Seizures KW - Electroencephalography KW - Spectral analysis KW - Gamma rhythm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852786578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsia&rft.atitle=TRPC3+channels+play+a+critical+role+in+the+theta+component+of+pilocarpine-induced+status+epilepticus+in+mice.&rft.au=Phelan%2C+Kevin+D%3BShwe%2C+U+Thaung%3BCozart%2C+Michael+A%3BWu%2C+Hong%3BMock%2C+Matthew+M%3BAbramowitz%2C+Joel%3BBirnbaumer%2C+Lutz%3BZheng%2C+Fang&rft.aulast=Phelan&rft.aufirst=Kevin&rft.date=2016-12-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Epilepsia&rft.issn=1528-1167&rft_id=info:doi/10.1111%2Fepi.13648 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/epi.13648 ER - TY - JOUR T1 - Modulation of cell death in human colorectal and breast cancer cells through a manganese chelate by involving GSH with intracellular p53 status. AN - 1852786717; 28012015 AB - Chemotherapy is central to current treatment modality especially for advanced and metastatic colorectal and breast cancers. Targeting the key molecular events of the neoplastic cells may open a possibility to treat cancer. Although some improvements in understanding of colorectal and breast cancer treatment have been recorded, the involvement of glutathione (GSH) and dependency of p53 status on the modulation of GSH-mediated treatment efficacy have been largely overlooked. Herein, we tried to decipher the underlying mechanism of the action of Mn-N-(2-hydroxyacetophenone) glycinate (MnNG) against differential p53 status bearing Hct116, MCF-7, and MDA-MB-468 cells on the backdrop of intracellular GSH level and reveal the role of p53 status in modulating GSH-dependant abrogation of MnNG-induced apoptosis in these cancer cells. Present study discloses that MnNG targets specifically wild-type-p53 expressing Hct116 and MCF-7 cells by significantly depleting both cytosolic, mitochondrial GSH, and modulating nuclear GSH through Glutathione reductase and Glutamate-cysteine ligase depletion that may in turn induce p53-mediated intrinsic apoptosis in them. Thus GSH addition abrogates p53-mediated apoptosis in wild-type-p53 expressing cells. GSH addition also overrides MnNG-induced modulation of phase II detoxifying parameters in them. However, GSH addition partially replenishes the down-regulated or modulated GSH pool in cytosol, mitochondria, and nucleus, and relatively abrogates MnNG-induced intrinsic apoptosis in p53-mutated MDA-MB-468 cells. On the contrary, although MnNG induces significant cell death in p53-null Hct116 cells, GSH addition fails to negate MnNG-induced cell death. Thus p53 status with intracellular GSH is critical for the modulation of MnNG-induced apoptosis. JF - Molecular and cellular biochemistry AU - Banerjee, Kaushik AU - Das, Satyajit AU - Majumder, Saikat AU - Majumdar, Subrata AU - Biswas, Jaydip AU - Choudhuri, Soumitra Kumar AD - Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, India. ; Division of Molecular Medicine, Bose Institute, Kolkata, India. ; Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700 026, India. soumitra01@yahoo.com. Y1 - 2016/12/23/ PY - 2016 DA - 2016 Dec 23 KW - p53 KW - Apoptosis KW - Glutathione KW - Schiff-based manganese complex KW - Colorectal and breast cancer KW - Phase II detoxifying enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852786717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biochemistry&rft.atitle=Modulation+of+cell+death+in+human+colorectal+and+breast+cancer+cells+through+a+manganese+chelate+by+involving+GSH+with+intracellular+p53+status.&rft.au=Banerjee%2C+Kaushik%3BDas%2C+Satyajit%3BMajumder%2C+Saikat%3BMajumdar%2C+Subrata%3BBiswas%2C+Jaydip%3BChoudhuri%2C+Soumitra+Kumar&rft.aulast=Banerjee&rft.aufirst=Kaushik&rft.date=2016-12-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biochemistry&rft.issn=1573-4919&rft_id=info:doi/10.1007%2Fs11010-016-2896-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11010-016-2896-6 ER - TY - JOUR T1 - Rare copy number variants in a population-based investigation of hypoplastic right heart syndrome. AN - 1852784515; 28009100 AB - Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS. We genotyped 32 HRHS cases identified from all New York State live births (1998-2005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were ≥20 Kb, contained ≥10 SNPs and had minimal overlap with CNVs from in-house controls, the Database of Genomic Variants, HapMap3, and Childrens Hospital of Philadelphia database. We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16-2p23 duplication spanning LBH, a limb and heart development transcription factor. Lbh mis-expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed SOS1, a factor associated with pulmonary valve stenosis in Noonan syndrome. Sos1-/- mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5 Mb deletion associated with Williams-Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24 Kb deletion upstream of the TGFβ ligand ITGB8. Embryos genetically null for Itgb8, and its intracellular interactant Band 4.1B, display lethal cardiac phenotypes. To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Birth defects research. Part A, Clinical and molecular teratology AU - Dimopoulos, Aggeliki AU - Sicko, Robert J AU - Kay, Denise M AU - Rigler, Shannon L AU - Druschel, Charlotte M AU - Caggana, Michele AU - Browne, Marilyn L AU - Fan, Ruzong AU - Romitti, Paul A AU - Brody, Lawrence C AU - Mills, James L AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. ; Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York. ; Congenital Malformations Registry, New York State Department of Health, Albany, New York. ; Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa. ; Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/12/23/ PY - 2016 DA - 2016 Dec 23 KW - hypoplastic right ventricle KW - LBH KW - hypoplastic right heart KW - ITGB8 KW - SOS1 KW - copy number variants KW - PRRX2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852784515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.atitle=Rare+copy+number+variants+in+a+population-based+investigation+of+hypoplastic+right+heart+syndrome.&rft.au=Dimopoulos%2C+Aggeliki%3BSicko%2C+Robert+J%3BKay%2C+Denise+M%3BRigler%2C+Shannon+L%3BDruschel%2C+Charlotte+M%3BCaggana%2C+Michele%3BBrowne%2C+Marilyn+L%3BFan%2C+Ruzong%3BRomitti%2C+Paul+A%3BBrody%2C+Lawrence+C%3BMills%2C+James+L&rft.aulast=Dimopoulos&rft.aufirst=Aggeliki&rft.date=2016-12-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.issn=1542-0760&rft_id=info:doi/10.1002%2Fbdra.23586 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/bdra.23586 ER - TY - JOUR T1 - Prediction of hERG Liability - Using SVM Classification, Bootstrapping and Jackknifing. AN - 1851297998; 28000393 AB - Drug-induced QT prolongation leads to life-threatening cardiotoxicity, mostly through blockage of the human ether-à-go-go-related gene (hERG) encoded potassium ion (K+ ) channels. The hERG channel is one of the most important antitargets to be addressed in the early stage of drug discovery process, in order to avoid more costly failures in the development phase. Using a thallium flux assay, 4,323 molecules were screened for hERG channel inhibition in a quantitative high throughput screening (qHTS) format. Here, we present support vector classification (SVC) models of hERG channel inhibition with the averaged area under the receiver operator characteristics curve (AUC-ROC) of 0.93 for the tested compounds. Both Jackknifing and bootstrapping have been employed to rebalance the heavily biased training datasets, and the impact of these two under-sampling rebalance methods on the performance of the predictive models is discussed. Our results indicated that the rebalancing techniques did not enhance the predictive power of the resulting models; instead, adoption of optimal cutoffs could restore the desirable balance of sensitivity and specificity of the binary classifiers. In an external validation set of 66 drug molecules, the SVC model exhibited an AUC-ROC of 0.86, further demonstrating the utility of this modeling approach to predict hERG liabilities. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. JF - Molecular informatics AU - Sun, Hongmao AU - Huang, Ruili AU - Xia, Menghang AU - Shahane, Sampada AU - Southall, Noel AU - Wang, Yuhong AD - National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/12/21/ PY - 2016 DA - 2016 Dec 21 KW - bootstrap KW - ROC KW - support vector classification KW - hERG KW - jackknife KW - rebalance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851297998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+informatics&rft.atitle=Prediction+of+hERG+Liability+-+Using+SVM+Classification%2C+Bootstrapping+and+Jackknifing.&rft.au=Sun%2C+Hongmao%3BHuang%2C+Ruili%3BXia%2C+Menghang%3BShahane%2C+Sampada%3BSouthall%2C+Noel%3BWang%2C+Yuhong&rft.aulast=Sun&rft.aufirst=Hongmao&rft.date=2016-12-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+informatics&rft.issn=1868-1751&rft_id=info:doi/10.1002%2Fminf.201600126 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/minf.201600126 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor-β/δ inhibits human neuroblastoma cell tumorigenesis by inducing p53- and SOX2-mediated cell differentiation. AN - 1851298646; 27996177 AB - Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator-activated receptor-β/δ, (PPARβ/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARβ/δ was over-expressed in three human neuroblastoma cell lines, NGP, SK-N-BE(2), and IMR-32, that exhibit high, medium, and low sensitivity, respectively, to retinoic acid-induced differentiation to determine if PPARβ/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment. All-trans-RA (atRA) decreased expression of SRY (sex determining region Y)-box 2 (SOX2), a stem cell regulator and marker of de-differentiation, in NGP and SK-N-BE(2) cells with inactive or mutant tumor suppressor p53, respectively. However, atRA did not suppress SOX2 expression in IMR-32 cells carrying wild-type p53. Over-expression and/or ligand activation of PPARβ/δ reduced the average volume and weight of ectopic tumor xenografts from NGP, SK-N-BE(2), or IMR-32 cells compared to controls. Compared with that found with atRA, PPARβ/δ suppressed SOX2 expression in NGP and SK-N-BE(2) cells and ectopic xenografts, and was also effective in suppressing SOX2 expression in IMR-32 cells that exhibit higher p53 expression compared to the former cell lines. Combined, these observations demonstrate that activating or over-expressing PPARβ/δ induces cell differentiation through p53- and SOX2-dependent signaling pathways in neuroblastoma cells and tumors. This suggests that combinatorial activation of both RARα and PPARβ/δ may be suitable as an alternative therapeutic approach for RA-resistant neuroblastoma patients. Published [2016]. This article is a U.S. Government work and is in the public domain in the USA. JF - Molecular carcinogenesis AU - Yao, Pei-Li AU - Chen, Liping AU - Dobrzański, Tomasz P AU - Zhu, Bokai AU - Kang, Boo-Hyon AU - Müller, Rolf AU - Gonzalez, Frank J AU - Peters, Jeffrey M AD - Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania. ; Non-clinical Research Institute, Chemon, Jeil-Ri, Yangji-Myeon, Cheoin-Gu, Yongin-Si, Gyeonggi-Do, Korea. ; Institute of Molecular Biology and Tumor Research, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany. ; Laboratory of Metabolism, National Cancer Institute, Bethesda, Maryland. Y1 - 2016/12/20/ PY - 2016 DA - 2016 Dec 20 KW - p53 KW - peroxisome proliferator-activated receptor-β/δ KW - SOX2 KW - neuroblastoma KW - retinoid acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851298646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Peroxisome+proliferator-activated+receptor-%CE%B2%2F%CE%B4+inhibits+human+neuroblastoma+cell+tumorigenesis+by+inducing+p53-+and+SOX2-mediated+cell+differentiation.&rft.au=Yao%2C+Pei-Li%3BChen%2C+Liping%3BDobrza%C5%84ski%2C+Tomasz+P%3BZhu%2C+Bokai%3BKang%2C+Boo-Hyon%3BM%C3%BCller%2C+Rolf%3BGonzalez%2C+Frank+J%3BPeters%2C+Jeffrey+M&rft.aulast=Yao&rft.aufirst=Pei-Li&rft.date=2016-12-20&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=1098-2744&rft_id=info:doi/10.1002%2Fmc.22607 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/mc.22607 ER - TY - JOUR T1 - Safety and Preclinical Efficacy of Aerosol Pioglitazone on Lung Adenoma Prevention in A/J Mice. AN - 1851302065; 27993834 AB - Pioglitazone is a PPARγ agonist commonly prescribed for the clinical treatment of diabetes. We sought to expand its use to lung cancer prevention in a benzo[a]pyrene (B[a]P) mouse model with direct lung delivery via inhalation. Initially, we conducted inhalational toxicity experiments with 0, 15, 50, 150, and 450 μg/kg body weight/day pioglitazone in 40 A/J mice. We examined the animals for any physical toxicity and bronchoalveolar lavage fluids for inflammatory and cytotoxicity markers. Doses up to and including 450 μg/kg bw/d failed to demonstrate toxicity with aerosol pioglitazone. For chemoprevention experiments, A/J mice were randomized to treatment groups of inhaled doses of 0, 50, 150, or 450 μg/kg bw/d pioglitazone 1 or 8 weeks after the last dose of B[a]P. For the early treatment group, we found up to 32% decrease in lung adenoma formation with 450 μg/kg bw/d pioglitazone. We repeated the treatments in a second late-stage experiment and found up to 44% decreases in lung adenoma formation in doses of pioglitazone of 150 and 450 μg/kg bw/day. Both the early- and the late-stage experiments demonstrated biologically relevant and statistically significant decreases in adenoma formation. We conclude that aerosol pioglitazone is well-tolerated in the A/J mouse model and a promising chemoprevention agent for the lower respiratory tract. Cancer Prev Res; 10(2); 1-9. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer prevention research (Philadelphia, Pa.) AU - Seabloom, Donna E AU - Galbraith, Arthur R AU - Haynes, Anna M AU - Antonides, Jennifer D AU - Wuertz, Beverly R AU - Miller, Wendy A AU - Miller, Kimberly A AU - Steele, Vernon E AU - Suen, Chen S AU - O'Sullivan, M Gerard AU - Ondrey, Frank G AD - AeroCore Inhalation Testing, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota. ; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. ; Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota. ; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland. ; Comparative Pathology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. ; AeroCore Inhalation Testing, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota. ondre002@umn.edu. Y1 - 2016/12/19/ PY - 2016 DA - 2016 Dec 19 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851302065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.atitle=Safety+and+Preclinical+Efficacy+of+Aerosol+Pioglitazone+on+Lung+Adenoma+Prevention+in+A%2FJ+Mice.&rft.au=Seabloom%2C+Donna+E%3BGalbraith%2C+Arthur+R%3BHaynes%2C+Anna+M%3BAntonides%2C+Jennifer+D%3BWuertz%2C+Beverly+R%3BMiller%2C+Wendy+A%3BMiller%2C+Kimberly+A%3BSteele%2C+Vernon+E%3BSuen%2C+Chen+S%3BO%27Sullivan%2C+M+Gerard%3BOndrey%2C+Frank+G&rft.aulast=Seabloom&rft.aufirst=Donna&rft.date=2016-12-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.issn=1940-6215&rft_id=info:doi/10.1158%2F1940-6207.CAPR-16-0174 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1158/1940-6207.CAPR-16-0174 ER - TY - JOUR T1 - Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development AN - 1846406312; PQ0003860101 AB - Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of the DLX5 (distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating the DLX5 gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells. Accordingly, one daughter cell inherits both expressed DLX5 copies while the other daughter inherits both epigenetically silenced ones from a single deterministic cell of the developing limb. Thus, differentiated daughter cells after further proliferation will correspondingly produce proximal/distal-limb tissues. Published results of a Chr. 7 translocation with a centromere-proximal breakpoint situated over 41 million bases away from the DLX locus, centromeric and DLX5-region inversions have satisfied key genetic and developmental biology predictions of the mechanism. Further genetic tests of the mechanism are proposed. We propose that the DNA double helical structure itself causes the development of sister cells' gene regulation asymmetry. We also argue against the conventionally invoked morphogen model of development.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. JF - Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences AU - Klar, Amar JS AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Center for Cancer Research, National Institutes of Health, , Building 539, Room 154, Frederick, MD 21702-1201, USA, klara@mail.nih.gov Y1 - 2016/12/19/ PY - 2016 DA - 2016 Dec 19 SP - 20150415 PB - Royal Society of London, 6 Carlton House Terrace London SW1Y 5AG United Kingdom VL - 371 IS - 1710 SN - 0962-8436, 0962-8436 KW - Ecology Abstracts KW - limb development KW - human split hand/foot malformation KW - selective chromatid segregation mechanism KW - selective DNA strand segregation mechanism KW - asymmetric cell division mechanism KW - DNA chirality-based developmental mechanism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846406312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Philosophical+Transactions+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.atitle=Split+hand%2Ffoot+malformation+genetics+supports+the+chromosome+7+copy+segregation+mechanism+for+human+limb+development&rft.au=Klar%2C+Amar+JS&rft.aulast=Klar&rft.aufirst=Amar&rft.date=2016-12-19&rft.volume=371&rft.issue=1710&rft.spage=20150415&rft.isbn=&rft.btitle=&rft.title=Philosophical+Transactions+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.issn=09628436&rft_id=info:doi/10.1098%2Frstb.2015.0415 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-07 DO - http://dx.doi.org/10.1098/rstb.2015.0415 ER - TY - JOUR T1 - Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1. AN - 1851294782; 27988521 AB - Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research. © 2016 S. Karger AG, Basel. JF - Dementia and geriatric cognitive disorders AU - Kristofikova, Zdenka AU - Ricny, Jan AU - Soukup, Ondrej AU - Korabecny, Jan AU - Nepovimova, Eugenie AU - Kuca, Kamil AU - Ripova, Daniela AD - Alzheimer Disease Center, National Institute of Mental Health, Klecany, Czech Republic. Y1 - 2016/12/17/ PY - 2016 DA - 2016 Dec 17 SP - 45 EP - 58 VL - 43 IS - 1-2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851294782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Dementia+and+geriatric+cognitive+disorders&rft.atitle=Inhibitors+of+Acetylcholinesterase+Derived+from+7-Methoxytacrine+and+Their+Effects+on+the+Choline+Transporter+CHT1.&rft.au=Kristofikova%2C+Zdenka%3BRicny%2C+Jan%3BSoukup%2C+Ondrej%3BKorabecny%2C+Jan%3BNepovimova%2C+Eugenie%3BKuca%2C+Kamil%3BRipova%2C+Daniela&rft.aulast=Kristofikova&rft.aufirst=Zdenka&rft.date=2016-12-17&rft.volume=43&rft.issue=1-2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Dementia+and+geriatric+cognitive+disorders&rft.issn=1421-9824&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer Patients: A Population-based Study. AN - 1851297756; 27993663 AB - Randomized trials have reported that intermittent androgen deprivation therapy (IADT) for patients with advanced prostate cancer (PCa) may improve sexual and physical functioning compared to continuous ADT (CADT) without compromising survival. It is unknown whether IADT alters the risk of serious toxicities associated with CADT. We conducted a population-based cohort study of 9,772 men aged 66 or older diagnosed with advanced PCa from 2002-2011 treated with ADT. We classified men as receiving IADT if they had at least one 90-day gap between the completion of an ADT therapeutic duration and the start of the following one, and had doctor visits or PSA testing during the gap. Outcomes included acute myocardial infarction (AMI), stroke, heart failure (HF), type-2-diabetes, and fracture. We used Cox-proportional hazard models to estimate hazard ratios (HRs) for the comparative risk between IADT and CADT of serious toxicities. A total of 2,113 (22%), 769 (9%), and 899 (9%) men had a new cardiovascular event, diabetes, or fracture, respectively, within 5 years of starting ADT. Compared to the CADT group, the IADT group showed lower risk of serious cardiovascular events (HR= 0.64, 95% confidence interval [CI]=0.53-0.77, p<0.0001), particularly in reducing the risk of HF (HR=0.62, 95% CI=0.49-0.78, p<0.0001) and fracture (HR=0.52, 95%CI= 0.38, 0.70, p<0.0001). IADT was associated with lower risk of HF and fracture compared to CADT, raising toxicity concerns for CADT relative to IADT and suggesting that IADT may represent a safer therapeutic choice in elderly men with advanced PCa. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. JF - The Journal of urology AU - Tsai, Huei-Ting AU - Pfeiffer, Ruth M AU - Philips, George K AU - Barac, Ana AU - Fu, Alex Z AU - Penson, David F AU - Zhou, Yingjun AU - Potosky, Arnold L AD - Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington D.C., USA. ; National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Medicine, Georgetown University Medical Center, Georgetown University, Washington D.C., USA. ; Division of Cardiology, MedStar Washington Hospital Center, Washington DC, United States. ; Department of Urologic Surgery, Vanderbilt University Medical Center. Y1 - 2016/12/16/ PY - 2016 DA - 2016 Dec 16 KW - comparative risk KW - intermittent androgen deprivation therapy KW - advanced prostate cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851297756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Panitumumab+in+combination+with+gemcitabine+and+oxaliplatin+does+not+prolong+survival+in+wild-type+KRAS+advanced+biliary+tract+cancer%3A+A+randomized+phase+2+trial+%28Vecti-BIL+study%29.&rft.au=Leone%2C+Francesco%3BMarino%2C+Donatella%3BCereda%2C+Stefano%3BFilippi%2C+Roberto%3BBelli%2C+Carmen%3BSpadi%2C+Rosella%3BNasti%2C+Guglielmo%3BMontano%2C+Massimo%3BAmatu%2C+Alessio%3BAprile%2C+Giuseppe%3BCagnazzo%2C+Celeste%3BFasola%2C+Gianpiero%3BSiena%2C+Salvatore%3BCiuffreda%2C+Libero%3BReni%2C+Michele%3BAglietta%2C+Massimo&rft.aulast=Leone&rft.aufirst=Francesco&rft.date=2016-02-15&rft.volume=122&rft.issue=4&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=1097-0142&rft_id=info:doi/10.1002%2Fcncr.29778 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.juro.2016.12.022 ER - TY - JOUR T1 - mTOR Inhibition Mitigates Enhanced mRNA Translation Associated with the Metastatic Phenotype of Osteosarcoma Cells In Vivo AN - 1859483732; PQ0003994022 AB - Purpose: To successfully metastasize, tumor cells must respond appropriately to biological stressors encountered during metastatic progression. We sought to test the hypothesis that enhanced efficiency of mRNA translation during periods of metastatic stress is required for metastatic competence of osteosarcoma and that this metastasis-specific adaptation is amenable to therapeutic intervention.Experimental Design: We employ novel reporter and proteomic systems that enable tracking of mRNA translation efficiency and output in metastatic osteosarcoma cells as they colonize the lungs. We test the potential to target mRNA translation as an antimetastatic therapeutic strategy through pharmacokinetic studies and preclinical assessment of the prototypic mTOR inhibitor, rapamycin, across multiple models of metastasis.Results: Metastatic osteosarcoma cells translate mRNA more efficiently than nonmetastatic cells during critical stressful periods of metastatic colonization of the lung. Rapamycin inhibits translational output during periods of metastatic stress, mitigates lung colonization, and prolongs survival. mTOR-inhibiting exposures of rapamycin are achievable in mice using treatment schedules that correspond to human doses well below the MTDs defined in human patients, and as such are very likely to be tolerated over long exposures alone and in combination with other agents.Conclusions: Metastatic competence of osteosarcoma cells is dependent on efficient mRNA translation during stressful periods of metastatic progression, and the mTOR inhibitor, rapamycin, can mitigate this translation and inhibit metastasis in vivo. Our data suggest that mTOR pathway inhibitors should be reconsidered in the clinic using rationally designed dosing schedules and clinical metrics related to metastatic progression. Clin Cancer Res; 22(24); 6129-41. [copy2016 AACR. JF - Clinical Cancer Research AU - Morrow, James J AU - Mendoza, Arnulfo AU - Koyen, Allyson AU - Lizardo, Michael M AU - Ren, Ling AU - Waybright, Timothy J AU - Hansen, Ryan J AU - Gustafson, Daniel L AU - Zhou, Ming AU - Fan, Timothy M AU - Scacheri, Peter C AU - Khanna, Chand AD - Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, ckhanna@ethosvet.com Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 6129 EP - 6141 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 24 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859483732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=mTOR+Inhibition+Mitigates+Enhanced+mRNA+Translation+Associated+with+the+Metastatic+Phenotype+of+Osteosarcoma+Cells+In+Vivo&rft.au=Morrow%2C+James+J%3BMendoza%2C+Arnulfo%3BKoyen%2C+Allyson%3BLizardo%2C+Michael+M%3BRen%2C+Ling%3BWaybright%2C+Timothy+J%3BHansen%2C+Ryan+J%3BGustafson%2C+Daniel+L%3BZhou%2C+Ming%3BFan%2C+Timothy+M%3BScacheri%2C+Peter+C%3BKhanna%2C+Chand&rft.aulast=Morrow&rft.aufirst=James&rft.date=2016-12-15&rft.volume=22&rft.issue=24&rft.spage=6129&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0326 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0326 ER - TY - JOUR T1 - Endothelial Nitric Oxide Synthase Traffic Inducer (NOSTRIN) is a Negative Regulator of Disease Aggressiveness in Pancreatic Cancer AN - 1859482293; PQ0003994008 AB - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is refractory to available treatments. Delineating critical pathways, responsible for disease aggressiveness and therapeutic resistance, may identify effective therapeutic targets. We aimed to identify key pathways contributing to disease aggressiveness by comparing gene expression profiles of tumors from early-stage PDAC cases with extremely poor survival ( less than or equal to 7 months) and those surviving 2 years or more following surgical resection.Experimental Design: Gene expression profiling was performed in tumors in a test cohort of PDAC (N = 50), which included short ( less than or equal to 7 months, N = 11) and long surviving ( greater than or equal to 2 years, N = 14) patients, using affymetrix GeneChip Human 1.0 ST array. Key genes associated with disease aggressiveness were identified, using Cox regression, Kaplan-Meier, and pathway analyses with validations in independent cohorts for mechanistic and functional analyses.Results: Gene expression profiling identified 1,820 differentially expressed genes between short and long survival groups with inflammatory gene network ranking first. Lower expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was associated with worst survival indicating its potential inhibitory role in disease progression. NOSTRIN overexpression suppressed migration and invasion of pancreatic cancer cells and enhanced sensitivity to chemotherapeutic drug gemcitabine. NOSTRIN inhibited production of nitric oxide (NO) by suppressing the activation of endothelial nitric oxide synthase (eNOS). Furthermore, miR-221, bound to the 3'UTR of NOSTRIN and suppressed its expression, and an increased miR-221 expression associated with poor survival in PDAC.Conclusions: Our findings showed that NOSTRIN is a potential negative regulator of disease aggressiveness, which may be targeted for designing improved treatment strategy in PDAC. Clin Cancer Res; 22(24); 5992-6001. [copy2016 AACR. JF - Clinical Cancer Research AU - Wang, Jian AU - Yang, Shouhui AU - He, Peijun AU - Schetter, Aaron J AU - Gaedcke, Jochen AU - Ghadimi, BMichael AU - Ried, Thomas AU - Yfantis, Harris G AU - Lee, Dong H AU - Gaida, Matthias M AU - Hanna, Nader AU - Alexander, HRichard AU - Hussain, SPerwez AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, Bethesda, Maryland, hussainp@mail.nih.gov Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 5992 EP - 6001 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 24 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859482293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Endothelial+Nitric+Oxide+Synthase+Traffic+Inducer+%28NOSTRIN%29+is+a+Negative+Regulator+of+Disease+Aggressiveness+in+Pancreatic+Cancer&rft.au=Wang%2C+Jian%3BYang%2C+Shouhui%3BHe%2C+Peijun%3BSchetter%2C+Aaron+J%3BGaedcke%2C+Jochen%3BGhadimi%2C+BMichael%3BRied%2C+Thomas%3BYfantis%2C+Harris+G%3BLee%2C+Dong+H%3BGaida%2C+Matthias+M%3BHanna%2C+Nader%3BAlexander%2C+HRichard%3BHussain%2C+SPerwez&rft.aulast=Wang&rft.aufirst=Jian&rft.date=2016-12-15&rft.volume=22&rft.issue=24&rft.spage=5992&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0511 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0511 ER - TY - JOUR T1 - Targeting Estrogen Receptor Signaling with Fulvestrant Enhances Immune and Chemotherapy-Mediated Cytotoxicity of Human Lung Cancer AN - 1859481189; PQ0003994028 AB - Purpose: The conversion of tumor cells from an epithelial to a mesenchymal-like phenotype, via a process designated as the epithelial-mesenchymal transition (EMT), is known to mediate tumor resistance to a variety of cell death inducers, including cytotoxic effector immune cells. The goal of this study was to identify and potentially repurpose FDA-approved compounds capable of reducing mesenchymal features of human lung carcinoma cells, which could be used in combination with immunotherapies or chemotherapeutic strategies to improve clinical responses.Experimental Design: In the current report, we have utilized a quantitative high-throughput screening (qHTS) of a pharmaceutical collection of more than 2,000 compounds to identify clinically approved drugs capable of augmenting the sensitivity of mesenchymal-like, lung cancer cells to immune- and chemotherapy-mediated lysis, both in vitro and in vivo.Results: The estrogen receptor antagonist fulvestrant was shown to reduce mesenchymal features of lung carcinoma cells, resulting in tumor sensitization to the cytotoxic effect of antigen-specific T cells, natural killer (NK) effector cells, and chemotherapy both in vivo and in vitro.Conclusions: To our knowledge, this is the first report defining a potential role for estrogenic signaling in promoting tumor resistance to immune-mediated cytotoxicity and chemotherapy in lung cancer. Our data demonstrate a robust association between the acquisition of mesenchymal attributes, therapeutic resistance of lung carcinoma cells, and the expression of estrogen receptor 1 (ESR1), supporting further investigations on the role of estrogen signaling in lung cancer progression via the induction of EMT. Clin Cancer Res; 22(24); 6204-16. [copy2016 AACR. JF - Clinical Cancer Research AU - Hamilton, Duane H AU - Griner, Lesley Mathews AU - Keller, Jonathan M AU - Hu, Xin AU - Southall, Noel AU - Marugan, Juan AU - David, Justin M AU - Ferrer, Marc AU - Palena, Claudia AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, palenac@mail.nih.gov Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 6204 EP - 6216 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 24 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859481189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Targeting+Estrogen+Receptor+Signaling+with+Fulvestrant+Enhances+Immune+and+Chemotherapy-Mediated+Cytotoxicity+of+Human+Lung+Cancer&rft.au=Hamilton%2C+Duane+H%3BGriner%2C+Lesley+Mathews%3BKeller%2C+Jonathan+M%3BHu%2C+Xin%3BSouthall%2C+Noel%3BMarugan%2C+Juan%3BDavid%2C+Justin+M%3BFerrer%2C+Marc%3BPalena%2C+Claudia&rft.aulast=Hamilton&rft.aufirst=Duane&rft.date=2016-12-15&rft.volume=22&rft.issue=24&rft.spage=6204&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-3059 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-3059 ER - TY - JOUR T1 - Minimally Toxic Dose of Lipopolysaccharide and α-Synuclein Oligomer Elicit Synergistic Dopaminergic Neurodegeneration: Role and Mechanism of Microglial NOX2 Activation. AN - 1852685149; 27975175 AB - The aim of this study is to investigate the role and mechanism of microglial NOX2 activation in minimally toxic dose of LPS and Syn-elicited synergistic dopaminergic neurodegeneration. NOX2+/+ and NOX2-/- mice and multiple primary cultures were treated with LPS and/or Syn in vivo and in vitro. Neuronal function and morphology were evaluated by uptake of related neurotransmitter and immunostaining with specific antibody. Levels of superoxide, intracellular reactive oxygen species, mRNA and protein of relevant molecules, and dopamine were detected. LPS and Syn synergistically induce selective and progressive dopaminergic neurodegeneration. Microglia are functionally and morphologically activated, contributing to synergistic dopaminergic neurotoxicity elicited by LPS and Syn. NOX2-/- mice are more resistant to synergistic neurotoxicity than NOX2+/+mice in vivo and in vitro, and NOX2 inhibitor protects against synergistic neurotoxicity through decreasing microglial superoxide production, illustrating a critical role of microglial NOX2. Microglial NOX2 is activated by LPS and Syn as mRNA and protein levels of NOX2 subunits P47and gp91 are enhanced. Molecules relevant to microglial NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-КBP50 as their mRNA and protein levels are elevated after treatment with LPS and Syn. Combination of exogenous and endogenous environmental factors with minimally toxic dose synergistically propagates dopaminergic neurodegeneration through activating microglial NOX2 and relevant signaling molecules, casting a new light for PD pathogenesis. JF - Molecular neurobiology AU - Zhang, Wei AU - Gao, Jun-Hua AU - Yan, Zhao-Fen AU - Huang, Xi-Yan AU - Guo, Peng AU - Sun, Li AU - Liu, Zhuo AU - Hu, Yang AU - Zuo, Li-Jun AU - Yu, Shu-Yang AU - Cao, Chen-Jie AU - Wang, Xiao-Min AU - Hong, Jau-Shyong AD - Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China. ttyyzw@163.com. ; Department of Neurology, Beijing Tiantian Hospital, Capital Medical University, Beijing, 100050, China. ; Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China. ; Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing, 100069, China. ; Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 KW - Parkinson disease KW - Microglial activation KW - Synergistic KW - Dopaminergic neurodegeneration KW - α-Synuclein oligomer KW - Lipopolysaccharide KW - Environmental factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852685149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+neurobiology&rft.atitle=Minimally+Toxic+Dose+of+Lipopolysaccharide+and+%CE%B1-Synuclein+Oligomer+Elicit+Synergistic+Dopaminergic+Neurodegeneration%3A+Role+and+Mechanism+of+Microglial+NOX2+Activation.&rft.au=Zhang%2C+Wei%3BGao%2C+Jun-Hua%3BYan%2C+Zhao-Fen%3BHuang%2C+Xi-Yan%3BGuo%2C+Peng%3BSun%2C+Li%3BLiu%2C+Zhuo%3BHu%2C+Yang%3BZuo%2C+Li-Jun%3BYu%2C+Shu-Yang%3BCao%2C+Chen-Jie%3BWang%2C+Xiao-Min%3BHong%2C+Jau-Shyong&rft.aulast=Zhang&rft.aufirst=Wei&rft.date=2016-12-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Molecular+neurobiology&rft.issn=1559-1182&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial. AN - 1852682595; 27978579 AB - KRAS mutations are common in pancreatic cancer, but directly targeting the KRAS protein has thus far been unsuccessful. The aim of this trial was to block the MEK and PI3K/AKT pathways downstream of the KRAS protein as an alternate treatment strategy to slow cancer growth and prolong survival. This was the first cooperative group trial to evaluate this strategy using molecularly targeted oral combination therapy for the treatment of chemotherapy-refractory pancreatic cancer. To compare selumetinib and MK-2206 vs modified FOLFOX (mFOLFOX) in patients with metastatic pancreatic cancer for whom gemcitabine-based therapy had failed. SWOG S1115 was a randomized phase 2 clinical trial. Between September 2012 and May 2014, 137 patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed were randomized to selumetinib plus MK-2206 or mFOLFOX. Patients were randomized in a 1:1 fashion and stratified according to duration of prior systemic therapy and presence of liver metastases. Patients received selumetinib 100 mg orally per day plus MK-2206 135 mg orally once per week or mFOLFOX (oxaliplatin, 85 mg/m2 intravenous, and fluorouracil, 2400 mg/m2 intravenous infusion over 46-48 hours) on days 1 and 15 of a 28-day cycle. The primary end point of the study was overall survival. Secondary objectives included evaluating toxic effects, objective tumor response, and progression-free survival. There were 58 patients in the selumetinib plus MK-2206 (experimental) arm (60% male; median [range] age, 69 [54-88] years) and 62 patients in the mFOLFOX arm (35% male; median [range] age, 65 [34-82] years). In the experimental arm, median overall survival was shorter (3.9 vs 6.7 months; HR, 1.37; 95% CI, 0.90-2.08; P = .15), as was median progression-free survival (1.9 vs 2.0 months; HR, 1.61; 95% CI, 1.07-2.43; P = .02). One vs 5 patients had a partial response and 12 vs 14 patients had stable disease in the experimental arm vs mFOLFOX arm. Grade 3 or higher toxic effects were observed in 39 patients treated with selumetinib and MK-2206 vs 23 patients treated with mFOLFOX. More patients in the experimental arm discontinued therapy due to adverse events (13 vs 7 patients). Dual targeting of the MEK and PI3K/AKT pathways downstream of KRAS by selumetinib plus MK-2206 did not improve overall survival in patients with metastatic pancreatic adenocarcinoma for whom gemcitabine-based chemotherapy had failed. This was the first randomized prospective evaluation of mFOLFOX in the US population that showed comparable results to CONKO-003 and PANCREOX. clinicaltrials.gov: NCT01658943. JF - JAMA oncology AU - Chung, Vincent AU - McDonough, Shannon AU - Philip, Philip A AU - Cardin, Dana AU - Wang-Gillam, Andrea AU - Hui, Laifong AU - Tejani, Mohamedtaki A AU - Seery, Tara E AU - Dy, Irene A AU - Al Baghdadi, Tareq AU - Hendifar, Andrew E AU - Doyle, L Austin AU - Lowy, Andrew M AU - Guthrie, Katherine A AU - Blanke, Charles D AU - Hochster, Howard S AD - City of Hope National Medical Center, Duarte, California. ; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington. ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. ; Vanderbilt University Medical Center, Nashville, Tennessee. ; Washington University in St Louis, St Louis, Missouri. ; Kaiser Permanente NCORP, Sacramento, California. ; University of Rochester, Rochester, New York. ; University of California, Irvine, Orange. ; Crossroads Cancer Center/Heartland NCORP, Effingham, Illinois. ; St Joseph Mercy Hospital/Michigan CRC NCORP, Ann Arbor. ; Cedars-Sinai Medical Center, Los Angeles, California. ; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland. ; University of California, San Diego, La Jolla. ; SWOG Group Chair's Office/Knight Cancer Institute, Oregon Health and Science University, Portland. ; Yale Cancer Center, New Haven, Connecticut. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852682595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA+oncology&rft.atitle=Effect+of+Selumetinib+and+MK-2206+vs+Oxaliplatin+and+Fluorouracil+in+Patients+With+Metastatic+Pancreatic+Cancer+After+Prior+Therapy%3A+SWOG+S1115+Study+Randomized+Clinical+Trial.&rft.au=Chung%2C+Vincent%3BMcDonough%2C+Shannon%3BPhilip%2C+Philip+A%3BCardin%2C+Dana%3BWang-Gillam%2C+Andrea%3BHui%2C+Laifong%3BTejani%2C+Mohamedtaki+A%3BSeery%2C+Tara+E%3BDy%2C+Irene+A%3BAl+Baghdadi%2C+Tareq%3BHendifar%2C+Andrew+E%3BDoyle%2C+L+Austin%3BLowy%2C+Andrew+M%3BGuthrie%2C+Katherine+A%3BBlanke%2C+Charles+D%3BHochster%2C+Howard+S&rft.aulast=Chung&rft.aufirst=Vincent&rft.date=2016-12-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=JAMA+oncology&rft.issn=2374-2445&rft_id=info:doi/10.1001%2Fjamaoncol.2016.5383 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1001/jamaoncol.2016.5383 ER - TY - JOUR T1 - Rev1 is a base excision repair enzyme with 5'-deoxyribose phosphate lyase activity. AN - 1852657660; 27683219 AB - Rev1 is a member of the Y-family of DNA polymerases and is known for its deoxycytidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. In light of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cells treated with a base excision repair-inducing agent, we questioned whether Rev1 could also be involved in base excision repair (BER). Here, we uncovered a weak 5'-deoxyribose phosphate (5'-dRP) lyase activity in mouse Rev1 and demonstrated the enzyme can mediate BER in vitro The full-length Rev1 protein and its catalytic core domain are similar in their ability to support BER in vitro The dRP lyase activity in both of these proteins was confirmed by NaBH4 reduction of the Schiff base intermediate and kinetics studies. Limited proteolysis, mass spectrometry and deletion analysis localized the dRP lyase active site to the C-terminal segment of Rev1's catalytic core domain. These results suggest that Rev1 could serve as a backup polymerase in BER and could potentially contribute to AID-initiated antibody diversification through this activity. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. JF - Nucleic acids research AU - Prasad, Rajendra AU - Poltoratsky, Vladimir AU - Hou, Esther W AU - Wilson, Samuel H AD - Genome Integrity and Structural Biology Laboratory, National Institutes of Health, NIEHS, 111 T.W. Alexander Drive, PO Box 12233, MD F3-01, Research Triangle Park, NC 27709, USA. ; Genome Integrity and Structural Biology Laboratory, National Institutes of Health, NIEHS, 111 T.W. Alexander Drive, PO Box 12233, MD F3-01, Research Triangle Park, NC 27709, USA wilson5@niehs.nih.gov. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 10824 EP - 10833 VL - 44 IS - 22 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852657660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Rev1+is+a+base+excision+repair+enzyme+with+5%27-deoxyribose+phosphate+lyase+activity.&rft.au=Prasad%2C+Rajendra%3BPoltoratsky%2C+Vladimir%3BHou%2C+Esther+W%3BWilson%2C+Samuel+H&rft.aulast=Prasad&rft.aufirst=Rajendra&rft.date=2016-12-15&rft.volume=44&rft.issue=22&rft.spage=10824&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates. AN - 1844608543; 27681141 AB - Although HIV-2 does not encode a vpu gene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit. Lentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode a vpu gene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single-amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Journal of virology AU - Chen, Chia-Yen AU - Shingai, Masashi AU - Welbourn, Sarah AU - Martin, Malcolm A AU - Borrego, Pedro AU - Taveira, Nuno AU - Strebel, Klaus AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA. ; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. ; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA kstrebel@nih.gov. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 11062 EP - 11074 VL - 90 IS - 24 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844608543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Antagonism+of+BST-2%2FTetherin+Is+a+Conserved+Function+of+the+Env+Glycoprotein+of+Primary+HIV-2+Isolates.&rft.au=Chen%2C+Chia-Yen%3BShingai%2C+Masashi%3BWelbourn%2C+Sarah%3BMartin%2C+Malcolm+A%3BBorrego%2C+Pedro%3BTaveira%2C+Nuno%3BStrebel%2C+Klaus&rft.aulast=Chen&rft.aufirst=Chia-Yen&rft.date=2016-12-15&rft.volume=90&rft.issue=24&rft.spage=11062&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation. AN - 1841793417; 27647490 AB - Both uncoupling protein 1 (UCP1) and UCP3 are important for mammalian thermoregulation. UCP1 and UCP3 in brown adipose tissue mediate early and late phases of sympathomimetic thermogenesis, respectively. Lipopolysaccharide thermogenesis requires skeletal muscle UCP3 but not UCP1. Acute noradrenaline-induced hyperthermia requires UCP1 but not UCP3. Loss of both UCP1 and UCP3 accelerate the loss of body temperature compared to UCP1KO alone during acute cold exposure. Uncoupling protein 1 (UCP1) is the established mediator of brown adipose tissue-dependent thermogenesis. In contrast, the role of UCP3, expressed in both skeletal muscle and brown adipose tissue, in thermoregulatory physiology is less well understood. Here, we show that mice lacking UCP3 (UCP3KO) have impaired sympathomimetic (methamphetamine) and completely abrogated lipopolysaccharide (LPS) thermogenesis, but a normal response to noradrenaline. By comparison, UCP1 knockout (UCP1KO) mice exhibit blunted methamphetamine and fully inhibited noradrenaline thermogenesis, but an increased febrile response to LPS. We further establish that mice lacking both UCP1 and 3 (UCPDK) fail to show methamphetamine-induced hyperthermia, and have a markedly accelerated loss of body temperature and survival after cold exposure compared to UCP1KO mice. Finally, we show that skeletal muscle-specific human UCP3 expression is able to significantly rescue LPS, but not sympathomimetic thermogenesis blunted in UCP3KO mice. These studies identify UCP3 as an important mediator of physiological thermogenesis and support a renewed focus on targeting UCP3 in metabolic physiology. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society. JF - The Journal of physiology AU - Riley, Christopher L AU - Dao, Christine AU - Kenaston, M Alexander AU - Muto, Luigina AU - Kohno, Shohei AU - Nowinski, Sara M AU - Solmonson, Ashley D AU - Pfeiffer, Matthew AU - Sack, Michael N AU - Lu, Zhongping AU - Fiermonte, Giuseppe AU - Sprague, Jon E AU - Mills, Edward M AD - Department of Molecular Biosciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX, 78712, USA. ; Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA. ; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy. ; Department of Biochemistry, The University of Utah, Salt Lake City, UT, 84112, USA. ; National Heart, Lung, and Blood Institute, Laboratory of Mitochondrial Biology and Metabolism, NIH, Bethesda, MD, 20892, USA. ; Cardiovascular and Pulmonary Branch and the Department of Biochemistry and Molecular Medicine, George Washington University, and the Veterans Affairs Medical Center, Washington, DC, 20422, 20052, USA. ; Department of Biosciences, Biotechnologies, and Biopharmaceutics and Center of Excellence in Comparative Genomics, University of Bari, 70125, Bari, Italy. ; The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University, Bowling Green, OH, 43403, USA. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 7455 EP - 7464 VL - 594 IS - 24 KW - uncoupling protein KW - brown adipose tissue KW - LPS KW - sympathomimetic KW - skeletal muscle KW - methamphetamine KW - thermogenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841793417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+physiology&rft.atitle=The+complementary+and+divergent+roles+of+uncoupling+proteins+1+and+3+in+thermoregulation.&rft.au=Riley%2C+Christopher+L%3BDao%2C+Christine%3BKenaston%2C+M+Alexander%3BMuto%2C+Luigina%3BKohno%2C+Shohei%3BNowinski%2C+Sara+M%3BSolmonson%2C+Ashley+D%3BPfeiffer%2C+Matthew%3BSack%2C+Michael+N%3BLu%2C+Zhongping%3BFiermonte%2C+Giuseppe%3BSprague%2C+Jon+E%3BMills%2C+Edward+M&rft.aulast=Riley&rft.aufirst=Christopher&rft.date=2016-12-15&rft.volume=594&rft.issue=24&rft.spage=7455&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=1469-7793&rft_id=info:doi/10.1113%2FJP272971 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1113/JP272971 ER - TY - JOUR T1 - PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud. AN - 1839127850; 27827819 AB - During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. © 2016. Published by The Company of Biologists Ltd. JF - Development (Cambridge, England) AU - Norrie, Jacqueline L AU - Li, Qiang AU - Co, Swanie AU - Huang, Bau-Lin AU - Ding, Ding AU - Uy, Jann C AU - Ji, Zhicheng AU - Mackem, Susan AU - Bedford, Mark T AU - Galli, Antonella AU - Ji, Hongkai AU - Vokes, Steven A AD - Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA. ; Cancer and Developmental Biology Laboratory, CCR, NCI, Frederick, MD 21702, USA. ; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3638, Baltimore, MD 21205, USA. ; Department of Epigenetics & Molecular Carcinogenesis, M.D. Anderson Cancer Center, 1808 Park Road 1C (P.O. Box 389), Smithville, TX 78957, USA. ; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA svokes@austin.utexas.edu. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 4608 EP - 4619 VL - 143 IS - 24 KW - BMP4 KW - Progenitor cells KW - Limb development KW - PRMT5 KW - SOX9 KW - Chondrogenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839127850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=PRMT5+is+essential+for+the+maintenance+of+chondrogenic+progenitor+cells+in+the+limb+bud.&rft.au=Norrie%2C+Jacqueline+L%3BLi%2C+Qiang%3BCo%2C+Swanie%3BHuang%2C+Bau-Lin%3BDing%2C+Ding%3BUy%2C+Jann+C%3BJi%2C+Zhicheng%3BMackem%2C+Susan%3BBedford%2C+Mark+T%3BGalli%2C+Antonella%3BJi%2C+Hongkai%3BVokes%2C+Steven+A&rft.aulast=Norrie&rft.aufirst=Jacqueline&rft.date=2016-12-15&rft.volume=143&rft.issue=24&rft.spage=4608&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=1477-9129&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-09 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 ER - TY - JOUR T1 - Differential modulation of FXR activity by chlorophacinone and ivermectin analogs. AN - 1835538159; 27773686 AB - Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches. (Z)-Guggulsterone, chlorophacinone, ivermectin, and their analogs were profiled for their ability to alter CDCA-mediated FXR binding using a panel of 154 coregulator motifs and to induce or inhibit transactivation and coactivator recruitment activities of constitutive androstane receptor (CAR), liver X receptor alpha (LXRα), or pregnane X receptor (PXR). Our results showed that chlorophacinone and ivermectin had distinct modes of action (MOA) in modulating FXR-coregulator interactions and compound selectivity against the four aforementioned functionally-relevant nuclear receptors. These findings collectively provide mechanistic insights regarding compound activities against FXR and possible explanations for in vivo toxicological observations of chlorophacinone, ivermectin, and their analogs. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Hsu, Chia-Wen AU - Hsieh, Jui-Hua AU - Huang, Ruili AU - Pijnenburg, Dirk AU - Khuc, Thai AU - Hamm, Jon AU - Zhao, Jinghua AU - Lynch, Caitlin AU - van Beuningen, Rinie AU - Chang, Xiaoqing AU - Houtman, René AU - Xia, Menghang AD - NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. ; National Toxicology Program, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. ; PamGene International B.V., Wolvenhoek 10, 5211 HH 's-Hertogenbosch, The Netherlands. ; Integrated Laboratory System, Inc., Morrisville, NC, USA. ; NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address: mxia@mail.nih.gov. Y1 - 2016/12/15/ PY - 2016 DA - 2016 Dec 15 SP - 138 EP - 148 VL - 313 KW - Farnesoid X receptor KW - Nuclear receptor KW - Ivermetin KW - Diphacinone KW - Tox21 KW - Chlorophacinone KW - Moxidectin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835538159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Differential+modulation+of+FXR+activity+by+chlorophacinone+and+ivermectin+analogs.&rft.au=Hsu%2C+Chia-Wen%3BHsieh%2C+Jui-Hua%3BHuang%2C+Ruili%3BPijnenburg%2C+Dirk%3BKhuc%2C+Thai%3BHamm%2C+Jon%3BZhao%2C+Jinghua%3BLynch%2C+Caitlin%3Bvan+Beuningen%2C+Rinie%3BChang%2C+Xiaoqing%3BHoutman%2C+Ren%C3%A9%3BXia%2C+Menghang&rft.aulast=Hsu&rft.aufirst=Chia-Wen&rft.date=2016-12-15&rft.volume=313&rft.issue=&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.10.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.10.017 ER - TY - JOUR T1 - Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting. AN - 1852679340; 27965307 AB - While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors. ACTIV therapy induced durable complete remission of a variety of Her2+ tumors, some in excess of 150 mm2, in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL-2, but were independent of IFN-gamma. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient. This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissues. Copyright ©2016, American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Slaney, Clare Y AU - von Scheidt, Bianca AU - Davenport, Alexander J AU - Beavis, Paul AU - Westwood, Jennifer A AU - Mardiana, Sherly AU - Tscharke, David AU - Ellis, Sarah AU - Prince, H Miles AU - Trapani, Joseph A AU - Johnstone, Ricky W AU - Smyth, Mark J AU - Teng, Michele W L AU - Ali, Aesha AU - Yu, Zhiya AU - Rosenberg, Steven A AU - Restifo, Nicholas P AU - Neeson, Paul J AU - Darcy, Phillip K AU - Kershaw, Michael H AD - Research, Peter MacCallum Cancer Centre. ; Cancer Immuonology Program, Peter Mac Research. ; Cancer Immunology Program, Peter MacCallum Cancer Centre. ; Cancer Immunology Program, Peter MacCallum Cancer Center. ; John Curtin School of Medical Research, Australian National University. ; Histology, Peter MacCallum Cancer Centre. ; Department of Cancer Medicine, Peter MacCallum Cancer Centre. ; Gene Regulation Laboratory, Peter MacCallum Cancer Centre. ; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute. ; Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute. ; Cancer Immunology Program, Peter MacCallum Cancer Research Centre. ; Surgery Branch, Center for Cancer Research, National Institutes of Health, National Cancer Institute. ; Surgery Branch, National Cancer Institute. ; Cancer Immunology Research, Peter MacCallum Cancer Center. ; Cancer Immunology Program, Peter MacCallum Cancer Center michael.kershaw@petermac.org. Y1 - 2016/12/13/ PY - 2016 DA - 2016 Dec 13 SN - 1078-0432, 1078-0432 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852679340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Dual-specific+chimeric+antigen+receptor+T+cells+and+an+indirect+vaccine+eradicate+a+variety+of+large+solid+tumors+in+an+immunocompetent%2C+self-antigen+setting.&rft.au=Slaney%2C+Clare+Y%3Bvon+Scheidt%2C+Bianca%3BDavenport%2C+Alexander+J%3BBeavis%2C+Paul%3BWestwood%2C+Jennifer+A%3BMardiana%2C+Sherly%3BTscharke%2C+David%3BEllis%2C+Sarah%3BPrince%2C+H+Miles%3BTrapani%2C+Joseph+A%3BJohnstone%2C+Ricky+W%3BSmyth%2C+Mark+J%3BTeng%2C+Michele+W+L%3BAli%2C+Aesha%3BYu%2C+Zhiya%3BRosenberg%2C+Steven+A%3BRestifo%2C+Nicholas+P%3BNeeson%2C+Paul+J%3BDarcy%2C+Phillip+K%3BKershaw%2C+Michael+H&rft.aulast=Slaney&rft.aufirst=Clare&rft.date=2016-12-13&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC. AN - 1852677322; 27965423 AB - ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5'-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification. Compared to cells from healthy subjects, induced pluripotent stem cell-derived mesenchymal stromal cells (iMSCs) from ACDC patients displayed accelerated calcification and increased TNAP activity when cultured under conditions that promote osteogenesis. TNAP activity generated adenosine in iMSCs derived from ACDC patients but not in iMSCs from control subjects, which have CD73. In response to osteogenic stimulation, ACDC patient-derived iMSCs had decreased amounts of the TNAP substrate PPi, an inhibitor of extracellular matrix calcification, and exhibited increased activation of AKT, mechanistic target of rapamycin (mTOR), and the 70-kDa ribosomal protein S6 kinase (p70S6K), a pathway that promotes calcification. In vivo, teratomas derived from ACDC patient cells showed extensive calcification and increased TNAP activity. Treating mice bearing these teratomas with an A2b adenosine receptor agonist, the mTOR inhibitor rapamycin, or the bisphosphonate etidronate reduced calcification. These results show that an increase of TNAP activity in ACDC contributes to ectopic calcification by disrupting the extracellular balance of PPi and Pi and identify potential therapeutic targets for ACDC. Copyright © 2016, American Association for the Advancement of Science. JF - Science signaling AU - Jin, Hui AU - St Hilaire, Cynthia AU - Huang, Yuting AU - Yang, Dan AU - Dmitrieva, Natalia I AU - Negro, Alejandra AU - Schwartzbeck, Robin AU - Liu, Yangtengyu AU - Yu, Zhen AU - Walts, Avram AU - Davaine, Jean-Michel AU - Lee, Duck-Yeon AU - Donahue, Danielle AU - Hsu, Kevin S AU - Chen, Jessica AU - Cheng, Tao AU - Gahl, William AU - Chen, Guibin AU - Boehm, Manfred AD - Center for Molecular Medicine, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA. ; Center for Molecular Medicine, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA. boehmm@nhlbi.nih.gov chengb@nhlbi.nih.gov. Y1 - 2016/12/13/ PY - 2016 DA - 2016 Dec 13 SP - 1 VL - 9 IS - 458 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852677322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+signaling&rft.atitle=Increased+activity+of+TNAP+compensates+for+reduced+adenosine+production+and+promotes+ectopic+calcification+in+the+genetic+disease+ACDC.&rft.au=Jin%2C+Hui%3BSt+Hilaire%2C+Cynthia%3BHuang%2C+Yuting%3BYang%2C+Dan%3BDmitrieva%2C+Natalia+I%3BNegro%2C+Alejandra%3BSchwartzbeck%2C+Robin%3BLiu%2C+Yangtengyu%3BYu%2C+Zhen%3BWalts%2C+Avram%3BDavaine%2C+Jean-Michel%3BLee%2C+Duck-Yeon%3BDonahue%2C+Danielle%3BHsu%2C+Kevin+S%3BChen%2C+Jessica%3BCheng%2C+Tao%3BGahl%2C+William%3BChen%2C+Guibin%3BBoehm%2C+Manfred&rft.aulast=Jin&rft.aufirst=Hui&rft.date=2016-12-13&rft.volume=9&rft.issue=458&rft.spage=ra121&rft.isbn=&rft.btitle=&rft.title=Science+signaling&rft.issn=1937-9145&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Interactions between ethanol and cigarette smoke in a mouse lung carcinogenesis model. AN - 1839122371; 27840117 AB - Both ethanol and cigarette smoke are classified as human carcinogens. They can synergize, especially in tissues of the upper aerodigestive tract that are targeted by both agents. The main objective of the present study was to evaluate the individual and combined effects of ethanol and smoke in the respiratory tract, either following transplacental exposure and/or postnatal exposure. We designed two consecutive studies in mouse models by exposing Swiss H mice to oral ethanol and/or inhaled mainstream cigarette smoke for up to 4 months, at various prenatal and postnatal life stages. Clastogenic effects and histopathological alterations were evaluated after 4 and 8 months, respectively. Ethanol was per se devoid of clastogenic effects in mouse peripheral blood erythrocytes. However, especially in mice exposed both transplacentally throughout pregnancy and in the postnatal life, ethanol administration was associated not only with liver damage but also with pro-angiogenetic effects in the lung by stimulating the proliferation of blood vessels. In addition, these mice developed pulmonary emphysema, alveolar epithelial hyperplasias, microadenomas, and benign tumors. On the other hand, ethanol interfered in the lung carcinogenesis process resulting from the concomitant exposure of mice to smoke. In fact, ethanol significantly attenuated some smoke-related preneoplastic and neoplastic lesions in the respiratory tract, such as alveolar epithelial hyperplasia, microadenomas, and even malignant tumors. In addition, ethanol attenuated cigarette smoke clastogenicity. In conclusion, preclinical studies provide evidence that, in spite of its pulmonary toxicity, ethanol may mitigate some noxious effects of cigarette smoke in the respiratory tract. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Toxicology AU - Balansky, Roumen AU - Ganchev, Gancho AU - Iltcheva, Marietta AU - Nikolov, Manasi AU - La Maestra, S AU - Micale, Rosanna T AU - Steele, Vernon E AU - De Flora, Silvio AD - National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: rubalansky@sbaloncology.bg. ; National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: drganchoganchev@abv.bg. ; National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: mariettailtcheva@yahoo.com. ; National Center of Oncology, Str. Plovdivsko pole 6, Sofia, 1756, Bulgaria. Electronic address: mdn@mail.bg. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: lamaestra78@yahoo.it. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: rosannamicale@yahoo.it. ; National Cancer Institute, Chemoprevention Agent Development Research Group, Division of Cancer Prevention,9609 Medical Center Drive, Bethesda, MD 20892, USA. Electronic address: steelev@mail.nih.gov. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa, Italy. Electronic address: sdf@unige.it. Y1 - 2016/12/12/ PY - 2016 DA - 2016 Dec 12 SP - 54 EP - 62 VL - 373 KW - Lung tumors KW - Histopathological alterations KW - Cytogenetic damage KW - Cigarette smoke KW - Ethanol UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839122371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Interactions+between+ethanol+and+cigarette+smoke+in+a+mouse+lung+carcinogenesis+model.&rft.au=Balansky%2C+Roumen%3BGanchev%2C+Gancho%3BIltcheva%2C+Marietta%3BNikolov%2C+Manasi%3BLa+Maestra%2C+S%3BMicale%2C+Rosanna+T%3BSteele%2C+Vernon+E%3BDe+Flora%2C+Silvio&rft.aulast=Balansky&rft.aufirst=Roumen&rft.date=2016-12-12&rft.volume=373&rft.issue=&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=1879-3185&rft_id=info:doi/10.1016%2Fj.tox.2016.11.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.tox.2016.11.008 ER - TY - JOUR T1 - The Cr-isotope signature of surface seawater - A global perspective AN - 1861076725; 786143-9 AB - This study presents chromium-isotope data (expressed as delta (super 53) Cr) and chromium concentrations (Cr) of surface seawater (0-2 m depth) from a variety of locations worldwide. In addition to samples from the open ocean (Arctic, Southern, Pacific, and Atlantic Oceans), samples were analysed from areas with more restricted water exchange rates (the Mediterranean Sea, Oresund, and Baltic Sea). The data indicate a heterogeneous distribution of delta (super 53) Cr in seawater with a total range from + 0.13 ppm to + 1.24 ppm. The data are in agreement with a previous study, which focused on depth profiles, suggesting that seawater heterogeneity in delta (super 53) Cr and Cr concentration can be explained using a single fractionation factor for Cr-reduction (epsilon = - 0.79 + or - 0.06 ppm 2SD). In basins with limited water exchange with the open ocean, however, local factors seem to control the Cr-isotope composition. JF - Chemical Geology AU - Paulukat, Cora AU - Gilleaudeau, Geoffrey J AU - Chernyavskiy, Pavel AU - Frei, Robert Y1 - 2016/12/09/ PY - 2016 DA - 2016 Dec 09 SP - 101 EP - 109 PB - Elsevier, Amsterdam VL - 444 SN - 0009-2541, 0009-2541 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1861076725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefinprocess&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Geology&rft.atitle=The+Cr-isotope+signature+of+surface+seawater+-+A+global+perspective&rft.au=Paulukat%2C+Cora%3BGilleaudeau%2C+Geoffrey+J%3BChernyavskiy%2C+Pavel%3BFrei%2C+Robert&rft.aulast=Paulukat&rft.aufirst=Cora&rft.date=2016-12-09&rft.volume=444&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Chemical+Geology&rft.issn=00092541&rft_id=info:doi/10.1016%2Fj.chemgeo.2016.10.004 L2 - http://www.sciencedirect.com/science/journal/00092541 LA - English DB - GeoRef N1 - Copyright - GeoRef in Process, Copyright 2017, American Geosciences Institute. After editing and indexing, this record will be added to Georef. Reference includes data from CAPCAS, Elsevier Scientific Publishers, Amsterdam, Netherlands N1 - Last updated - 2017-01-24 N1 - CODEN - CHGEAD DO - http://dx.doi.org/10.1016/j.chemgeo.2016.10.004 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor-β/δ modulates mast cell phenotype. AN - 1847892341; 27935639 AB - The peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is known to have multiple anti-inflammatory effects, typically observed in endothelial cells, macrophages, T cells and B cells. Despite the fact that mast cells are important mediators of inflammation, to date, the role of PPARβ/δ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPARβ/δ modulates mast cell phenotype. Bone-marrow-derived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ+/+ mice expressed higher levels of high-affinity IgE receptor (FcεRI) compared with Pparβ/δ-/- mice. BMMCs from Pparβ/δ+/+ mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Pparβ/δ-/- mice. Resting BMMCs from Pparβ/δ+/+ mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase Cγ1 and extracellular signal-regulated kinases compared with Pparβ/δ-/- mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPARβ/δ expression. This study demonstrates that PPARβ/δ is an important regulator of mast cell phenotype. © 2016 John Wiley & Sons Ltd. JF - Immunology AU - Yao, Pei-Li AU - Morales, Jose L AU - Gonzalez, Frank J AU - Peters, Jeffrey M AD - Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, USA. ; Laboratory of Metabolism, National Cancer Institute, Bethesda, MD, USA. Y1 - 2016/12/09/ PY - 2016 DA - 2016 Dec 09 KW - inflammation KW - peroxisome proliferator-activated receptor-β/δ KW - cytokine KW - bone marrow-derived mast cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847892341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology&rft.atitle=Peroxisome+proliferator-activated+receptor-%CE%B2%2F%CE%B4+modulates+mast+cell+phenotype.&rft.au=Yao%2C+Pei-Li%3BMorales%2C+Jose+L%3BGonzalez%2C+Frank+J%3BPeters%2C+Jeffrey+M&rft.aulast=Yao&rft.aufirst=Pei-Li&rft.date=2016-12-09&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+proteome+research&rft.issn=1535-3907&rft_id=info:doi/10.1021%2Facs.jproteome.5b00957 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1111/imm.12699 ER - TY - JOUR T1 - Development and Validation of a Computational Model for Androgen Receptor Activity. AN - 1847891450; 27933809 AB - Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference. The in vitro HTS assays probed perturbations of the AR pathway at multiple points (receptor binding, coregulator recruitment, gene transcription, and protein production) and multiple cell types. Confirmatory in vitro antagonist assay data and cytotoxicity information were used as additional flags for potential nonspecific activity. Validating such alternative testing strategies requires high-quality reference data. We compiled 158 putative androgen-active and -inactive chemicals from a combination of international test method validation efforts and semiautomated systematic literature reviews. Detailed in vitro assay information and results were compiled into a single database using a standardized ontology. Reference chemical concentrations that activated or inhibited AR pathway activity were identified to establish a range of potencies with reproducible reference chemical results. Comparison with existing Tier 1 AR binding data from the U.S. EPA Endocrine Disruptor Screening Program revealed that the model identified binders at relevant test concentrations (<100 μM) and was more sensitive to antagonist activity. The AR pathway model based on the ToxCast/Tox21 assays had balanced accuracies of 95.2% for agonist (n = 29) and 97.5% for antagonist (n = 28) reference chemicals. Out of 1855 chemicals screened in the AR pathway model, 220 chemicals demonstrated AR agonist or antagonist activity and an additional 174 chemicals were predicted to have potential weak AR pathway activity. JF - Chemical research in toxicology AU - Kleinstreuer, Nicole C AU - Ceger, Patricia AU - Watt, Eric D AU - Martin, Matthew AU - Houck, Keith AU - Browne, Patience AU - Thomas, Russell S AU - Casey, Warren M AU - Dix, David J AU - Allen, David AU - Sakamuru, Srilatha AU - Xia, Menghang AU - Huang, Ruili AU - Judson, Richard AD - NIH/NIEHS/DNTP/The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods , Research Triangle Park, North Carolina 27713, United States. ; Integrated Laboratory Systems, Inc. , Research Triangle Park, North Carolina 27560, United States. ; EPA/ORD/National Center for Computational Toxicology , Research Triangle Park, North Carolina 27711, United States. ; OECD Environment Directorate, Environment Health and Safety Division , Paris 75775, France. ; EPA/OCSPP/Office of Science Coordination and Policy , Washington, DC, 20460, United States. ; NIH/National Center for Advancing Translational Sciences , Bethesda, Maryland 20892, United States. Y1 - 2016/12/09/ PY - 2016 DA - 2016 Dec 09 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847891450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Development+and+Validation+of+a+Computational+Model+for+Androgen+Receptor+Activity.&rft.au=Kleinstreuer%2C+Nicole+C%3BCeger%2C+Patricia%3BWatt%2C+Eric+D%3BMartin%2C+Matthew%3BHouck%2C+Keith%3BBrowne%2C+Patience%3BThomas%2C+Russell+S%3BCasey%2C+Warren+M%3BDix%2C+David+J%3BAllen%2C+David%3BSakamuru%2C+Srilatha%3BXia%2C+Menghang%3BHuang%2C+Ruili%3BJudson%2C+Richard&rft.aulast=Kleinstreuer&rft.aufirst=Nicole&rft.date=2016-12-09&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=1520-5010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - HPV 16 E5 oncoprotein is expressed in early stage carcinogenesis and can be a target of immunotherapy. AN - 1847898485; 27929754 AB - HPV16 persistent infection is a well-known condition that precedes human cancer development. High risk HPV E5 proteins cooperate with E6/E7 oncogenes to promote hyper-proliferation of infected cells leading to possible cancer progression. Thus, presence of E5 viral transcripts could be a key marker of active infection and, in turn, a target of immunotherapy. Purpose of the study is to detect E5 transcripts in clinical samples and to explore the activity of novel anti-HPV16 E5 DNA vaccines. HPV transcripts were detected by PCR with specific primers encompassing the splice-donor sites of E5 transcript. For E5-based immunotherapies, 2 E5-based versions of DNA vaccines carrying whole E5 gene or a synthetic multiepitope gene were improved by fusion to sequence of PVX coat protein. These vaccines were challenged with a new luminescent animal model based on C3-Luc cell line. E5 transcripts were detected in clinical samples of women with HPV positive low-grade SIL, demonstrating the validity of our test. In C3 pre-clinical mouse model, vaccine candidates were able to induce a strong cellular immunity as indicated by ELISPOT assays. In addition, E5-CP vaccines elicited strong anti-tumor effects as showed by decreased tumor growth monitored by animal imaging. The tumor growth inhibition was comparable to those obtained with anti-E7 DNA vaccines. In conclusion, detection of E5 transcripts in clinical samples indicates that E5 is a possible target of immunotherapy. Data from pre-clinical model demonstrate that E5 genetic immunization is feasible, efficacious and could be utilized in clinical trials. JF - Human vaccines & immunotherapeutics AU - Paolini, Francesca AU - Curzio, Gianfranca AU - Cordeiro, Marcelo Nazario AU - Massa, Silvia AU - Mariani, Luciano AU - Pimpinelli, Fulvia AU - de Freitas, Antonio Carlos AU - Franconi, Rosella AU - Venuti, Aldo AD - a Regina Elena National Cancer Institute, HPV Unit , Rome , Italy. ; b Federal University of Pernambuco , Department of Genetics , LEMTE , Pernambuco , Brazil. ; c ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, C.R. Casaccia , Rome , Italy. ; d San Gallicano Dermatologic Institute , Rome , Italy. Y1 - 2016/12/08/ PY - 2016 DA - 2016 Dec 08 SP - 1 EP - 7 KW - immunotherapy KW - E5 KW - therapeutic vaccine KW - HPV transcripts KW - HPV KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1847898485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+vaccines+%26+immunotherapeutics&rft.atitle=HPV+16+E5+oncoprotein+is+expressed+in+early+stage+carcinogenesis+and+can+be+a+target+of+immunotherapy.&rft.au=Paolini%2C+Francesca%3BCurzio%2C+Gianfranca%3BCordeiro%2C+Marcelo+Nazario%3BMassa%2C+Silvia%3BMariani%2C+Luciano%3BPimpinelli%2C+Fulvia%3Bde+Freitas%2C+Antonio+Carlos%3BFranconi%2C+Rosella%3BVenuti%2C+Aldo&rft.aulast=Paolini&rft.aufirst=Francesca&rft.date=2016-12-08&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Human+vaccines+%26+immunotherapeutics&rft.issn=2164-554X&rft_id=info:doi/10.1080%2F21645515.2017.1264777 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-08 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1080/21645515.2017.1264777 ER - TY - JOUR T1 - Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers. AN - 1846721880; 27924834 AB - Follicular lymphoma (FL) is an uncurable cancer characterized by progressive severity of relapses. We analyzed sequence context specificity of mutations in the B cells from a large cohort of FL patients. We revealed substantial excess of mutations within a novel hybrid nucleotide motif: the signature of somatic hypermutation (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps the CpG methylation site. This finding implies that in FL the SHM machinery acts at genomic sites containing methylated cytosine. We identified the prevalence of this hybrid mutational signature in many other types of human cancer, suggesting that AID-mediated, CpG-methylation dependent mutagenesis is a common feature of tumorigenesis. JF - Scientific reports AU - Rogozin, Igor B AU - Lada, Artem G AU - Goncearenco, Alexander AU - Green, Michael R AU - De, Subhajyoti AU - Nudelman, German AU - Panchenko, Anna R AU - Koonin, Eugene V AU - Pavlov, Youri I AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. ; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. ; Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA. ; Department of Neurology and Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, USA. Y1 - 2016/12/07/ PY - 2016 DA - 2016 Dec 07 SP - 38133 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846721880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Activation+induced+deaminase+mutational+signature+overlaps+with+CpG+methylation+sites+in+follicular+lymphoma+and+other+cancers.&rft.au=Rogozin%2C+Igor+B%3BLada%2C+Artem+G%3BGoncearenco%2C+Alexander%3BGreen%2C+Michael+R%3BDe%2C+Subhajyoti%3BNudelman%2C+German%3BPanchenko%2C+Anna+R%3BKoonin%2C+Eugene+V%3BPavlov%2C+Youri+I&rft.aulast=Rogozin&rft.aufirst=Igor&rft.date=2016-12-07&rft.volume=6&rft.issue=&rft.spage=38133&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep38133 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep38133 ER - TY - JOUR T1 - Deletion of IQGAP1 promotes Helicobacter pylori-induced gastric dysplasia in mice and acquisition of cancer stem cell properties in vitro. AN - 1835407132; 27729612 AB - Helicobacter pylori infection is responsible for gastric carcinogenesis but host factors are also implicated. IQGAP1, a scaffolding protein of the adherens junctions interacting with E-cadherin, regulates cellular plasticity and proliferation. In mice, IQGAP1 deficiency leads to gastric hyperplasia. The aim of this study was to elucidate the consequences of IQGAP1 deletion on H. pylori-induced gastric carcinogenesis.Transgenic mice deleted for iqgap1 and WT littermates were infected with Helicobacter sp., and histopathological analyses of the gastric mucosa were performed. IQGAP1 and E-cadherin expression was evaluated in gastric tissues and in gastric epithelial cell lines in response to H. pylori infection. The consequences of IQGAP1 deletion on gastric epithelial cell behaviour and on the acquisition of cancer stem cell (CSC)-like properties were evaluated. After one year of infection, iqgap1+/- mice developed more preneoplastic lesions and up to 8 times more gastro-intestinal neoplasia (GIN) than WT littermates. H. pylori infection induced IQGAP1 and E-cadherin delocalization from cell-cell junctions. In vitro, knock-down of IQGAP1 favoured the acquisition of a mesenchymal phenotype and CSC-like properties induced by H. pylori infection.Our results indicate that alterations in IQGAP1 signalling promote the emergence of CSCs and gastric adenocarcinoma development in the context of an H. pylori infection. JF - Oncotarget AU - Bessède, Emilie AU - Molina, Silvia AU - Amador, Luis Acuña AU - Dubus, Pierre AU - Staedel, Cathy AU - Chambonnier, Lucie AU - Buissonnière, Alice AU - Sifré, Elodie AU - Giese, Alban AU - Bénéjat, Lucie AU - Rousseau, Benoît AU - Costet, Pierre AU - Sacks, David B AU - Mégraud, Francis AU - Varon, Christine AD - Bacteriology Laboratory, University of Bordeaux, Bordeaux, France. ; EA2406 Histologie et Pathologie Moléculaire des Tumeurs, University of Bordeaux, Bordeaux, France. ; 'RNA: Natural and Artificial Regulation' (ARNA) Laboratory, University of Bordeaux, Bordeaux, France. ; Service Commun des Animaleries, Animalerie A2, University of Bordeaux, Bordeaux, France. ; Service Commun des Animaleries, Animalerie Transgénique, University of Bordeaux, Bordeaux, France. ; Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/12/06/ PY - 2016 DA - 2016 Dec 06 SP - 80688 EP - 80699 VL - 7 IS - 49 KW - gastric cancer KW - CD44 KW - Zeb KW - EMT KW - E-cadherin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835407132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncotarget&rft.atitle=Deletion+of+IQGAP1+promotes+Helicobacter+pylori-induced+gastric+dysplasia+in+mice+and+acquisition+of+cancer+stem+cell+properties+in+vitro.&rft.au=Bess%C3%A8de%2C+Emilie%3BMolina%2C+Silvia%3BAmador%2C+Luis+Acu%C3%B1a%3BDubus%2C+Pierre%3BStaedel%2C+Cathy%3BChambonnier%2C+Lucie%3BBuissonni%C3%A8re%2C+Alice%3BSifr%C3%A9%2C+Elodie%3BGiese%2C+Alban%3BB%C3%A9n%C3%A9jat%2C+Lucie%3BRousseau%2C+Beno%C3%AEt%3BCostet%2C+Pierre%3BSacks%2C+David+B%3BM%C3%A9graud%2C+Francis%3BVaron%2C+Christine&rft.aulast=Bess%C3%A8de&rft.aufirst=Emilie&rft.date=2016-12-06&rft.volume=7&rft.issue=49&rft.spage=80688&rft.isbn=&rft.btitle=&rft.title=Oncotarget&rft.issn=1949-2553&rft_id=info:doi/10.18632%2Foncotarget.12486 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.18632/oncotarget.12486 ER - TY - JOUR T1 - Disease drivers of aging AN - 1855080217; PQ0003960484 AB - It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. JF - Annals of the New York Academy of Sciences AU - Hodes, Richard J AU - Sierra, Felipe AU - Austad, Steven N AU - Epel, Elissa AU - Neigh, Gretchen N AU - Erlandson, Kristine M AU - Schafer, Marissa J AU - LeBrasseur, Nathan K AU - Wiley, Christopher AU - Campisi, Judith AU - Sehl, Mary E AU - Scalia, Rosario AU - Eguchi, Satoru AU - Kasinath, Balakuntalam S AU - Halter, Jeffrey B AU - Cohen, Harvey Jay AU - Demark-Wahnefried, Wendy AU - Ahles, Tim A AU - Barzilai, Nir AU - Hurria, Arti AU - Hunt, Peter W AD - National Institute on Aging, Bethesda, Maryland. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 45 EP - 68 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1386 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855080217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Disease+drivers+of+aging&rft.au=Hodes%2C+Richard+J%3BSierra%2C+Felipe%3BAustad%2C+Steven+N%3BEpel%2C+Elissa%3BNeigh%2C+Gretchen+N%3BErlandson%2C+Kristine+M%3BSchafer%2C+Marissa+J%3BLeBrasseur%2C+Nathan+K%3BWiley%2C+Christopher%3BCampisi%2C+Judith%3BSehl%2C+Mary+E%3BScalia%2C+Rosario%3BEguchi%2C+Satoru%3BKasinath%2C+Balakuntalam+S%3BHalter%2C+Jeffrey+B%3BCohen%2C+Harvey+Jay%3BDemark-Wahnefried%2C+Wendy%3BAhles%2C+Tim+A%3BBarzilai%2C+Nir%3BHurria%2C+Arti%3BHunt%2C+Peter+W&rft.aulast=Hodes&rft.aufirst=Richard&rft.date=2016-12-01&rft.volume=1386&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13299 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-04 DO - http://dx.doi.org/10.1111/nyas.13299 ER - TY - JOUR T1 - Reverse geroscience: how does exposure to early diseases accelerate the age-related decline in health? AN - 1855077200; PQ0003960483 AB - Aging is the major risk factor for both the development of chronic diseases and loss of functional capacity. Geroscience provides links among the biology of aging, the biology of disease, and the physiology of frailty, three fields where enormous progress has been made in the last few decades. While, previously, the focus was on the role of aging in susceptibility to disease and disability, the other side of this relationship, which is the contribution of disease to aging, has been less explored at the molecular/cellular level. Indeed, the role of childhood or early adulthood exposure to chronic disease and/or treatment on accelerating aging phenotypes is well known in epidemiology, but the biological basis is poorly understood. A recent summit co-organized by the National Institutes of Health GeroScience Interest Group and the New York Academy of Sciences explored these relationships, using three chronic diseases as examples: cancer, HIV/AIDS, and diabetes. The epidemiological literature clearly indicates that early exposure to any of these diseases and/or their treatments results in an acceleration of the appearance of aging phenotypes, including loss of functional capacity and accelerated appearance of clinical symptoms of aging-related diseases not obviously related to the earlier event. The discussions at the summit focused on the molecular and cellular relationships between each of these diseases and the recently defined molecular and cellular pillars of aging. Two major conclusions from the meeting include the desire to refine an operational definition of aging and to concomitantly develop biomarkers of aging, in order to move from chronological to physiological age. The discussion also opened a dialogue on the possibility of improving late-life outcomes in patients affected by chronic disease by including age-delaying modalities along with the standard care for the disease in question. JF - Annals of the New York Academy of Sciences AU - Kohanski, Ronald A AU - Deeks, Steven G AU - Gravekamp, Claudia AU - Halter, Jeffrey B AU - High, Kevin AU - Hurria, Arti AU - Fuldner, Rebecca AU - Green, Paige AU - Huebner, Robin AU - Macchiarini, Francesca AU - Sierra, Felipe AD - Division of Aging Biology, National Institute on Aging, NIH, Bethesda, Maryland. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 30 EP - 44 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1386 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855077200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Reverse+geroscience%3A+how+does+exposure+to+early+diseases+accelerate+the+age-related+decline+in+health%3F&rft.au=Kohanski%2C+Ronald+A%3BDeeks%2C+Steven+G%3BGravekamp%2C+Claudia%3BHalter%2C+Jeffrey+B%3BHigh%2C+Kevin%3BHurria%2C+Arti%3BFuldner%2C+Rebecca%3BGreen%2C+Paige%3BHuebner%2C+Robin%3BMacchiarini%2C+Francesca%3BSierra%2C+Felipe&rft.aulast=Kohanski&rft.aufirst=Ronald&rft.date=2016-12-01&rft.volume=1386&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13297 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-04 DO - http://dx.doi.org/10.1111/nyas.13297 ER - TY - JOUR T1 - Cell lineage responses to photobiomodulation therapy AN - 1855074864; PQ0003962077 AB - Photobiomodulation (PBM) therapy has been noted to promote cell proliferation and growth in many different cell types shown both in vitro and in vivo. Currently, treatment regimens are used in the clinic for a variety of ailments, including wound healing. However, most protocols treat an anatomical site without considering individual cell types constituting the target tissues. This study investigates the maximal dose threshold for oral keratinocyte and fibroblast cell types treated with near-infrared laser therapy. We observed keratinocytes have increased sensitivity to laser irradiances (>0.047 W/cm super(2), 300 sec, 14.2 J/cm super(2)) compared to the fibroblast cells (>0.057 W/cm super(2), 300 sec, 15.1 J/cm super(2)) (p < 0.0001). Laser treatments were noted to generate increased reactive oxygen species (ROS) levels in keratinocytes compared to fibroblasts that appeared to inversely correlate with higher basal catalase expression. To validate these observations, melatonin was used to treat keratinocytes to induce catalase activity (p < 0.0001). Increased melatonin-induced catalase levels were noted to significantly improve keratinocyte survival to phototoxic laser doses. These observations suggest that clinical laser dosing should account for differential effects of lasers on individual cell types to improve safety and clinical efficacy of PBM therapy. Distinct effects of dose-dependent laser treatments on discrete cell lineages indicate that illumination of a treatment site must include careful attention to individual targets within this area. Variations in inherent lineage-dependent ubiquitous photoresponses could be attributed to presence or absence of specific photoreception molecules as well as biochemical mediators or neutralizers. A specific example outlined in this study is variable concentrations of ROS neutralizing agent, Catalase in epithelial versus fibroblasts. JF - Journal of Biophotonics AU - Engel, Karl W AU - Khan, Imran AU - Arany, Praveen R AD - Cell Regulation and Control Unit, National Institute of Dental and Craniofacial Research, National Institute of Health, 30 Convent Drive, Bethesda, MD 20814, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1148 EP - 1156 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 9 IS - 11-12 SN - 1864-063X, 1864-063X KW - Biotechnology and Bioengineering Abstracts KW - Cell lineage KW - I.R. radiation KW - Reactive oxygen species KW - Illumination KW - Wound healing KW - Lasers KW - Melatonin KW - Keratinocytes KW - Cell proliferation KW - Catalase KW - Fibroblasts KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855074864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biophotonics&rft.atitle=Cell+lineage+responses+to+photobiomodulation+therapy&rft.au=Engel%2C+Karl+W%3BKhan%2C+Imran%3BArany%2C+Praveen+R&rft.aulast=Engel&rft.aufirst=Karl&rft.date=2016-12-01&rft.volume=9&rft.issue=11-12&rft.spage=1148&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biophotonics&rft.issn=1864063X&rft_id=info:doi/10.1002%2Fjbio.201600025 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Cell lineage; I.R. radiation; Illumination; Reactive oxygen species; Wound healing; Melatonin; Lasers; Keratinocytes; Cell proliferation; Catalase; Fibroblasts DO - http://dx.doi.org/10.1002/jbio.201600025 ER - TY - JOUR T1 - Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data. AN - 1854618540; 28036406 AB - Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R2) for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017) and incorporating functional annotation data further improved R2 to 3.53% (P = 2×10-5). Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure. JF - PLoS genetics AU - Shi, Jianxin AU - Park, Ju-Hyun AU - Duan, Jubao AU - Berndt, Sonja T AU - Moy, Winton AU - Yu, Kai AU - Song, Lei AU - Wheeler, William AU - Hua, Xing AU - Silverman, Debra AU - Garcia-Closas, Montserrat AU - Hsiung, Chao Agnes AU - Figueroa, Jonine D AU - Cortessis, Victoria K AU - Malats, Núria AU - Karagas, Margaret R AU - Vineis, Paolo AU - Chang, I-Shou AU - Lin, Dongxin AU - Zhou, Baosen AU - Seow, Adeline AU - Matsuo, Keitaro AU - Hong, Yun-Chul AU - Caporaso, Neil E AU - Wolpin, Brian AU - Jacobs, Eric AU - Petersen, Gloria M AU - Klein, Alison P AU - Li, Donghui AU - Risch, Harvey AU - Sanders, Alan R AU - Hsu, Li AU - Schoen, Robert E AU - Brenner, Hermann AU - MGS (Molecular Genetics of Schizophrenia) GWAS Consortium AU - GECCO (The Genetics and Epidemiology of Colorectal Cancer Consortium) AU - GAME-ON/TRICL (Transdisciplinary Research in Cancer of the Lung) GWAS Consortium AU - PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations) Consortium AU - PanScan Consortium AU - GAME-ON/ELLIPSE Consortium AU - Stolzenberg-Solomon, Rachael AU - Gejman, Pablo AU - Lan, Qing AU - Rothman, Nathaniel AU - Amundadottir, Laufey T AU - Landi, Maria Teresa AU - Levinson, Douglas F AU - Chanock, Stephen J AU - Chatterjee, Nilanjan AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. ; Department of Statistics, Dongguk University, Seoul, Korea. ; Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, University of Chicago Pritzker School of Medicine, Evanston, Illinois, United States of America. ; Dept. of Statistics, Northern Illinois University, DeKalb, Illinois, United States of America. ; Information Management Services, Inc., Rockville, Maryland, United States of America. ; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. ; Department of Preventive Medicine and Department of Obstetrics and Gynecology, USC Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America. ; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ; Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America. ; Human Genetics Foundation, Turin, Italy. ; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan. ; Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ; Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China. ; Saw Swee Hock School of Public Health, National University of Singapore, Singapore. ; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan. ; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. ; Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America. ; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. ; Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. ; Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America. ; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America. ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. ; Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America. ; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. ; MGS (Molecular Genetics of Schizophrenia) GWAS Consortium ; GECCO (The Genetics and Epidemiology of Colorectal Cancer Consortium) ; GAME-ON/TRICL (Transdisciplinary Research in Cancer of the Lung) GWAS Consortium ; PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations) Consortium ; PanScan Consortium ; GAME-ON/ELLIPSE Consortium ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, United States of America. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 VL - 12 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854618540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+genetics&rft.atitle=Winner%27s+Curse+Correction+and+Variable+Thresholding+Improve+Performance+of+Polygenic+Risk+Modeling+Based+on+Genome-Wide+Association+Study+Summary-Level+Data.&rft.au=Shi%2C+Jianxin%3BPark%2C+Ju-Hyun%3BDuan%2C+Jubao%3BBerndt%2C+Sonja+T%3BMoy%2C+Winton%3BYu%2C+Kai%3BSong%2C+Lei%3BWheeler%2C+William%3BHua%2C+Xing%3BSilverman%2C+Debra%3BGarcia-Closas%2C+Montserrat%3BHsiung%2C+Chao+Agnes%3BFigueroa%2C+Jonine+D%3BCortessis%2C+Victoria+K%3BMalats%2C+N%C3%BAria%3BKaragas%2C+Margaret+R%3BVineis%2C+Paolo%3BChang%2C+I-Shou%3BLin%2C+Dongxin%3BZhou%2C+Baosen%3BSeow%2C+Adeline%3BMatsuo%2C+Keitaro%3BHong%2C+Yun-Chul%3BCaporaso%2C+Neil+E%3BWolpin%2C+Brian%3BJacobs%2C+Eric%3BPetersen%2C+Gloria+M%3BKlein%2C+Alison+P%3BLi%2C+Donghui%3BRisch%2C+Harvey%3BSanders%2C+Alan+R%3BHsu%2C+Li%3BSchoen%2C+Robert+E%3BBrenner%2C+Hermann%3BMGS+%28Molecular+Genetics+of+Schizophrenia%29+GWAS+Consortium%3BGECCO+%28The+Genetics+and+Epidemiology+of+Colorectal+Cancer+Consortium%29%3BGAME-ON%2FTRICL+%28Transdisciplinary+Research+in+Cancer+of+the+Lung%29+GWAS+Consortium%3BPRACTICAL+%28PRostate+cancer+AssoCiation+group+To+Investigate+Cancer+Associated+aLterations%29+Consortium%3BPanScan+Consortium%3BGAME-ON%2FELLIPSE+Consortium%3BStolzenberg-Solomon%2C+Rachael%3BGejman%2C+Pablo%3BLan%2C+Qing%3BRothman%2C+Nathaniel%3BAmundadottir%2C+Laufey+T%3BLandi%2C+Maria+Teresa%3BLevinson%2C+Douglas+F%3BChanock%2C+Stephen+J%3BChatterjee%2C+Nilanjan&rft.aulast=Shi&rft.aufirst=Jianxin&rft.date=2016-12-01&rft.volume=12&rft.issue=12&rft.spage=e1006493&rft.isbn=&rft.btitle=&rft.title=PLoS+genetics&rft.issn=1553-7404&rft_id=info:doi/10.1371%2Fjournal.pgen.1006493 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-30 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1371/journal.pgen.1006493 ER - TY - JOUR T1 - Drug induced interstitial lung disease in oncology phase I trials. AN - 1854104420; 27685762 AB - Interstitial lung disease is a serious drug-related condition that can cause life threatening organ failure. The incidence and risk factors of drug-induced interstitial lung disease (DILD) are unknown in oncology phase I trials. This study analyzed clinical information from 8906 patients with malignancies who were enrolled in 470 phase I trials sponsored by the Cancer Therapy Evaluation Program, National Cancer Institute, from 1988 to 2014. Logistic and Cox statistical analyses were utilized to determine clinical differences between patients who developed DILD and patients who did not. In this study, the overall incidence rate of patients with pulmonary toxicity was 2.7%. The overall incidence rate for DILD was 0.77%, whereas for grade 3 or 4 DILD it was 0.31%. Median time to occurrence of DILD was 1.4 months. The Cox hazard analysis indicated smaller body surface area and a combination of thoracic radiation with investigational drug regimens were significant risk factors for time to occurrence of interstitial lung disease. Investigators should carefully monitor for DILD in oncology patients enrolled in phase I trials with identified risk factors. A 6-month observation period would be sufficient to detect the onset of most DILD in such patients. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. JF - Cancer science AU - Yonemori, Kan AU - Hirakawa, Akihiro AU - Kawachi, Asuka AU - Kinoshita, Fumie AU - Okuma, Hitomi AU - Nishikawa, Tadaaki AU - Tamura, Kenji AU - Fujiwara, Yasuhiro AU - Takebe, Naoko AD - Department of Breast and Medical Oncology, National Cancer Center Hospital, National Cancer Center, Tokyo, Japan. ; Biostatistics and Bioinformatics Section, Center for Advanced Medicine and Clinical Research, Graduate School of Medicine, Nagoya University, Nagoya, Japan. ; Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Rockville, Maryland, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1830 EP - 1836 VL - 107 IS - 12 KW - investigational new drug KW - Drug induced interstitial lung disease KW - oncology KW - phase I trial pulmonary toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1854104420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+science&rft.atitle=Drug+induced+interstitial+lung+disease+in+oncology+phase%C2%A0I+trials.&rft.au=Yonemori%2C+Kan%3BHirakawa%2C+Akihiro%3BKawachi%2C+Asuka%3BKinoshita%2C+Fumie%3BOkuma%2C+Hitomi%3BNishikawa%2C+Tadaaki%3BTamura%2C+Kenji%3BFujiwara%2C+Yasuhiro%3BTakebe%2C+Naoko&rft.aulast=Yonemori&rft.aufirst=Kan&rft.date=2016-12-01&rft.volume=107&rft.issue=12&rft.spage=1830&rft.isbn=&rft.btitle=&rft.title=Cancer+science&rft.issn=1349-7006&rft_id=info:doi/10.1111%2Fcas.13087 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cas.13087 ER - TY - JOUR T1 - Beyond RCHOP: A Blueprint for Diffuse Large B Cell Lymphoma Research. AN - 1852692133; 27986884 AB - Diffuse large B cell lymphoma (DLBCL) comprises multiple molecular and biological subtypes, resulting in a broad range of clinical outcomes. With standard chemoimmunotherapy, there remains an unacceptably high treatment failure rate in certain DLBCL subsets: activated B cell (ABC) DLBCL, double-hit lymphoma defined by the dual translocation of MYC and BCL2, dual protein-expressing lymphomas defined by the overexpression of MYC and BCL2, and older patients and those with central nervous system involvement. The main research challenges for DLBCL are to accurately identify molecular subsets and to determine if specific chemotherapy platforms and targeted agents offer differential benefit. The ultimate goal should be to maximize initial cure rates to improve long-term survival while minimizing toxicity. In particular, a frontline trial should focus on biologically defined risk groups not likely to be cured with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP). An additional challenge is to develop effective and personalized strategies in the relapsed setting, for which there is no current standard other than autologous stem cell transplantation, which benefits a progressively smaller proportion of patients. Relapsed/refractory DLBCL is the ideal setting for testing novel agents and new biomarker tools and will require a national call for biopsies to optimize discovery in this setting. Accordingly, the development of tools with both prognostic and predictive utility and the individualized application of new therapies should be the main priorities. This report identifies clinical research priorities for critical areas of unmet need in this disease. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US. JF - Journal of the National Cancer Institute AU - Nowakowski, Grzegorz S AU - Blum, Kristie A AU - Kahl, Brad S AU - Friedberg, Jonathan W AU - Baizer, Lawrence AU - Little, Richard F AU - Maloney, David G AU - Sehn, Laurie H AU - Williams, Michael E AU - Wilson, Wyndham H AU - Leonard, John P AU - Smith, Sonali M AD - Department of Medicine, Mayo Clinic, Rochester, MN (GSN); Department of Internal Medicine, Ohio State University, Columbus, OH (KAB); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials (LB), Division of Cancer Treatment and Diagnosis (RFL), and Center for Cancer Research (WHW), National Cancer Institute, National Institute of Health, Bethesda, MD; Division of Oncology, University of Washington, Seattle WA (DGM); British Colombia Cancer Agency, Vancouver, BC (LHS); Department of Medicine, University of Virginia, Charlottesville, VA (MEW); Department of Medicine, Weil Cornell University, New York, NY (JPL); Department of Medicine, University of Chicago, Chicago, IL (SMS) nowakowski.grzegorz@mayo.edu. ; Department of Medicine, Mayo Clinic, Rochester, MN (GSN); Department of Internal Medicine, Ohio State University, Columbus, OH (KAB); Department of Medicine, Oncology Division, Washington University, St. Louis, MO (BSK); Wilmot Cancer Center and Division of Hematology/Oncology, University of Rochester, Rochester, NY (JWF); Coordinating Center for Clinical Trials (LB), Division of Cancer Treatment and Diagnosis (RFL), and Center for Cancer Research (WHW), National Cancer Institute, National Institute of Health, Bethesda, MD; Division of Oncology, University of Washington, Seattle WA (DGM); British Colombia Cancer Agency, Vancouver, BC (LHS); Department of Medicine, University of Virginia, Charlottesville, VA (MEW); Department of Medicine, Weil Cornell University, New York, NY (JPL); Department of Medicine, University of Chicago, Chicago, IL (SMS). Y1 - 2016/12// PY - 2016 DA - December 2016 VL - 108 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1852692133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Beyond+RCHOP%3A+A+Blueprint+for+Diffuse+Large+B+Cell+Lymphoma+Research.&rft.au=Nowakowski%2C+Grzegorz+S%3BBlum%2C+Kristie+A%3BKahl%2C+Brad+S%3BFriedberg%2C+Jonathan+W%3BBaizer%2C+Lawrence%3BLittle%2C+Richard+F%3BMaloney%2C+David+G%3BSehn%2C+Laurie+H%3BWilliams%2C+Michael+E%3BWilson%2C+Wyndham+H%3BLeonard%2C+John+P%3BSmith%2C+Sonali+M&rft.aulast=Nowakowski&rft.aufirst=Grzegorz&rft.date=2016-12-01&rft.volume=108&rft.issue=12&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Repeated measures analysis of associations between urinary bisphenol-A concentrations and biomarkers of inflammation and oxidative stress in pregnancy AN - 1850783340; PQ0003895727 AB - Bisphenol-A (BPA) exposure occurs commonly and may adversely impact pregnancy. Endocrine disruption is posited as the primary mechanism of action, but oxidative stress and inflammation pathways may also be important. We investigated associations between BPA exposure and oxidative stress and inflammation in 482 pregnant women. Participants were recruited early in pregnancy and provided urine and plasma at up to four visits. We measured total BPA and two biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane) in urine from each visit. Inflammation markers, including C-reactive protein and four cytokines were measured in plasma from the same time points. In adjusted models, an interquartile range increase in BPA was associated with significant increases in both oxidative stress biomarkers (5-9% increase). Additionally, we observed significantly higher IL-6 concentrations in association with an interquartile range increase in BPA (8.95% increase). These systemic changes consequent to BPA exposure may mediate adverse birth outcomes and/or fetal development. JF - Reproductive Toxicology AU - Ferguson, Kelly K AU - Cantonwine, David E AU - McElrath, Thomas F AU - Mukherjee, Bhramar AU - Meeker, John D AD - Epidemiology Branch, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC, USA Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 93 EP - 98 PB - Elsevier B.V., Box 882 New York NY 10159 United States VL - 66 SN - 0890-6238, 0890-6238 KW - Toxicology Abstracts KW - BPA Bisphenol-A KW - PPAR peroxisome proliferator activated receptor KW - 8-OHdG 8-hydroxydeoxyguanosine KW - CRP C-reactive protein KW - LOD limit of detection KW - BMI body mass index KW - IQR interquartile range KW - MEHP mono-2-ethylhexyl phthalate KW - MEHHP mono-2-ethyl-5-hydroxyhexyl phthalate KW - MEOHP mono-2-ethyl-5-oxohexyl phthalate KW - MECPP mono-2-ethyl-5-carboxypentyl phthalate KW - MBzP mono-benzyl phthalate KW - MBP mono-n-butyl phthalate KW - MiBP mono-iso-butyl phthalate KW - MEP mono-ethyl phthalate KW - MCPP mono-carboxypropyl phthalate KW - BPA KW - Oxidative stress KW - Inflammation KW - IL-6 KW - Pregnancy KW - Biomarkers KW - Longitudinal KW - Interleukin 6 KW - Endocrine disruptors KW - Development KW - biomarkers KW - Fetuses KW - Models KW - 8-Hydroxydeoxyguanosine KW - Bisphenol A KW - Birth KW - Urine KW - C-reactive protein KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850783340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Repeated+measures+analysis+of+associations+between+urinary+bisphenol-A+concentrations+and+biomarkers+of+inflammation+and+oxidative+stress+in+pregnancy&rft.au=Ferguson%2C+Kelly+K%3BCantonwine%2C+David+E%3BMcElrath%2C+Thomas+F%3BMukherjee%2C+Bhramar%3BMeeker%2C+John+D&rft.aulast=Ferguson&rft.aufirst=Kelly&rft.date=2016-12-01&rft.volume=66&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2Fj.reprotox.2016.10.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Interleukin 6; Endocrine disruptors; Development; biomarkers; Fetuses; Inflammation; Pregnancy; Models; Birth; Bisphenol A; 8-Hydroxydeoxyguanosine; Oxidative stress; Urine; C-reactive protein DO - http://dx.doi.org/10.1016/j.reprotox.2016.10.002 ER - TY - JOUR T1 - Association Between Type-specific HPV Infections and hTERT DNA Methylation in Patients with Invasive Cervical Cancer AN - 1850781098; PQ0003898673 AB - Background: There exists limited information on the role of hTERT methylation, and its association with type-specific HPV infections in cervical cancer. Materials and Methods: Eighty-seven frozen samples were analyzed for type-specific HPV infection using a GP5 super(+)/GP6 super(+) PCR-RLB assay (RLB). hTERT DNA methylation analysis was performed using a newly developed PCR-RLB-hTERT. Results: Ninety-three percent of samples were HPV-positive and fifteen different types were detected. hTERT methylation analysis of region 1 revealed no methylation in 78.8% of the samples and partial methylation in 21.2%. In region two, 68.2% showed no methylation and 31.8% showed a pattern of partial methylation. An association between the alpha 9 and alpha 7 species with a pattern of no methylation of hTERT in the region 1 was established (p=0.02 and p=0.03, respectively). Conclusion: Differences in patterns of methylation of the hTERT core promoter [region 1 (nt -208 to -1) and region 2 (nt +1 to +104) relative to first ATG] are related to the HPV species present. JF - Cancer Genomics & Proteomics AU - Molano, Monica AU - Moreno-Acosta, Pablo AU - Morales, NicolAs AU - Burgos, Marcela AU - Buitrago, Lina AU - Gamboa, Oscar AU - Alvarez, Rayner AU - Garland, Suzanne M AU - Tabrizi, Sepehr N AU - Steenbergen, Renske DM AU - Mejia, Juan Carlos AD - Research Group in Cancer Biology, Research Branch, National Cancer Institute, Bogota, Colombia, pmoreno@cancer.gov.co Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 483 EP - 491 PB - International Institute of Anticancer Research, 1st km Kapandritiou-Kalamou Road Kapandriti Attiki 19014 Greece VL - 13 IS - 6 SN - 1109-6535, 1109-6535 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Oncogenes & Growth Factors Abstracts KW - DNA methylation KW - uterine cervical neoplasms KW - telomerase reverse transcriptase KW - papillomavirus infections KW - Promoters KW - Invasiveness KW - Cervical cancer KW - Papillomaviridae KW - proteomics KW - Infection KW - G 07880:Human Genetics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850781098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Genomics+%26+Proteomics&rft.atitle=Association+Between+Type-specific+HPV+Infections+and+hTERT+DNA+Methylation+in+Patients+with+Invasive+Cervical+Cancer&rft.au=Molano%2C+Monica%3BMoreno-Acosta%2C+Pablo%3BMorales%2C+NicolAs%3BBurgos%2C+Marcela%3BBuitrago%2C+Lina%3BGamboa%2C+Oscar%3BAlvarez%2C+Rayner%3BGarland%2C+Suzanne+M%3BTabrizi%2C+Sepehr+N%3BSteenbergen%2C+Renske+DM%3BMejia%2C+Juan+Carlos&rft.aulast=Molano&rft.aufirst=Monica&rft.date=2016-12-01&rft.volume=13&rft.issue=6&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Cancer+Genomics+%26+Proteomics&rft.issn=11096535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Promoters; Invasiveness; Cervical cancer; DNA methylation; proteomics; telomerase reverse transcriptase; Infection; Papillomaviridae ER - TY - JOUR T1 - Active follow-up versus passive linkage with cancer registries for case ascertainment in a cohort AN - 1850778382; PQ0003896823 AB - Background Ascertaining incident cancers is a critical component of cancer-focused epidemiologic cohorts and of cancer prevention trials. Potential methods: for cancer case ascertainment include active follow-up and passive linkage with state cancer registries. Here we compare the two approaches in a large cancer screening trial. Methods The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial enrolled 154,955 subjects at ten U.S. centers and followed them for all-cancer incidence. Cancers were ascertained by an active follow-up process involving annual questionnaires, retrieval of records and medical record abstracting to ascertain and confirm cancers. For a subset of centers, linkage with state cancer registries was also performed. We assessed the agreement of the two methods in ascertaining incident cancers from 1993 to 2009 in 80,083 subjects from six PLCO centers where cancers were ascertained both by active follow-up and through linkages with 14 state registries. Results The ratio (times 100) of confirmed cases ascertained by registry linkage compared to active follow-up was 96.4 (95% CI: 95.1-98.2). Of cancers ascertained by either method, 86.6% and 83.5% were identified by active follow-up and by registry linkage, respectively. Of cancers missed by active follow-up, 30% were after subjects were lost to follow-up and 16% were reported but could not be confirmed. Of cancers missed by the registries, 27% were not sent to the state registry of the subject's current address at the time of linkage. Conclusion Linkage with state registries identified a similar number of cancers as active follow-up and can be a cost-effective method to ascertain incident cancers in a large cohort. JF - Cancer Epidemiology AU - Pinsky, P F AU - Yu, K AU - Black, A AU - Huang, W Y AU - Prorok, P C AD - Division of Cancer Prevention, National Cancer Institute, United States Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 26 EP - 31 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 45 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - Cancer registries KW - Linkage KW - Active-follow-up KW - Case ascertainment KW - Inventories KW - Ovarian cancer KW - medical records KW - Phospholipase C KW - Prostate KW - Cancer KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850778382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Active+follow-up+versus+passive+linkage+with+cancer+registries+for+case+ascertainment+in+a+cohort&rft.au=Pinsky%2C+P+F%3BYu%2C+K%3BBlack%2C+A%3BHuang%2C+W+Y%3BProrok%2C+P+C&rft.aulast=Pinsky&rft.aufirst=P&rft.date=2016-12-01&rft.volume=45&rft.issue=&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 6 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Ovarian cancer; Inventories; medical records; Phospholipase C; Prostate; Cancer DO - http://dx.doi.org/10.1016/j.canep.2016.09.003 ER - TY - JOUR T1 - Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study. AN - 1846721957; 27923066 AB - Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10-50). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5×10-4) were associated with increased risk of distant metastasis. Our study's limitations include a small number of LUAD patients for subgroup analyses and a single-sample design for investigation of subclonality. These data provide a genomic characterization of LUAD pathogenesis and progression. The distinct clonal and subclonal mutation signatures suggest possible diverse carcinogenesis pathways for endogenous and exogenous exposures, and may serve as a foundation for more effective treatments for this lethal disease. LUAD's high heterogeneity emphasizes the need to further study this tumor type and to associate genomic findings with clinical outcomes. JF - PLoS medicine AU - Shi, Jianxin AU - Hua, Xing AU - Zhu, Bin AU - Ravichandran, Sarangan AU - Wang, Mingyi AU - Nguyen, Cu AU - Brodie, Seth A AU - Palleschi, Alessandro AU - Alloisio, Marco AU - Pariscenti, Gianluca AU - Jones, Kristine AU - Zhou, Weiyin AU - Bouk, Aaron J AU - Boland, Joseph AU - Hicks, Belynda AU - Risch, Adam AU - Bennett, Hunter AU - Luke, Brian T AU - Song, Lei AU - Duan, Jubao AU - Liu, Pengyuan AU - Kohno, Takashi AU - Chen, Qingrong AU - Meerzaman, Daoud AU - Marconett, Crystal AU - Laird-Offringa, Ite AU - Mills, Ian AU - Caporaso, Neil E AU - Gail, Mitchell H AU - Pesatori, Angela C AU - Consonni, Dario AU - Bertazzi, Pier Alberto AU - Chanock, Stephen J AU - Landi, Maria Teresa AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. ; Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, Maryland, United States of America. ; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland, United States of America. ; Division of Thoracic Surgery, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. ; Division of Thoracic Surgery, Istituto Clinico Humanitas, Rozzano, Milan, Italy. ; Thoracic Surgery Unit, Community Hospital, Brescia, Italy. ; Information Management Services, Inc., Rockville, Maryland, United States of America. ; Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, University of Chicago Pritzker School of Medicine, Evanston, Illinois, United States of America. ; Department of Physiology & Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America. ; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. ; Departments of Surgery and of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America. ; Prostate Cancer UK/Movember Centre of Excellence for Prostate Cancer Research, Centre for Cancer Research and Cell Biology, Queen's University, Belfast, United Kingdom. ; Epidemiology Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 VL - 13 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846721957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+medicine&rft.atitle=Somatic+Genomics+and+Clinical+Features+of+Lung+Adenocarcinoma%3A+A+Retrospective+Study.&rft.au=Shi%2C+Jianxin%3BHua%2C+Xing%3BZhu%2C+Bin%3BRavichandran%2C+Sarangan%3BWang%2C+Mingyi%3BNguyen%2C+Cu%3BBrodie%2C+Seth+A%3BPalleschi%2C+Alessandro%3BAlloisio%2C+Marco%3BPariscenti%2C+Gianluca%3BJones%2C+Kristine%3BZhou%2C+Weiyin%3BBouk%2C+Aaron+J%3BBoland%2C+Joseph%3BHicks%2C+Belynda%3BRisch%2C+Adam%3BBennett%2C+Hunter%3BLuke%2C+Brian+T%3BSong%2C+Lei%3BDuan%2C+Jubao%3BLiu%2C+Pengyuan%3BKohno%2C+Takashi%3BChen%2C+Qingrong%3BMeerzaman%2C+Daoud%3BMarconett%2C+Crystal%3BLaird-Offringa%2C+Ite%3BMills%2C+Ian%3BCaporaso%2C+Neil+E%3BGail%2C+Mitchell+H%3BPesatori%2C+Angela+C%3BConsonni%2C+Dario%3BBertazzi%2C+Pier+Alberto%3BChanock%2C+Stephen+J%3BLandi%2C+Maria+Teresa&rft.aulast=Bae&rft.aufirst=Jisuk&rft.date=2016-02-01&rft.volume=543&rft.issue=&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2015.11.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-12-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1371/journal.pmed.1002162 ER - TY - JOUR T1 - Genetic diversity of Klebsiella pneumoniae isolates during an outbreak in a non-human primate research colony AN - 1846409917; PQ0003857925 AB - Background Klebsiella pneumoniae can be a serious pathogen in non-human primates, particularly Neotropical monkeys. Methods During a K. pneumoniae outbreak in an owl monkey research colony, 13 K. pneumoniae isolates were DNA fingerprinted by automated repetitive extragenic palindromic-polymerase chain reaction and the profiles compared to isolates obtained from other non-human primate species during the same time period and isolates from previous outbreaks. Results Eleven different types of K. pneumoniae were circulating in the owl monkey colony at the time of the outbreak. When comparing owl monkey isolates relatedness to previous colony outbreak isolates and squirrel monkey and capuchin monkey isolates, all were different. Conclusions These results agree with recent reports where K. pneumoniae nosocomial isolates in hospital settings can have high genetic diversity, and multiple strains can be circulating simultaneously. This potential genetic diversity should be considered when designing strategies for controlling K. pneumoniae outbreaks in captive non-human primate colonies. JF - Journal of Medical Primatology (Online) AU - Gozalo, Alfonso S AU - Elkins, William R AU - Lambert, Lynn E AU - Stock, Frida AU - Thomas, Marvin L AU - Woodward, Ruth A AD - Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 312 EP - 317 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 45 IS - 6 SN - 0047-2565, 0047-2565 KW - Microbiology Abstracts B: Bacteriology; CSA Neurosciences Abstracts KW - Saimiri KW - Colonies KW - DNA KW - Genetic diversity KW - Pathogens KW - Klebsiella pneumoniae KW - Hospitals KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846409917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Medical+Primatology+%28Online%29&rft.atitle=Genetic+diversity+of+Klebsiella+pneumoniae+isolates+during+an+outbreak+in+a+non-human+primate+research+colony&rft.au=Gozalo%2C+Alfonso+S%3BElkins%2C+William+R%3BLambert%2C+Lynn+E%3BStock%2C+Frida%3BThomas%2C+Marvin+L%3BWoodward%2C+Ruth+A&rft.aulast=Gozalo&rft.aufirst=Alfonso&rft.date=2016-12-01&rft.volume=45&rft.issue=6&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Primatology+%28Online%29&rft.issn=00472565&rft_id=info:doi/10.1111%2Fjmp.12229 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2017-02-01 N1 - SubjectsTermNotLitGenreText - Colonies; DNA; Genetic diversity; Pathogens; Hospitals; Saimiri; Klebsiella pneumoniae DO - http://dx.doi.org/10.1111/jmp.12229 ER - TY - JOUR T1 - Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose, Route, and Repeated Administration. AN - 1846365671; 27613714 AB - 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB; MW 549.92 g/mol; CAS 183658-27-7) is a brominated component of flame retardant mixtures used as substitutes for some PBDEs. EH-TBB is added to various consumer products, including polyurethane foams, and has been detected in humans. The present study characterized the fate of EH-TBB in rodents. [14C]-labeled EH-TBB was absorbed, metabolized, and eliminated via the urine and feces following single administrations of 0.1-100 µmol/kg (∼0.05-55 mg/kg) or repeated administration (0.1 µmol/kg/day × 5-10 days) by gavage to female Hsd:Sprague DawleySD (SD) rats. Cumulative excretion via feces increased (39-60%) with dose (0.1-10 µmol/kg) with corresponding decreases in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [14C]-radioactivity in urine and feces of a 100 µmol/kg oral dose was noted. Recovery was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1 µmol/kg dose in urine and less in feces than did gavaged rats, indicating partial biliary elimination of systemically available compound. No tissue bioaccumulation was found for rats given 5 oral daily doses of EH-TBB. Parent molecule was not detected in urine whereas 2 metabolites, tetrabromobenzoic acid (TBBA), a TBBA-sulfate conjugate, and a TBBA-glycine conjugate were identified. EH-TBB and TBBA were identified in extracts from feces. Data from gavaged male B6C3F1/Tac mice indicated minimal sex- or species differences are likely for the disposition of EH-TBB. Approximately 85% of a 0.1 µmol/kg dose was absorbed from the gut. Overall absorption of EH-TBB is expected to be even greater at lower levels. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Knudsen, Gabriel A AU - Sanders, J Michael AU - Birnbaum, Linda S AD - NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina gabriel.knudsen@nih.gov. ; NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 392 EP - 402 VL - 154 IS - 2 KW - metabolism. KW - 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate KW - disposition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846365671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Disposition+of+the+Emerging+Brominated+Flame+Retardant%2C+2-Ethylhexyl+2%2C3%2C4%2C5-Tetrabromobenzoate%2C+in+Female+SD+Rats+and+Male+B6C3F1+Mice%3A+Effects+of+Dose%2C+Route%2C+and+Repeated+Administration.&rft.au=Knudsen%2C+Gabriel+A%3BSanders%2C+J+Michael%3BBirnbaum%2C+Linda+S&rft.aulast=Knudsen&rft.aufirst=Gabriel&rft.date=2016-12-01&rft.volume=154&rft.issue=2&rft.spage=392&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage. AN - 1846024050; 27543075 AB - Tyrosyl DNA phosphodiesterase 2 (TDP2) is a multifunctional protein implicated in DNA repair, signal transduction and transcriptional regulation. In its DNA repair role, TDP2 safeguards genome integrity by hydrolyzing 5'-tyrosyl DNA adducts formed by abortive topoisomerase II (Top2) cleavage complexes to allow error-free repair of DNA double-strand breaks, thereby conferring cellular resistance against Top2 poisons. TDP2 consists of a C-terminal catalytic domain responsible for its phosphodiesterase activity, and a functionally uncharacterized N-terminal region. Here, we demonstrate that this N-terminal region contains a ubiquitin (Ub)-associated (UBA) domain capable of binding multiple forms of Ub with distinct modes of interactions and preference for either K48- or K63-linked polyUbs over monoUb. The structure of TDP2 UBA bound to monoUb shows a canonical mode of UBA-Ub interaction. However, the absence of the highly conserved MGF motif and the presence of a fourth α-helix make TDP2 UBA distinct from other known UBAs. Mutations in the TDP2 UBA-Ub binding interface do not affect nuclear import of TDP2, but severely compromise its ability to repair Top2-mediated DNA damage, thus establishing the importance of the TDP2 UBA-Ub interaction in DNA repair. The differential binding to multiple Ub forms could be important for responding to DNA damage signals under different contexts or to support the multi-functionality of TDP2. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. JF - Nucleic acids research AU - Rao, Timsi AU - Gao, Rui AU - Takada, Saeko AU - Al Abo, Muthana AU - Chen, Xiang AU - Walters, Kylie J AU - Pommier, Yves AU - Aihara, Hideki AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. ; Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. ; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA aihar001@umn.edu. Y1 - 2016/12/01/ PY - 2016 DA - 2016 Dec 01 SP - 10201 EP - 10215 VL - 44 IS - 21 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846024050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Novel+TDP2-ubiquitin+interactions+and+their+importance+for+the+repair+of+topoisomerase+II-mediated+DNA+damage.&rft.au=Rao%2C+Timsi%3BGao%2C+Rui%3BTakada%2C+Saeko%3BAl+Abo%2C+Muthana%3BChen%2C+Xiang%3BWalters%2C+Kylie+J%3BPommier%2C+Yves%3BAihara%2C+Hideki&rft.aulast=Rao&rft.aufirst=Timsi&rft.date=2016-12-01&rft.volume=44&rft.issue=21&rft.spage=10201&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Stability of core language skill across the first decade of life in children at biological and social risk AN - 1845015267 AB - Background Command of language is a fundamental skill, a cornerstone of multiple cognitive and socioemotional aspects of development, and a necessary ingredient of successful adjustment and functioning in society. Little is known about the developmental stability of language in at-risk youth or which biological and social risk factors moderate stability. Methods This four-wave 10-year prospective longitudinal study evaluated stability of core language skill in 1,780 children in varying categories of biological and social risk in a multiage, multidomain, multimeasure, and multireporter framework. Results Structural equation modeling supported loadings of diverse age-appropriate measures of child language on single latent variables of core language skill at 15 and 25 months and 5 and 11 years, respectively. Core language skill was stable over the first decade of life; significant and comparable stability coefficients were obtained for children with diverse biological and social risks, including poor health, welfare status, teen motherhood, ethnicity, gender, birth order, and families that changed in income and maternal education over the study period; stability in language was strong even accounting for child nonverbal intelligence and social competence, maternal education and language, and the family home environment. Conclusions Core language skill varies in stability with age but is robustly stable in children regardless of multiple biological and social risk factors. JF - Journal of Child Psychology and Psychiatry AU - Bornstein, Marc H AU - Hahn, Chun-Shin AU - Putnick, Diane L AD - Child and Family Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Public Health Service, Bethesda, MD, USA ; Child and Family Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Public Health Service, Bethesda, MD, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1434 EP - 1443 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 12 KW - Psychology KW - At risk KW - Intelligence KW - Birth order KW - Socioemotional aspects KW - Home environment KW - Risk factors KW - Ethnicity KW - Health status KW - Welfare KW - Social competence KW - Motherhood KW - Nonverbal intelligence KW - Adolescent motherhood KW - Childbirth UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845015267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Stability+of+core+language+skill+across+the+first+decade+of+life+in+children+at+biological+and+social+risk&rft.au=Bornstein%2C+Marc+H%3BHahn%2C+Chun-Shin%3BPutnick%2C+Diane+L&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2016-12-01&rft.volume=57&rft.issue=12&rft.spage=1434&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12632 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/jcpp.12632 ER - TY - JOUR T1 - Commentary: Mapping the young, resilient brain - reflections on Burt et al. (2016) AN - 1845015051 AB - The resilience of many children in the face of adversity has long been a research focus. The study by Burt et al. delineates the neuroanatomy of resilience, using in vivo magnetic resonance images acquired on 1,800 youth. They find that resilient youth had a larger right lateral prefrontal cortex compared to youth who either lacked resilience or did not experience adversity. The size of the right lateral prefrontal cortex was further associated with a likelihood of a maladaptive problem of alcohol use. These findings implicate high-order regulatory processes supported by the right lateral prefrontal cortex as pivotal in resilience. The study also sets the stage for exploring how neuroimaging data, combined with behavioral and genomic information might be used to assess treatment efficacy and identify children who need therapeutic interventions to boost their resilience. Read the full article at doi: 10.1111/jcpp.12552 JF - Journal of Child Psychology and Psychiatry AU - Shaw, Philip AD - Neurobehavioral Clinical Research Section, Social and Behavioral Research Branch, National Human Genome Research Institute and the National Institute of Mental Health, Bethesda, MD, USA ; Neurobehavioral Clinical Research Section, Social and Behavioral Research Branch, National Human Genome Research Institute and the National Institute of Mental Health, Bethesda, MD, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1465 EP - 1466 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 12 KW - Psychology KW - Neuroimaging KW - Young people KW - Adversity KW - Brain KW - Neuroanatomy KW - Cortex KW - Efficacy KW - Mapping KW - Problem drinking KW - Resilience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1845015051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Commentary%3A+Mapping+the+young%2C+resilient+brain+-+reflections+on+Burt+et%26amp%3B%23xa0%3Bal.+%282016%29&rft.au=Shaw%2C+Philip&rft.aulast=Shaw&rft.aufirst=Philip&rft.date=2016-12-01&rft.volume=57&rft.issue=12&rft.spage=1465&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12613 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/jcpp.12613 ER - TY - JOUR T1 - The experience of electroconvulsive therapy and its impact on associated stigma: A meta-analysis AN - 1844719041 AB - Background: Despite its efficacy and safety, electroconvulsive therapy (ECT) is underutilized, in part due to stigma associated with the treatment. Aims: The aim of this study was to test the hypothesis that experiencing ECT has an impact on associated stigma, as measured by patient and family knowledge of and attitudes toward ECT. Methods: A comprehensive literature search was conducted using MEDLINE, EMBASE and PsycINFO. Studies with cross-sectional and/or longitudinal designs were identified. Studies were further categorized into subcategories based on participant type (patients or patient family members) and outcome domain (knowledge or attitudes). Effect size (Cohen's d ) was calculated for each study and then integrated into each subcategory (participant type by outcome domain) using a random effect model. Results: Eight studies were identified as being eligible for analysis. Two studies were cross-sectional, five were longitudinal and one incorporated both designs. Analysis of the longitudinal studies indicated that experiencing ECT both increased knowledge of and improved attitudes toward ECT in patients; in family members of patients, analysis showed significant positive change in knowledge of ECT, but no significant change in attitudes toward ECT. Conclusion: Experience with ECT may have a positive impact on knowledge of and attitudes toward ECT. However, the quality of evidence of included studies was low; further research is required in order to clarify the relationship and to identify information of use to individuals considering ECT as a treatment option. JF - The International Journal of Social Psychiatry AU - Aoki, Yuta AU - Yamaguchi, Sosei AU - Ando, Shuntaro AU - Sasaki, Natsuki AU - Bernick, Peter J AU - Akiyama, Tsuyoshi AD - The Child Study Center, New York University Langone Medical Center, New York, NY, USA; Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan ; Department of Psychiatric Rehabilitation, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan ; Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan; Department of Psychiatry and Behavioral Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan ; Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan ; Center for Health and Community Medicine and the Student Accessibility Office, Nagasaki University, Nagasaki, Japan ; Department of Neuropsychiatry, NTT Medical Center Tokyo, Tokyo, Japan ; The Child Study Center, New York University Langone Medical Center, New York, NY, USA; Department of Neuropsychiatry, The University of Tokyo, Tokyo, Japan Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 708 EP - 718 CY - London PB - SAGE PUBLICATIONS, INC. VL - 62 IS - 8 SN - 0020-7640 KW - Medical Sciences--Psychiatry And Neurology KW - Attitude KW - electroconvulsive therapy KW - meta-analysis KW - stigma KW - systematic review KW - Electroconvulsive therapy KW - Studies KW - Attitudes KW - Patients KW - Stigma KW - Positive action KW - Analysis KW - Efficacy KW - Relatives KW - Safety KW - Stigmatization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844719041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+International+Journal+of+Social+Psychiatry&rft.atitle=The+experience+of+electroconvulsive+therapy+and+its+impact+on+associated+stigma%3A+A+meta-analysis&rft.au=Aoki%2C+Yuta%3BYamaguchi%2C+Sosei%3BAndo%2C+Shuntaro%3BSasaki%2C+Natsuki%3BBernick%2C+Peter+J%3BAkiyama%2C+Tsuyoshi&rft.aulast=Aoki&rft.aufirst=Yuta&rft.date=2016-12-01&rft.volume=62&rft.issue=8&rft.spage=708&rft.isbn=&rft.btitle=&rft.title=The+International+Journal+of+Social+Psychiatry&rft.issn=00207640&rft_id=info:doi/10.1177%2F0020764016675379 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2016 N1 - Last updated - 2017-01-29 DO - http://dx.doi.org/10.1177/0020764016675379 ER - TY - JOUR T1 - Update on Burkitt Lymphoma. AN - 1844354298; 27888884 AB - Because of its rarity and high curability, progress in advancing therapeutics in Burkitt lymphoma (BL) has been difficult. Over recent years, several new mutations that cooperate with MYC have been identified, and this has paved the way for testing novel agents in the disease. One of the challenges of most standard approaches typically used is severe treatment-related toxicity that often leads to discontinuation of therapy. To that point, there has been recent success developing intermediate intensity approaches that are well tolerated in all patient groups and maintain high cure rates in a multicenter setting. Published by Elsevier Inc. JF - Hematology/oncology clinics of North America AU - Dunleavy, Kieron AU - Little, Richard F AU - Wilson, Wyndham H AD - Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: dunleavk@mail.nih.gov. ; HIV and Stem Cell Therapeutics, Cancer Therapeutic Evaluation Program (CTEP), National Cancer Institute, Bethesda, MD 20892, USA. ; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1333 EP - 1343 VL - 30 IS - 6 KW - Risk-adapted KW - Endemic KW - CCND3 KW - Sporadic KW - Burkitt lymphoma KW - ID3 KW - TCF3 KW - MYC UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844354298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology%2Foncology+clinics+of+North+America&rft.atitle=Update+on+Burkitt+Lymphoma.&rft.au=Dunleavy%2C+Kieron%3BLittle%2C+Richard+F%3BWilson%2C+Wyndham+H&rft.aulast=Dunleavy&rft.aufirst=Kieron&rft.date=2016-12-01&rft.volume=30&rft.issue=6&rft.spage=1333&rft.isbn=&rft.btitle=&rft.title=Hematology%2Foncology+clinics+of+North+America&rft.issn=1558-1977&rft_id=info:doi/10.1016%2Fj.hoc.2016.07.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.hoc.2016.07.009 ER - TY - JOUR T1 - Anal human papillomavirus in HIV-uninfected men who have sex with men: incidence and clearance rates, duration of infection, and risk factors. AN - 1844352031; 27585942 AB - Little is known regarding the natural history of anal human papillomavirus (HPV) infection. We aimed to evaluate incidence and clearance rates, their risk factors, and duration of anal HPV infection in HIV-uninfected men who have sex with men (MSM). A longitudinal study was conducted. Anal samples were analysed using the Linear Array HPV Genotyping test. Incidence and clearance rates, and corresponding risk factors, were estimated using a two-state Markov model. Overall, 155 MSM (median age 33.4 years) attending the largest sexually transmitted infection (STI) centre in Rome, Italy, were followed for a median of 12.2 months (Q1-Q3: 7.0-18.1). Incidence and clearance rates for any HPV were 85.6 (95% CI: 58.4-125.4) and 35.6 (95% CI: 24.7-51.5) × 1000 person-months, respectively; the median duration of infection was 9.4 months (Q1-Q3: 7.5-12.1). Receptive anal sex emerged as the only risk factor for the acquisition of any HPV (Hazard Ratio, HR = 2.65, 95% CI: 1.16-6.06). The incidence rates for carcinogenic and non-carcinogenic types were 42.3 (95% CI: 29.2-61.4) and 29.2 (95% CI: 19.5-43.7) × 1000 person-months, respectively (p = 0.13); their clearance rates were 62.9 (95% CI: 45.1-87.7) and 65.7 (95% CI: 47.4-91.0) × 1000 person-months, respectively (p = 0.83). HPV16 showed the lowest clearance rate among carcinogenic types (59.7 × 1000 person-months), and a duration of infection of 16.8 months. In conclusion, a higher incidence rate was observed for carcinogenic compared to non-carcinogenic HPV types, although the difference was not significant. HPV16 emerged as the type with the longest duration of infection and the lowest clearance rate among carcinogenic types. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases AU - Donà, M G AU - Vescio, M F AU - Latini, A AU - Giglio, A AU - Moretto, D AU - Frasca, M AU - Benevolo, M AU - Rollo, F AU - Colafigli, M AU - Cristaudo, A AU - Giuliani, M AD - STI/HIV Unit, UOC Dermatologia Infettiva e Allergologica, San Gallicano Dermatological Institute (IFO-IRCCS), Rome, Italy. Electronic address: mariagabriella.dona@ifo.gov.it. ; Infectious, Parasitic and Immunomediated Diseases Department, Istituto Superiore di Sanità, Rome, Italy. ; STI/HIV Unit, UOC Dermatologia Infettiva e Allergologica, San Gallicano Dermatological Institute (IFO-IRCCS), Rome, Italy. ; Microbiology and Clinical Pathology Department, San Gallicano Dermatological Institute (IFO-IRCCS), Rome, Italy. ; Pathology Department, Regina Elena National Cancer Institute (IFO-IRCCS), Rome, Italy. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1004.e1 EP - 1004.e7 VL - 22 IS - 12 KW - Men who have sex with men KW - Risk factors KW - Anal infection KW - HIV-negative KW - Incidence KW - Clearance KW - Markov KW - Human papillomavirus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844352031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+microbiology+and+infection+%3A+the+official+publication+of+the+European+Society+of+Clinical+Microbiology+and+Infectious+Diseases&rft.atitle=Anal+human+papillomavirus+in+HIV-uninfected+men+who+have+sex+with+men%3A+incidence+and+clearance+rates%2C+duration+of+infection%2C+and+risk+factors.&rft.au=Don%C3%A0%2C+M+G%3BVescio%2C+M+F%3BLatini%2C+A%3BGiglio%2C+A%3BMoretto%2C+D%3BFrasca%2C+M%3BBenevolo%2C+M%3BRollo%2C+F%3BColafigli%2C+M%3BCristaudo%2C+A%3BGiuliani%2C+M&rft.aulast=Don%C3%A0&rft.aufirst=M&rft.date=2016-12-01&rft.volume=22&rft.issue=12&rft.spage=1004.e1&rft.isbn=&rft.btitle=&rft.title=Clinical+microbiology+and+infection+%3A+the+official+publication+of+the+European+Society+of+Clinical+Microbiology+and+Infectious+Diseases&rft.issn=1469-0691&rft_id=info:doi/10.1016%2Fj.cmi.2016.08.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cmi.2016.08.011 ER - TY - JOUR T1 - Identification of novel SNPs associated with risk and prognosis in patients with castration-resistant prostate cancer. AN - 1844021333; 27883295 AB - Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. No relation to risk was found. Three SNPs were associated with CRPC prognosis in Caucasians: ABCB11 rs7602171G>A (p = 0.003; n = 30; hazard ratio [HR]: 0.307), GSTP1 rs1799811C>T (p = 0.001; n = 38; HR: 0.254) and SLC5A6 rs1395 (p = 0.004; n = 35; HR: 3.15). Two other polymorphisms among Caucasians were associated with interesting trends: ABCB4 rs2302387C>T (p = 0.039) and ABCC5 rs939339A>G (p = 0.018). This exploratory study is the first to show that polymorphisms in several absorption, distribution, metabolism and elimination genes may be associated with CRPC prognosis. JF - Pharmacogenomics AU - Sissung, Tristan M AU - Deeken, John AU - Leibrand, Crystal R AU - Price, Douglas K AU - Ehrlich, Sheryl AU - Steinberg, Seth M AU - Liewehr, David J AU - Dahut, William AU - Figg, William D AD - Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA. ; Inova Comprehensive Cancer & Research Institute, Falls Church, VA 22042, USA. ; Molecular Pharmacology Program, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA. ; Biostatistics & Data Management Section, Office of the Clinical Director, National Cancer Institute, NIH, Shady Grove, MD 20850, USA. ; Prostate Cancer Clinical Research Section, Genitourinary Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1979 EP - 1986 VL - 17 IS - 18 KW - transport KW - metabolism KW - castration-resistant prostate cancer KW - genotype KW - survival KW - outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844021333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Identification+of+novel+SNPs+associated+with+risk+and+prognosis+in+patients+with+castration-resistant+prostate+cancer.&rft.au=Sissung%2C+Tristan+M%3BDeeken%2C+John%3BLeibrand%2C+Crystal+R%3BPrice%2C+Douglas+K%3BEhrlich%2C+Sheryl%3BSteinberg%2C+Seth+M%3BLiewehr%2C+David+J%3BDahut%2C+William%3BFigg%2C+William+D&rft.aulast=Sissung&rft.aufirst=Tristan&rft.date=2016-12-01&rft.volume=17&rft.issue=18&rft.spage=1979&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=1744-8042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. AN - 1841794380; 27863194 AB - Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma-associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy ( P = .03). Significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma-associated herpesvirus viral load at week 4 ( P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Polizzotto, Mark N AU - Uldrick, Thomas S AU - Wyvill, Kathleen M AU - Aleman, Karen AU - Peer, Cody J AU - Bevans, Margaret AU - Sereti, Irini AU - Maldarelli, Frank AU - Whitby, Denise AU - Marshall, Vickie AU - Goncalves, Priscila H AU - Khetani, Vikram AU - Figg, William D AU - Steinberg, Seth M AU - Zeldis, Jerome B AU - Yarchoan, Robert AD - Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 4125 EP - 4131 VL - 34 IS - 34 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841794380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Pomalidomide+for+Symptomatic+Kaposi%27s+Sarcoma+in+People+With+and+Without+HIV+Infection%3A+A+Phase+I%2FII+Study.&rft.au=Polizzotto%2C+Mark+N%3BUldrick%2C+Thomas+S%3BWyvill%2C+Kathleen+M%3BAleman%2C+Karen%3BPeer%2C+Cody+J%3BBevans%2C+Margaret%3BSereti%2C+Irini%3BMaldarelli%2C+Frank%3BWhitby%2C+Denise%3BMarshall%2C+Vickie%3BGoncalves%2C+Priscila+H%3BKhetani%2C+Vikram%3BFigg%2C+William+D%3BSteinberg%2C+Seth+M%3BZeldis%2C+Jerome+B%3BYarchoan%2C+Robert&rft.aulast=Polizzotto&rft.aufirst=Mark&rft.date=2016-12-01&rft.volume=34&rft.issue=34&rft.spage=4125&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mesothelin Immunotherapy for Cancer: Ready for Prime Time? AN - 1841794130; 27863199 AB - Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Hassan, Raffit AU - Thomas, Anish AU - Alewine, Christine AU - Le, Dung T AU - Jaffee, Elizabeth M AU - Pastan, Ira AD - Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 4171 EP - 4179 VL - 34 IS - 34 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841794130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Mesothelin+Immunotherapy+for+Cancer%3A+Ready+for+Prime+Time%3F&rft.au=Hassan%2C+Raffit%3BThomas%2C+Anish%3BAlewine%2C+Christine%3BLe%2C+Dung+T%3BJaffee%2C+Elizabeth+M%3BPastan%2C+Ira&rft.aulast=Hassan&rft.aufirst=Raffit&rft.date=2016-12-01&rft.volume=34&rft.issue=34&rft.spage=4171&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Predispositions to Lymphoma: A Practical Review for Genetic Counselors AN - 1841002335 AB - This review provides a synopsis for genetic counselors of the major concepts of lymphoma predisposition: genomic instability, immune deficiency, inappropriate lymphoproliferation, and chronic antigen stimulation. We discuss syndromes typifying each of these mechanisms. Importantly, our review of the genetic counseling literature reveals sparse discussion of genetically-based immune-mediated lymphoma predisposition, which we address in depth here. We aim to increase awareness among genetic counselors and colleagues in oncology about familial susceptibility and facilitate critical thinking about lymphoma risk assessment. Clinical application of this knowledge is aided by recommendations for collection of personal and family history to guide risk assessment and testing. Lastly, we include a special discussion of genetic counseling issues including perceptions of the context, nature, and magnitude of lymphoma risk, as well as coping with awareness of susceptibility to lymphoma. JF - Journal of Genetic Counseling AU - Similuk, Morgan AU - Rao, V Koneti AU - Churpek, Jane AU - Lenardo, Michael AD - National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA ; University of Chicago Medical Center, Chicago, IL, USA ; National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1157 EP - 1170 CY - New York PB - Springer Science & Business Media VL - 25 IS - 6 SN - 1059-7700 KW - Psychology KW - Lymphoma KW - Heredity KW - Predisposition KW - Cancer KW - Mechanism KW - Genetic counseling KW - Risk assessment KW - Immunology KW - Susceptibility KW - Oncology KW - Stimulation KW - Counselling KW - Clinical assessment KW - Genetic family histories KW - Inappropriateness KW - Critical thinking KW - Clinical guidelines KW - Coping KW - Genetic counselling UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841002335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Journal+of+Genetic+Counseling&rft.atitle=Predispositions+to+Lymphoma%3A+A+Practical+Review+for+Genetic+Counselors&rft.au=Similuk%2C+Morgan%3BRao%2C+V+Koneti%3BChurpek%2C+Jane%3BLenardo%2C+Michael&rft.aulast=Similuk&rft.aufirst=Morgan&rft.date=2016-12-01&rft.volume=25&rft.issue=6&rft.spage=1157&rft.isbn=&rft.btitle=&rft.title=Journal+of+Genetic+Counseling&rft.issn=10597700&rft_id=info:doi/10.1007%2Fs10897-016-9979-0 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Journal of Genetic Counseling is a copyright of Springer, 2016. N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1007/s10897-016-9979-0 ER - TY - JOUR T1 - Respiratory toxicity and immunotoxicity evaluations of microparticle and nanoparticle C60 fullerene aggregates in mice and rats following nose-only inhalation for 13 weeks. AN - 1839740976; 27618498 AB - C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1 nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50 nm [nano-C60] and 1 μm [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks. Exposure concentrations were selected to allow for data evaluations using both mass-based and particle surface area-based exposure metrics. Nano-C60 exposure levels selected were 0.5 and 2 mg/m3 (0.033 and 0.112 m2/m3), while micro-C60 exposures were 2, 15 and 30 mg/m3 (0.011, 0.084 and 0.167 m2/m3). There were no systemic effects on innate, cell-mediated, or humoral immune function. Pulmonary inflammatory responses (histiocytic infiltration, macrophage pigmentation, chronic inflammation) were concentration-dependent and corresponded to increases in monocyte chemoattractant protein (MCP)-1 (rats) and macrophage inflammatory protein (MIP)-1α (mice) in bronchoalveolar lavage (BAL) fluid. Lung overload may have contributed to the pulmonary inflammatory responses observed following nano-C60 exposure at 2 mg/m3 and micro-C60 exposure at 30 mg/m3. Phenotype shifts in cells recovered from the BAL were also observed in all C60-exposed rats, regardless of the level of exposure. Overall, more severe pulmonary effects were observed for nano-C60 than for micro-C60 for mass-based exposure comparisons. However, for surface-area-based exposures, more severe pulmonary effects were observed for micro-C60 than for nano-C60, highlighting the importance of dosimetry when evaluating toxicity between nano- and microparticles. JF - Nanotoxicology AU - Sayers, Brian C AU - Germolec, Dori R AU - Walker, Nigel J AU - Shipkowski, Kelly A AU - Stout, Matthew D AU - Cesta, Mark F AU - Roycroft, Joseph H AU - White, Kimber L AU - Baker, Gregory L AU - Dill, Jeffrey A AU - Smith, Matthew J AD - a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA. ; b Department of Pharmacology and Toxicology , Virginia Commonwealth University , Richmond , VA , USA. ; c Battelle Toxicology Northwest , Richland , WA , USA , and. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1458 EP - 1468 VL - 10 IS - 10 KW - inhalation KW - Buckminsterfullerene KW - pulmonary inflammation KW - immunotoxicity KW - nanoparticles UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839740976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nanotoxicology&rft.atitle=Respiratory+toxicity+and+immunotoxicity+evaluations+of+microparticle+and+nanoparticle+C60+fullerene+aggregates+in+mice+and+rats+following+nose-only+inhalation+for+13+weeks.&rft.au=Sayers%2C+Brian+C%3BGermolec%2C+Dori+R%3BWalker%2C+Nigel+J%3BShipkowski%2C+Kelly+A%3BStout%2C+Matthew+D%3BCesta%2C+Mark+F%3BRoycroft%2C+Joseph+H%3BWhite%2C+Kimber+L%3BBaker%2C+Gregory+L%3BDill%2C+Jeffrey+A%3BSmith%2C+Matthew+J&rft.aulast=Sayers&rft.aufirst=Brian&rft.date=2016-12-01&rft.volume=10&rft.issue=10&rft.spage=1458&rft.isbn=&rft.btitle=&rft.title=Nanotoxicology&rft.issn=1743-5404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 ER - TY - JOUR T1 - Phase I study of RO4929097 with bevacizumab in patients with recurrent malignant glioma. AN - 1839106459; 27826680 AB - Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combination of bevacizumab and RO4929097, an inhibitor of the notch signaling cascade. A phase I clinical trial was conducted through the Adult Brain Tumor Consortium in subjects with recurrent malignant glioma. Primary objectives were to assess safety and to define the maximum tolerated dose of RO4929097 in combination with bevacizumab. Secondary objectives were to determine overall survival, progression free survival, radiographic response, pharmacokinetic evaluation, and tissue biomarker analysis. Thirteen subjects were enrolled. Of the three subjects treated with the highest dose of RO4929097, one grade 3 toxicity and one grade 2 toxicity were observed. Definitive maximum tolerated dose of RO4929097 in combination with bevacizumab was not identified due to manufacturer's decision to halt drug production. 2 of 12 evaluable subjects demonstrated radiographic response; one subject experienced CR and the second PR. The median overall survival was 10.9 months with a median progression-free survival of 3.7 months. Two subjects remained free of disease progression at 6 months from treatment initiation. PK evaluation did not identify clinically significant drug-drug interactions. All analyzed tissue specimens revealed activation of notch signaling. Combination of RO4929097 and bevacizumab was well-tolerated. Given the compelling scientific rationale, additional studies of antiangiogenic and notch signaling inhibitors should be considered. JF - Journal of neuro-oncology AU - Pan, Edward AU - Supko, Jeffrey G AU - Kaley, Thomas J AU - Butowski, Nicholas A AU - Cloughesy, Timothy AU - Jung, Jinkyu AU - Desideri, Serena AU - Grossman, Stuart AU - Ye, Xiaobu AU - Park, Deric M AD - Department of Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA. Edward.Pan@UTSouthwestern.edu. ; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. ; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ; Department of Neurological Surgery, University of California, San Francisco, CA, USA. ; Department of Neurology, University of California, Los Angeles, CA, USA. ; Neuro-Oncology Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. ; Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA. ; Neuro-Oncology Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. deric.park@nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 571 EP - 579 VL - 130 IS - 3 KW - Gamma secretase KW - Notch KW - Glioma KW - Bevacizumab KW - Clinical trial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839106459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuro-oncology&rft.atitle=Phase+I+study+of+RO4929097+with+bevacizumab+in+patients+with+recurrent+malignant+glioma.&rft.au=Pan%2C+Edward%3BSupko%2C+Jeffrey+G%3BKaley%2C+Thomas+J%3BButowski%2C+Nicholas+A%3BCloughesy%2C+Timothy%3BJung%2C+Jinkyu%3BDesideri%2C+Serena%3BGrossman%2C+Stuart%3BYe%2C+Xiaobu%3BPark%2C+Deric+M&rft.aulast=Pan&rft.aufirst=Edward&rft.date=2016-12-01&rft.volume=130&rft.issue=3&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=1573-7373&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - HIV Transmission Risk Behavior in a Cohort of HIV-Infected Treatment-Naïve Men and Women in the United States AN - 1838984969 AB - Antiretroviral therapy (ART) can minimize HIV transmission. Prevention benefits may be compromised by barriers to virologic suppression, and by increased condomless sex among those initiating ART. We evaluated condomless sex in a cohort of HIVinfected US individuals poised to initiate ART in a clinical trial. We assessed partner and sex act type, condom use, and perception of infectiousness. Six percent of participants reported as not infectious; men who have sex with men were more likely to perceive high infectivity. Prevalence of condomless sex was 44 %; 74 % of those also reported homosexual acquisition of HIV. Predictors of increased risk of condomless sex included greater numbers of lifetime partners, recent stimulant drug use and an HIV-positive or unknown serostatus partner. In the context of serodifferent partners, lower perception of infectiousness was also associated with a higher risk of condomless sex. Results highlight opportunities for prevention education for HIV infected individuals at ART initiation. JF - AIDS and Behavior AU - Landovitz, Raphael J AU - Tran, Thuy Tien; T AU - Cohn, Susan E AU - Ofotokun, Ighovwhera AU - Godfrey, Catherine AU - Kuritzkes, Daniel R AU - Lennox, Jeffrey L AU - Currier, Judith S AU - Ribaudo, Heather J AD - Division of Infectious Diseases, UCLA Center for Clinical AIDS Research and Education, University of California, Los Angeles, Los Angeles, CA, USA ; Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA, USA ; Division of Infectious Diseases, Northwestern University School of Medicine, Chicago, IL, USA ; Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA ; Therapeutics Research Branch, Division of AIDS, National Institutes of Health, Bethesda, MD, USA ; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA ; Division of Infectious Diseases, UCLA Center for Clinical AIDS Research and Education, University of California, Los Angeles, Los Angeles, CA, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 2983 EP - 2995 CY - New York PB - Springer Science & Business Media VL - 20 IS - 12 SN - 1090-7165 KW - Psychology KW - Condom use KW - HIV transmission KW - ART-naïve KW - Behavior KW - Acquired Immune Deficiency Syndrome KW - Prevention KW - Drug Abuse KW - Homosexuality KW - Sexual Behavior KW - Treatment KW - Medications KW - Risk KW - 6126:acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1838984969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=HIV+Transmission+Risk+Behavior+in+a+Cohort+of+HIV-Infected+Treatment-Na%C3%AFve+Men+and+Women+in+the+United+States&rft.au=Landovitz%2C+Raphael+J%3BTran%2C+Thuy+Tien%3B+T%3BCohn%2C+Susan+E%3BOfotokun%2C+Ighovwhera%3BGodfrey%2C+Catherine%3BKuritzkes%2C+Daniel+R%3BLennox%2C+Jeffrey+L%3BCurrier%2C+Judith+S%3BRibaudo%2C+Heather+J&rft.aulast=Landovitz&rft.aufirst=Raphael&rft.date=2016-12-01&rft.volume=20&rft.issue=12&rft.spage=2983&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1365-2 LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2017-01-10 DO - http://dx.doi.org/10.1007/s10461-016-1365-2 ER - TY - JOUR T1 - A high-throughput functional genomics workflow based on CRISPR/Cas9-mediated targeted mutagenesis in zebrafish. AN - 1836734396; 27809318 AB - The zebrafish is a popular model organism for studying development and disease, and genetically modified zebrafish provide an essential tool for functional genomic studies. Numerous publications have demonstrated the efficacy of gene targeting in zebrafish using CRISPR/Cas9, and they have included descriptions of a variety of tools and methods for guide RNA synthesis and mutant identification. However, most of the published techniques are not readily scalable to increase throughput. We recently described a CRISPR/Cas9-based high-throughput mutagenesis and phenotyping pipeline in zebrafish. Here, we present a complete workflow for this pipeline, including target selection; cloning-free single-guide RNA (sgRNA) synthesis; microinjection; validation of the target-specific activity of the sgRNAs; founder screening to identify germline-transmitting mutations by fluorescence PCR; determination of the exact lesion by Sanger or next-generation sequencing (including software for analysis); and genotyping in the F1 or subsequent generations. Using these methods, sgRNAs can be evaluated in 3 d, zebrafish germline-transmitting mutations can be identified within 3 months and stable lines can be established within 6 months. Realistically, two researchers can target tens to hundreds of genes per year using this protocol. JF - Nature protocols AU - Varshney, Gaurav K AU - Carrington, Blake AU - Pei, Wuhong AU - Bishop, Kevin AU - Chen, Zelin AU - Fan, Chunxin AU - Xu, Lisha AU - Jones, Marypat AU - LaFave, Matthew C AU - Ledin, Johan AU - Sood, Raman AU - Burgess, Shawn M AD - Developmental Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Zebrafish Core, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai, China. ; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Organismal Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 2357 EP - 2375 VL - 11 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836734396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+protocols&rft.atitle=A+high-throughput+functional+genomics+workflow+based+on+CRISPR%2FCas9-mediated+targeted+mutagenesis+in+zebrafish.&rft.au=Varshney%2C+Gaurav+K%3BCarrington%2C+Blake%3BPei%2C+Wuhong%3BBishop%2C+Kevin%3BChen%2C+Zelin%3BFan%2C+Chunxin%3BXu%2C+Lisha%3BJones%2C+Marypat%3BLaFave%2C+Matthew+C%3BLedin%2C+Johan%3BSood%2C+Raman%3BBurgess%2C+Shawn+M&rft.aulast=Varshney&rft.aufirst=Gaurav&rft.date=2016-12-01&rft.volume=11&rft.issue=12&rft.spage=2357&rft.isbn=&rft.btitle=&rft.title=Nature+protocols&rft.issn=1750-2799&rft_id=info:doi/10.1038%2Fnprot.2016.141 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nprot.2016.141 ER - TY - JOUR T1 - Differential susceptibility to acetaminophen-induced liver injury in sub-strains of C57BL/6 mice: 6N versus 6J. AN - 1835540209; 27773698 AB - Mouse models of acetaminophen (APAP) hepatotoxicity are considered relevant for the human pathophysiology. The C57BL/6 strain is most popular because it is the background strain of gene knock-out mice. However, conflicting results in the literature may have been caused by sub-strain mismatches, e.g. C57BL/6J and C57BL/6N. This study was initiated to determine the mechanism behind the sub-strain susceptibility to APAP toxicity. C57BL/6N and C57BL/6J mice were dosed with 200 mg/kg APAP and sacrificed at different time points. C57BL/6N mice developed significantly more liver injury as measured by plasma ALT activities and histology. Although there was no difference in glutathione depletion or cytochrome P450 activity between groups, C57BL/6N had a higher glutathione disulfide-to-glutathione ratio and more APAP protein adducts. C57BL/6N showed more mitochondrial translocation of phospho-JNK and BAX, and more release of mitochondrial intermembrane proteins apoptosis-inducing factor (AIF), second mitochondria-derived activator of caspases (SMAC), which caused more DNA fragmentation. The increased mitochondrial dysfunction was confirmed in vitro as C57BL/6N hepatocytes had a more precipitous drop in JC-1 fluorescence after APAP exposure. C57BL/6N mice are more susceptible to APAP-induced hepatotoxicity, likely due to increased formation of APAP-protein adducts and a subsequent enhancement of mitochondrial dysfunction associated with aggravated nuclear DNA fragmentation. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Duan, Luqi AU - Davis, John S AU - Woolbright, Benjamin L AU - Du, Kuo AU - Cahkraborty, Mala AU - Weemhoff, James AU - Jaeschke, Hartmut AU - Bourdi, Mohammed AD - Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: lduan@kumc.edu. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20850, USA. Electronic address: John.Davis@nih.gov. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: bwoolbright@kmc.edu. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: kdu@kumc.edu. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20850, USA. Electronic address: mala.cahkraborty@nih.gov. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: jweemhoff@kumc.edu. ; Department of Pharmacology, Toxicology & Therapeutics, Kansas City, KS, 66160, USA. Electronic address: hjaeschke@kumc.edu. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20850, USA. Electronic address: mohammed.bourdi@nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 107 EP - 118 VL - 98 KW - DNA fragmentation KW - Protein adducts KW - C57BL/6 sub-strains KW - Acetaminophen hepatotoxicity KW - Mitochondrial dysfunction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835540209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Differential+susceptibility+to+acetaminophen-induced+liver+injury+in%C2%A0sub-strains+of+C57BL%2F6+mice%3A+6N+versus+6J.&rft.au=Duan%2C+Luqi%3BDavis%2C+John+S%3BWoolbright%2C+Benjamin+L%3BDu%2C+Kuo%3BCahkraborty%2C+Mala%3BWeemhoff%2C+James%3BJaeschke%2C+Hartmut%3BBourdi%2C+Mohammed&rft.aulast=Duan&rft.aufirst=Luqi&rft.date=2016-12-01&rft.volume=98&rft.issue=&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.10.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.10.021 ER - TY - JOUR T1 - Dose-response assessment of the dermal toxicity of Virginia cedarwood oil in F344/N rats and B6C3F1/N mice. AN - 1835517347; 27769849 AB - Virginia cedarwood oil is widely used as a fragrance material in household and personal products and as a naturally derived pesticide alternative. Due to conflicting literature on dermal exposures in animals and humans, concern for safe levels of human exposure remains. The present study evaluated the toxicity of cedarwood oil applied dermally to F344/N rats and B6C3F1/N mice for 13 weeks. Groups of 10 male and female rats and mice received no treatment (untreated control) or were administered cedarwood oil in 95% aqueous ethanol dermally at concentrations ranging from 0% (vehicle control), 6.25%, 12.5%, 25%, 50%, and 100% (undiluted). Rats and mice developed extensive skin lesions at the site of application. Benchmark dose modeling (BMD) was performed for the significantly increased skin lesions observed in the rat, to provide perspective for risk assessment applications. Benchmark dose modeling levels (BMDL) of 0.65 to 2.1% and 1.2 to 4.4% (equivalent to 13 to 42 mg/kg and 24 to 48 mg/kg, respectively) cedarwood oil were calculated for the most sensitive endpoint of epidermal hyperplasia in female rats and chronic active inflammation in male rats, respectively. These BMDL levels coincide with reported use levels in cosmetics and pesticides, raising the concern for human exposure. Published by Elsevier Ltd. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Catlin, Natasha R AU - Herbert, Ron AU - Janardhan, Kyathanahalli AU - Hejtmancik, Milton R AU - Fomby, Laurene M AU - Vallant, Molly AU - Kissling, Grace E AU - DeVito, Michael J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: natasha.catlin@nih.gov. ; National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. ; Integrated Laboratory Systems, Inc, Morrisville, NC 27560, USA. ; Battelle, Columbus, OH 43201, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 159 EP - 168 VL - 98 KW - Cedarwood oil KW - Skin KW - Benchmark dose UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835517347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Dose-response+assessment+of+the+dermal+toxicity+of+Virginia+cedarwood+oil+in+F344%2FN+rats+and+B6C3F1%2FN+mice.&rft.au=Catlin%2C+Natasha+R%3BHerbert%2C+Ron%3BJanardhan%2C+Kyathanahalli%3BHejtmancik%2C+Milton+R%3BFomby%2C+Laurene+M%3BVallant%2C+Molly%3BKissling%2C+Grace+E%3BDeVito%2C+Michael+J&rft.aulast=Catlin&rft.aufirst=Natasha&rft.date=2016-12-01&rft.volume=98&rft.issue=&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.10.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.10.016 ER - TY - JOUR T1 - Pharmacokinetics of Unboosted Atazanavir in Treatment-experienced HIV-infected Children, Adolescents and Young Adults. AN - 1835504152; 27583590 AB - HIV protease inhibitor use in pediatrics is challenging due to the poor palatability and/or toxicity of concomitant low-dose ritonavir. Atazanavir without ritonavir (unboosted) is not recommended for patients with prior virologic failure, a common problem for perinatally-infected adolescents. Atazanavir 400 mg once-daily provided suboptimal exposure. Higher unboosted doses or splitting the daily dose to twice-daily warrants investigation in this treatment-experienced population. JF - The Pediatric infectious disease journal AU - Cressey, Tim R AU - Hazra, Rohan AU - Wiznia, Andrew AU - Foca, Marc AU - Jean-Philippe, Patrick AU - Graham, Bobbie AU - King, Jennifer R AU - Britto, Paula AU - Carey, Vincent J AU - Acosta, Edward P AU - Yogev, Ram AU - IMPAACT P1058A Team AD - From the *Program for HIV Prevention and Treatment (IRD UMI 174), Faculty of Associated Medical Sciences, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand; †Harvard T.H Chan School of Public Health, Boston, Massachusetts; ‡National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Pediatric Infectious Disease Branch, Bethesda, Maryland; §Jacobi Medical Center, Bronx, New York; ¶Columbia University Medical Center, New York, New York; ‖HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to NIAID, NIH, DHHS, Bethesda, Maryland; **Frontier Science & Technology, Amherst, New York, New York; ††University of Alabama at Birmingham, Birmingham, Alabama; and ‡‡Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois. ; IMPAACT P1058A Team Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1333 EP - 1335 VL - 35 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835504152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Pharmacokinetics+of+Unboosted+Atazanavir+in+Treatment-experienced+HIV-infected+Children%2C+Adolescents+and+Young+Adults.&rft.au=Cressey%2C+Tim+R%3BHazra%2C+Rohan%3BWiznia%2C+Andrew%3BFoca%2C+Marc%3BJean-Philippe%2C+Patrick%3BGraham%2C+Bobbie%3BKing%2C+Jennifer+R%3BBritto%2C+Paula%3BCarey%2C+Vincent+J%3BAcosta%2C+Edward+P%3BYogev%2C+Ram%3BIMPAACT+P1058A+Team&rft.aulast=Cressey&rft.aufirst=Tim&rft.date=2016-12-01&rft.volume=35&rft.issue=12&rft.spage=1333&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=1532-0987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - RNA interference mediated downregulation of human telomerase reverse transcriptase (hTERT) in LN18 cells. AN - 1835491579; 27757712 AB - Human telomerase reverse transcriptase (hTERT) gene is a biomarker for the targeted therapy in various cancers. Presence of increased telomerase activity is a common feature of all cancers including glioblastoma. Both RNA and catalytic subunits of hTERT are the target sites for blocking its activity. The current study focuses on the expression of hTERT in glioblastoma and its regulation using two different novel siRNAs (small interfering RNA). Our patient data demonstrated increased expression of hTERT, which could be correlated with carcinogenesis in glioma. In vitro studies in siRNA transfected LN18 cells confirmed significant cell death (p < 0.05) as evidenced by MTT and trypan blue exclusion assay. These results were further supported by flow cytometry data, which showed significant increase in early and late apoptosis. The hTERT mRNA expression was effectively downregulated by 45 and 39 % with siRNA1 and siRNA2, respectively. These results were further confirmed by immunoblotting analysis (p < 0.05). Our results suggest that both the siRNAs effectively down regulated the expression of hTERT at mRNA and protein levels, thereby decreasing cell viability and proliferation rate. Hence siRNA mediated downregulation of hTERT could be a potential therapeutic avenue in glioblastoma. JF - Cytotechnology AU - Lavanya, Ch AU - Sibin, M K AU - Srinivas Bharath, M M AU - Manoj, M Jeru AU - Venkataswamy, Manjunatha M AU - Bhat, Dhananjaya I AU - Narasinga Rao, K V L AU - Chetan, G K AD - Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. ; Department of Neuro-chemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. ; Department of Neurovirology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. ; Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India. ; Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India. drchetangk@gmail.com. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 2311 EP - 2321 VL - 68 IS - 6 SN - 0920-9069, 0920-9069 KW - Glioblastoma KW - LN18 cell line KW - Apoptosis KW - Small interfering RNA KW - hTERT UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835491579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotechnology&rft.atitle=RNA+interference+mediated+downregulation+of+human+telomerase+reverse+transcriptase+%28hTERT%29+in+LN18+cells.&rft.au=Lavanya%2C+Ch%3BSibin%2C+M+K%3BSrinivas+Bharath%2C+M+M%3BManoj%2C+M+Jeru%3BVenkataswamy%2C+Manjunatha+M%3BBhat%2C+Dhananjaya+I%3BNarasinga+Rao%2C+K+V+L%3BChetan%2C+G+K&rft.aulast=Lavanya&rft.aufirst=Ch&rft.date=2016-12-01&rft.volume=68&rft.issue=6&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Cytotechnology&rft.issn=09209069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identification and characterization of PPARα ligands in the hippocampus. AN - 1835442303; 27748752 AB - Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions. JF - Nature chemical biology AU - Roy, Avik AU - Kundu, Madhuchhanda AU - Jana, Malabendu AU - Mishra, Rama K AU - Yung, Yeni AU - Luan, Chi-Hao AU - Gonzalez, Frank J AU - Pahan, Kalipada AD - Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. ; Medicinal and Synthetic Chemistry Core, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA. ; Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA. ; High Throughput Analysis Laboratory and Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1075 EP - 1083 VL - 12 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835442303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+chemical+biology&rft.atitle=Identification+and+characterization+of+PPAR%CE%B1+ligands+in+the+hippocampus.&rft.au=Roy%2C+Avik%3BKundu%2C+Madhuchhanda%3BJana%2C+Malabendu%3BMishra%2C+Rama+K%3BYung%2C+Yeni%3BLuan%2C+Chi-Hao%3BGonzalez%2C+Frank+J%3BPahan%2C+Kalipada&rft.aulast=Roy&rft.aufirst=Avik&rft.date=2016-12-01&rft.volume=12&rft.issue=12&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=Nature+chemical+biology&rft.issn=1552-4469&rft_id=info:doi/10.1038%2Fnchembio.2204 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nchembio.2204 ER - TY - JOUR T1 - Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress and apoptosis in mice. AN - 1835409331; 27732911 AB - We hypothesized that dietary walnut would prevent high-fat-diet (HFD)-induced hepatic apoptosis based on its antioxidant properties. Male C57BL/6J mice were fed a rodent chow or HFD (45% energy-derived)±walnuts (21.5% energy-derived) for 6 weeks. Liver histological and biochemical analyses revealed significantly elevated fat accumulation in mice fed HFD compared to mice fed the chow or HFD±walnuts. Walnut supplementation prevented HFD-mediated alteration of the levels of key proteins in lipid homeostasis such as Sirt1, AMPK and FAS, leading to decreased fat accumulation. In addition, walnut supplementation to HFD significantly decreased the hepatic levels of cytochrome P450-2E1, nitrated proteins and lipid peroxidation. Furthermore, walnut supplementation decreased the activated cell-death-associated p-JNK and p-p38K accompanied with increased hepatocyte apoptosis in HFD group. The beneficial effects of dietary walnut likely result, at least partially, from its antioxidant ingredients and attenuating HFD-induced hepatic steatosis, nitroxidative stress and apoptosis. Published by Elsevier Inc. JF - The Journal of nutritional biochemistry AU - Choi, Youngshim AU - Abdelmegeed, Mohamed A AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Electronic address: bj.song@nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 70 EP - 80 VL - 38 KW - JNK KW - Walnut KW - Apoptosis KW - Oxidative stress KW - High-fat diet KW - Liver KW - CYP2E1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835409331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutritional+biochemistry&rft.atitle=Preventive+effects+of+dietary+walnuts+on+high-fat-induced+hepatic+fat+accumulation%2C+oxidative+stress+and+apoptosis+in+mice.&rft.au=Choi%2C+Youngshim%3BAbdelmegeed%2C+Mohamed+A%3BSong%2C+Byoung-Joon&rft.aulast=Choi&rft.aufirst=Youngshim&rft.date=2016-12-01&rft.volume=38&rft.issue=&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutritional+biochemistry&rft.issn=1873-4847&rft_id=info:doi/10.1016%2Fj.jnutbio.2016.08.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jnutbio.2016.08.013 ER - TY - JOUR T1 - Editor's Highlight: Comparative Toxicity of Organophosphate Flame Retardants and Polybrominated Diphenyl Ethers to Caenorhabditis elegans. AN - 1835377030; 27566445 AB - With the phasing-out of the polybrominated diphenyl ether (PBDE) flame retardants due to concerns regarding their potential developmental toxicity, the use of replacement compounds such as organophosphate flame retardants (OPFRs) has increased. Limited toxicity data are currently available to estimate the potential adverse health effects of the OPFRs. The toxicological effects of 4 brominated flame retardants, including 3 PBDEs and 3,3',5,5'-tetrabromobisphenol A, were compared with 6 aromatic OPFRs and 2 aliphatic OPFRs. The effects of these chemicals were determined using 3 biological endpoints in the nematode Caenorhabditis elegans (feeding, larval development, and reproduction). Because C. elegans development was previously reported to be sensitive to mitochondrial function, results were compared with those from an in vitro mitochondrial membrane permeabilization (MMP) assay. Overall 11 of the 12 flame retardants were active in 1 or more C. elegans biological endpoints, with only tris(2-chloroethyl) phosphate inactive across all endpoints including the in vitro MMP assay. For 2 of the C. elegans endpoints, at least 1 OPFR had similar toxicity to the PBDEs: triphenyl phosphate (TPHP) inhibited larval development at levels comparable to the 3 PBDEs; whereas TPHP and isopropylated phenol phosphate (IPP) affected C. elegans reproduction at levels similar to the PBDE commercial mixture, DE-71. The PBDEs reduced C. elegans feeding at lower concentrations than any OPFR. In addition, 9 of the 11 chemicals that inhibited C. elegans larval development also caused significant mitochondrial toxicity. These results suggest that some of the replacement aromatic OPFRs may have levels of toxicity comparable to PBDEs. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Behl, Mamta AU - Rice, Julie R AU - Smith, Marjo V AU - Co, Caroll A AU - Bridge, Matthew F AU - Hsieh, Jui-Hua AU - Freedman, Jonathan H AU - Boyd, Windy A AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. ; Social & Scientific Systems, Inc., Durham, North Carolina. ; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina boydw@niehs.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 241 EP - 252 VL - 154 IS - 2 KW - flame retardants KW - Caenorhabditis elegans KW - mitochondrial toxicity. UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835377030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Editor%27s+Highlight%3A+Comparative+Toxicity+of+Organophosphate+Flame+Retardants+and+Polybrominated+Diphenyl+Ethers+to+Caenorhabditis+elegans.&rft.au=Behl%2C+Mamta%3BRice%2C+Julie+R%3BSmith%2C+Marjo+V%3BCo%2C+Caroll+A%3BBridge%2C+Matthew+F%3BHsieh%2C+Jui-Hua%3BFreedman%2C+Jonathan+H%3BBoyd%2C+Windy+A&rft.aulast=Behl&rft.aufirst=Mamta&rft.date=2016-12-01&rft.volume=154&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - A simple tube adapter to expedite and automate thawing of viably frozen cells. AN - 1835372137; 27594593 AB - Although cryopreserved cell specimens are used throughout biomedical research, the process for thawing samples is labor-intensive and prone to error. Here we describe a small laboratory device that couples an uncapped vial of frozen cells to a conical tube containing warm cell culture media. The entire complex is loaded directly into a centrifuge; within 5min, cells are thawed and diluted out of toxic cryopreservation medium. The recovery and viability of cells are slightly reduced compared to the common (traditional) method. However, antigen-specific T-cell function is not affected. Since no technician time is required (beyond uncapping of vials), our device allows the parallel processing of as many samples as a centrifuge can hold (up to 96, in some models). Moreover, since the samples are not thawed manually in a water bath, the problems associated with technician-to-technician differences in sample handling are minimized, as is the potential for contamination. Importantly, the elimination of substantial labor involving subjective decisions standardizes this process and can reduce variability in results from cryopreserved specimens. Copyright © 2016. Published by Elsevier B.V. JF - Journal of immunological methods AU - Beddall, Margaret AU - Chattopadhyay, Pratip K AU - Kao, Shing-Fen AU - Foulds, Kathy AU - Roederer, Mario AD - ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, United States. ; ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, United States. Electronic address: pchattop@mail.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 74 EP - 78 VL - 439 KW - T-cells KW - flow cytometry KW - Cryopreservation KW - Immunoassay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835372137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunological+methods&rft.atitle=A+simple+tube+adapter+to+expedite+and+automate+thawing+of+viably+frozen+cells.&rft.au=Beddall%2C+Margaret%3BChattopadhyay%2C+Pratip+K%3BKao%2C+Shing-Fen%3BFoulds%2C+Kathy%3BRoederer%2C+Mario&rft.aulast=Beddall&rft.aufirst=Margaret&rft.date=2016-12-01&rft.volume=439&rft.issue=&rft.spage=74&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=1872-7905&rft_id=info:doi/10.1016%2Fj.jim.2016.08.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jim.2016.08.009 ER - TY - JOUR T1 - Off-pathway assembly of fimbria subunits is prevented by chaperone CfaA of CFA/I fimbriae from enterotoxigenic E. coli. AN - 1835369711; 27627030 AB - The assembly of the class 5 colonization factor antigen I (CFA/I) fimbriae of enterotoxigenic E. coli was proposed to proceed via the alternate chaperone-usher pathway. Here, we show that in the absence of the chaperone CfaA, CfaB, the major pilin subunit of CFA/I fimbriae, is able to spontaneously refold and polymerize into cyclic trimers. CfaA kinetically traps CfaB to form a metastable complex that can be stabilized by mutations. Crystal structure of the stabilized complex reveals distinctive interactions provided by CfaA to trap CfaB in an assembly competent state through donor-strand complementation (DSC) and cleft-mediated anchorage. Mutagenesis indicated that DSC controls the stability of the chaperone-subunit complex and the cleft-mediated anchorage of the subunit C-terminus additionally assist in subunit refolding. Surprisingly, over-stabilization of the chaperone-subunit complex led to delayed fimbria assembly, whereas destabilizing the complex resulted in no fimbriation. Thus, CfaA acts predominantly as a kinetic trap by stabilizing subunit to avoid its off-pathway self-polymerization that results in energetically favorable trimers and could serve as a driving force for CFA/I pilus assembly, representing an energetic landscape unique to class 5 fimbria assembly. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Molecular Microbiology published by John Wiley & Sons Ltd. JF - Molecular microbiology AU - Bao, Rui AU - Liu, Yang AU - Savarino, Stephen J AU - Xia, Di AD - Division of Infectious Diseases, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospitals, Sichuan University, Chengdu, 610041, China. ; Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD, 20910-7500, USA. ; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 975 EP - 991 VL - 102 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835369711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+microbiology&rft.atitle=Off-pathway+assembly+of+fimbria+subunits+is+prevented+by+chaperone+CfaA+of+CFA%2FI+fimbriae+from+enterotoxigenic+E.+coli.&rft.au=Bao%2C+Rui%3BLiu%2C+Yang%3BSavarino%2C+Stephen+J%3BXia%2C+Di&rft.aulast=Bao&rft.aufirst=Rui&rft.date=2016-12-01&rft.volume=102&rft.issue=6&rft.spage=975&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=1365-2958&rft_id=info:doi/10.1111%2Fmmi.13530 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/mmi.13530 ER - TY - JOUR T1 - Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer. AN - 1835366182; 27531700 AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer- related deaths. PDAC remains one of the most difficult-to-treat cancers, owing to its unique pathobiological features: a nearly impenetrable desmoplastic stroma, and hypovascular and hypoperfused tumour vessels render most treatment options largely ineffective. Progress in understanding the pathobiology and signalling pathways involved in disease progression is helping researchers to develop novel ways to fight PDAC, including improved nanotechnology-based drug-delivery platforms that have the potential to overcome the biological barriers of the disease that underlie persistent drug resistance. So-called 'nanomedicine' strategies have the potential to enable targeting of the Hedgehog-signalling pathway, the autophagy pathway, and specific RAS-mutant phenotypes, among other pathological processes of the disease. These novel therapies, alone or in combination with agents designed to disrupt the pathobiological barriers of the disease, could result in superior treatments, with increased efficacy and reduced off-target toxicities compared with the current standard-of-care regimens. By overcoming drug-delivery challenges, advances can be made in the treatment of PDAC, a disease for which limited improvement in overall survival has been achieved over the past several decades. We discuss the approaches to nanomedicine that have been pursued to date and those that are the focus of ongoing research, and outline their potential, as well as the key challenges that must be overcome. JF - Nature reviews. Clinical oncology AU - Adiseshaiah, Pavan P AU - Crist, Rachael M AU - Hook, Sara S AU - McNeil, Scott E AD - Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 750 EP - 765 VL - 13 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835366182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Clinical+oncology&rft.atitle=Nanomedicine+strategies+to+overcome+the+pathophysiological+barriers+of+pancreatic+cancer.&rft.au=Adiseshaiah%2C+Pavan+P%3BCrist%2C+Rachael+M%3BHook%2C+Sara+S%3BMcNeil%2C+Scott+E&rft.aulast=Adiseshaiah&rft.aufirst=Pavan&rft.date=2016-12-01&rft.volume=13&rft.issue=12&rft.spage=750&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Clinical+oncology&rft.issn=1759-4782&rft_id=info:doi/10.1038%2Fnrclinonc.2016.119 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nrclinonc.2016.119 ER - TY - JOUR T1 - Autocrine IL-10 functions as a rheostat for M1 macrophage glycolytic commitment by tuning nitric oxide production. AN - 1835365897; 27676159 AB - Inflammatory maturation of M1 macrophages by proinflammatory stimuli such as toll like receptor ligands results in profound metabolic reprogramming resulting in commitment to aerobic glycolysis as evidenced by repression of mitochondrial oxidative phosphorylation (OXPHOS) and enhanced glucose utilization. In contrast, "alternatively activated" macrophages adopt a metabolic program dominated by fatty acid-fueled OXPHOS. Despite the known importance of these developmental stages on the qualitative aspects of an inflammatory response, relatively little is know regarding the regulation of these metabolic adjustments. Here we provide evidence that the immunosuppressive cytokine IL-10 defines a metabolic regulatory loop. Our data show for the first time that lipopolysaccharide (LPS)-induced glycolytic flux controls IL-10-production via regulation of mammalian target of rapamycin (mTOR) and that autocrine IL-10 in turn regulates macrophage nitric oxide (NO) production. Genetic and pharmacological manipulation of IL-10 and nitric oxide (NO) establish that metabolically regulated autocrine IL-10 controls glycolytic commitment by limiting NO-mediated suppression of OXPHOS. Together these data support a model where autocine IL-10 production is controlled by glycolytic flux in turn regulating glycolytic commitment by preserving OXPHOS via suppression of NO. We propose that this IL-10-driven metabolic rheostat maintains metabolic equilibrium during M1 macrophage differentiation and that perturbation of this regulatory loop, either directly by exogenous cellular sources of IL-10 or indirectly via limitations in glucose availability, skews the cellular metabolic program altering the balance between inflammatory and immunosuppressive phenotypes. Copyright © 2016. Published by Elsevier B.V. JF - Redox biology AU - Baseler, Walter A AU - Davies, Luke C AU - Quigley, Laura AU - Ridnour, Lisa A AU - Weiss, Jonathan M AU - Hussain, S Perwez AU - Wink, David A AU - McVicar, Daniel W AD - Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States. ; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States; Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, United States. ; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States. Electronic address: mcvicard@mail.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 12 EP - 23 VL - 10 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835365897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=The+new+psychoactive+substances+5-%282-aminopropyl%29indole+%285-IT%29+and+6-%282-aminopropyl%29indole+%286-IT%29+interact+with+monoamine+transporters+in+brain+tissue.&rft.au=Marusich%2C+Julie+A%3BAntonazzo%2C+Kateland+R%3BBlough%2C+Bruce+E%3BBrandt%2C+Simon+D%3BKavanagh%2C+Pierce+V%3BPartilla%2C+John+S%3BBaumann%2C+Michael+H&rft.aulast=Marusich&rft.aufirst=Julie&rft.date=2016-02-01&rft.volume=101&rft.issue=&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2015.09.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.redox.2016.09.005 ER - TY - JOUR T1 - Equilibrative nucleoside transporter ENT1 as a biomarker of Huntington disease. AN - 1835365254; 27567601 AB - The initial goal of this study was to investigate alterations in adenosine A2A receptor (A2AR) density or function in a rat model of Huntington disease (HD) with reported insensitivity to an A2AR antagonist. Unsuspected negative results led to the hypothesis of a low striatal adenosine tone and to the search for the mechanisms involved. Extracellular striatal concentrations of adenosine were measured with in vivo microdialysis in two rodent models of early neuropathological stages of HD disease, the Tg51 rat and the zQ175 knock-in mouse. In view of the crucial role of the equilibrative nucleoside transporter (ENT1) in determining extracellular content of adenosine, the binding properties of the ENT1 inhibitor [3H]-S-(4-Nitrobenzyl)-6-thioinosine were evaluated in zQ175 mice and the differential expression and differential coexpression patterns of the ENT1 gene (SLC29A1) were analyzed in a large human cohort of HD disease and controls. Extracellular striatal levels of adenosine were significantly lower in both animal models as compared with control littermates and striatal ENT1 binding sites were significantly upregulated in zQ175 mice. ENT1 transcript was significantly upregulated in HD disease patients at an early neuropathological severity stage, but not those with a higher severity stage, relative to non-demented controls. ENT1 transcript was differentially coexpressed (gained correlations) with several other genes in HD disease subjects compared to the control group. The present study demonstrates that ENT1 and adenosine constitute biomarkers of the initial stages of neurodegeneration in HD disease and also predicts that ENT1 could constitute a new therapeutic target to delay the progression of the disease. Published by Elsevier Inc. JF - Neurobiology of disease AU - Guitart, Xavier AU - Bonaventura, Jordi AU - Rea, William AU - Orrú, Marco AU - Cellai, Lucrezia AU - Dettori, Ilaria AU - Pedata, Felicita AU - Brugarolas, Marc AU - Cortés, Antonio AU - Casadó, Vicent AU - Chang, Ching-Pang AU - Narayanan, Manikandan AU - Chern, Yijuang AU - Ferré, Sergi AD - Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, United States. ; Department NEUROFARBA, Division of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy. ; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Center for Biomedical Research in Neurodegenerative Diseases Network and Institute of Biomedicine, 08028 Barcelona, Spain. ; Division of Neuroscience Institute of Biomedical Sciences, Academia Sinica, 11529 Taipei, Taiwan. ; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States. ; Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, United States. Electronic address: sferre@intra.nida.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 47 EP - 53 VL - 96 KW - A(2A) receptor KW - Huntington disease KW - ENT1 KW - Adenosine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835365254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+disease&rft.atitle=Equilibrative+nucleoside+transporter+ENT1+as+a+biomarker+of+Huntington+disease.&rft.au=Guitart%2C+Xavier%3BBonaventura%2C+Jordi%3BRea%2C+William%3BOrr%C3%BA%2C+Marco%3BCellai%2C+Lucrezia%3BDettori%2C+Ilaria%3BPedata%2C+Felicita%3BBrugarolas%2C+Marc%3BCort%C3%A9s%2C+Antonio%3BCasad%C3%B3%2C+Vicent%3BChang%2C+Ching-Pang%3BNarayanan%2C+Manikandan%3BChern%2C+Yijuang%3BFerr%C3%A9%2C+Sergi&rft.aulast=Guitart&rft.aufirst=Xavier&rft.date=2016-12-01&rft.volume=96&rft.issue=&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+disease&rft.issn=1095-953X&rft_id=info:doi/10.1016%2Fj.nbd.2016.08.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.nbd.2016.08.013 ER - TY - JOUR T1 - Prenatal mercury exposure and offspring behaviour in childhood and adolescence. AN - 1835358317; 27633321 AB - There is considerable discussion over the possible harm caused by fetal exposure to mercury, but evidence of such harm is contradictory at levels commonly found in populations with moderate intakes of fish. Further information is needed to inform debate and clarify policy recommendations. Data were collected prospectively for the Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood taken in the first half of pregnancy was assayed for mercury. The outcomes were offspring behavioural assessments collected using the Strengths and Difficulties Questionnaire at seven time points between ages 4 and 16-17 years; five were completed by the mother and two by the teacher. Socioeconomic and biological confounders were first taken into account; further analyses added maternal blood selenium. Separate analyses compared the relationships between prenatal mercury levels and behaviour traits treated as continuous measures in women who ate fish with those who ate no fish in order to determine whether the relationships differed; the hypothesis was that fish consumption had benefits on the brain and masked any mercury effects. In order to prevent Type II errors, the P value for significance was set at 0.10. Prenatal mercury measurements and offspring behaviour results were available for between 2776 (at 47 months) to 1599 mother-child pairs (at 16-17 years). Even given a P value of 0.10, the number of significant results was no greater than expected apart from the relationships with peer problems at 4, 6 and 10-11 years where the relationships with prenatal mercury were negative (i.e. the greater the level of mercury the fewer the problems the child had with his/her peers). There were no significant differences between the associations with mercury found among the offspring of women who ate fish in pregnancy and those who did not, nor did adjustment for selenium make a difference. There were no adverse effects of maternal prenatal mercury levels on the behaviour of the offspring. A similar lack of relationship was found when the analyses were confined to those offspring whose mothers had eaten fish in pregnancy, and no consistent differences were found between the fish and non-fish eaters. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved. JF - Neurotoxicology AU - Golding, Jean AU - Gregory, Steven AU - Emond, Alan AU - Iles-Caven, Yasmin AU - Hibbeln, Joseph AU - Taylor, Caroline M AD - Centre for Child and Adolescent Health, University of Bristol, UK. Electronic address: jean.golding@bristol.ac.uk. ; Centre for Child and Adolescent Health, University of Bristol, UK. ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 87 EP - 94 VL - 57 KW - Child behaviour KW - Dietary fish KW - ALSPAC KW - Prenatal mercury exposure KW - Adolescent behaviour UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835358317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Prenatal+mercury+exposure+and+offspring+behaviour+in+childhood+and+adolescence.&rft.au=Golding%2C+Jean%3BGregory%2C+Steven%3BEmond%2C+Alan%3BIles-Caven%2C+Yasmin%3BHibbeln%2C+Joseph%3BTaylor%2C+Caroline+M&rft.aulast=Golding&rft.aufirst=Jean&rft.date=2016-12-01&rft.volume=57&rft.issue=&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=1872-9711&rft_id=info:doi/10.1016%2Fj.neuro.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuro.2016.09.003 ER - TY - JOUR T1 - Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children. AN - 1835352444; 27697762 AB - Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg-1 daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (Cmax) and areas under the concentration-time curve from 0 to 24 h (AUC0-24) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of <1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22; P = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Antimicrobial agents and chemotherapy AU - Lestner, Jodi M AU - Groll, Andreas H AU - Aljayyoussi, Ghaith AU - Seibel, Nita L AU - Shad, Aziza AU - Gonzalez, Corina AU - Wood, Lauren V AU - Jarosinski, Paul F AU - Walsh, Thomas J AU - Hope, William W AD - Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom jlestner@liverpool.ac.uk. ; Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children's Hospital Münster, Münster, Germany. ; Liverpool School of Tropical Medicine, Liverpool, United Kingdom. ; Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. ; Clinical Investigations Branch, Cancer Treatment Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA. ; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Georgetown University Medical Center, Washington, DC, USA. ; Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. ; Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA. ; Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 7340 EP - 7346 VL - 60 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835352444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Population+Pharmacokinetics+of+Liposomal+Amphotericin+B+in+Immunocompromised+Children.&rft.au=Lestner%2C+Jodi+M%3BGroll%2C+Andreas+H%3BAljayyoussi%2C+Ghaith%3BSeibel%2C+Nita+L%3BShad%2C+Aziza%3BGonzalez%2C+Corina%3BWood%2C+Lauren+V%3BJarosinski%2C+Paul+F%3BWalsh%2C+Thomas+J%3BHope%2C+William+W&rft.aulast=Lestner&rft.aufirst=Jodi&rft.date=2016-12-01&rft.volume=60&rft.issue=12&rft.spage=7340&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=1098-6596&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The Afro-Cardiac Study: Cardiovascular Disease Risk and Acculturation in West African Immigrants in the United States: Rationale and Study Design AN - 1829718292 AB - Cardiovascular disease (CVD) remains the leading cause of death in the United States (US). African-descent populations bear a disproportionate burden of CVD risk factors. With the increase in the number of West African immigrants (WAIs) to the US over the past decades, it is imperative to specifically study this new and substantial subset of the African-descent population and how acculturation impacts their CVD risk. The Afro-Cardiac study, a community-based cross-sectional study of adult WAIs in the Baltimore-Washington metropolis. Guided by the PRECEDE-PROCEED model, we used a modification of the World Health Organization Steps survey to collect data on demographics, socioeconomic status, migration-related factors and behaviors. We obtained physical, biochemical, acculturation measurements as well as a socio-demographic and health history. Our study provides critical data on the CVD risk of WAIs. The framework used is valuable for future epidemiological studies addressing CVD risk and acculturation among immigrants. JF - Journal of Immigrant and Minority Health AU - Commodore-mensah, Yvonne AU - Sampah, Maame AU - Berko, Charles AU - Cudjoe, Joycelyn AU - Abu-bonsrah, Nancy AU - Obisesan, Olawunmi AU - Agyemang, Charles AU - Adeyemo, Adebowale AU - Himmelfarb, Cheryl Dennison AD - Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA ; Johns Hopkins School of Medicine, Baltimore, MD, USA ; Department of Internal Medicine, St. Agnes Hospital, Baltimore, MD, USA ; Johns Hopkins School of Nursing, Baltimore, MD, USA ; A.T Still University, Kirksville, MO, USA ; Amsterdam Medical Centre, University of Amsterdam, Amsterdam, Netherlands ; Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA ; Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1301 EP - 1308 CY - New York PB - Springer Science & Business Media VL - 18 IS - 6 SN - 1557-1912 KW - Medical Sciences KW - African immigrants KW - Cardiovascular disease KW - Immigrants KW - Acculturation KW - Sociodemographic aspects KW - Modification KW - Socioeconomic status KW - African people KW - Migration KW - Death KW - Cardiovascular diseases KW - Risk factors KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1829718292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immigrant+and+Minority+Health&rft.atitle=The+Afro-Cardiac+Study%3A+Cardiovascular+Disease+Risk+and+Acculturation+in+West+African+Immigrants+in+the+United+States%3A+Rationale+and+Study+Design&rft.au=Commodore-mensah%2C+Yvonne%3BSampah%2C+Maame%3BBerko%2C+Charles%3BCudjoe%2C+Joycelyn%3BAbu-bonsrah%2C+Nancy%3BObisesan%2C+Olawunmi%3BAgyemang%2C+Charles%3BAdeyemo%2C+Adebowale%3BHimmelfarb%2C+Cheryl+Dennison&rft.aulast=Commodore-mensah&rft.aufirst=Yvonne&rft.date=2016-12-01&rft.volume=18&rft.issue=6&rft.spage=1301&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immigrant+and+Minority+Health&rft.issn=15571912&rft_id=info:doi/10.1007%2Fs10903-015-0291-0 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-10-18 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10903-015-0291-0 ER - TY - JOUR T1 - Cheminformatics analysis of the AR agonist and antagonist datasets in PubChem AN - 1827902304; PQ0003731672 AB - As one of the largest publicly accessible databases for hosting chemical structures and biological activities, PubChem has been processing bioassay submissions from the community since 2004. With the increase in volume for the deposited data in PubChem, the diversity and wealth of information content also grows. Recently, the Tox21 program, has deposited a series of pairwise data in PubChem regarding to different mechanism of actions (MOA), such as androgen receptor (AR) agonist and antagonist datasets, to study cell toxicity. To the best of our knowledge, little work has been reported from cheminformatics study for these especially pairwise datasets, which may provide insight into the mechanism of actions of the compounds and relationship between chemical structures and functions, as well as guidance for lead compound selection and optimization. Thus, to fill the gap, we performed a comprehensive cheminformatics analysis, including scaffold analysis, matched molecular pair (MMP) analysis as well as activity cliff analysis to investigate the structural characteristics and discontinued structure-activity relationship of the individual dataset (i.e., AR agonist dataset or AR antagonist dataset) and the combined dataset (i.e., the common compounds between the AR agonist and antagonist datasets). Scaffolds associated only with potential agonists or antagonists were identified. MMP-based activity cliffs, as well as a small group of compounds with dual MOA reported were recognized and analyzed. Moreover, MOA-cliff, a novel concept, was proposed to indicate one pair of structurally similar molecules which exhibit opposite MOA. Cheminformatics methods were successfully applied to the pairwise AR datasets and the identified molecular scaffold characteristics, MMPs as well as activity cliffs might provide useful information when designing new lead compounds for the androgen receptor. JF - Journal of Cheminformatics AU - Hao, Ming AU - Bryant, Stephen H AU - Wang, Yanli AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA, ywang@ncbi.nlm.nih.gov Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 EP - 13 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 8 IS - 1 KW - Biotechnology and Bioengineering Abstracts KW - Androgen receptors KW - Databases KW - Computer programs KW - Data processing KW - Informatics KW - Toxicity KW - Structure-activity relationships KW - scaffolds KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827902304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cheminformatics&rft.atitle=Cheminformatics+analysis+of+the+AR+agonist+and+antagonist+datasets+in+PubChem&rft.au=Hao%2C+Ming%3BBryant%2C+Stephen+H%3BWang%2C+Yanli&rft.aulast=Hao&rft.aufirst=Ming&rft.date=2016-12-01&rft.volume=8&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cheminformatics&rft.issn=1758-2946&rft_id=info:doi/10.1186%2Fs13321-016-0150-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 34 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Androgen receptors; Computer programs; Databases; Data processing; Informatics; Toxicity; Structure-activity relationships; scaffolds DO - http://dx.doi.org/10.1186/s13321-016-0150-6 ER - TY - JOUR T1 - Literature information in PubChem: associations between PubChem records and scientific articles AN - 1827902115; PQ0003731662 AB - PubChem is an open archive consisting of a set of three primary public databases (BioAssay, Compound, and Substance). It contains information on a broad range of chemical entities, including small molecules, lipids, carbohydrates, and (chemically modified) amino acid and nucleic acid sequences (including siRNA and miRNA). Currently (as of Nov. 2015), PubChem contains more than 150 million depositor-provided chemical substance descriptions, 60 million unique chemical structures, and 225 million biological activity test results provided from over 1 million biological assay records. Many PubChem records (substances, compounds, and assays) include depositor-provided cross-references to scientific articles in PubMed. Some PubChem contributors provide bioactivity data extracted from scientific articles. Literature-derived bioactivity data complement high-throughput screening (HTS) data from the concluded NIH Molecular Libraries Program and other HTS projects. Some journals provide PubChem with information on chemicals that appear in their newly published articles, enabling concurrent publication of scientific articles in journals and associated data in public databases. In addition, PubChem links records to PubMed articles indexed with the Medical Subject Heading (MeSH) controlled vocabulary thesaurus. Literature information, both provided by depositors and derived from MeSH annotations, can be accessed using PubChem's web interfaces, enabling users to explore information available in literature related to PubChem records beyond typical web search results. [Figure not available: see fulltext.] JF - Journal of Cheminformatics AU - Kim, Sunghwan AU - Thiessen, Paul A AU - Cheng, Tiejun AU - Yu, Bo AU - Shoemaker, Benjamin A AU - Wang, Jiyao AU - Bolton, Evan E AU - Wang, Yanli AU - Bryant, Stephen H AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Department of Health and Human Services, 8600 Rockville Pike, Bethesda, MD, 20894, USA, kimsungh@ncbi.nlm.nih.gov Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1 EP - 15 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 8 IS - 1 KW - Biotechnology and Bioengineering Abstracts KW - Databases KW - Computer programs KW - Data processing KW - nucleic acids KW - siRNA KW - Informatics KW - Lipids KW - miRNA KW - high-throughput screening KW - Carbohydrates KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827902115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cheminformatics&rft.atitle=Literature+information+in+PubChem%3A+associations+between+PubChem+records+and+scientific+articles&rft.au=Kim%2C+Sunghwan%3BThiessen%2C+Paul+A%3BCheng%2C+Tiejun%3BYu%2C+Bo%3BShoemaker%2C+Benjamin+A%3BWang%2C+Jiyao%3BBolton%2C+Evan+E%3BWang%2C+Yanli%3BBryant%2C+Stephen+H&rft.aulast=Kim&rft.aufirst=Sunghwan&rft.date=2016-12-01&rft.volume=8&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cheminformatics&rft.issn=1758-2946&rft_id=info:doi/10.1186%2Fs13321-016-0142-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 31 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Computer programs; Databases; nucleic acids; Data processing; siRNA; Informatics; Lipids; miRNA; high-throughput screening; Carbohydrates DO - http://dx.doi.org/10.1186/s13321-016-0142-6 ER - TY - JOUR T1 - A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer. AN - 1826727501; 27439894 AB - Background Cabozantinib and gemcitabine improve tumor control in pancreatic ductal adenocarcinoma (PDAC) in preclinical models through c-Met inhibition. We sought to determine the maximum tolerated dose (MTD) of this combination in patients with advanced PDAC. Methods Patients with ≤1 prior treatment and adequate performance status were eligible. Cabozantinib was given orally once daily, beginning day (-)7 and continued with gemcitabine given intravenously on days 1, 8, and 15 every 28 days. Dose level was assigned using Time to Event Continual Reassessment Method (TITE-CRM). Primary endpoint was MTD, defined as the highest dose level at which ≤25 % of patients incurred a dose-limiting toxicity (DLT). Secondary endpoints included response rate, progression-free survival (PFS), overall survival (OS) and urinary biomarker assessment. Results Twelve patients were enrolled and treated with 10 patients evaluable for DLT. The probability of DLT was >25 % for all dose levels tested, and thus an MTD was not determined. DLTs included grade 3 ALT/AST elevations and thrombocytopenia. Three patients had partial responses, but each discontinued therapy due to toxicity. Median PFS and OS were 4.7 (95 % CI: 1.4-9.7) and 10.1 months (95 % CI: 3.6-20.6). Exploratory biomarker analysis showed correlation of c-Met and VEGF levels with response. Conclusions An MTD for the combination was not established. Cabozantinib and gemcitabine appear impractical for further development due to DLT at low doses and continuing toxicities with ongoing therapy. Acknowledging the small sample size, responses were seen suggesting further investigation of c-Met inhibition in PDAC may be warranted. JF - Investigational new drugs AU - Zhen, David B AU - Griffith, Kent A AU - Ruch, Joshua M AU - Camphausen, Kevin AU - Savage, Jason E AU - Kim, Edward J AU - Sahai, Vaibhav AU - Simeone, Diane M AU - Zalupski, Mark M AD - Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, 3-219 CC, 1500 E Medical Center Dr., SPC 5934, Ann Arbor, MI, 48109-5934, USA. ; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA. ; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA. ; Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, 3-219 CC, 1500 E Medical Center Dr., SPC 5934, Ann Arbor, MI, 48109-5934, USA. zalupski@med.umich.edu. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 733 EP - 739 VL - 34 IS - 6 KW - XL-184 KW - Pancreatic cancer KW - Cabozantinib KW - Gemcitabine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826727501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=A+phase+I+trial+of+cabozantinib+and+gemcitabine+in+advanced+pancreatic+cancer.&rft.au=Zhen%2C+David+B%3BGriffith%2C+Kent+A%3BRuch%2C+Joshua+M%3BCamphausen%2C+Kevin%3BSavage%2C+Jason+E%3BKim%2C+Edward+J%3BSahai%2C+Vaibhav%3BSimeone%2C+Diane+M%3BZalupski%2C+Mark+M&rft.aulast=Zhen&rft.aufirst=David&rft.date=2016-12-01&rft.volume=34&rft.issue=6&rft.spage=733&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=1573-0646&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on Occurrence and Severity of Alcoholic Hepatitis. AN - 1826704402; 27320325 AB - Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort, consisting of subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex. We compared data from 145 patients with AH and 124 controls based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the timeline followback method, the Alcohol Use Disorders Identification Test, and the National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses to assess the effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH. Cases with AH were older (47 vs 44 y; P = .03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with AH. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for the severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single-nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P = .007). Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for AH may be associated with the PNPLA3 rs738409 polymorphism. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association AU - Liangpunsakul, Suthat AU - Puri, Puneet AU - Shah, Vijay H AU - Kamath, Patrick AU - Sanyal, Arun AU - Urban, Thomas AU - Ren, Xiaowei AU - Katz, Barry AU - Radaeva, Svetlana AU - Chalasani, Naga AU - Crabb, David W AU - Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium AD - Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Medicine, Roudebush Veterans Administration Medical Center, Indianapolis, Indiana. Electronic address: sliangpu@iupui.edu. ; Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia. ; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. ; Division of Pharmacotherapy and Experimental Therapeutics, Center for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina. ; Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University School of Medicine, Indianapolis, Indiana. ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland. ; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. ; Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Eskenazi Health, Indianapolis, Indiana. ; Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1831 EP - 1838.e3 VL - 14 IS - 12 KW - Body Weight KW - Gender KW - TLFB KW - Alcoholic Hepatitis KW - TREAT KW - Alcohol Intake UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826704402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.atitle=Effects+of+Age%2C+Sex%2C+Body+Weight%2C+and+Quantity+of+Alcohol+Consumption+on+Occurrence+and+Severity+of+Alcoholic+Hepatitis.&rft.au=Liangpunsakul%2C+Suthat%3BPuri%2C+Puneet%3BShah%2C+Vijay+H%3BKamath%2C+Patrick%3BSanyal%2C+Arun%3BUrban%2C+Thomas%3BRen%2C+Xiaowei%3BKatz%2C+Barry%3BRadaeva%2C+Svetlana%3BChalasani%2C+Naga%3BCrabb%2C+David+W%3BTranslational+Research+and+Evolving+Alcoholic+Hepatitis+Treatment+Consortium&rft.aulast=Liangpunsakul&rft.aufirst=Suthat&rft.date=2016-12-01&rft.volume=14&rft.issue=12&rft.spage=1831&rft.isbn=&rft.btitle=&rft.title=Clinical+gastroenterology+and+hepatology+%3A+the+official+clinical+practice+journal+of+the+American+Gastroenterological+Association&rft.issn=1542-7714&rft_id=info:doi/10.1016%2Fj.cgh.2016.05.041 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cgh.2016.05.041 ER - TY - JOUR T1 - Age-dependent PPARα activation induces hepatic sulfatide accumulation in transgenic mice carrying the hepatitis C virus core gene. AN - 1826704368; 27318478 AB - Sulfatides, a type of glycosphingolipid, are associated with carcinogenesis. Peroxisome proliferator-activated receptor α (PPARα) is involved in the regulation of sulfatide metabolism as well as in cancer development. We previously reported that transgenic (Tg) mice expressing hepatitis C virus core protein (HCVcp) exhibited age-dependent PPARα activation and carcinogenesis in liver. However, the metabolism of sulfatides in hepatocellular carcinoma is unknown. To examine the relationship between sulfatide metabolism, carcinogenesis, HCVcp, and PPARα, age-dependent changes of these factors were examined in HCVcpTg, PPARα inhibitor-treated HCVcpTg, and non-Tg mice. The sulfatide content in liver, the hepatic expression of two key enzymes catalyzing the initial and last reactions in sulfatide synthesis, the hepatic expression of known sulfatide-transferring protein, oxidative stress, and hepatic PPARα expression and its activation were age-dependently increased in HCVcpTg mice. The increased synthesis and accumulation of sulfatides and PPARα activation were significantly enhanced in liver cancer lesions. These changes were attenuated by PPARα inhibitor treatment and not observed in non-Tg mice. These results suggest that HCVcp-induced age-dependent PPARα activation increases synthesis of sulfatides and the resulting sulfatide accumulation affects HCV-related liver cancer. The monitoring of hepatic sulfatide content and the modulation of sulfatide generation by intervention using a PPARα inhibitor might be useful for the prediction and prevention of HCV-related hepatocarcinogenesis, respectively. JF - Glycoconjugate journal AU - Tian, Yangyang AU - Yang, Yang AU - Zhang, Xiaowei AU - Nakajima, Takero AU - Tanaka, Naoki AU - Sugiyama, Eiko AU - Kamijo, Yuji AU - Lu, Yu AU - Moriya, Kyoji AU - Koike, Kazuhiko AU - Gonzalez, Frank J AU - Aoyama, Toshifumi AD - Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, 390-8621, Japan. ; Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China. ; Department of Nutritional Science, Prefectural College, Nagano, Nagano, 380-8525, Japan. ; Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. yujibeat@shinshu-u.ac.jp. ; Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. ; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 927 EP - 936 VL - 33 IS - 6 KW - Sphingolipid KW - HCV KW - Sulfatide KW - Cancer KW - PPARα KW - Core protein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826704368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glycoconjugate+journal&rft.atitle=Age-dependent+PPAR%CE%B1+activation+induces+hepatic+sulfatide+accumulation+in+transgenic+mice+carrying+the+hepatitis+C+virus+core+gene.&rft.au=Tian%2C+Yangyang%3BYang%2C+Yang%3BZhang%2C+Xiaowei%3BNakajima%2C+Takero%3BTanaka%2C+Naoki%3BSugiyama%2C+Eiko%3BKamijo%2C+Yuji%3BLu%2C+Yu%3BMoriya%2C+Kyoji%3BKoike%2C+Kazuhiko%3BGonzalez%2C+Frank+J%3BAoyama%2C+Toshifumi&rft.aulast=Tian&rft.aufirst=Yangyang&rft.date=2016-12-01&rft.volume=33&rft.issue=6&rft.spage=927&rft.isbn=&rft.btitle=&rft.title=Glycoconjugate+journal&rft.issn=1573-4986&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma. AN - 1826693603; 27232378 AB - Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016. © 2016 Wiley Periodicals, Inc. JF - Head & neck AU - Geiger, Jessica L AU - Bauman, Julie E AU - Gibson, Michael K AU - Gooding, William E AU - Varadarajan, Prakash AU - Kotsakis, Athanasios AU - Martin, Daniel AU - Gutkind, Jorge Silvio AU - Hedberg, Matthew L AU - Grandis, Jennifer R AU - Argiris, Athanassios AD - Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania. ; Department of Internal Medicine, Division of Hematology/Oncology, Case Western University, Cleveland, Ohio. ; Biostatistics Facility, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. ; Department of Medicine, Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. ; School of Medicine, University of Crete, Crete, Greece. ; National Institute of Dental and Craniofacial Research, Bethesda, Maryland. ; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. ; Department of Otolaryngology, University of California San Francisco, San Francisco, California. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1759 EP - 1764 VL - 38 IS - 12 KW - PIK3CA mutations KW - mammalian target of rapamycin (mTOR) inhibitors KW - head and neck squamous cell carcinoma (HNSCC) KW - clinical trial KW - everolimus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826693603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Head+%26+neck&rft.atitle=Phase+II+trial+of+everolimus+in+patients+with+previously+treated+recurrent+or+metastatic+head+and+neck+squamous+cell+carcinoma.&rft.au=Geiger%2C+Jessica+L%3BBauman%2C+Julie+E%3BGibson%2C+Michael+K%3BGooding%2C+William+E%3BVaradarajan%2C+Prakash%3BKotsakis%2C+Athanasios%3BMartin%2C+Daniel%3BGutkind%2C+Jorge+Silvio%3BHedberg%2C+Matthew+L%3BGrandis%2C+Jennifer+R%3BArgiris%2C+Athanassios&rft.aulast=Geiger&rft.aufirst=Jessica&rft.date=2016-12-01&rft.volume=38&rft.issue=12&rft.spage=1759&rft.isbn=&rft.btitle=&rft.title=Head+%26+neck&rft.issn=1097-0347&rft_id=info:doi/10.1002%2Fhed.24501 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hed.24501 ER - TY - JOUR T1 - Impact of lysosome status on extracellular vesicle content and release. AN - 1826689810; 27238186 AB - Extracellular vesicles (EVs) are nanoscale size bubble-like membranous structures released from cells. EVs contain RNA, lipids and proteins and are thought to serve various roles including intercellular communication and removal of misfolded proteins. The secretion of misfolded and aggregated proteins in EVs may be a cargo disposal alternative to the autophagy-lysosomal and ubiquitin-proteasome pathways. In this review we will discuss the importance of lysosome functionality for the regulation of EV secretion and content. Exosomes are a subtype of EVs that are released by the fusion of multivesicular bodies (MVB) with the plasma membrane. MVBs can also fuse with lysosomes, and the trafficking pathway of MVBs can therefore determine whether or not exosomes are released from cells. Here we summarize data from studies of the effects of lysosome inhibition on the secretion of EVs and on the possibility that cells compensate for lysosome malfunction by disposal of potentially toxic cargos in EVs. A better understanding of the molecular mechanisms that regulate trafficking of MVBs to lysosomes and the plasma membrane may advance an understanding of diseases in which pathogenic proteins, lipids or infectious agents accumulate within or outside of cells. Copyright © 2016. Published by Elsevier B.V. JF - Ageing research reviews AU - Eitan, Erez AU - Suire, Caitlin AU - Zhang, Shi AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA. Electronic address: erez.eitan@nih.gov. ; Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 65 EP - 74 VL - 32 KW - Parkinson’s disease KW - Alzheimer’s disease KW - Niemann pick disease KW - HIV AIDS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826689810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ageing+research+reviews&rft.atitle=Impact+of+lysosome+status+on+extracellular+vesicle+content+and+release.&rft.au=Eitan%2C+Erez%3BSuire%2C+Caitlin%3BZhang%2C+Shi%3BMattson%2C+Mark+P&rft.aulast=Eitan&rft.aufirst=Erez&rft.date=2016-12-01&rft.volume=32&rft.issue=&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Ageing+research+reviews&rft.issn=1872-9649&rft_id=info:doi/10.1016%2Fj.arr.2016.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.arr.2016.05.001 ER - TY - JOUR T1 - The role of hepatitis E virus infection in adult Americans with acute liver failure. AN - 1826689111; 27215797 AB - Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG- subjects (63% vs. 70%; P = 0.018). Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. (Hepatology 2016;64:1870-1880). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Fontana, Robert John AU - Engle, Ronald E AU - Scaglione, Steven AU - Araya, Victor AU - Shaikh, Obaid AU - Tillman, Holly AU - Attar, Nahid AU - Purcell, Robert H AU - Lee, William M AU - US Acute Liver Failure Study Group AD - Department of Internal Medicine, University of Michigan, Ann Arbor, MI. ; National Institute of Allergy and Infectious Diseases, Bethesda, MD. ; Department of Internal Medicine, Loyola Medical Center, Maywood, IL. ; Einstein Medical Center, Philadelphia, PA. ; Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA. ; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC. ; University of Texas Southwestern, Dallas, TX. ; US Acute Liver Failure Study Group Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1870 EP - 1880 VL - 64 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826689111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=The+role+of+hepatitis+E+virus+infection+in+adult+Americans+with+acute+liver+failure.&rft.au=Fontana%2C+Robert+John%3BEngle%2C+Ronald+E%3BScaglione%2C+Steven%3BAraya%2C+Victor%3BShaikh%2C+Obaid%3BTillman%2C+Holly%3BAttar%2C+Nahid%3BPurcell%2C+Robert+H%3BLee%2C+William+M%3BUS+Acute+Liver+Failure+Study+Group&rft.aulast=Fontana&rft.aufirst=Robert&rft.date=2016-12-01&rft.volume=64&rft.issue=6&rft.spage=1870&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28649 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28649 ER - TY - JOUR T1 - Critical concepts, practice recommendations, and research perspectives of pixantrone therapy in non-Hodgkin lymphoma: a SIE, SIES, and GITMO consensus paper. AN - 1826680952; 27124765 AB - In this paper, we present a review of critical concepts and research perspectives and produce recommendations on the optimal use of pixantrone in non-Hodgkin lymphoma (NHL) by group discussion from an expert panel appointed by the Italian Society of Hematology and the affiliate societies, Società Italiana di Ematologia Sperimentale and Gruppo Italiano Trapianto di Midollo Osseo. Recommendations were produced using the Delphi process. Scientific evidence on pixantrone efficacy was analyzed using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology in the areas where at least one randomized trial was published. The following key issues were addressed for practical recommendations: pixantrone monotherapy in aggressive relapsed or refractory non-Hodgkin B-cell lymphomas and toxicity risk management in patients candidates to pixantrone. After a balanced and value-oriented discussion, the panel agreed that the benefit/risk profile was in favor of pixantrone in the treatment of adult patients with multiply relapsed or refractory aggressive NHL B-cell lymphomas. Pixantrone was deemed to be contraindicated in patients with uncontrolled cardiovascular disease. Despite a low rate of cardiotoxicity of pixantrone reported in clinical trials, the panel recommended that all patients receiving pixantrone should undergo periodical cardiac monitoring. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. JF - European journal of haematology AU - Zinzani, Pier Luigi AU - Corradini, Paolo AU - Martelli, Maurizio AU - Minotti, Giorgio AU - Oliva, Stefano AU - Spina, Michele AU - Barosi, Giovanni AU - Tura, Sante AD - Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy. ; Division of Hematology and Bone Marrow Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano, Milan, Italy. ; Dipartimento Biotecnologie Cellulari ed Ematologia, Universitá La Sapienza, Rome, Italy. ; Department of Medicine and Units of Drug Sciences and Clinical Pharmacology, University Campus Bio-Medico, Rome, Italy. ; Cardiology Unit, National Cancer Institute IRCCS "Giovanni Paolo II", Bari, Italy. ; Division of Medical Oncology A, National Cancer Institute, Aviano, Italy. ; Center of the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy. ; University of Bologna, Bologna, Italy. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 554 EP - 561 VL - 97 IS - 6 KW - guidelines KW - pixantrone KW - GRADE methodology KW - non-Hodgkin lymphoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826680952?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+haematology&rft.atitle=Critical+concepts%2C+practice+recommendations%2C+and+research+perspectives+of+pixantrone+therapy+in+non-Hodgkin+lymphoma%3A+a+SIE%2C+SIES%2C+and+GITMO+consensus+paper.&rft.au=Zinzani%2C+Pier+Luigi%3BCorradini%2C+Paolo%3BMartelli%2C+Maurizio%3BMinotti%2C+Giorgio%3BOliva%2C+Stefano%3BSpina%2C+Michele%3BBarosi%2C+Giovanni%3BTura%2C+Sante&rft.aulast=Zinzani&rft.aufirst=Pier&rft.date=2016-12-01&rft.volume=97&rft.issue=6&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=European+journal+of+haematology&rft.issn=1600-0609&rft_id=info:doi/10.1111%2Fejh.12768 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/ejh.12768 ER - TY - JOUR T1 - MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1. AN - 1826677374; 27157613 AB - ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC. TZ and lapatinib ability to block extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase (PI3K)/AKT in sensitive cells inhibits c-Myc activation, which results in upregulation of miR-16. Forced expression of miR-16 inhibited in vitro proliferation in BC and GC cells, both sensitive and resistant to TZ and lapatinib, as well as in a preclinical BC model resistant to these agents. This reveals miR-16 role as tumor suppressor in ErbB-2-positive BC and GC. Using genome-wide expression studies and miRNA target prediction algorithms, we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. Supporting the clinical relevance of our results, we found that high levels of miR-16 and low or null FUBP1 expression correlate with TZ response in ErbB-2-positive primary BCs. These findings highlight a potential role of miR-16 and FUBP1 as biomarkers of sensitivity to TZ therapy. Furthermore, we revealed miR-16 as an innovative therapeutic agent for TZ- and lapatinib-resistant ErbB-2-positive BC and GC. JF - Oncogene AU - Venturutti, L AU - Cordo Russo, R I AU - Rivas, M A AU - Mercogliano, M F AU - Izzo, F AU - Oakley, R H AU - Pereyra, M G AU - De Martino, M AU - Proietti, C J AU - Yankilevich, P AU - Roa, J C AU - Guzmán, P AU - Cortese, E AU - Allemand, D H AU - Huang, T H AU - Charreau, E H AU - Cidlowski, J A AU - Schillaci, R AU - Elizalde, P V AD - Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina. ; Department of Medicine, Weill Cornell Medicine, New York, NY, USA. ; Department of Health and Human Services, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. ; Instituto de Investigación en Biomedicina de Buenos Aires, CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina. ; Departamento de Anatomía Patológica (BIOREN), Universidad de La Frontera, Temuco, Chile. ; Servicio de Ginecología, Hospital Aeronáutico Central, Buenos Aires, Argentina. ; Unidad de Patología Mamaria, Hospital General de Agudos 'Juan A Fernández', Buenos Aires, Argentina. ; Department of Molecular Medicine/Institute of Biotechnology, Cancer Therapy and Research Center, University of Texas, San Antonio, TX, USA. Y1 - 2016/12/01/ PY - 2016 DA - 2016 Dec 01 SP - 6189 EP - 6202 VL - 35 IS - 48 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826677374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=MiR-16+mediates+trastuzumab+and+lapatinib+response+in+ErbB-2-positive+breast+and+gastric+cancer+via+its+novel+targets+CCNJ+and+FUBP1.&rft.au=Venturutti%2C+L%3BCordo+Russo%2C+R+I%3BRivas%2C+M+A%3BMercogliano%2C+M+F%3BIzzo%2C+F%3BOakley%2C+R+H%3BPereyra%2C+M+G%3BDe+Martino%2C+M%3BProietti%2C+C+J%3BYankilevich%2C+P%3BRoa%2C+J+C%3BGuzm%C3%A1n%2C+P%3BCortese%2C+E%3BAllemand%2C+D+H%3BHuang%2C+T+H%3BCharreau%2C+E+H%3BCidlowski%2C+J+A%3BSchillaci%2C+R%3BElizalde%2C+P+V&rft.aulast=Venturutti&rft.aufirst=L&rft.date=2016-12-01&rft.volume=35&rft.issue=48&rft.spage=6189&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2016.151 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2016.151 ER - TY - JOUR T1 - Influence of 6-Hydroxydopamine Toxicity on α-Synuclein Phosphorylation, Resting Vesicle Expression, and Vesicular Dopamine Release. AN - 1826666228; 27064513 AB - Post mortem studies on familial and sporadic Parkinson's disease patient striatal tissue have shown that nearly 90% of α-synuclein deposited in Lewy-bodies is phosphorylated at serine-129 (pSyn-129) as opposed to only 4% in normal human brain. We aimed to find the influence of endogenous neurotoxin 6-hydroxydopamine (6-OHDA) on α-synuclein phosphorylation, resting vesicles, and vesicular dopamine release. The relative distribution of pSyn-129+ cells in apoptotic and non-apoptotic populations at different 6-OHDA concentrations was assessed along with changes in oxidant-antioxidant system, mitochondrial membrane-potential, and intracellular-Ca2+ . Exposing SH-SY5Y cells to different concentrations of 6-OHDA for 48 h showed cell-death and apoptosis. Immunocytochemical analysis indicated an increase in pSyn-129 with increasing 6-OHDA concentration, and ELISA-estimation showed a significant increase in the pSyn-129 to α-synuclein ratio. FACS analysis also showed a significant increase in pSyn-129; and at sub-lethal 6-OHDA concentrations, pSyn-129+ cells were primarily distributed in the non-apoptotic population, suggesting that phosphorylation of α-synuclein precedes apoptosis. At higher 6-OHDA concentrations, the pSyn-129+ cell count significantly increased in the apoptotic population and decreased in the non-apoptotic population. Cytosolic co-localization of α-synuclein and ubiquitin was noticed at higher doses of 6-OHDA. FACS analysis showed decrease in vesicular monoamine transporter-2 (VMAT2) expression in 6-OHDA-treated cells, confirmed by reduction in functional dopamine-release on KCl and ATP stimulation. Significant decrease in VMAT2 expression and vesicular dopamine-release were observed with the lower 6-OHDA concentration, together with mild occurrence of apoptosis and significant increase in phosphorylated α-synuclein. This suggests that at sub-lethal 6-OHDA concentrations, the decrease in resting vesicles (VMAT2) and vesicular dopamine release are not attributable to apoptotic cell death and occur concomitantly with the phosphorylation of α-synuclein. J. Cell. Biochem. 117: 2719-2736, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. JF - Journal of cellular biochemistry AU - Ganapathy, Kavina AU - Datta, Indrani AU - Sowmithra, Sowmithra AU - Joshi, Preeti AU - Bhonde, Ramesh AD - School of Regenerative Medicine, Manipal University, Bengaluru, Karnataka, India. ; Department of Biophysics, National Institute of Mental Health and Neurosciences, an Institute of National Importance, Bengaluru, Karnataka, India. indranidatta.nimhans@gmail.com. ; Department of Biophysics, National Institute of Mental Health and Neurosciences, an Institute of National Importance, Bengaluru, Karnataka, India. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 2719 EP - 2736 VL - 117 IS - 12 KW - APOPTOSIS KW - SUB-LETHAL CONCENTRATION OF 6-OHDA KW - PHOSPHO SERINE129 α-SYNUCLEIN KW - MITOCHONDRIAL MEMBRANE POTENTIAL KW - VESICULAR MONOAMINE TRANSPORTER KW - IN VITRO PD MODEL UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826666228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Influence+of+6-Hydroxydopamine+Toxicity+on+%CE%B1-Synuclein+Phosphorylation%2C+Resting+Vesicle+Expression%2C+and+Vesicular+Dopamine+Release.&rft.au=Ganapathy%2C+Kavina%3BDatta%2C+Indrani%3BSowmithra%2C+Sowmithra%3BJoshi%2C+Preeti%3BBhonde%2C+Ramesh&rft.aulast=Ganapathy&rft.aufirst=Kavina&rft.date=2016-12-01&rft.volume=117&rft.issue=12&rft.spage=2719&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=1097-4644&rft_id=info:doi/10.1002%2Fjcb.25570 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/jcb.25570 ER - TY - JOUR T1 - PPARα-dependent cholesterol/testosterone disruption in Leydig cells mediates 2,4-dichlorophenoxyacetic acid-induced testicular toxicity in mice. AN - 1826658977; 26838045 AB - It was reported that 2,4-dichlorophenoxyacetic acid (2,4-D), a commonly used herbicide and a possible endocrine disruptor, can disturb spermatogenesis, but the precise mechanism is not understood. Since 2,4-D is a weak peroxisome proliferator in hepatocytes and peroxisome proliferator-activated receptor α (PPARα) is also expressed in Leydig cells, this study aimed to investigate the link between PPARα and 2,4-D-mediated testicular dysfunction. 2,4-D (130 mg/kg/day) was administered to wild-type and Ppara-null mice for 2 weeks, and the alterations in testis and testosterone/cholesterol metabolism in Leydig cells were examined. Treatment with 2,4-D markedly decreased testicular testosterone in wild-type mice, leading to degeneration of spermatocytes and Sertoli cells. The 2,4-D decreased cholesterol levels in Leydig cells of wild-type mice through down-regulating the expression of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 and reductase, involved in de novo cholesterogenesis. However, the mRNAs encoding the important proteins involved in testosterone synthesis were unchanged by 2,4-D except for CYP17A1, indicating that exhausted cholesterol levels in the cells is a main reason for reduced testicular testosterone. Additionally, pregnancy rate and the number of pups between 2,4-D-treated wild-type male mice and untreated female mice were significantly lower compared with those between untreated couples. These phenomena were not observed in 2,4-D-treated Ppara-null males. Collectively, these results suggest a critical role for PPARα in 2,4-D-induced testicular toxicity due to disruption of cholesterol/testosterone homeostasis in Leydig cells. This study yields novel insights into the possible mechanism of testicular dysfunction and male infertility caused by 2,4-D. JF - Archives of toxicology AU - Harada, Yukiko AU - Tanaka, Naoki AU - Ichikawa, Motoki AU - Kamijo, Yuji AU - Sugiyama, Eiko AU - Gonzalez, Frank J AU - Aoyama, Toshifumi AD - Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. ; Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. naopi@shinshu-u.ac.jp. ; Department of Family and Child Nursing, Shinshu University School of Health Sciences, Matsumoto, Japan. ; Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. ; Department of Nutritional Science, Nagano Prefectural College, Nagano, Japan. ; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 3061 EP - 3071 VL - 90 IS - 12 KW - Testosterone KW - 2,4-dichlorophenoxyacetic acid KW - Testicular toxicity KW - Leydig cell KW - Cholesterol KW - PPARα UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826658977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=PPAR%CE%B1-dependent+cholesterol%2Ftestosterone+disruption+in+Leydig+cells+mediates+2%2C4-dichlorophenoxyacetic+acid-induced+testicular+toxicity+in+mice.&rft.au=Harada%2C+Yukiko%3BTanaka%2C+Naoki%3BIchikawa%2C+Motoki%3BKamijo%2C+Yuji%3BSugiyama%2C+Eiko%3BGonzalez%2C+Frank+J%3BAoyama%2C+Toshifumi&rft.aulast=Harada&rft.aufirst=Yukiko&rft.date=2016-12-01&rft.volume=90&rft.issue=12&rft.spage=3061&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=1432-0738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-02-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - BODY SIZE-SPECIFIC EFFECTIVE DOSE CONVERSION COEFFICIENTS FOR CT SCANS. AN - 1826644645; 26755767 AB - Effective dose from computed tomography (CT) examinations is usually estimated using the scanner-provided dose-length product and using conversion factors, also known as k-factors, which correspond to scan regions and differ by age according to five categories: 0, 1, 5, 10 y and adult. However, patients often deviate from the standard body size on which the conversion factor is based. In this study, a method for deriving body size-specific k-factors is presented, which can be determined from a simple regression curve based on patient diameter at the centre of the scan range. Using the International Commission on Radiological Protection reference paediatric and adult computational phantoms paired with Monte Carlo simulation of CT X-ray beams, the authors derived a regression-based k-factor model for the following CT scan types: head-neck, head, neck, chest, abdomen, pelvis, abdomen-pelvis (AP) and chest-abdomen-pelvis (CAP). The resulting regression functions were applied to a total of 105 paediatric and 279 adult CT scans randomly sampled from patients who underwent chest, AP and CAP scans at the National Institutes of Health Clinical Center. The authors have calculated and compared the effective doses derived from the conventional age-specific k-factors with the values computed using their body size-specific k-factor. They found that by using the age-specific k-factor, paediatric patients tend to have underestimates (up to 3-fold) of effective dose, while underweight and overweight adult patients tend to have underestimates (up to 2.6-fold) and overestimates (up to 4.6-fold) of effective dose, respectively, compared with the effective dose determined from their body size-dependent factors. The authors present these size-specific k-factors as an alternative to the existing age-specific factors. The body size-specific k-factor will assess effective dose more precisely and on a more individual level than the conventional age-specific k-factors and, hence, improve awareness of the true exposure, which is important for the clinical community to understand. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. JF - Radiation protection dosimetry AU - Romanyukha, Anna AU - Folio, Les AU - Lamart, Stephanie AU - Simon, Steven L AU - Lee, Choonsik AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA. ; Radiology and Imaging Sciences Clinical Center, National Institutes of Health, Bethesda, MD, USA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA leechoonsik@mail.nih.gov. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 428 EP - 437 VL - 172 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826644645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+protection+dosimetry&rft.atitle=BODY+SIZE-SPECIFIC+EFFECTIVE+DOSE+CONVERSION+COEFFICIENTS+FOR+CT+SCANS.&rft.au=Romanyukha%2C+Anna%3BFolio%2C+Les%3BLamart%2C+Stephanie%3BSimon%2C+Steven+L%3BLee%2C+Choonsik&rft.aulast=Romanyukha&rft.aufirst=Anna&rft.date=2016-12-01&rft.volume=172&rft.issue=4&rft.spage=428&rft.isbn=&rft.btitle=&rft.title=Radiation+protection+dosimetry&rft.issn=1742-3406&rft_id=info:doi/10.1093%2Frpd%2Fncv511 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-01-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/rpd/ncv511 ER - TY - JOUR T1 - Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease. AN - 1826627541; 26405062 AB - A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans In this article, we report that supplementation of this cranberry extract delayed Aβ toxicity-triggered body paralysis in the C elegans AD model. Genetic analyses indicated that the cranberry-mediated Aβ toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C elegans against Aβ toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated Aβ toxicity in C elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. JF - The journals of gerontology. Series A, Biological sciences and medical sciences AU - Guo, Hong AU - Cao, Min AU - Zou, Sige AU - Ye, Boping AU - Dong, Yuqing AD - Department of Biological Sciences, Clemson University, South Carolina. ; Functional Genomics Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland. ; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. ; Department of Biological Sciences, Clemson University, South Carolina. ydong@clemson.edu. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 1564 EP - 1573 VL - 71 IS - 12 KW - hsf-1 KW - Proteostasis KW - Alzheimer’s disease KW - β-Amyloid KW - Cranberry KW - Caenorhabditis elegans UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826627541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journals+of+gerontology.+Series+A%2C+Biological+sciences+and+medical+sciences&rft.atitle=Cranberry+Extract+Standardized+for+Proanthocyanidins+Alleviates+%CE%B2-Amyloid+Peptide+Toxicity+by+Improving+Proteostasis+Through+HSF-1+in+Caenorhabditis+elegans+Model+of+Alzheimer%27s+Disease.&rft.au=Guo%2C+Hong%3BCao%2C+Min%3BZou%2C+Sige%3BYe%2C+Boping%3BDong%2C+Yuqing&rft.aulast=Guo&rft.aufirst=Hong&rft.date=2016-12-01&rft.volume=71&rft.issue=12&rft.spage=1564&rft.isbn=&rft.btitle=&rft.title=The+journals+of+gerontology.+Series+A%2C+Biological+sciences+and+medical+sciences&rft.issn=1758-535X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2015-09-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Attention training normalises combat-related post-traumatic stress disorder effects on emotional Stroop performance using lexically matched word lists AN - 1822503465 AB - We examined two groups of combat veterans, one with post-traumatic stress disorder (PTSD) (n = 27) and another without PTSD (n = 16), using an emotional Stroop task (EST) with word lists matched across a series of lexical variables (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD exhibited a strong EST effect (longer colour-naming latencies for combat-relevant words as compared to neutral words). Veterans without PTSD produced no such effect, t < .918, p > .37. Participants with PTSD then completed eight sessions of attention training (Attention Control Training or Attention Bias Modification Training) with a dot-probe task utilising threatening and neutral faces. After training, participants-especially those undergoing Attention Control Training-no longer produced longer colour-naming latencies for combat-related words as compared to other words, indicating normalised attention allocation processes after treatment. JF - Cognition & Emotion AU - Khanna, Maya M AU - Badura-Brack, Amy S AU - McDermott, Timothy J AU - Shepherd, Alex AU - Heinrichs-Graham, Elizabeth AU - Pine, Daniel S AU - Bar-Haim, Yair AU - Wilson, Tony W AD - Department of Psychology, Creighton University, Omaha, NE, USA ; Department of Psychology, University of Nebraska-Omaha, Omaha, NE, USA ; National Institute of Mental Health, Rockville, MD, USA ; Department of Psychology and Neuroscience, School of Psychological Sciences, Tel-Aviv University, Tel Aviv-Yafo, Isreal ; Department of Pharmacology and Experimental Neuroscience, Department of Neurological Sciences, and the Center for Magnetoencephalography, University of Nebraska Medical Center, Omaha, NE, USA ; Department of Psychology, Creighton University, Omaha, NE, USA Y1 - 2016/12// PY - 2016 DA - Dec 2016 SP - 1521 EP - 1528 CY - Hove PB - Taylor & Francis Ltd. VL - 30 IS - 8 SN - 0269-9931 KW - Psychology KW - PTSD KW - attention training KW - emotional Stroop KW - lexically matched lists KW - attention bias modification KW - Combat related posttraumatic stress disorder KW - Modification KW - Attentional bias KW - Emotional Stroop task KW - Veterans KW - Words KW - Naming KW - Threatening KW - Traumatic stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1822503465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cognition+%26+Emotion&rft.atitle=Attention+training+normalises+combat-related+post-traumatic+stress+disorder+effects+on+emotional+Stroop+performance+using+lexically+matched+word+lists&rft.au=Khanna%2C+Maya+M%3BBadura-Brack%2C+Amy+S%3BMcDermott%2C+Timothy+J%3BShepherd%2C+Alex%3BHeinrichs-Graham%2C+Elizabeth%3BPine%2C+Daniel+S%3BBar-Haim%2C+Yair%3BWilson%2C+Tony+W&rft.aulast=Khanna&rft.aufirst=Maya&rft.date=2016-12-01&rft.volume=30&rft.issue=8&rft.spage=1521&rft.isbn=&rft.btitle=&rft.title=Cognition+%26+Emotion&rft.issn=02699931&rft_id=info:doi/10.1080%2F02699931.2015.1076769 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2015 Taylor & Francis N1 - Last updated - 2016-09-26 DO - http://dx.doi.org/10.1080/02699931.2015.1076769 ER - TY - JOUR T1 - Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint? AN - 1814660433; 27558401 AB - Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis. The interrelated multiple hypotheses that are presented for the first time in this article are extension of author's earlier series of 'accidental' discoveries on the role of inflammation in developmental stages of immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of data on chronic diseases suggest that nearly all age-associated illnesses, generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g., hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g., accelerated neurodegenerative and autoimmune diseases or site-specific cancers and metastasis) are variations of hypersensitivity responses of tissues that are manifested as different diseases in immune-responsive or immune-privileged tissues. Continuous release/presence of low level histamine (subclinical) in circulation could contribute to sustained oxidative stress and induction of 'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms of cumulative delayed hypersensitivity responses that would induce immunological chaos in favor of tissue growth in target tissues. Shared or special features of growth from fetus development into adulthood and aging processes and carcinogenesis are briefly compared with regard to energy requirements of highly complex function of Yin and Yang. Features of Yang (growth-promoting) arm of acute inflammation during fetus and cancer growth will be compared for consuming low energy from glycolysis (Warburg effect). Growth of fetus and cancer cells under hypoxic conditions and impaired mitochondrial energy requirements of tissues including metabolism of essential branched amino acids (e.g., val, leu, isoleu) will be compared for proposing a working model for future systematic research on cancer biology, prevention and therapy. Presentation of a working model provides insightful clues into bioenergetics that are required for fetus growth (absence of external threat and lack of high energy-demands of Yin events and parasite-like survival in host), normal growth in adulthood (balance in Yin and Yang processes) or disease processes and carcinogenesis (loss of balance in Yin-Yang). Future studies require focusing on dynamics and promotion of natural/inherent balance between Yin (tumoricidal) and Yang (tumorigenic) of effective immunity that develop after birth. Lawless growth of cancerous cells and loss of cell contact inhibition could partially be due to impaired mitochondria (mitophagy) that influence metabolism of branched chain amino acids for biosynthesis of structural proteins. The author invites interested scientists with diverse expertise to provide comments, confirm, dispute and question and/or expand and collaborate on many components of the proposed working model with the goal to better understand cancer biology for future designs of cost-effective research and clinical trials and prevention of cancer. Initial events during oxidative stress-induced damages to DNA/RNA repair mechanisms and inappropriate expression of inflammatory mediators are potentially correctable, preventable or druggable, if future studies were to focus on systematic understanding of early altered immune response dynamics toward multistep chronic diseases and carcinogenesis. JF - Clinical and translational medicine AU - Khatami, Mahin AD - National Cancer Institute (NCI), the National Institutes of Health (NIH), Bethesda, MD, USA. mkgoodness@aol.com. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 35 VL - 5 IS - 1 KW - Bioenergetics KW - Allergy KW - Fetal growth KW - Aging KW - Angiogenesis KW - Mitochondria KW - Branched amino acids KW - Cancer KW - Histamine KW - Taurine KW - Hypersensitivity KW - Yin and Yang of inflammation KW - Placenta KW - Immune-privileged and immune-responsive tissues UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814660433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+translational+medicine&rft.atitle=Is+cancer+a+severe+delayed+hypersensitivity+reaction+and+histamine+a+blueprint%3F&rft.au=Khatami%2C+Mahin&rft.aulast=Khatami&rft.aufirst=Mahin&rft.date=2016-12-01&rft.volume=5&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Clinical+and+translational+medicine&rft.issn=&rft_id=info:doi/10.1186%2Fs40169-016-0108-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-25 N1 - Date created - 2016-08-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s40169-016-0108-3 ER - TY - JOUR T1 - Impact of work-related cancers in Taiwan-Estimation with QALY (quality-adjusted life year) and healthcare costs. AN - 1804861949; 27413666 AB - This study estimates the annual numbers of eight work-related cancers, total losses of quality-adjusted life years (QALYs), and lifetime healthcare expenditures that possibly could be saved by improving occupational health in Taiwan. Three databases were interlinked: the Taiwan Cancer Registry, the National Mortality Registry, and the National Health Insurance Research Database. Annual numbers of work-related cancers were estimated based on attributable fractions (AFs) abstracted from a literature review. The survival functions for eight cancers were estimated and extrapolated to lifetime using a semi-parametric method. A convenience sample of 8846 measurements of patients' quality of life with EQ-5D was collected for utility values and multiplied by survival functions to estimate quality-adjusted life expectancies (QALEs). The loss-of-QALE was obtained by subtracting the QALE of cancer from age- and sex-matched referents simulated from national vital statistics. The lifetime healthcare expenditures were estimated by multiplying the survival probability with mean monthly costs paid by the National Health Insurance for cancer diagnosis and treatment and summing this for the expected lifetime. A total of 3010 males and 726 females with eight work-related cancers were estimated in 2010. Among them, lung cancer ranked first in terms of QALY loss, with an annual total loss-of-QALE of 28,463 QALYs and total lifetime healthcare expenditures of US$36.6 million. Successful prevention of eight work-related cancers would not only avoid the occurrence of 3736 cases of cancer, but would also save more than US$70 million in healthcare costs and 46,750 QALYs for the Taiwan society in 2010. JF - Preventive medicine reports AU - Lee, Lukas Jyuhn-Hsiarn AU - Lin, Cheng-Kuan AU - Hung, Mei-Chuan AU - Wang, Jung-Der AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan. ; Department of Environmental Health, Harvard T.H. Chan School of Public Health, United States; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. ; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 87 EP - 93 VL - 4 KW - LTHE, Lifetime healthcare expenditure KW - QALY, Quality-adjusted life year KW - NMR, National Mortality Registry KW - QOL, Quality of life KW - DALY, Disability-adjusted life year KW - Quality-adjusted life expectancy (QALE) KW - AF, Attributable fraction KW - WHO, World Health Organization KW - TCR, Taiwan Cancer Registry KW - Attributable fraction (AF) KW - Work-related cancer KW - CAREX, CARcinogen EXposure KW - IARC, International Agency for Research on Cancer KW - NHIRD, National Health Insurance Research Database KW - NHI, National Health Insurance KW - Lifetime healthcare expenditure (LTHE) KW - QALE, Quality-adjusted life expectancy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804861949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Preventive+medicine+reports&rft.atitle=Impact+of+work-related+cancers+in+Taiwan-Estimation+with+QALY+%28quality-adjusted+life+year%29+and+healthcare+costs.&rft.au=Lee%2C+Lukas+Jyuhn-Hsiarn%3BLin%2C+Cheng-Kuan%3BHung%2C+Mei-Chuan%3BWang%2C+Jung-Der&rft.aulast=Lee&rft.aufirst=Lukas&rft.date=2016-12-01&rft.volume=4&rft.issue=&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Preventive+medicine+reports&rft.issn=&rft_id=info:doi/10.1016%2Fj.pmedr.2016.05.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-14 N1 - Date created - 2016-07-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.pmedr.2016.05.015 ER - TY - JOUR T1 - Engineering anti-Lewis-Y hu3S193 antibodies with improved therapeutic ratio for radioimmunotherapy of epithelial cancers. AN - 1774528217; 26983636 AB - The aim of the study was to explore Fc mutations of a humanised anti-Lewis-Y antibody (IgG1) hu3S193 as a strategy to improve therapeutic ratios for therapeutic payload delivery. Four hu3S193 variants (I253A, H310A, H435A and I253A/H310A) were generated via site-directed mutagenesis and radiolabelled with diagnostic isotopes iodine-125 or indium-111. Biodistribution studies in Lewis-Y-positive tumour-bearing mice were used to calculate the dose in tumours and organs for therapeutic isotopes (iodine-131, yttrium-90 and lutetium-177). (111)In-labelled I253A and H435A showed similar slow kinetics (t 1/2β, 63.2 and 62.2 h, respectively) and a maximum tumour uptake of 33.11 ± 4.05 and 33.69 ± 3.77 percentage injected dose per gramme (%ID/g), respectively. (111)In-labelled I253A/H310A cleared fastest (t 1/2β, 9.1 h) with the lowest maximum tumour uptake (23.72 ± 0.85 %ID/g). The highest increase in tumour-to-blood area under the curve (AUC) ratio was observed with the metal-labelled mutants ((90)Y and (177)Lu). (177)Lu-CHX-A" DTPA-hu3S193 I253A/H310A (6:1) showed the highest tumour-to-blood AUC ratio compared to wild type (3:1) and other variants and doubling of calculated dose to tumour based on red marrow dose constraints. These results suggest that hu3S193 Fc can be engineered with improved therapeutic ratios for (90)Y- and (177)Lu-based therapy, with the best candidate being hu3S193 I253A/H310A for (177)Lu-based therapy. JF - EJNMMI research AU - Burvenich, Ingrid J G AU - Lee, Fook-Thean AU - O'Keefe, Graeme J AU - Makris, Dahna AU - Cao, Diana AU - Gong, Sylvia AU - Rigopoulos, Angela AU - Allan, Laura C AU - Brechbiel, Martin W AU - Liu, Zhanqi AU - Ramsland, Paul A AU - Scott, Andrew M AD - Tumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia. ; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia. ; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia. ; Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; School of Science, RMIT University, Bundoora, VIC, Australia. ; Tumour Targeting Laboratory, Ludwig Institute for Cancer Research and Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia. andrew.scott@onjcri.org.au. Y1 - 2016/12// PY - 2016 DA - December 2016 SP - 26 VL - 6 IS - 1 KW - Lewis-Y KW - Small animal imaging KW - Payload delivery KW - Antibody engineering KW - Therapeutic ratio UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1774528217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EJNMMI+research&rft.atitle=Engineering+anti-Lewis-Y+hu3S193+antibodies+with+improved+therapeutic+ratio+for+radioimmunotherapy+of+epithelial+cancers.&rft.au=Burvenich%2C+Ingrid+J+G%3BLee%2C+Fook-Thean%3BO%27Keefe%2C+Graeme+J%3BMakris%2C+Dahna%3BCao%2C+Diana%3BGong%2C+Sylvia%3BRigopoulos%2C+Angela%3BAllan%2C+Laura+C%3BBrechbiel%2C+Martin+W%3BLiu%2C+Zhanqi%3BRamsland%2C+Paul+A%3BScott%2C+Andrew+M&rft.aulast=Burvenich&rft.aufirst=Ingrid+J&rft.date=2016-12-01&rft.volume=6&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=EJNMMI+research&rft.issn=&rft_id=info:doi/10.1186%2Fs13550-016-0180-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-03-17 N1 - Date created - 2016-03-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13550-016-0180-0 ER - TY - JOUR T1 - Prediction of pharmacokinetic and toxicological parameters of a 4-phenylcoumarin isolated from geopropolis: In silico and in vitro approaches. AN - 1835540190; 27773722 AB - In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array. CNM did not pass all parameters of Lipinski's rule of five, with a predicted low oral bioavailability and high plasma protein binding, but with good predicted blood brain barrier penetration. CNM was predicted to show low affinity to cytochrome P450 family members. Furthermore, the predicted Ames test indicated potential mutagenicity of CNM. Also, the probability of toxicity for organs and tissues was classified as moderate and high for liver and kidney, and moderate and low for skin and eye irritation, respectively. The PCR array analysis showed that CNM significantly upregulated about 7% of all DNA damage-related genes. By exploring the biological function of these genes, it was found that the predicted CNM genotoxicity is likely to be mediated by apoptosis. The predicted ADME/Tox profile suggests that external use of CNM may be preferable to systemic exposure, while its genotoxicity was characterized by the upregulation of apoptosis-related genes after treatment. The combined use of in silico and in vitro approaches to evaluate these parameters generated useful hypotheses to guide further preclinical studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Toxicology letters AU - da Cunha, Marcos Guilherme AU - Franco, Gilson César Nobre AU - Franchin, Marcelo AU - Beutler, John A AU - de Alencar, Severino Matias AU - Ikegaki, Masaharu AU - Rosalen, Pedro Luiz AD - Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), SP, Brazil; Molecular Targets Laboratory, National Cancer Institute (NCI), National Institute of Health (NIH), Frederick, MD, USA. ; Department of General Biology, Laboratory of Physiology and Pathophysiology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil. ; Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), SP, Brazil. ; Molecular Targets Laboratory, National Cancer Institute (NCI), National Institute of Health (NIH), Frederick, MD, USA. ; Department of Agri-Food industry, Food and Nutrition, "Luiz de Queiroz" College of Agriculture, University of São Paulo (USP), Piracicaba, SP, Brazil. ; College of Pharmaceutical Sciences, Federal University of Alfenas, Minas Gerais, Brazil. ; Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), SP, Brazil. Electronic address: rosalen@fop.unicamp.br. Y1 - 2016/11/30/ PY - 2016 DA - 2016 Nov 30 SP - 6 EP - 10 VL - 263 KW - In silico KW - Genotoxicity KW - Coumarin KW - in vitro KW - Geopropolis KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835540190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Prediction+of+pharmacokinetic+and+toxicological+parameters+of+a+4-phenylcoumarin+isolated+from+geopropolis%3A+In+silico+and+in+vitro+approaches.&rft.au=da+Cunha%2C+Marcos+Guilherme%3BFranco%2C+Gilson+C%C3%A9sar+Nobre%3BFranchin%2C+Marcelo%3BBeutler%2C+John+A%3Bde+Alencar%2C+Severino+Matias%3BIkegaki%2C+Masaharu%3BRosalen%2C+Pedro+Luiz&rft.aulast=da+Cunha&rft.aufirst=Marcos&rft.date=2016-11-30&rft.volume=263&rft.issue=&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=1879-3169&rft_id=info:doi/10.1016%2Fj.toxlet.2016.10.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.toxlet.2016.10.010 ER - TY - JOUR T1 - Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin. AN - 1844603624; 27897082 AB - The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice. CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule. CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice. In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy. JF - Redox report : communications in free radical research AU - Basu, Abhishek AU - Bhattacharjee, Arin AU - Hajra, Subhadip AU - Samanta, Amalesh AU - Bhattacharya, Sudin AD - a Department of Cancer Chemoprevention , Chittaranjan National Cancer Institute , Kolkata , India. ; b Division of Microbiology, Department of Pharmaceutical Technology , Jadavpur University , Kolkata , India. Y1 - 2016/11/29/ PY - 2016 DA - 2016 Nov 29 SP - 1 EP - 11 KW - Vanadium KW - kidney damage KW - apoptosis KW - reactive oxygen species KW - Nrf2/ARE pathway KW - antioxidant enzymes KW - atomic absorption spectroscopy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844603624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Redox+report+%3A+communications+in+free+radical+research&rft.atitle=Ameliorative+effect+of+an+oxovanadium+%28IV%29+complex+against+oxidative+stress+and+nephrotoxicity+induced+by+cisplatin.&rft.au=Basu%2C+Abhishek%3BBhattacharjee%2C+Arin%3BHajra%2C+Subhadip%3BSamanta%2C+Amalesh%3BBhattacharya%2C+Sudin&rft.aulast=Basu&rft.aufirst=Abhishek&rft.date=2016-11-29&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Redox+report+%3A+communications+in+free+radical+research&rft.issn=1743-2928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Ruxolitinib in clinical practice for primary and secondary myelofibrosis: an analysis of safety and efficacy of Gruppo Laziale of Ph-negative MPN. AN - 1844351083; 27889820 AB - Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the treatment of primary and secondary myelofibrosis (MF). Aim of our study is to report safety and efficacy of ruxolitinib in 98 patients affected by MF treated outside clinical trials and collected and treated consecutively by the Lazio Cooperative Group for Ph negative myeloproliferative diseases.There were 45 males and 53 females; median age was 61.8 years (range 35.3-88). Forty-five patients were diagnosed as primary MF and 53 as secondary MF. Seventy-seven patients (78.5%) experienced constitutional symptoms at baseline, and out of 94 patients tested, 66 (70%) were JAK2V617F mutated. Overall, 40 patients received hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic approaches, whereas 28 were treated with ruxolitinib frontline. Median time from diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. Fifty-eight patients (59%) required a dose reduction during the first 3 months due to hematological toxicity in the majority of cases. At 48 weeks, 52% of patients obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6 patients (6%) a CI, and 28 patients (28.5%) a spleen response. Overall, 66% of patients had disappearance of baseline symptoms burden. After 1 year, of 72 evaluable patients, 52% achieved and maintained a clinical benefit. Adverse events of special interest at any grade included anemia (39.7%), thrombocytopenia (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16 months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21 patients (21%) discontinued the drug. The results of this retrospective multicentric analysis confirmed the efficacy of ruxolitinib outside clinical trials with more than half of treated patients achieving and maintaining a clinical benefit and most of them reporting relief from symptoms. JF - Annals of hematology AU - Breccia, Massimo AU - Andriani, Alessandro AU - Montanaro, Marco AU - Abruzzese, Elisabetta AU - Buccisano, Francesco AU - Cedrone, Michele AU - Centra, Antonietta AU - Villivà, Nicoletta AU - Celesti, Francesca AU - Trawinska, Malgorzata Monica AU - Massaro, Fulvio AU - Di Veroli, Ambra AU - Anaclerico, Barbara AU - Colafigli, Gioia AU - Molica, Matteo AU - Spadea, Antonio AU - Petriccione, Luca AU - Cimino, Giuseppe AU - Latagliata, Roberto AD - Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy. breccia@bce.uniroma1.it. ; Hematology, Nuovo Regina Margherita Hospital, Rome, Italy. ; Hematology, Belcolle Hospital, Viterbo, Italy. ; Hematology, S. Eugenio Hospital, Rome, Italy. ; Tor Vergata University, Rome, Italy. ; Hematology, S. Giovanni Hospital, Rome, Italy. ; Hematology, S. Maria Goretti Hospital, Latina, Italy. ; Azienda Policlinico Umberto 1-Sapienza University, Rome, Italy. ; Hematology and Stem Cell Transplantation Unit, Regina Elena National Cancer Institute, Rome, Italy. ; Hematology, Fabrizio Spaziani Hospital, Frosinone, Italy. Y1 - 2016/11/26/ PY - 2016 DA - 2016 Nov 26 KW - Ruxolitinib KW - Myelofibrosis KW - Response rate KW - Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844351083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hormones+%26+cancer&rft.atitle=Estrogen+Metabolism+and+Risk+of+Postmenopausal+Endometrial+and+Ovarian+Cancer%3A+the+B+%E2%88%BC+FIT+Cohort.&rft.au=Dallal%2C+Cher+M%3BLacey%2C+James+V%3BPfeiffer%2C+Ruth+M%3BBauer%2C+Douglas+C%3BFalk%2C+Roni+T%3BBuist%2C+Diana+S+M%3BCauley%2C+Jane+A%3BHue%2C+Trisha+F%3BLaCroix%2C+Andrea+Z%3BTice%2C+Jeffrey+A%3BVeenstra%2C+Timothy+D%3BXu%2C+Xia%3BBrinton%2C+Louise+A%3BB%E2%88%BCFIT+Research+Group&rft.aulast=Dallal&rft.aufirst=Cher&rft.date=2016-02-01&rft.volume=7&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Hormones+%26+cancer&rft.issn=1868-8500&rft_id=info:doi/10.1007%2Fs12672-015-0237-y LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Regulation of Cytochrome P450 2B10 (CYP2B10) Expression in Liver by Peroxisome Proliferator-activated Receptor-β/δ Modulation of SP1 Promoter Occupancy. AN - 1835517050; 27765815 AB - Alcoholic liver disease is a pathological condition caused by overconsumption of alcohol. Because of the high morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying its etiology and to develop new treatments. Because peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease. Chronic ethanol treatment causes increased hepatic CYP2B10 expression inPparβ/δ+/+ mice but not in Pparβ/δ-/- mice. Nuclear and cytosolic localization of the constitutive androstane receptor (CAR), a transcription factor known to regulate Cyp2b10 expression, was not different between genotypes. PPARγ co-activator 1α, a co-activator of both CAR and PPARβ/δ, was up-regulated in Pparβ/δ+/+ liver following ethanol exposure, but not in Pparβ/δ-/- liver. Functional mapping of the Cyp2b10 promoter and ChIP assays revealed that PPARβ/δ-dependent modulation of SP1 promoter occupancy up-regulated Cyp2b10 expression in response to ethanol. These results suggest that PPARβ/δ regulates Cyp2b10 expression indirectly by modulating SP1 and PPARγ co-activator 1α expression and/or activity independent of CAR activity. Ligand activation of PPARβ/δ attenuates ethanol-induced Cyp2b10 expression in Pparβ/δ+/+ liver but not in Pparβ/δ-/- liver. Strikingly, Cyp2b10 suppression by ligand activation of PPARβ/δ following ethanol treatment occurred in hepatocytes and was mediated by paracrine signaling from Kupffer cells. Combined, results from the present study demonstrate a novel regulatory role of PPARβ/δ in modulating CYP2B10 that may contribute to the etiology of alcoholic liver disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Koga, Takayuki AU - Yao, Pei-Li AU - Goudarzi, Maryam AU - Murray, Iain A AU - Balandaram, Gayathri AU - Gonzalez, Frank J AU - Perdew, Gary H AU - Fornace, Albert J AU - Peters, Jeffrey M AD - From the Department of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, Pennsylvania 16802. ; the Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, D. C., 20057, and. ; the Laboratory of Metabolism, National Cancer Institute, Bethesda, Maryland 20892. ; From the Department of Veterinary and Biomedical Sciences and the Center of Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, Pennsylvania 16802, jmp21@psu.edu. Y1 - 2016/11/25/ PY - 2016 DA - 2016 Nov 25 SP - 25255 EP - 25263 VL - 291 IS - 48 KW - Kupffer cells KW - cytochrome P450 2B10 KW - peroxisome proliferator-activated receptor (PPAR) KW - liver injury KW - peroxisome proliferator-activated receptor-β/δ KW - gene regulation KW - liver KW - cytochrome P450 KW - alcoholic liver disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835517050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+Cytochrome+P450+2B10+%28CYP2B10%29+Expression+in+Liver+by+Peroxisome+Proliferator-activated+Receptor-%CE%B2%2F%CE%B4+Modulation+of+SP1+Promoter+Occupancy.&rft.au=Koga%2C+Takayuki%3BYao%2C+Pei-Li%3BGoudarzi%2C+Maryam%3BMurray%2C+Iain+A%3BBalandaram%2C+Gayathri%3BGonzalez%2C+Frank+J%3BPerdew%2C+Gary+H%3BFornace%2C+Albert+J%3BPeters%2C+Jeffrey+M&rft.aulast=Koga&rft.aufirst=Takayuki&rft.date=2016-11-25&rft.volume=291&rft.issue=48&rft.spage=25255&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling: A POTENTIAL ROLE FOR LIPID-PROTEIN ADDUCTS. AN - 1835359842; 27703007 AB - When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species. As expected, O3-derived oxysterols have a pro-inflammatory effect and increase NF-κB activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O3 Additionally, exposure of LXR knock-out mice to O3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Speen, Adam M AU - Kim, Hye-Young H AU - Bauer, Rebecca N AU - Meyer, Megan AU - Gowdy, Kymberly M AU - Fessler, Michael B AU - Duncan, Kelly E AU - Liu, Wei AU - Porter, Ned A AU - Jaspers, Ilona AD - From the Curriculum in Toxicology, Departments of Pediatrics and Microbiology and Immunology, Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599. ; the Department of Chemistry and Center for Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235. ; the Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, and. ; the Immunity, Inflammation, and Disease Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709. ; From the Curriculum in Toxicology, Departments of Pediatrics and Microbiology and Immunology, Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599, ilona_jaspers@med.unc.edu. Y1 - 2016/11/25/ PY - 2016 DA - 2016 Nov 25 SP - 25192 EP - 25206 VL - 291 IS - 48 KW - secosterol A KW - oxysterol KW - ozone KW - lung KW - liver X receptor KW - inflammation KW - ABC transporter KW - lipid-protein interaction KW - cholesterol KW - epithelial cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835359842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Ozone-derived+Oxysterols+Affect+Liver+X+Receptor+%28LXR%29+Signaling%3A+A+POTENTIAL+ROLE+FOR+LIPID-PROTEIN+ADDUCTS.&rft.au=Speen%2C+Adam+M%3BKim%2C+Hye-Young+H%3BBauer%2C+Rebecca+N%3BMeyer%2C+Megan%3BGowdy%2C+Kymberly+M%3BFessler%2C+Michael+B%3BDuncan%2C+Kelly+E%3BLiu%2C+Wei%3BPorter%2C+Ned+A%3BJaspers%2C+Ilona&rft.aulast=Speen&rft.aufirst=Adam&rft.date=2016-11-25&rft.volume=291&rft.issue=48&rft.spage=25192&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Reproductive history and risk of colorectal adenocarcinoma in parous women: a Nordic population-based case-control study. AN - 1835379465; 27701386 AB - Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women. JF - British journal of cancer AU - Bjørge, Tone AU - Gissler, Mika AU - Ording, Anne Gulbech AU - Engeland, Anders AU - Glimelius, Ingrid AU - Leinonen, Maarit AU - Sørensen, Henrik Toft AU - Tretli, Steinar AU - Ekbom, Anders AU - Troisi, Rebecca AU - Grotmol, Tom AD - Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. ; National Institute for Health and Welfare (THL), Helsinki, Finland. ; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. ; Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. ; Cancer Society of Finland, Finnish Cancer Registry, Helsinki, Finland. ; Cancer Registry of Norway, Oslo, Norway. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Y1 - 2016/11/22/ PY - 2016 DA - 2016 Nov 22 SP - 1416 EP - 1420 VL - 115 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835379465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Reproductive+history+and+risk+of+colorectal+adenocarcinoma+in+parous+women%3A+a+Nordic+population-based+case-control+study.&rft.au=Bj%C3%B8rge%2C+Tone%3BGissler%2C+Mika%3BOrding%2C+Anne+Gulbech%3BEngeland%2C+Anders%3BGlimelius%2C+Ingrid%3BLeinonen%2C+Maarit%3BS%C3%B8rensen%2C+Henrik+Toft%3BTretli%2C+Steinar%3BEkbom%2C+Anders%3BTroisi%2C+Rebecca%3BGrotmol%2C+Tom&rft.aulast=Bj%C3%B8rge&rft.aufirst=Tone&rft.date=2016-11-22&rft.volume=115&rft.issue=11&rft.spage=1416&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=1532-1827&rft_id=info:doi/10.1038%2Fbjc.2016.315 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/bjc.2016.315 ER - TY - JOUR T1 - Transcriptional Induction of Periostin by a Sulfatase 2-TGFβ1-SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma. AN - 1842599925; 27872089 AB - Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 1-14. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer research AU - Chen, Gang AU - Nakamura, Ikuo AU - Dhanasekaran, Renumathy AU - Iguchi, Eriko AU - Tolosa, Ezequiel J AU - Romecin, Paola A AU - Vera, Renzo E AU - Almada, Luciana L AU - Miamen, Alexander G AU - Chaiteerakij, Roongruedee AU - Zhou, Mengtao AU - Asiedu, Michael K AU - Moser, Catherine D AU - Han, Shaoshan AU - Hu, Chunling AU - Banini, Bubu A AU - Oseini, Abdul M AU - Chen, Yichun AU - Fang, Yong AU - Yang, Dongye AU - Shaleh, Hassan M AU - Wang, Shaoqing AU - Wu, Dehai AU - Song, Tao AU - Lee, Ju-Seog AU - Thorgeirsson, Snorri S AU - Chevet, Eric AU - Shah, Vijay H AU - Fernandez-Zapico, Martin E AU - Roberts, Lewis R AD - Division of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. ; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. ; Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota. ; Department of Systems Biology, MD Anderson Cancer Center, Houston, Texas. ; Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland. ; INSERM U1242, Chemistry, Oncogenesis Stress Signaling, Université Rennes 1, and Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France. ; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. roberts.lewis@mayo.edu. Y1 - 2016/11/21/ PY - 2016 DA - 2016 Nov 21 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842599925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Transcriptional+Induction+of+Periostin+by+a+Sulfatase+2-TGF%CE%B21-SMAD+Signaling+Axis+Mediates+Tumor+Angiogenesis+in+Hepatocellular+Carcinoma.&rft.au=Chen%2C+Gang%3BNakamura%2C+Ikuo%3BDhanasekaran%2C+Renumathy%3BIguchi%2C+Eriko%3BTolosa%2C+Ezequiel+J%3BRomecin%2C+Paola+A%3BVera%2C+Renzo+E%3BAlmada%2C+Luciana+L%3BMiamen%2C+Alexander+G%3BChaiteerakij%2C+Roongruedee%3BZhou%2C+Mengtao%3BAsiedu%2C+Michael+K%3BMoser%2C+Catherine+D%3BHan%2C+Shaoshan%3BHu%2C+Chunling%3BBanini%2C+Bubu+A%3BOseini%2C+Abdul+M%3BChen%2C+Yichun%3BFang%2C+Yong%3BYang%2C+Dongye%3BShaleh%2C+Hassan+M%3BWang%2C+Shaoqing%3BWu%2C+Dehai%3BSong%2C+Tao%3BLee%2C+Ju-Seog%3BThorgeirsson%2C+Snorri+S%3BChevet%2C+Eric%3BShah%2C+Vijay+H%3BFernandez-Zapico%2C+Martin+E%3BRoberts%2C+Lewis+R&rft.aulast=Chen&rft.aufirst=Gang&rft.date=2016-11-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=1538-7445&rft_id=info:doi/10.1158%2F0008-5472.CAN-15-2556 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-22 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1158/0008-5472.CAN-15-2556 ER - TY - JOUR T1 - Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. AN - 1835399335; 27722328 AB - The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments. JF - Chemical Society reviews AU - Zhou, Zijian AU - Song, Jibin AU - Nie, Liming AU - Chen, Xiaoyuan AD - Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. nielm@xmu.edu.cn and Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA. shawn.chen@nih.gov. ; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA. shawn.chen@nih.gov. ; Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China. nielm@xmu.edu.cn. Y1 - 2016/11/21/ PY - 2016 DA - 2016 Nov 21 SP - 6597 EP - 6626 VL - 45 IS - 23 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835399335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Society+reviews&rft.atitle=Reactive+oxygen+species+generating+systems+meeting+challenges+of+photodynamic+cancer+therapy.&rft.au=Zhou%2C+Zijian%3BSong%2C+Jibin%3BNie%2C+Liming%3BChen%2C+Xiaoyuan&rft.aulast=Zhou&rft.aufirst=Zijian&rft.date=2016-11-21&rft.volume=45&rft.issue=23&rft.spage=6597&rft.isbn=&rft.btitle=&rft.title=Chemical+Society+reviews&rft.issn=1460-4744&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Phenanthriplatin Acts As a Covalent Poison of Topoisomerase II Cleavage Complexes. AN - 1835390280; 27648475 AB - Drugs capable of trapping topoisomerase II (Top2), an essential enzyme that cleaves DNA to remove naturally occurring knots and tangles, can serve as potent anticancer agents. The monofunctional platinum agent phenanthriplatin, cis-[Pt(NH3)2(phenanthridine)Cl](NO3), is shown here to trap Top2 in addition to its known modes of inhibition of DNA and RNA polymerases. Its potency therefore combines diverse modes of action by which phenanthriplatin kills cancer cells. The observation that phenanthriplatin can act as a Top2 poison highlights opportunities to design nonclassical platinum anticancer agents with this novel mechanism of action. Such complexes have the potential to overcome current limitations with chemotherapy, such as resistance, and to provide treatment options for cancers that do not respond well to classical agents. Covalent DNA-platinum lesions implicated in Top2 poisoning are distinctive from those generated by known therapeutic topoisomerase poisons, which typically exert their action by reversible binding at the interface of Top2-DNA cleavage complexes. JF - ACS chemical biology AU - Riddell, Imogen A AU - Agama, Keli AU - Park, Ga Young AU - Pommier, Yves AU - Lippard, Stephen J AD - Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. ; Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. Y1 - 2016/11/18/ PY - 2016 DA - 2016 Nov 18 SP - 2996 EP - 3001 VL - 11 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835390280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+chemical+biology&rft.atitle=Phenanthriplatin+Acts+As+a+Covalent+Poison+of+Topoisomerase+II+Cleavage+Complexes.&rft.au=Riddell%2C+Imogen+A%3BAgama%2C+Keli%3BPark%2C+Ga+Young%3BPommier%2C+Yves%3BLippard%2C+Stephen+J&rft.aulast=Riddell&rft.aufirst=Imogen&rft.date=2016-11-18&rft.volume=11&rft.issue=11&rft.spage=2996&rft.isbn=&rft.btitle=&rft.title=ACS+chemical+biology&rft.issn=1554-8937&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 ER - TY - JOUR T1 - Role of the lipid-regulated NF-κB/IL-6/STAT3 axis in alpha-naphthyl isothiocyanate-induced liver injury. AN - 1841138389; 27853831 AB - Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1. ANIT also increased NF-κB/IL-6/STAT3 signaling, and in vitro luciferase reporter gene assays revealed that LPC 18:0 and LPC 18:1 can activate NF-κB in a concentration-dependent manner. Activation of PPARα through feeding mice a Wy-14,643-containing diet (0.1%) reduced ANIT-induced liver injury, as indicated by lowered ALT and AST levels, and liver histology. In conclusion, the present study demonstrated a role for the lipid-regulated NF-κB/IL-6/STAT3 axis in ANIT-induced hepatotoxicity, and that PPARα may be a potential therapeutic target for the prevention of drug-induced cholestatic liver injury. JF - Archives of toxicology AU - Fang, Zhong-Ze AU - Tanaka, Naoki AU - Lu, Dan AU - Jiang, Chang-Tao AU - Zhang, Wei-Hua AU - Zhang, Chunze AU - Du, Zuo AU - Fu, Zhi-Wei AU - Gao, Peng AU - Cao, Yun-Feng AU - Sun, Hong-Zhi AU - Zhu, Zhi-Tu AU - Cai, Yan AU - Krausz, Kristopher W AU - Yao, Zhi AU - Gonzalez, Frank J AD - Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China. ; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA. ; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 30070, China. ; Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300121, China. ; Key Laborotary of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou, Liaoning, China. ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The First Affiliated Hospital of Liaoning Medical University, No. 457, Zhongshan Road, Dalian, 116023, China. ; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 30070, China. yaozhi@tijmu.edu.cn. ; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA. gonzalef@mail.nih.gov. Y1 - 2016/11/16/ PY - 2016 DA - 2016 Nov 16 KW - Drug toxicity KW - NF-κB/IL-6/STAT3 axis KW - Metabolomics KW - Alpha-naphthyl isothiocyanate UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1841138389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=Role+of+the+lipid-regulated+NF-%CE%BAB%2FIL-6%2FSTAT3+axis+in+alpha-naphthyl+isothiocyanate-induced+liver+injury.&rft.au=Fang%2C+Zhong-Ze%3BTanaka%2C+Naoki%3BLu%2C+Dan%3BJiang%2C+Chang-Tao%3BZhang%2C+Wei-Hua%3BZhang%2C+Chunze%3BDu%2C+Zuo%3BFu%2C+Zhi-Wei%3BGao%2C+Peng%3BCao%2C+Yun-Feng%3BSun%2C+Hong-Zhi%3BZhu%2C+Zhi-Tu%3BCai%2C+Yan%3BKrausz%2C+Kristopher+W%3BYao%2C+Zhi%3BGonzalez%2C+Frank+J&rft.aulast=Fang&rft.aufirst=Zhong-Ze&rft.date=2016-11-16&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=1432-0738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual AN - 1846422792; PQ0003881661 AB - Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. copyright 2016 AACR.See related commentary by Mileham and Kim, p. 5397 JF - Clinical Cancer Research AU - Massett, Holly A AU - Mishkin, Grace AU - Rubinstein, Larry AU - Ivy, SPercy AU - Denicoff, Andrea AU - Godwin, Elizabeth AU - DiPiazza, Kate AU - Bolognese, Jennifer AU - Zwiebel, James A AU - Abrams, Jeffrey S AD - National Cancer Institute, Bethesda, Maryland, massetth@mail.nih.gov Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 5408 EP - 5416 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 22 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Toxicity KW - Clinical trials KW - Cancer KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846422792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Challenges+Facing+Early+Phase+Trials+Sponsored+by+the+National+Cancer+Institute%3A+An+Analysis+of+Corrective+Action+Plans+to+Improve+Accrual&rft.au=Massett%2C+Holly+A%3BMishkin%2C+Grace%3BRubinstein%2C+Larry%3BIvy%2C+SPercy%3BDenicoff%2C+Andrea%3BGodwin%2C+Elizabeth%3BDiPiazza%2C+Kate%3BBolognese%2C+Jennifer%3BZwiebel%2C+James+A%3BAbrams%2C+Jeffrey+S&rft.aulast=Massett&rft.aufirst=Holly&rft.date=2016-11-15&rft.volume=22&rft.issue=22&rft.spage=5408&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0338 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Toxicity; Clinical trials; Cancer DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0338 ER - TY - JOUR T1 - Circulating Tumor DNA as an Early Indicator of Response to T-cell Transfer Immunotherapy in Metastatic Melanoma AN - 1846407346; PQ0003881670 AB - Purpose: Adoptive transfer of activated autologous tumor-infiltrating lymphocytes (TIL) can mediate complete, durable regressions in patients with metastatic melanoma. Responding patients generally do not have significant changes in noncutaneous RECIST targets before 30 to 60 days following TIL infusion, and complete responses are often not confirmed for 1 to 2 years. There is a critical need for a biomarker that can provide early information regarding the likelihood and duration of a response to enable rational decisions about altering therapy. We wished to evaluate the role of circulating tumor DNA (ctDNA) in separating responding from nonresponding patients.Experimental Design: We studied BRAF V600E ctDNA levels by a sensitive allele-specific PCR assay in 388 serum samples from 48 patients who received TIL immunotherapy at the NCI and correlated differences in the dynamic patterns of their ctDNA measurements with response outcomes.Results: A strong correlation was found between the presence or absence of an early serum peak of V600E ctDNA, and the likelihood of an objective response. Furthermore, patients that developed an early ctDNA peak and cleared their serum of V600E ctDNA were highly likely to achieve a complete response over the next 1 to 2 years. Patients that showed no peak of V600E ctDNA failed to achieve an objective response, with one exception.Conclusions: We show that the dynamic changes occurring in BRAF V600E ctDNA levels within the first month following T-cell transfer immunotherapy in metastatic melanoma can be used to rapidly identify responding from nonresponding patients, potentially allowing clinicians to make critical treatment-related decisions in a more timely manner. These data also suggest that the majority of tumor killing by TIL occurs very early after the initiation of therapy. Clin Cancer Res; 22(22); 5480-6. copyright 2016 AACR. JF - Clinical Cancer Research AU - Xi, Liqiang AU - Pham, Trinh Hoc-Tran AU - Payabyab, Eden C AU - Sherry, Richard M AU - Rosenberg, Steven A AU - Raffeld, Mark AD - Molecular Diagnostics Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, mraff@mail.nih.gov Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 5480 EP - 5486 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 22 SN - 1078-0432, 1078-0432 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Data processing KW - Immunotherapy KW - Tumor-infiltrating lymphocytes KW - Tumors KW - biomarkers KW - Cancer KW - Melanoma KW - Metastases KW - Decision making KW - Lymphocytes T KW - Adoptive transfer KW - Polymerase chain reaction KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846407346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Circulating+Tumor+DNA+as+an+Early+Indicator+of+Response+to+T-cell+Transfer+Immunotherapy+in+Metastatic+Melanoma&rft.au=Xi%2C+Liqiang%3BPham%2C+Trinh+Hoc-Tran%3BPayabyab%2C+Eden+C%3BSherry%2C+Richard+M%3BRosenberg%2C+Steven+A%3BRaffeld%2C+Mark&rft.aulast=Xi&rft.aufirst=Liqiang&rft.date=2016-11-15&rft.volume=22&rft.issue=22&rft.spage=5480&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0613 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2017-02-01 N1 - SubjectsTermNotLitGenreText - Metastases; Decision making; Data processing; Immunotherapy; Adoptive transfer; Lymphocytes T; Polymerase chain reaction; Tumor-infiltrating lymphocytes; Tumors; biomarkers; Cancer; Melanoma DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0613 ER - TY - JOUR T1 - The National Disease Research Interchange and Collaborators on: What Are the Major Hurdles to the Recovery of Human Tissue to Advance Research? AN - 1839737563; 27845557 JF - Biopreservation and biobanking AU - VonDran, Melissa AU - Thomas, Jeffrey A AU - Freund, Michelle P AU - Ritsick, Maggie AU - Orr, Maureen AU - Kaye, Wendy E AU - Bakker, Annette AU - Knight, Pamela AD - 1 National Disease Research Interchange , Philadelphia, Pennsylvania. ; 2 Office of Technology Development and Coordination, NIH NeuroBioBank, National Institute of Mental Health , NIH, Bethesda, Maryland. ; 3 McKing Consulting Corporation , Atlanta, Georgia . ; 4 Agency for Toxic Substances and Disease Registry , Atlanta, Georgia . ; 5 Children's Tumor Foundation , New York, New York. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839737563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biopreservation+and+biobanking&rft.atitle=The+National+Disease+Research+Interchange+and+Collaborators+on%3A+What+Are+the+Major+Hurdles+to+the+Recovery+of+Human+Tissue+to+Advance+Research%3F&rft.au=VonDran%2C+Melissa%3BThomas%2C+Jeffrey+A%3BFreund%2C+Michelle+P%3BRitsick%2C+Maggie%3BOrr%2C+Maureen%3BKaye%2C+Wendy+E%3BBakker%2C+Annette%3BKnight%2C+Pamela&rft.aulast=VonDran&rft.aufirst=Melissa&rft.date=2016-11-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Biopreservation+and+biobanking&rft.issn=1947-5543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation-Induced Pulmonary Fibrosis in a Murine Model. AN - 1835527932; 27663762 AB - Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for β-galactosidase activity. Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 ± 11.8 μg per lung; irradiation plus rapamycin, 21.4 ± 6.0 μg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1β and transforming growth factor β induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes. Published by Elsevier Inc. JF - International journal of radiation oncology, biology, physics AU - Chung, Eun Joo AU - Sowers, Anastasia AU - Thetford, Angela AU - McKay-Corkum, Grace AU - Chung, Su I AU - Mitchell, James B AU - Citrin, Deborah E AD - Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. Electronic address: citrind@mail.nih.gov. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 857 EP - 866 VL - 96 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835527932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Mammalian+Target+of+Rapamycin+Inhibition+With+Rapamycin+Mitigates+Radiation-Induced+Pulmonary+Fibrosis+in+a+Murine+Model.&rft.au=Chung%2C+Eun+Joo%3BSowers%2C+Anastasia%3BThetford%2C+Angela%3BMcKay-Corkum%2C+Grace%3BChung%2C+Su+I%3BMitchell%2C+James+B%3BCitrin%2C+Deborah+E&rft.aulast=Chung&rft.aufirst=Eun&rft.date=2016-11-15&rft.volume=96&rft.issue=4&rft.spage=857&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=1879-355X&rft_id=info:doi/10.1016%2Fj.ijrobp.2016.07.026 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ijrobp.2016.07.026 ER - TY - JOUR T1 - Electrophysiological characterization of Nsc-34 cell line using Microelectrode Array. AN - 1835525005; 27772743 AB - Neurons communicate with each other through intricate network to evolve higher brain functions. The electrical activity of the neurons plays a crucial role in shaping the connectivity. With motor neurons being vulnerable to neurodegenerative diseases, understanding the electrophysiological properties of motor neurons is the need of the hour, in order to comprehend the impairment of connectivity in these diseases. NSC-34 cell line serves as an excellent model to study the properties of motor neurons as they express Choline acetyltransferase (ChAT). Although NSC-34 cell lines have been used to study the effect of various toxicological, neurotrophic and neuroprotective agents, the electrical activity of these cells has not been elucidated. In the current study, we have characterized the electrophysiological properties of NSC-34 cell lines using Micro-Electrode Array (MEA) as a tool. Based on the spike waveform, firing frequency, auto- and cross-correlogram analysis, we demonstrate that NSC-34 cell culture has >2 distinct types of neuronal population: principal excitatory neurons, putative interneurons and unclassified neurons. The presence of interneurons in the NSC-34 culture was characterized by increased expression of GAD-67 markers. Thus, finding an understanding of the electrophysiological properties of different population of neurons in NSC-34 cell line, will have multiple applications in the treatment of neurological disorders. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of the neurological sciences AU - Sabitha, K R AU - Sanjay, D AU - Savita, B AU - Raju, T R AU - Laxmi, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru 560 029, India. ; Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru 560 029, India. Electronic address: laxmir@gmail.com. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 134 EP - 139 VL - 370 KW - NSC-34 cell line KW - Motor neurons KW - Microelectrode Array KW - Electrophysiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835525005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+neurological+sciences&rft.atitle=Electrophysiological+characterization+of+Nsc-34+cell+line+using+Microelectrode+Array.&rft.au=Sabitha%2C+K+R%3BSanjay%2C+D%3BSavita%2C+B%3BRaju%2C+T+R%3BLaxmi%2C+T+R&rft.aulast=Sabitha&rft.aufirst=K&rft.date=2016-11-15&rft.volume=370&rft.issue=&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+neurological+sciences&rft.issn=1878-5883&rft_id=info:doi/10.1016%2Fj.jns.2016.09.038 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jns.2016.09.038 ER - TY - JOUR T1 - Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP). AN - 1835418628; 27732871 AB - 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [14C]-EH-TBB or [14C]-BEH-TEBP was applied to human or rat skin at 100nmol/cm2 using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove "unabsorbed" [14C]-radioactivity after continuous exposure (24h). "Absorbed" was quantified using dermally retained [14C]-radioactivity; "penetrated" was calculated based on [14C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24pmol-eq/cm2/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24h (maximum flux was 464±65pmol-eq/cm2/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16±7pmol-eq/cm2/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [14C]-radioactivity in the perfusion media could not be characterized. <1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested. 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92g/mol logPest: 7.73-8.75 (12)) Abdallah et al., 2015a. Other published abbreviations for 2-ethylhexyl-2,3,4,5-tetrabromobenzoate are TBB EHTeBB or EHTBB Abdallah and Harrad, 2011. bis(2-ethylhexyl) tetrabromophthalate (PubChem CID: 117291; CAS No. 26040-51-7 FW: 706.14g/mol logPest: 9.48-11.95 (12)). Other published abbreviations for bis(2-ethylhexyl)tetrabromophthalate are TeBrDEPH TBPH or BEHTBP. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Knudsen, Gabriel A AU - Hughes, Michael F AU - Sanders, J Michael AU - Hall, Samantha M AU - Birnbaum, Linda S AD - NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA. Electronic address: gabriel.knudsen@nih.gov. ; Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. ; NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 117 EP - 127 VL - 311 KW - Bis(2-ethylhexyl) tetrabromophthalate KW - 2-Ethylhexyl 2–3,4,5-tetrabromobenzoate KW - Dermal bioavailability KW - Parallelogram method KW - Brominated flame retardant KW - Persistent organic pollutant UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835418628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Estimation+of+human+percutaneous+bioavailability+for+two+novel+brominated+flame+retardants%2C+2-ethylhexyl+2%2C3%2C4%2C5-tetrabromobenzoate+%28EH-TBB%29+and+bis%282-ethylhexyl%29+tetrabromophthalate+%28BEH-TEBP%29.&rft.au=Knudsen%2C+Gabriel+A%3BHughes%2C+Michael+F%3BSanders%2C+J+Michael%3BHall%2C+Samantha+M%3BBirnbaum%2C+Linda+S&rft.aulast=Knudsen&rft.aufirst=Gabriel&rft.date=2016-11-15&rft.volume=311&rft.issue=&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.10.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.10.005 ER - TY - JOUR T1 - Genetic variants in PTPRD and risk of gestational diabetes mellitus. AN - 1835418111; 27738328 AB - Genome-wide association studies (GWASs) showed that two single nucleotide polymorphisms (SNPs) (rs17584499 and rs649891) in the protein tyrosine phosphatase receptor type D (PTPRD) were associated with type 2 diabetes (T2D). We sought to determine the influence of the PTPRD variants on the gestational diabetes mellitus (GDM) risk. In this research, two SNPs in PTPRD reported in T2D GWASs and six PTPRD expression-related SNPs were genotyped in 964 GDM cases and 1,021 controls using the Sequenom platform. Logistic regression analyses in additive models showed consistently significant associations of PTPRD rs10511544 A>C, rs10756026 T>A and rs10809070 C>G with a decreased risk of GDM [adjusted OR (95% CI) = 0.83 (0.72-0.97) for rs10511544; adjusted OR (95% CI) = 0.81 (0.70-0.94) for rs10756026; adjusted OR (95% CI) = 0.78 (0.65-0.92) for rs10809070]. Furthermore, the risk of GDM was significantly decreased with an increasing number of variant alleles of the three SNPs in a dose-dependent manner (Ptrend = 0.008). Moreover, the haplotype containing variant alleles of the three SNPs were significantly associated with a decreased risk of GDM [adjusted OR (95% CI) = 0.77 (0.64-0.92), P = 0.005], when compared with the most frequent haplotype. However, there were no significant associations for the SNPs reported in the T2D GWASs. Altogether, these findings indicate that the variants of rs10511544, rs10756026 and rs10809070 in PTPRD may contribute to a decreased susceptibility to GDM. Further validation in different ethnic backgrounds and biological function analyses are needed. JF - Oncotarget AU - Chen, Ting AU - Xu, Juan AU - Liu, Guangquan AU - Liu, Heng AU - Chen, Minjian AU - Qin, Yufeng AU - Wu, Wei AU - Xia, Yankai AU - Ji, Chenbo AU - Guo, Xirong AU - Wen, Juan AU - Wang, Xinru AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China. ; Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China. ; Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 76101 EP - 76107 VL - 7 IS - 46 KW - PTPRD KW - polymorphism KW - susceptibility KW - gestational diabetes mellitus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835418111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncotarget&rft.atitle=Genetic+variants+in+PTPRD+and+risk+of+gestational+diabetes+mellitus.&rft.au=Chen%2C+Ting%3BXu%2C+Juan%3BLiu%2C+Guangquan%3BLiu%2C+Heng%3BChen%2C+Minjian%3BQin%2C+Yufeng%3BWu%2C+Wei%3BXia%2C+Yankai%3BJi%2C+Chenbo%3BGuo%2C+Xirong%3BWen%2C+Juan%3BWang%2C+Xinru&rft.aulast=Chen&rft.aufirst=Ting&rft.date=2016-11-15&rft.volume=7&rft.issue=46&rft.spage=76101&rft.isbn=&rft.btitle=&rft.title=Oncotarget&rft.issn=1949-2553&rft_id=info:doi/10.18632%2Foncotarget.12599 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.18632/oncotarget.12599 ER - TY - JOUR T1 - The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer. AN - 1835409757; 27732956 AB - Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. PBLs isolated from 59 chemotherapy-naïve GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software. The mean ± SEM (standard error of the mean) of endogenous DNA damage level was 5.25 ± 0.64. Patients with DNA damage levels lower than mean had significantly better progression free survival (hazard ratio [HR] = 0.19, 95% CI (0.04 - 0.96), P = 0.01) and overall survival (HR = 0.00, 95% CI (0.00 - 0.0), P < 0.001) compared to patients with DNA damage levels higher than mean. Moreover, there was significant correlation between the DNA damage level and presence of mediastinal lymph nodes metastases, IGCCCG (International Germ Cell Cancer Collaborative Group) risk group, and serum tumor markers level. These data suggest that DNA damage levels in PBLs of GCT patients may serve as an important prognostic marker early identifying patients with poor outcome. JF - Oncotarget AU - Sestakova, Zuzana AU - Kalavska, Katarina AU - Hurbanova, Lenka AU - Jurkovicova, Dana AU - Gursky, Jan AU - Chovanec, Michal AU - Svetlovska, Daniela AU - Miskovska, Vera AU - Obertova, Jana AU - Palacka, Patrik AU - Rejlekova, Katarina AU - Sycova-Mila, Zuzana AU - Cingelova, Silvia AU - Spanik, Stanislav AU - Mardiak, Jozef AU - Chovanec, Miroslav AU - Mego, Michal AD - Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia. ; nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia. ; Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia. ; st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia. ; Department of Oncology, National Cancer Institute, Bratislava, Slovakia. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 75996 EP - 76005 VL - 7 IS - 46 KW - prognostic marker KW - DNA damage KW - germ cell tumors KW - cisplatin KW - DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835409757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncotarget&rft.atitle=The+prognostic+value+of+DNA+damage+level+in+peripheral+blood+lymphocytes+of+chemotherapy-na%C3%AFve+patients+with+germ+cell+cancer.&rft.au=Sestakova%2C+Zuzana%3BKalavska%2C+Katarina%3BHurbanova%2C+Lenka%3BJurkovicova%2C+Dana%3BGursky%2C+Jan%3BChovanec%2C+Michal%3BSvetlovska%2C+Daniela%3BMiskovska%2C+Vera%3BObertova%2C+Jana%3BPalacka%2C+Patrik%3BRejlekova%2C+Katarina%3BSycova-Mila%2C+Zuzana%3BCingelova%2C+Silvia%3BSpanik%2C+Stanislav%3BMardiak%2C+Jozef%3BChovanec%2C+Miroslav%3BMego%2C+Michal&rft.aulast=Sestakova&rft.aufirst=Zuzana&rft.date=2016-11-15&rft.volume=7&rft.issue=46&rft.spage=75996&rft.isbn=&rft.btitle=&rft.title=Oncotarget&rft.issn=1949-2553&rft_id=info:doi/10.18632%2Foncotarget.12515 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.18632/oncotarget.12515 ER - TY - JOUR T1 - Altered glutamate release in the dorsal striatum of the MitoPark mouse model of Parkinson's disease. AN - 1834995342; 27659966 AB - Mitochondrial dysfunction has been implicated in the degeneration of dopamine (DA) neurons in Parkinson's disease (PD). In addition, animal models of PD utilizing neurotoxins, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have shown that these toxins disrupt mitochondrial respiration by targeting complex I of the electron transport chain, thereby impairing DA neurons in these models. A MitoPark mouse model was created to mimic the mitochondrial dysfunction observed in the DA system of PD patients. These mice display the same phenotypic characteristics as PD, including accelerated decline in motor function and DAergic systems with age. Previously, these mice have responded to L-Dopa treatment and develop L-Dopa induced dyskinesia (LID) as they age. A potential mechanism involved in the formation of LID is greater glutamate release into the dorsal striatum as a result of altered basal ganglia neurocircuitry due to reduced nigrostriatal DA neurotransmission. Therefore, the focus of this study was to assess various indicators of glutamate neurotransmission in the dorsal striatum of MitoPark mice at an age in which nigrostriatal DA has degenerated. At 28 weeks of age, MitoPark mice had, upon KCl stimulation, greater glutamate release in the dorsal striatum compared to control mice. In addition, uptake kinetics were slower in MitoPark mice. These findings were coupled with reduced expression of the glutamate re-uptake transporter, GLT-1, thus providing an environment suitable for glutamate excitotoxic events, leading to altered physiological function in these mice. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Brain research AU - Farrand, Ariana Q AU - Gregory, Rebecca A AU - Bäckman, Cristina M AU - Helke, Kristi L AU - Boger, Heather A AD - Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB 403, MSC 510, Charleston, SC 29425, USA. ; Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB 403, MSC 510, Charleston, SC 29425, USA; Department of Comparative Medicine, Medical University of South Carolina, 114 Doughty St, STB 648, MSC 777, Charleston, SC 29425, USA. ; Integrative Neuroscience Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21224, USA. ; Department of Comparative Medicine, Medical University of South Carolina, 114 Doughty St, STB 648, MSC 777, Charleston, SC 29425, USA. ; Department of Neuroscience and Center on Aging, Medical University of South Carolina, 173 Ashley Ave, BSB 403, MSC 510, Charleston, SC 29425, USA. Electronic address: boger@musc.edu. Y1 - 2016/11/15/ PY - 2016 DA - 2016 Nov 15 SP - 88 EP - 94 VL - 1651 KW - In vivo electrochemistry KW - MitoPark KW - Dopamine KW - Glutamate KW - Striatum KW - Neurodegeneration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834995342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Altered+glutamate+release+in+the+dorsal+striatum+of+the+MitoPark+mouse+model+of+Parkinson%27s+disease.&rft.au=Farrand%2C+Ariana+Q%3BGregory%2C+Rebecca+A%3BB%C3%A4ckman%2C+Cristina+M%3BHelke%2C+Kristi+L%3BBoger%2C+Heather+A&rft.aulast=Farrand&rft.aufirst=Ariana&rft.date=2016-11-15&rft.volume=1651&rft.issue=&rft.spage=88&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=1872-6240&rft_id=info:doi/10.1016%2Fj.brainres.2016.09.025 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.brainres.2016.09.025 ER - TY - JOUR T1 - Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer. AN - 1839106785; 27841323 AB - Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-γ compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer. JF - Scientific reports AU - Janakiram, Naveena B AU - Mohammed, Altaf AU - Bryant, Taylor AU - Zhang, Yuting AU - Brewer, Misty AU - Duff, Ashley AU - Biddick, Laura AU - Singh, Anil AU - Lightfoot, Stan AU - Steele, Vernon E AU - Rao, Chinthalapally V AD - Center for Cancer Prevention and Drug Development, Department of Medicine, Hematology Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. ; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2016/11/14/ PY - 2016 DA - 2016 Nov 14 SP - 37046 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839106785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Potentiating+NK+cell+activity+by+combination+of+Rosuvastatin+and+Difluoromethylornithine+for+effective+chemopreventive+efficacy+against+Colon+Cancer.&rft.au=Janakiram%2C+Naveena+B%3BMohammed%2C+Altaf%3BBryant%2C+Taylor%3BZhang%2C+Yuting%3BBrewer%2C+Misty%3BDuff%2C+Ashley%3BBiddick%2C+Laura%3BSingh%2C+Anil%3BLightfoot%2C+Stan%3BSteele%2C+Vernon+E%3BRao%2C+Chinthalapally+V&rft.aulast=Janakiram&rft.aufirst=Naveena&rft.date=2016-11-14&rft.volume=6&rft.issue=&rft.spage=37046&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep37046 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep37046 ER - TY - JOUR T1 - Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine. AN - 1839131535; 27660390 AB - Numerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols κ and η in vitro The primer extension reaction catalyzed by human replicative pol α was strongly blocked by 8-oxo-rG. pol κ inefficiently bypassed rG and 8-oxo-rG compared with dG and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG), whereas pol η easily bypassed the ribonucleotides. pol α exclusively inserted dAMP opposite 8-oxo-rG. Interestingly, pol κ preferentially inserted dCMP opposite 8-oxo-rG, whereas the insertion of dAMP was favored opposite 8-oxo-dG. In addition, pol η accurately bypassed 8-oxo-rG. Furthermore, we examined the activity of the base excision repair (BER) enzymes 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease 1 on the substrates, including rG and 8-oxo-rG. Both BER enzymes were completely inactive against 8-oxo-rG in DNA. However, OGG1 suppressed 8-oxo-rG excision by RNase H2, which is involved in the removal of ribonucleotides from DNA. These results suggest that the different sugar backbones between 8-oxo-rG and 8-oxo-dG alter the capacity of TLS and repair of 8-oxoguanine. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Sassa, Akira AU - Çağlayan, Melike AU - Rodriguez, Yesenia AU - Beard, William A AU - Wilson, Samuel H AU - Nohmi, Takehiko AU - Honma, Masamitsu AU - Yasui, Manabu AD - From the Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and a-sassa@nihs.go.jp. ; the Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. ; From the Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and. ; From the Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan and m-yasui@nihs.go.jp. Y1 - 2016/11/11/ PY - 2016 DA - 2016 Nov 11 SP - 24314 EP - 24323 VL - 291 IS - 46 KW - DNA damage KW - base excision repair (BER) KW - 8-oxoguanine (8-oxoG) KW - translesion DNA synthesis KW - DNA polymerase KW - ribonucleotide KW - oxidative stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839131535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Impact+of+Ribonucleotide+Backbone+on+Translesion+Synthesis+and+Repair+of+7%2C8-Dihydro-8-oxoguanine.&rft.au=Sassa%2C+Akira%3B%C3%87a%C4%9Flayan%2C+Melike%3BRodriguez%2C+Yesenia%3BBeard%2C+William+A%3BWilson%2C+Samuel+H%3BNohmi%2C+Takehiko%3BHonma%2C+Masamitsu%3BYasui%2C+Manabu&rft.aulast=Sassa&rft.aufirst=Akira&rft.date=2016-11-11&rft.volume=291&rft.issue=46&rft.spage=24314&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Selenoprotein Gene Nomenclature. AN - 1835507096; 27645994 AB - The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15-kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV), and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing, and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Gladyshev, Vadim N AU - Arnér, Elias S AU - Berry, Marla J AU - Brigelius-Flohé, Regina AU - Bruford, Elspeth A AU - Burk, Raymond F AU - Carlson, Bradley A AU - Castellano, Sergi AU - Chavatte, Laurent AU - Conrad, Marcus AU - Copeland, Paul R AU - Diamond, Alan M AU - Driscoll, Donna M AU - Ferreiro, Ana AU - Flohé, Leopold AU - Green, Fiona R AU - Guigó, Roderic AU - Handy, Diane E AU - Hatfield, Dolph L AU - Hesketh, John AU - Hoffmann, Peter R AU - Holmgren, Arne AU - Hondal, Robert J AU - Howard, Michael T AU - Huang, Kaixun AU - Kim, Hwa-Young AU - Kim, Ick Young AU - Köhrle, Josef AU - Krol, Alain AU - Kryukov, Gregory V AU - Lee, Byeong Jae AU - Lee, Byung Cheon AU - Lei, Xin Gen AU - Liu, Qiong AU - Lescure, Alain AU - Lobanov, Alexei V AU - Loscalzo, Joseph AU - Maiorino, Matilde AU - Mariotti, Marco AU - Sandeep Prabhu, K AU - Rayman, Margaret P AU - Rozovsky, Sharon AU - Salinas, Gustavo AU - Schmidt, Edward E AU - Schomburg, Lutz AU - Schweizer, Ulrich AU - Simonović, Miljan AU - Sunde, Roger A AU - Tsuji, Petra A AU - Tweedie, Susan AU - Ursini, Fulvio AU - Whanger, Philip D AU - Zhang, Yan AD - From the Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, vgladyshev@rics.bwh.harvard.edu. ; the Department of Medical Biochemistry and Biophysics (MBB), Division of Biochemistry, Karolinska Institutet, SE-171 77, Stockholm, Sweden. ; the Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813. ; the German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany. ; the HUGO Gene Nomenclature Committee (HGNC), European Bioinformatics Institute-European Molecular Biology Laboratory (EMBL-EBI), Hinxton CB10 1SD, United Kingdom. ; the Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232. ; the Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892. ; the Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; the Centre International de Recherche en Infectiologie, CIRI, INSERM U1111, and CNRS/ENS UMR5308, 69007 Lyon, France. ; the Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany. ; the Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854. ; the Department of Pathology, University of Illinois at Chicago, Chicago, Illinois 60607. ; the Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195. ; the Pathophysiology of Striated Muscles Laboratory, Unit of Functional and Adaptive Biology (BFA), University Paris Diderot, Sorbonne Paris Cité, BFA, UMR CNRS 8251, 75250 Paris, France. ; the Universidad de la República, Facultad de Medicina, Departamento de Bioquímica, 11800 Montevideo, Uruguay. ; the Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom. ; the Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain. ; the Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115. ; the Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom. ; the Department of Biochemistry, University of Vermont, Burlington, Vermont 05405. ; the Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112. ; the Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, Peoples Republic of China. ; the Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 42415, South Korea. ; the College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea. ; the Institute for Experimental Endocrinology, Charité-Universitaetsmedizin Berlin, D-13353 Berlin, Germany. ; the Architecture et Réactivité de l'ARN, Université de Strasbourg, Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg, France. ; the KSQ Therapeutics, Cambridge, Massachusetts 02139. ; the School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea. ; the Department of Animal Science, Cornell University, Ithaca, New York 14853. ; the Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Science, Shenzhen University, Shenzhen, 518060, Guangdong Province, Peoples Republic of China. ; From the Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. ; the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. ; the Department of Molecular Medicine, University of Padova, I-35121 Padova, Italy. ; the Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802. ; the Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom. ; the Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716. ; the Cátedra de Inmunología, Facultad de Química, Instituto de Higiene, CP11600 Montevideo, Uruguay. ; the Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59717. ; the Rheinische Friedrich-Wilhelms Universität Bonn, Institut für Biochemie und Molekularbiologie, 53115 Bonn, Germany. ; the Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607. ; the Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706. ; the Department of Biological Sciences, Towson University, Towson, Maryland 21252, and. ; the Department of Environmental and Molecular Toxicology, College of Agricultural Sciences, Oregon State University, Corvallis, Oregon 97331. Y1 - 2016/11/11/ PY - 2016 DA - 2016 Nov 11 SP - 24036 EP - 24040 VL - 291 IS - 46 KW - nomenclature KW - selenoprotein KW - gene name KW - selenium KW - selenocysteine KW - structure-function KW - genomics KW - function UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835507096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Selenoprotein+Gene+Nomenclature.&rft.au=Gladyshev%2C+Vadim+N%3BArn%C3%A9r%2C+Elias+S%3BBerry%2C+Marla+J%3BBrigelius-Floh%C3%A9%2C+Regina%3BBruford%2C+Elspeth+A%3BBurk%2C+Raymond+F%3BCarlson%2C+Bradley+A%3BCastellano%2C+Sergi%3BChavatte%2C+Laurent%3BConrad%2C+Marcus%3BCopeland%2C+Paul+R%3BDiamond%2C+Alan+M%3BDriscoll%2C+Donna+M%3BFerreiro%2C+Ana%3BFloh%C3%A9%2C+Leopold%3BGreen%2C+Fiona+R%3BGuig%C3%B3%2C+Roderic%3BHandy%2C+Diane+E%3BHatfield%2C+Dolph+L%3BHesketh%2C+John%3BHoffmann%2C+Peter+R%3BHolmgren%2C+Arne%3BHondal%2C+Robert+J%3BHoward%2C+Michael+T%3BHuang%2C+Kaixun%3BKim%2C+Hwa-Young%3BKim%2C+Ick+Young%3BK%C3%B6hrle%2C+Josef%3BKrol%2C+Alain%3BKryukov%2C+Gregory+V%3BLee%2C+Byeong+Jae%3BLee%2C+Byung+Cheon%3BLei%2C+Xin+Gen%3BLiu%2C+Qiong%3BLescure%2C+Alain%3BLobanov%2C+Alexei+V%3BLoscalzo%2C+Joseph%3BMaiorino%2C+Matilde%3BMariotti%2C+Marco%3BSandeep+Prabhu%2C+K%3BRayman%2C+Margaret+P%3BRozovsky%2C+Sharon%3BSalinas%2C+Gustavo%3BSchmidt%2C+Edward+E%3BSchomburg%2C+Lutz%3BSchweizer%2C+Ulrich%3BSimonovi%C4%87%2C+Miljan%3BSunde%2C+Roger+A%3BTsuji%2C+Petra+A%3BTweedie%2C+Susan%3BUrsini%2C+Fulvio%3BWhanger%2C+Philip+D%3BZhang%2C+Yan&rft.aulast=Gladyshev&rft.aufirst=Vadim&rft.date=2016-11-11&rft.volume=291&rft.issue=46&rft.spage=24036&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells. AN - 1839115643; 27838387 AB - To identify vascular disruptor compounds (VDCs), this study utilized an in vivo zebrafish embryo vascular model in conjunction with a mouse endothelial cell model to screen a subset of the U.S. Environmental Protection Agency (EPA) ToxCast Phase I chemical inventory. In zebrafish, 161 compounds were screened and 34 were identified by visual inspection as VDCs, of which 28 were confirmed as VDCs by quantitative image analysis. Testing of the zebrafish VDCs for their capacity to inhibit endothelial tube formation in the murine yolk-sac-derived endothelial cell line C166 identified 22 compounds that both disrupted zebrafish vascular development and murine endothelial in vitro tubulogenesis. Putative molecular targets for the VDCs were predicted using EPA's Toxicological Prioritization Index tool and a VDC signature based on a proposed adverse outcome pathway for developmental vascular toxicity. In conclusion, our screening approach identified 22 novel VDCs, some of which were active at nanomolar concentrations. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Reproductive toxicology (Elmsford, N.Y.) AU - McCollum, Catherine W AU - Conde-Vancells, Javier AU - Hans, Charu AU - Vazquez-Chantada, Mercedes AU - Kleinstreuer, Nicole AU - Tal, Tamara AU - Knudsen, Thomas AU - Shah, Shishir S AU - Merchant, Fatima A AU - Finnell, Richard H AU - Gustafsson, Jan-Åke AU - Cabrera, Robert AU - Bondesson, Maria AD - Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA. ; Department of Nutritional Sciences, Dell Pediatric Research Institute, The University of Texas at Austin, Austin, TX 78723, USA. ; Department of Computer Science, University of Houston, Houston, TX 77204, USA. ; NIEHS/DNTP/NICEATM, RTP, NC 27560, USA. ; U.S. EPA/ORD/ISTD, RTP, NC 27711, USA. ; U.S. EPA/ORD/NCCT RTP, NC 27711, USA. ; Department of Computer Science, University of Houston, Houston, TX 77204, USA; Department of Engineering Technology, University of Houston, Houston, TX 77204, USA. ; Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA; Department of Biosciences and Nutrition, Novum, Karolinska Institutet, 141 83 Stockholm, Sweden. ; Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA; Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA. Electronic address: mbondessonbolin@uh.edu. Y1 - 2016/11/10/ PY - 2016 DA - 2016 Nov 10 KW - Mouse endothelial cells KW - Vascular disruptor compounds KW - Angiogenesis KW - Zebrafish KW - Vascular development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839115643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Identification+of+vascular+disruptor+compounds+by+analysis+in+zebrafish+embryos+and+mouse+embryonic+endothelial+cells.&rft.au=McCollum%2C+Catherine+W%3BConde-Vancells%2C+Javier%3BHans%2C+Charu%3BVazquez-Chantada%2C+Mercedes%3BKleinstreuer%2C+Nicole%3BTal%2C+Tamara%3BKnudsen%2C+Thomas%3BShah%2C+Shishir+S%3BMerchant%2C+Fatima+A%3BFinnell%2C+Richard+H%3BGustafsson%2C+Jan-%C3%85ke%3BCabrera%2C+Robert%3BBondesson%2C+Maria&rft.aulast=McCollum&rft.aufirst=Catherine&rft.date=2016-11-10&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=1873-1708&rft_id=info:doi/10.1016%2Fj.reprotox.2016.11.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.reprotox.2016.11.005 ER - TY - JOUR T1 - Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria. AN - 1839107904; 27826141 AB - Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms. JF - Emerging microbes & infections AU - Sun, Wei AU - Weingarten, Rebecca A AU - Xu, Miao AU - Southall, Noel AU - Dai, Sheng AU - Shinn, Paul AU - Sanderson, Philip E AU - Williamson, Peter R AU - Frank, Karen M AU - Zheng, Wei AD - National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA. ; Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/11/09/ PY - 2016 DA - 2016 Nov 09 SP - 1 VL - 5 IS - 11 KW - Anti-Bacterial Agents KW - 0 KW - Antirheumatic Agents KW - Drug Combinations KW - Auranofin KW - 3H04W2810V KW - Colistin KW - Z67X93HJG1 KW - Index Medicus KW - Pseudomonas aeruginosa -- growth & development KW - Acinetobacter Infections -- microbiology KW - Bacterial Infections -- microbiology KW - Humans KW - Klebsiella pneumoniae -- isolation & purification KW - Acinetobacter baumannii -- growth & development KW - Acinetobacter baumannii -- drug effects KW - Klebsiella pneumoniae -- growth & development KW - Pseudomonas aeruginosa -- isolation & purification KW - Klebsiella pneumoniae -- drug effects KW - Pseudomonas aeruginosa -- drug effects KW - Drug Synergism KW - Acinetobacter baumannii -- isolation & purification KW - Auranofin -- pharmacology KW - Colistin -- pharmacology KW - Anti-Bacterial Agents -- pharmacology KW - Antirheumatic Agents -- pharmacology KW - Drug Resistance, Multiple, Bacterial KW - Microbial Sensitivity Tests KW - Drug Discovery -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839107904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+microbes+%26+infections&rft.atitle=Rapid+antimicrobial+susceptibility+test+for+identification+of+new+therapeutics+and+drug+combinations+against+multidrug-resistant+bacteria.&rft.au=Sun%2C+Wei%3BWeingarten%2C+Rebecca+A%3BXu%2C+Miao%3BSouthall%2C+Noel%3BDai%2C+Sheng%3BShinn%2C+Paul%3BSanderson%2C+Philip+E%3BWilliamson%2C+Peter+R%3BFrank%2C+Karen+M%3BZheng%2C+Wei&rft.aulast=Sun&rft.aufirst=Wei&rft.date=2016-11-09&rft.volume=5&rft.issue=11&rft.spage=e116&rft.isbn=&rft.btitle=&rft.title=Emerging+microbes+%26+infections&rft.issn=2222-1751&rft_id=info:doi/10.1038%2Femi.2016.123 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-31 N1 - Date created - 2016-11-09 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1038/emi.2016.123 ER - TY - JOUR T1 - l-tetrahydropalmatine reduces nicotine self-administration and reinstatement in rats. AN - 1837031128; 27817750 AB - The negative consequences of nicotine use are well known and documented, however, abstaining from nicotine use and achieving abstinence poses a major challenge for the majority of nicotine users trying to quit. l-Tetrahydropalmatine (l-THP), a compound extracted from the Chinese herb Corydalis, displayed utility in the treatment of cocaine and heroin addiction via reduction of drug-intake and relapse. The present study examined the effects of l-THP on abuse-related effects of nicotine. Self-administration and reinstatement testing was conducted. Rats trained to self-administer nicotine (0.03 mg/kg/injection) under a fixed-ratio 5 schedule (FR5) of reinforcement were pretreated with l-THP (3 or 5 mg/kg), varenicline (1 mg/kg), bupropion (40 mg/kg), or saline before daily 2-h sessions. Locomotor, food, and microdialysis assays were also conducted in separate rats. l-THP significantly reduced nicotine self-administration (SA). l-THP's effect was more pronounced than the effect of varenicline and similar to the effect of bupropion. In reinstatement testing, animals were pretreated with the same compounds, challenged with nicotine (0.3 mg/kg, s.c.), and reintroduced to pre-extinction conditions. l-THP blocked reinstatement of nicotine seeking more effectively than either varenicline or bupropion. Locomotor data revealed that therapeutic doses of l-THP had no inhibitory effects on ambulatory ability and that l-THP (3 and 5 mg/kg) significantly blocked nicotine induced hyperactivity when administered before nicotine. In in-vivo microdialysis experiments, l-THP, varenicline, and bupropion alone elevated extracellular dopamine (DA) levels in the nucleus accumbens shell (nAcb). Since l-THP reduces nicotine taking and blocks relapse it could be a useful alternative to varenicline and bupropion as a treatment for nicotine addiction. JF - BMC pharmacology & toxicology AU - Faison, Shamia L AU - Schindler, Charles W AU - Goldberg, Steven R AU - Wang, Jia Bei AD - Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA. ; Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, MD, USA. ; Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, USA. jwang@rx.umaryland.edu. Y1 - 2016/11/07/ PY - 2016 DA - 2016 Nov 07 SP - 49 VL - 17 IS - 1 KW - levo-Tetrahydropalmatine KW - Nicotine KW - Addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837031128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+pharmacology+%26+toxicology&rft.atitle=l-tetrahydropalmatine+reduces+nicotine+self-administration+and+reinstatement+in+rats.&rft.au=Faison%2C+Shamia+L%3BSchindler%2C+Charles+W%3BGoldberg%2C+Steven+R%3BWang%2C+Jia+Bei&rft.aulast=Faison&rft.aufirst=Shamia&rft.date=2016-11-07&rft.volume=17&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=BMC+pharmacology+%26+toxicology&rft.issn=2050-6511&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5. AN - 1837026227; 27819327 AB - Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1.5. FS50 exhibits high specificity for NaV1.5, since 10 μM FS50 had no discernable effect on voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglia or VGSC forms individually expressed in HEK 293T cells. Furthermore, intravenous injection of FS50 into rats and monkeys elicited recovery from arrhythmia induced by BaCl2, as would be expected from a blockade of NaV1.5. The crystal structure of FS50 revealed a βαββ domain similar to that of scorpion β toxin and a small N-terminal βαβ domain. Site-directed mutagenesis experiments have implicated a basic surface including the side chains of Arg 6, His 11 and Lys 32 as potentially important in the FS50 NaV1.5 interaction. JF - Scientific reports AU - Xu, Xueqing AU - Zhang, Bei AU - Yang, Shilong AU - An, Su AU - Ribeiro, José M C AU - Andersen, John F AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China. ; The Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. ; The Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20852 USA. Y1 - 2016/11/07/ PY - 2016 DA - 2016 Nov 07 SP - 36574 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837026227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Structure+and+Function+of+FS50%2C+a+salivary+protein+from+the+flea+Xenopsylla+cheopis+that+blocks+the+sodium+channel+NaV1.5.&rft.au=Xu%2C+Xueqing%3BZhang%2C+Bei%3BYang%2C+Shilong%3BAn%2C+Su%3BRibeiro%2C+Jos%C3%A9+M+C%3BAndersen%2C+John+F&rft.aulast=Xu&rft.aufirst=Xueqing&rft.date=2016-11-07&rft.volume=6&rft.issue=&rft.spage=36574&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep36574 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep36574 ER - TY - JOUR T1 - Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide: MECHANISTIC DETAILS STUDIED BY SPECTROSCOPY IN COMBINATION WITH MICROSCOPY. AN - 1836729698; 27679488 AB - The aggregation of insulin into amyloid fibers has been a limiting factor in the development of fast acting insulin analogues, creating a demand for excipients that limit aggregation. Despite the potential demand, inhibitors specifically targeting insulin have been few in number. Here we report a non-toxic and serum stable-designed heptapeptide, KR7 (KPWWPRR-NH2), that differs significantly from the primarily hydrophobic sequences that have been previously used to interfere with insulin amyloid fibrillation. Thioflavin T fluorescence assays, circular dichroism spectroscopy, and one-dimensional proton NMR experiments suggest KR7 primarily targets the fiber elongation step with little effect on the early oligomerization steps in the lag time period. From confocal fluorescence and atomic force microscopy experiments, the net result appears to be the arrest of aggregation in an early, non-fibrillar aggregation stage. This mechanism is noticeably different from previous peptide-based inhibitors, which have primarily shifted the lag time with little effect on later stages of aggregation. As insulin is an important model system for understanding protein aggregation, the new peptide may be an important tool for understanding peptide-based inhibition of amyloid formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Ratha, Bhisma N AU - Ghosh, Anirban AU - Brender, Jeffrey R AU - Gayen, Nilanjan AU - Ilyas, Humaira AU - Neeraja, Chilukoti AU - Das, Kali P AU - Mandal, Atin K AU - Bhunia, Anirban AD - From the Department of Biophysics and. ; Radiation Biology Branch, National Institutes of Health, Bethesda, Maryland 20814. ; Department of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India. ; TIFR Centre for Interdisciplinary Sciences (TCIS), Narsingi, Hyderabad 500075, India, and. ; Department of Chemistry, 93/1 APC Road, Bose Institute, Kolkata 700009, India. ; From the Department of Biophysics and anirbanbhunia@gmail.com bhunia@jcbose.ac.in. Y1 - 2016/11/04/ PY - 2016 DA - 2016 Nov 04 SP - 23545 EP - 23556 VL - 291 IS - 45 KW - atomic force microscopy (AFM) KW - fluorescence anisotropy KW - insulin KW - inhibitor KW - amyloid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836729698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Inhibition+of+Insulin+Amyloid+Fibrillation+by+a+Novel+Amphipathic+Heptapeptide%3A+MECHANISTIC+DETAILS+STUDIED+BY+SPECTROSCOPY+IN+COMBINATION+WITH+MICROSCOPY.&rft.au=Ratha%2C+Bhisma+N%3BGhosh%2C+Anirban%3BBrender%2C+Jeffrey+R%3BGayen%2C+Nilanjan%3BIlyas%2C+Humaira%3BNeeraja%2C+Chilukoti%3BDas%2C+Kali+P%3BMandal%2C+Atin+K%3BBhunia%2C+Anirban&rft.aulast=Ratha&rft.aufirst=Bhisma&rft.date=2016-11-04&rft.volume=30&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Fundamental+%26+clinical+pharmacology&rft.issn=1472-8206&rft_id=info:doi/10.1111%2Ffcp.12157 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - 2ZP6; PDB N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture. AN - 1836726594; 27814246 AB - Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial-mixture (CM-HBCD) composed of 3 main stereoisomers: α-HBCD (10%); β-HBCD (10%); γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife. Considering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, metabolomics was performed on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures, developmental outcomes, and predict health risks. Ten postnatal day (PND) female C57BL/6 mice were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. NMR metabolomics was used to analyze 60 µL serum aliquots of blood collected 4 days post-oral exposure. Infantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment- and dose-groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate and acetoacetate, were non-statistically elevated, compared to mean control levels, in all treatment- and dose-groups while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD, and was non-significantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment- and dose group. Metabolites significant in differentiating treatment- and dose-groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively. We demonstrate that four days following a single neonatal oral exposure to α-, γ-, and CM-HBCD results in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action. JF - Environmental health perspectives AU - Szabo, David T AU - Pathmasiri, Wimal AU - Sumner, Susan AU - Birnbaum, Linda S AD - US Environmental Protection Agency, National Human Environmental Exposure Research Laboratory, Research Triangle Park, North Carolina, USA. ; Discovery Sciences, Research Triangle Institute International, Research Triangle Park, North Carolina, USA. ; National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, North Carolina, USA. Y1 - 2016/11/04/ PY - 2016 DA - 2016 Nov 04 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836726594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Serum+Metabolomic+Profiles+in+Neonatal+Mice+following+Oral+Brominated+Flame+Retardant+Exposures+to+Hexabromocyclododecane+%28HBCD%29+Alpha%2C+Gamma%2C+and+Commercial+Mixture.&rft.au=Szabo%2C+David+T%3BPathmasiri%2C+Wimal%3BSumner%2C+Susan%3BBirnbaum%2C+Linda+S&rft.aulast=Szabo&rft.aufirst=David&rft.date=2016-11-04&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - TNF-α modulates genome-wide redistribution of ΔNp63α/TAp73 and NF-κB cREL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer. AN - 1826672972; 27132513 AB - The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ΔNp63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs comodulated by cREL/ΔNp63/TAp73 transcription factors we uncovered in head and neck squamous cell carcinomas (HNSCCs). However, how inflammatory gene signatures and cREL/p63/p73 targets are comodulated genome wide is unclear. Here, we examined how the inflammatory factor tumor necrosis factor-α (TNF-α) broadly modulates redistribution of cREL with ΔNp63α/TAp73 complexes and signatures genome wide in the HNSCC model UM-SCC46 using chromatin immunoprecipitation sequencing (ChIP-seq). TNF-α enhanced genome-wide co-occupancy of cREL with ΔNp63α on TP53/p63 sites, while unexpectedly promoting redistribution of TAp73 from TP53 to activator protein-1 (AP-1) sites. cREL, ΔNp63α and TAp73 binding and oligomerization on NF-κB-, TP53- or AP-1-specific sequences were independently validated by ChIP-qPCR (quantitative PCR), oligonucleotide-binding assays and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53-, AP-1- and NF-κB-specific REs or p21, SERPINE1 and IL-6 promoter luciferase reporter activities. Concurrently, TNF-α regulated a broad gene network with cobinding activities for cREL, ΔNp63α and TAp73 observed upon array profiling and reverse transcription-PCR. Overlapping target gene signatures were observed in squamous cancer subsets and in inflamed skin of transgenic mice overexpressing ΔNp63α. Furthermore, multiple target genes identified in this study were linked to TP63 and TP73 activity and increased gene expression in large squamous cancer samples from PanCancer 12 TCGA by CircleMap. PARADIGM inferred pathway analysis revealed the network connection of TP63 and NF-κB complexes through an AP-1 hub, further supporting our findings. Thus, inflammatory cytokine TNF-α mediates genome-wide redistribution of the cREL/p63/p73, and AP-1 interactome, to diminish TAp73 tumor suppressor function and reciprocally activate NF-κB and AP-1 gene programs implicated in malignancy. JF - Oncogene AU - Si, H AU - Lu, H AU - Yang, X AU - Mattox, A AU - Jang, M AU - Bian, Y AU - Sano, E AU - Viadiu, H AU - Yan, B AU - Yau, C AU - Ng, S AU - Lee, S K AU - Romano, R-A AU - Davis, S AU - Walker, R L AU - Xiao, W AU - Sun, H AU - Wei, L AU - Sinha, S AU - Benz, C C AU - Stuart, J M AU - Meltzer, P S AU - Van Waes, C AU - Chen, Z AD - Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA. ; Department of Chemistry and Biochemistry, University of California, San Diego, CA, USA. ; Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior, Ciudad Universitaria, Mexico City, MÉXICO. ; LKS Faculty of Medicine and School of Biomedical Sciences, LKS Faculty of Medicine and Center of Genome Sciences, The University of Hong Kong, Hong Kong, China. ; Buck Institute for Research on Aging, Novato, CA, USA. ; Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA. ; Department of Biochemistry, State University of New York at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, Buffalo, New York, USA. ; Cancer Genetics Branch, National Cancer Institute, Bethesda, Maryland, USA. ; Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AK, USA. ; Biodata Mining and Discovery Section, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA. ; Clinical Immunology Section, National Eye Institute, NIH, Bethesda, Maryland, USA. Y1 - 2016/11/03/ PY - 2016 DA - 2016 Nov 03 SP - 5781 EP - 5794 VL - 35 IS - 44 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826672972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=TNF-%CE%B1+modulates+genome-wide+redistribution+of+%CE%94Np63%CE%B1%2FTAp73+and+NF-%CE%BAB+cREL+interactive+binding+on+TP53+and+AP-1+motifs+to+promote+an+oncogenic+gene+program+in+squamous+cancer.&rft.au=Si%2C+H%3BLu%2C+H%3BYang%2C+X%3BMattox%2C+A%3BJang%2C+M%3BBian%2C+Y%3BSano%2C+E%3BViadiu%2C+H%3BYan%2C+B%3BYau%2C+C%3BNg%2C+S%3BLee%2C+S+K%3BRomano%2C+R-A%3BDavis%2C+S%3BWalker%2C+R+L%3BXiao%2C+W%3BSun%2C+H%3BWei%2C+L%3BSinha%2C+S%3BBenz%2C+C+C%3BStuart%2C+J+M%3BMeltzer%2C+P+S%3BVan+Waes%2C+C%3BChen%2C+Z&rft.aulast=Si&rft.aufirst=H&rft.date=2016-11-03&rft.volume=35&rft.issue=44&rft.spage=5781&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2016.112 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2016.112 ER - TY - JOUR T1 - Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response AN - 1850780150; PQ0003898815 AB - We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ~1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. JF - Cold Spring Harbor Molecular Case Studies AU - Biswas, Romi AU - Gao, Shaojian AU - Cultraro, Constance M AU - Maity, Tapan K AU - Venugopalan, Abhilash AU - Abdullaev, Zied AU - Shaytan, Alexey K AU - Carter, Corey A AU - Thomas, Anish AU - Rajan, Arun AD - Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA Y1 - 2016/11// PY - 2016 DA - November 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States VL - 2 IS - 6 KW - Biotechnology and Bioengineering Abstracts KW - ErbB-2 protein KW - Chemotherapy KW - Tumors KW - Migration KW - Lymph nodes KW - Models KW - Metastases KW - DNA damage KW - Genomic instability KW - Oncogenes KW - Lung KW - Adenocarcinoma KW - Translocation KW - Mutation KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850780150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Molecular+Case+Studies&rft.atitle=Genomic+profiling+of+multiple+sequentially+acquired+tumor+metastatic+sites+from+an+%22exceptional+responder%22+lung+adenocarcinoma+patient+reveals+extensive+genomic+heterogeneity+and+novel+somatic+variants+driving+treatment+response&rft.au=Biswas%2C+Romi%3BGao%2C+Shaojian%3BCultraro%2C+Constance+M%3BMaity%2C+Tapan+K%3BVenugopalan%2C+Abhilash%3BAbdullaev%2C+Zied%3BShaytan%2C+Alexey+K%3BCarter%2C+Corey+A%3BThomas%2C+Anish%3BRajan%2C+Arun&rft.aulast=Biswas&rft.aufirst=Romi&rft.date=2016-11-01&rft.volume=2&rft.issue=6&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Molecular+Case+Studies&rft.issn=2373-2873&rft_id=info:doi/10.1101%2Fmcs.a001263 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - ErbB-2 protein; Chemotherapy; Tumors; Migration; Lymph nodes; Models; Metastases; DNA damage; Oncogenes; Genomic instability; Lung; Adenocarcinoma; Mutation; Translocation DO - http://dx.doi.org/10.1101/mcs.a001263 ER - TY - JOUR T1 - Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat With Incident Atrial Fibrillation (from the Framingham Heart Study) AN - 1846419309; PQ0003845105 AB - Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third-Generation Cohorts who participated in the multidetector computed tomography substudy examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and gender-adjusted incident AF rate per 1,000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and gender-adjusted model, greater pericardial fat (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03 to 1.34) and intrathoracic fat (HR 1.24, 95% CI 1.06 to 1.45) were associated with an increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99 to 1.30) for pericardial fat, 1.19 (1.01 to 1.40) for intrathoracic fat, and 1.09 (0.93 to 1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of body mass index, none of the associations remained significant (all p >0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. JF - American Journal of Cardiology AU - Lee, Jane J AU - Yin, Xiaoyan AU - Hoffmann, Udo AU - Fox, Caroline S AU - Benjamin, Emelia J AD - Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and, Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1486 EP - 1492 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 118 IS - 10 SN - 0002-9149, 0002-9149 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Obesity KW - Age KW - Fibrillation KW - Risk factors KW - Computed tomography KW - Progeny KW - Body mass index KW - Models KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846419309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Cardiology&rft.atitle=Relation+of+Pericardial+Fat%2C+Intrathoracic+Fat%2C+and+Abdominal+Visceral+Fat+With+Incident+Atrial+Fibrillation+%28from+the+Framingham+Heart+Study%29&rft.au=Lee%2C+Jane+J%3BYin%2C+Xiaoyan%3BHoffmann%2C+Udo%3BFox%2C+Caroline+S%3BBenjamin%2C+Emelia+J&rft.aulast=Lee&rft.aufirst=Jane&rft.date=2016-11-01&rft.volume=118&rft.issue=10&rft.spage=1486&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Cardiology&rft.issn=00029149&rft_id=info:doi/10.1016%2Fj.amjcard.2016.08.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 30 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Heart; Obesity; Age; Risk factors; Fibrillation; Computed tomography; Progeny; Body mass index; Models DO - http://dx.doi.org/10.1016/j.amjcard.2016.08.011 ER - TY - JOUR T1 - Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility AN - 1846418070; PQ0003879920 AB - Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerability-for example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic. JF - AIDS Research and Human Retroviruses AU - Porter, Kristen A AU - Turpin, Jim AU - Begg, Lisa AU - Brown, Gina AU - Chakhtoura, Nahida AU - Church, Elizabeth AU - Grossman, Cynthia AU - Wira, Charles AU - Veronese, Fulvia AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1149 EP - 1158 PB - Mary Ann Liebert, Inc., 140 Huguenot Street New Rochelle NY 10801 United States VL - 32 IS - 10-11 SN - 0889-2229, 0889-2229 KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - HIV KW - HIV/AIDS pathogenesis KW - HIV transmission KW - HIV prevention KW - mucosal KW - Acquired immune deficiency syndrome KW - Prevention KW - Lentivirus KW - Injuries KW - Retroviridae KW - Physiology KW - Intervention KW - Socioeconomics KW - Infection KW - Violence KW - Adolescents KW - H 6000:Natural Disasters/Civil Defense/Emergency Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846418070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Understanding+the+Intersection+of+Young+Age%2C+Mucosal+Injury%2C+and+HIV+Susceptibility&rft.au=Porter%2C+Kristen+A%3BTurpin%2C+Jim%3BBegg%2C+Lisa%3BBrown%2C+Gina%3BChakhtoura%2C+Nahida%3BChurch%2C+Elizabeth%3BGrossman%2C+Cynthia%3BWira%2C+Charles%3BVeronese%2C+Fulvia&rft.aulast=Porter&rft.aufirst=Kristen&rft.date=2016-11-01&rft.volume=32&rft.issue=10-11&rft.spage=1149&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/10.1089%2Faid.2016.0206 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 48 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Prevention; Acquired immune deficiency syndrome; Injuries; Physiology; Socioeconomics; Intervention; Infection; Violence; Adolescents; Lentivirus; Retroviridae DO - http://dx.doi.org/10.1089/aid.2016.0206 ER - TY - JOUR T1 - Type I Interferon-Mediated Induction of Antiviral Genes and Proteins Fails to Protect Cells from the Cytopathic Effects of Sendai Virus Infection AN - 1846405368; PQ0003818914 AB - Sendai virus (SeV), a murine paramyxovirus, has been used to study the induction of type I interferon (IFN) subtypes in robust quantities. Few studies have measured whether the IFN that SeV induces actually fulfills its intended purpose of interfering with virus-mediated effects in the cells in which it is produced. We determined the effects of IFN on SeV-mediated cytopathic effects (CPE) and the ability of IFN to protect against virus infection. SeV-induced biologically active IFN resulted in Jak/STAT activation and the production of a number of interferon-stimulated genes (ISGs). However, these responses did not inhibit SeV replication or CPE. This observation was not due to SeV effects on canonical IFN signaling. Furthermore, pretreating cells with type I IFN and establishing an antiviral state before infection did not mediate SeV effects. Therefore, the induction of canonical IFN signaling pathways and ISGs does not always confer protection against the IFN-inducing virus. Because type I IFNs are approved to treat various infections, our findings suggest that typical markers of IFN activity may not be indicative of a protective antiviral response and should not be used alone to determine whether an antiviral state against a particular virus is achieved. JF - Journal of Interferon & Cytokine Research AU - Bedsaul, Jacquelyn R AU - Zaritsky, Luna A AU - Zoon, Kathryn C AD - Cytokine Biology Section, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 652 EP - 665 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 United States VL - 36 IS - 11 SN - 1079-9907, 1079-9907 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - interferon KW - Sendai virus KW - antiviral state KW - signaling KW - Interferon KW - Replication KW - Antiviral state KW - Paramyxovirus KW - Infection KW - Signal transduction KW - A 01340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846405368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Interferon+%26+Cytokine+Research&rft.atitle=Type+I+Interferon-Mediated+Induction+of+Antiviral+Genes+and+Proteins+Fails+to+Protect+Cells+from+the+Cytopathic+Effects+of+Sendai+Virus+Infection&rft.au=Bedsaul%2C+Jacquelyn+R%3BZaritsky%2C+Luna+A%3BZoon%2C+Kathryn+C&rft.aulast=Bedsaul&rft.aufirst=Jacquelyn&rft.date=2016-11-01&rft.volume=36&rft.issue=11&rft.spage=652&rft.isbn=&rft.btitle=&rft.title=Journal+of+Interferon+%26+Cytokine+Research&rft.issn=10799907&rft_id=info:doi/10.1089%2Fjir.2016.0051 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 50 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Interferon; Replication; Antiviral state; Infection; Signal transduction; Sendai virus; Paramyxovirus DO - http://dx.doi.org/10.1089/jir.2016.0051 ER - TY - JOUR T1 - Transcription Factor GLIS3: A New and Critical Regulator of Postnatal Stages of Mouse Spermatogenesis AN - 1846400355; PQ0003835262 AB - Abstract In this study, we identify a novel and essential role for the Krueppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in the regulation of postnatal spermatogenesis. We show that GLIS3 is expressed in gonocytes, spermatogonial stem cells (SSCs) and spermatogonial progenitors (SPCs), but not in differentiated spermatogonia and later stages of spermatogenesis or in somatic cells. Spermatogenesis is greatly impaired in GLIS3 knockout mice. Loss of GLIS3 function causes a moderate reduction in the number of gonocytes, but greatly affects the generation of SSCs/SPCs, and as a consequence the development of spermatocytes. Gene expression profiling demonstrated that the expression of genes associated with undifferentiated spermatogonia was dramatically decreased in GLIS3-deficient mice and that the cytoplasmic-to-nuclear translocation of FOXO1, which marks the gonocyte-to-SSC transition and is necessary for SSC self-renewal, is inhibited. These observations suggest that GLIS3 promotes the gonocyte-to-SSC transition and is a critical regulator of the dynamics of early postnatal spermatogenesis. Stem Cells 2016; 34:2772-2783 JF - Stem Cells AU - Kang, Hong Soon AU - Chen, Liang-Yu AU - Lichti-Kaiser, Kristin AU - Liao, Grace AU - Gerrish, Kevin AU - Bortner, Carl D AU - Yao, Humphrey H-C AU - Eddy, Edward M AU - Jetten, Anton M AD - Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2772 EP - 2783 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 11 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Stem cells KW - Transcription factors KW - Zinc finger proteins KW - FOXO1 protein KW - Somatic cells KW - Spermatogenesis KW - Translocation KW - Spermatocytes KW - Spermatogonia KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846400355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Transcription+Factor+GLIS3%3A+A+New+and+Critical+Regulator+of+Postnatal+Stages+of+Mouse+Spermatogenesis&rft.au=Kang%2C+Hong+Soon%3BChen%2C+Liang-Yu%3BLichti-Kaiser%2C+Kristin%3BLiao%2C+Grace%3BGerrish%2C+Kevin%3BBortner%2C+Carl+D%3BYao%2C+Humphrey+H-C%3BEddy%2C+Edward+M%3BJetten%2C+Anton+M&rft.aulast=Kang&rft.aufirst=Hong&rft.date=2016-11-01&rft.volume=34&rft.issue=11&rft.spage=2772&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2449 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Gene expression; Stem cells; Transcription factors; Zinc finger proteins; FOXO1 protein; Somatic cells; Translocation; Spermatogenesis; Spermatocytes; Spermatogonia DO - http://dx.doi.org/10.1002/stem.2449 ER - TY - JOUR T1 - The long terminal repeat negative control region is a critical element for insertional oncogenesis after gene transfer into hematopoietic progenitors with Moloney murine leukemia viral vectors AN - 1846399307; PQ0003838671 AB - Integrating vectors based on gamma -retroviruses and containing full-length long terminal repeats (LTRs) have been associated with activation of oncogene expression and leukemogenesis in human gene therapy trials. Identification of the specific molecular elements of the LTRs that have a role in insertional oncogenesis events is important as it can lead to the development of safer gene transfer vectors. The negative control region (NCR) of the LTR is a particularly well-conserved sequence among mammalian gamma -retroviruses with demonstrated regulatory activity of gene transcription in hematopoietic cells, which led us to hypothesize that this region may have a role in insertional oncogenesis after gamma -retroviral vector (GV)-mediated gene transfer into hematopoietic progenitors. We used an in vitro assay of murine bone marrow cell immortalization to compare the immortalization capabilities of a series of GVs carrying murine leukemia virus (MLV) LTR deletion mutants. Compared with GV carrying the full-length MLV LTR, deletion of the complete LTR enhancer sequence showed significant reduction of immortalization rates. However, the use of a mutant LTR deleted of the enhancer sequence, with exception of the NCR, did not affect immortalization. Importantly, the inclusion of an LTR mutant devoid only of the NCR did show significant reduction of immortalization rates compared with the full LTR sequence. Therefore, our data point to the NCR as a key element for immortalization and justify additional studies to evaluate its specific role in MLV-mediated insertional oncogenesis. JF - Gene Therapy AU - Ikawa, Y AU - Uchiyama, T AU - Jagadeesh, G J AU - Candotti, F AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute (NHGRI), Bethesda, MD, USA; Department of Pediatrics, Kanazawa University Hospital, Kanazawa, Japan Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 815 EP - 818 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 23 IS - 11 SN - 0969-7128, 0969-7128 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Cell immortalization KW - Data processing KW - Deletion mutant KW - Gene therapy KW - Long terminal repeat KW - Regulatory sequences KW - Retroviridae KW - Tumorigenesis KW - Bone marrow KW - Leukemogenesis KW - Transcription KW - Expression vectors KW - Enhancers KW - Stem cells KW - Oncogenes KW - Hemopoiesis KW - Immortalization KW - W 30905:Medical Applications KW - G 07880:Human Genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846399307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=The+long+terminal+repeat+negative+control+region+is+a+critical+element+for+insertional+oncogenesis+after+gene+transfer+into+hematopoietic+progenitors+with+Moloney+murine+leukemia+viral+vectors&rft.au=Ikawa%2C+Y%3BUchiyama%2C+T%3BJagadeesh%2C+G+J%3BCandotti%2C+F&rft.aulast=Ikawa&rft.aufirst=Y&rft.date=2016-11-01&rft.volume=23&rft.issue=11&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fgt.2016.51 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Cell immortalization; Deletion mutant; Data processing; Gene therapy; Long terminal repeat; Regulatory sequences; Tumorigenesis; Leukemogenesis; Bone marrow; Transcription; Expression vectors; Enhancers; Stem cells; Oncogenes; Hemopoiesis; Immortalization; Retroviridae DO - http://dx.doi.org/10.1038/gt.2016.51 ER - TY - JOUR T1 - Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior. AN - 1842601058; 27870848 AB - The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior. JF - PLoS genetics AU - Ben-Moshe Livne, Zohar AU - Alon, Shahar AU - Vallone, Daniela AU - Bayleyen, Yared AU - Tovin, Adi AU - Shainer, Inbal AU - Nisembaum, Laura G AU - Aviram, Idit AU - Smadja-Storz, Sima AU - Fuentes, Michael AU - Falcón, Jack AU - Eisenberg, Eli AU - Klein, David C AU - Burgess, Harold A AU - Foulkes, Nicholas S AU - Gothilf, Yoav AD - Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel. ; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany. ; Unit on Behavioral Neurogenetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America. ; Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins, Observatoire Océanologique, Banyuls/Mer, France. ; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel. ; Section on Neuroendocrinology and Office of the Scientific Directory, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1 VL - 12 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1842601058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+genetics&rft.atitle=Genetically+Blocking+the+Zebrafish+Pineal+Clock+Affects+Circadian+Behavior.&rft.au=Ben-Moshe+Livne%2C+Zohar%3BAlon%2C+Shahar%3BVallone%2C+Daniela%3BBayleyen%2C+Yared%3BTovin%2C+Adi%3BShainer%2C+Inbal%3BNisembaum%2C+Laura+G%3BAviram%2C+Idit%3BSmadja-Storz%2C+Sima%3BFuentes%2C+Michael%3BFalc%C3%B3n%2C+Jack%3BEisenberg%2C+Eli%3BKlein%2C+David+C%3BBurgess%2C+Harold+A%3BFoulkes%2C+Nicholas+S%3BGothilf%2C+Yoav&rft.aulast=Ben-Moshe+Livne&rft.aufirst=Zohar&rft.date=2016-11-01&rft.volume=12&rft.issue=11&rft.spage=e1006445&rft.isbn=&rft.btitle=&rft.title=PLoS+genetics&rft.issn=1553-7404&rft_id=info:doi/10.1371%2Fjournal.pgen.1006445 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1371/journal.pgen.1006445 ER - TY - JOUR T1 - Ferumoxytol as an intraprostatic MR contrast agent for lymph node mapping of the prostate: a feasibility study in non-human primates AN - 1837336120; PQ0003757229 AB - Background A variety of magnetic resonance (MR) lymphographic agents have been proposed for mapping the lymph nodes draining the prostate. Purpose To investigate the feasibility of using ferumoxytol (an FDA-approved iron oxide agent) for lymph node mapping of the prostate on imaging (MRI) in a non-human primate (NHP) Macaque model. Material and Methods Four NHPs weighing 5-13kg underwent injection of ferumoxytol after a needle was introduced transrectally under MRI guidance into the prostate using a commercially available intrarectal MRI biopsy guide. Ferumoxytol was administered at dosage in the range of 0.15-0.75mg Fe/kg in a fixed injection volume of 0.2mL. T1-weighted MRI was performed at 3T starting immediately and extending at least 45min post-injection. Two readers evaluated the images in consensus. The NHPs tolerated the ferumoxytol injections at all doses with no evident side effects. Results It was determined that the lowest dose of 0.15mg Fe/kg produced the best outcome in terms of lymph node visualization and draining nodes were reliably visualized at this dose and volume. Conclusion Thus, MRI with intraprostatic injection of ferumoxytol may be considered an effective T1 contrast agent for prospective mapping of lymph nodes draining the prostate and, thus, for attempted sentinel lymph node identification in prostate cancer. Large clinical trials to determine safety and efficacy are needed. JF - Acta Radiologica AU - Sankineni, Sandeep AU - Smedley, Jeremy AU - Bernardo, Marcelino AU - Brown, Anna M AU - Johnson, Linda AU - Muller, Berrend AU - Griffiths, Gary L AU - Kobayashi, Hisataka AU - Rais-Bahrami, Soroush AU - Pinto, Peter A AU - Wood, Bradford J AU - Keele, Brandon AU - Choyke, Peter L AU - Turkbey, Baris AD - 1 .Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, turkbeyi@mail.nih.gov Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1396 EP - 1401 PB - Sage Publications, Inc., 2455 Teller Road Thousand Oaks CA 91320 United States VL - 57 IS - 11 SN - 0284-1851, 0284-1851 KW - Biotechnology and Bioengineering Abstracts KW - Ferumoxytol KW - lymph node KW - prostate cancer KW - iron oxide nanoparticles KW - magnetic resonance imaging (MRI) KW - iron oxides KW - Macaca KW - Magnetic resonance imaging KW - Animal models KW - Biopsy KW - Clinical trials KW - Lymph nodes KW - Prostate cancer KW - Computed tomography KW - Contrast media KW - N.M.R. KW - Mapping KW - Side effects KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837336120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+Radiologica&rft.atitle=Ferumoxytol+as+an+intraprostatic+MR+contrast+agent+for+lymph+node+mapping+of+the+prostate%3A+a+feasibility+study+in+non-human+primates&rft.au=Sankineni%2C+Sandeep%3BSmedley%2C+Jeremy%3BBernardo%2C+Marcelino%3BBrown%2C+Anna+M%3BJohnson%2C+Linda%3BMuller%2C+Berrend%3BGriffiths%2C+Gary+L%3BKobayashi%2C+Hisataka%3BRais-Bahrami%2C+Soroush%3BPinto%2C+Peter+A%3BWood%2C+Bradford+J%3BKeele%2C+Brandon%3BChoyke%2C+Peter+L%3BTurkbey%2C+Baris&rft.aulast=Sankineni&rft.aufirst=Sandeep&rft.date=2016-11-01&rft.volume=57&rft.issue=11&rft.spage=1396&rft.isbn=&rft.btitle=&rft.title=Acta+Radiologica&rft.issn=02841851&rft_id=info:doi/10.1177%2F0284185115586023 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Number of references - 9 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Prostate cancer; iron oxides; Computed tomography; Magnetic resonance imaging; Animal models; Contrast media; N.M.R.; Biopsy; Mapping; Clinical trials; Side effects; Lymph nodes; Macaca DO - http://dx.doi.org/10.1177/0284185115586023 ER - TY - JOUR T1 - Gene-environment interactions linking air pollution and inflammation in Parkinson's disease AN - 1837321812; PQ0003763505 AB - Both air pollution exposure and systemic inflammation have been linked to Parkinson's disease (PD). In the PASIDA study, 408 incident cases of PD diagnosed in 2006-2009 and their 495 population controls were interviewed and provided DNA samples. Markers of long term traffic related air pollution measures were derived from geographic information systems (GIS)-based modeling. Furthermore, we genotyped functional polymorphisms in genes encoding proinflammatory cytokines, namely rs1800629 in TNF alpha (tumor necrosis factor alpha) and rs16944 in IL1B (interleukin-1 beta ). In logistic regression models, long-term exposure to NO2 increased PD risk overall (odds ratio (OR)=1.06 per 2.94 mu g/m3 increase, 95% CI=1.00-1.13). The OR for PD in individuals with high NO2 exposure (75th percentile) and the AA genotype of IL1B rs16944 was 3.10 (95% CI=1.14-8.38) compared with individuals with lower NO2 exposure (<75th percentile) and the GG genotype. The interaction term was nominally significant on the multiplicative scale (p=0.01). We did not find significant gene-environment interactions with TNF rs1800629. Our finds may provide suggestive evidence that a combination of traffic-related air pollution and genetic variation in the proinflammatory cytokine gene IL1B contribute to risk of developing PD. However, as statistical evidence was only modest in this large sample we cannot rule out that these results represent a chance finding, and additional replication efforts are warranted. JF - Environmental Research AU - Lee, Pei-Chen AU - Raaschou-Nielsen, Ole AU - Lill, Christina M AU - Bertram, Lars AU - Sinsheimer, Janet S AU - Hansen, Johnni AU - Ritz, Beate AD - Department of Health Care Management, College of Health Technology, National Taipei University of Nursing and Health Sciences, 89, Nei-Chiang St. Wan-Hua Dist, Taipei 10845, Taiwan Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 713 EP - 720 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 151 SN - 0013-9351, 0013-9351 KW - Genetics Abstracts; Pollution Abstracts; Environment Abstracts KW - PM10 particles of less than 10 mu m diameter KW - PM2.5 particles of less than 2.5 mu m diameter KW - O3 ozone KW - CO carbon monoxide KW - NO2 nitrogen dioxide KW - SO2 sulfur dioxide KW - IQR interquartile range KW - SD standard deviation KW - PD Parkinson's disease KW - GIS geographic information systems KW - TNF alpha tumor necrosis factor alpha KW - IL1B interleukin-1 beta KW - CNS central nervous system KW - Traffic-related air pollution KW - Inflammation KW - Parkinson's disease KW - Gene-environment interaction KW - Statistics KW - Gene polymorphism KW - Tumor necrosis factor KW - Interleukin 1 KW - Remote sensing KW - Genetic diversity KW - Genotypes KW - Models KW - Risk factors KW - Regression analysis KW - Replication KW - Tumors KW - Traffic KW - Air pollution KW - Neurodegenerative diseases KW - Population control KW - Movement disorders KW - DNA KW - Geographic information systems KW - Tumor necrosis factor- alpha KW - G 07720:Immunogenetics KW - P 0000:AIR POLLUTION KW - ENA 01:Air Pollution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837321812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=Gene-environment+interactions+linking+air+pollution+and+inflammation+in+Parkinson%27s+disease&rft.au=Lee%2C+Pei-Chen%3BRaaschou-Nielsen%2C+Ole%3BLill%2C+Christina+M%3BBertram%2C+Lars%3BSinsheimer%2C+Janet+S%3BHansen%2C+Johnni%3BRitz%2C+Beate&rft.aulast=Lee&rft.aufirst=Pei-Chen&rft.date=2016-11-01&rft.volume=151&rft.issue=&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1016%2Fj.envres.2016.09.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Statistics; Replication; Tumor necrosis factor; Parkinson's disease; Gene polymorphism; Interleukin 1; Genetic diversity; Traffic; Inflammation; Models; Air pollution; Neurodegenerative diseases; Movement disorders; Regression analysis; Tumor necrosis factor- alpha; Geographic information systems; Population control; Risk factors; DNA; Remote sensing; Tumors; Genotypes DO - http://dx.doi.org/10.1016/j.envres.2016.09.006 ER - TY - JOUR T1 - Health Disparities and the Microbiome AN - 1837316662; PQ0003764019 AB - An individual's microbiome is likely to be an important contributor to certain health disparity diseases and conditions. We present a framework to study the role of the microbiome and the multiple factors that are likely to influence differences in disease predisposition, onset, and progression at the individual and population level. JF - Trends in Microbiology AU - Findley, Keisha AU - Williams, David R AU - Grice, Elizabeth A AU - Bonham, Vence L AD - Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, 31 Center Drive Room B1B37-G, Bethesda, MD 20892, USA Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 847 EP - 850 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 24 IS - 11 SN - 0966-842X, 0966-842X KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - microbiome KW - health disparities KW - interdisciplinary studies KW - environment KW - Reviews KW - Population levels KW - A 01490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837316662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=Health+Disparities+and+the+Microbiome&rft.au=Findley%2C+Keisha%3BWilliams%2C+David+R%3BGrice%2C+Elizabeth+A%3BBonham%2C+Vence+L&rft.aulast=Findley&rft.aufirst=Keisha&rft.date=2016-11-01&rft.volume=24&rft.issue=11&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2Fj.tim.2016.08.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Reviews; Population levels DO - http://dx.doi.org/10.1016/j.tim.2016.08.001 ER - TY - JOUR T1 - FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence AN - 1837310053; PQ0003759942 AB - Background A common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. Methods Forty-nine patients with PTSD and AD were admitted for 4 weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. Results FAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. Conclusions This is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics. In patients with PTSD and comorbid alcohol dependence, a common single nucleotide polymorphism (C385A) in the fatty acid amide hydrolase (FAAH) gene is associated with a marked increase in serum anandamide levels and with faster decline of the anxiety responses to a stressor. These findings indicate that FAAH 385A variation facilitates habituation to and extinction of chronic stress response, without influencing response to acute stress. This points to the endocannabinoid pathway as a promising target for future antistress therapeutics. JF - Alcoholism: Clinical and Experimental Research AU - Spagnolo, Primavera A AU - Ramchandani, Vijay A AU - Schwandt, Melanie L AU - Kwako, Laura E AU - George, David T AU - Mayo, Leah M AU - Hillard, Cecilia J AU - Heilig, Markus AD - Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2426 EP - 2434 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 40 IS - 11 SN - 0145-6008, 0145-6008 KW - Toxicology Abstracts KW - Detoxification KW - Anandamide KW - Anxiety KW - Extinction KW - Arousal KW - Stress KW - Drug abuse KW - biomarkers KW - Clinical trials KW - Post-traumatic stress disorder KW - Homozygotes KW - Habituation KW - Fatty-acid amide hydrolase KW - Drug dependence KW - Mental disorders KW - Cannabinoids KW - Single-nucleotide polymorphism KW - Alcoholism KW - 2-Arachidonylglycerol KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837310053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%3A+Clinical+and+Experimental+Research&rft.atitle=FAAH+Gene+Variation+Moderates+Stress+Response+and+Symptom+Severity+in+Patients+with+Posttraumatic+Stress+Disorder+and+Comorbid+Alcohol+Dependence&rft.au=Spagnolo%2C+Primavera+A%3BRamchandani%2C+Vijay+A%3BSchwandt%2C+Melanie+L%3BKwako%2C+Laura+E%3BGeorge%2C+David+T%3BMayo%2C+Leah+M%3BHillard%2C+Cecilia+J%3BHeilig%2C+Markus&rft.aulast=Spagnolo&rft.aufirst=Primavera&rft.date=2016-11-01&rft.volume=40&rft.issue=11&rft.spage=2426&rft.isbn=&rft.btitle=&rft.title=Alcoholism%3A+Clinical+and+Experimental+Research&rft.issn=01456008&rft_id=info:doi/10.1111%2Facer.13210 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Detoxification; Extinction; Anxiety; Anandamide; Arousal; Stress; Drug abuse; Post-traumatic stress disorder; Clinical trials; biomarkers; Homozygotes; Fatty-acid amide hydrolase; Habituation; Drug dependence; Mental disorders; Cannabinoids; Single-nucleotide polymorphism; Alcoholism; 2-Arachidonylglycerol DO - http://dx.doi.org/10.1111/acer.13210 ER - TY - JOUR T1 - Do coping strategies mediate the effects of emotional support on emotional well-being among Spanish-speaking Latina breast cancer survivors? AN - 1836009687 AB - Objective This study aimed to assess the relationship between emotional social support and emotional well-being among Latina immigrants with breast cancer and test whether two culturally relevant coping strategies, fatalism and acceptance, mediate this relationship. Methods One hundred fifty Spanish-speaking Latinas within 1 year of breast cancer diagnosis participating in a randomized trial of a stress management intervention were assessed in person at baseline and via telephone 6 months later. Survey measures included baseline emotional support, fatalism, and acceptance and emotional well-being 6 months later. Generalized linear models estimated direct effects of emotional support on emotional well-being and indirect effects through fatalism and acceptance. Results Mean age was 50.1 (SD=10.9) years; most women had low education and acculturation levels. Emotional support was negatively associated with fatalism (r=-0.24, p<0.01) and positively associated with acceptance (r=0.30, p<0.001). Emotional support (r=0.23, p=0.005) and acceptance (r=0.28, p=0.001) were positively associated with emotional well-being, whereas fatalism (r=-0.36, p<0.0001) was negatively associated with emotional well-being. In multivariable models, emotional support was associated with emotional well-being (b=0.88, 95% CI: 0.24, 1.52). This direct effect remained significant when additionally controlling for fatalism (b=0.66, 95% CI: 0.03, 1.30) and acceptance (b=0.73, 95% CI: 0.09, 1.37) in separate models. There was a significant indirect effect of emotional support on emotional well-being through fatalism (b=0.21, 95% CI: 0.04, 0.51) as well as a marginally significant effect through acceptance (b=0.15, 95% CI: 0.001, 0.43). Conclusions Emotional support may increase well-being among Spanish-speaking Latina cancer survivors by reducing cancer fatalism.Copyright © 2015 John Wiley & Sons, Ltd. JF - Psycho-Oncology AU - Gonzales, Felisa A AU - Hurtado-de-Mendoza, Alejandra AU - Santoyo-Olsson, Jasmine AU - Napoles, Anna María AD - Cancer Prevention Fellowship Program, Healthcare Delivery Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA ; Department of Oncology, Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA ; Division of General Internal Medicine and the Center for Aging in Diverse Communities, Department of Medicine, University of California San Francisco, San Francisco, CA, USA ; Cancer Prevention Fellowship Program, Healthcare Delivery Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1286 EP - 1292 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 25 IS - 11 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Women KW - Acceptance KW - Indirect effects KW - Survivors KW - Coping strategies KW - Emotional wellbeing KW - Breast cancer KW - Immigrants KW - Linear models KW - Latin American people KW - Emotional support KW - Acculturation KW - Fatalism KW - Stress management KW - Diagnosis KW - Social support UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1836009687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=Do+coping+strategies+mediate+the+effects+of+emotional+support+on+emotional+well-being+among+Spanish-speaking+Latina+breast+cancer+survivors%3F&rft.au=Gonzales%2C+Felisa+A%3BHurtado-de-Mendoza%2C+Alejandra%3BSantoyo-Olsson%2C+Jasmine%3BNapoles%2C+Anna+Mar%C3%ADa&rft.aulast=Gonzales&rft.aufirst=Felisa&rft.date=2016-11-01&rft.volume=25&rft.issue=11&rft.spage=1286&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.3953 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 John Wiley & Sons, Ltd. N1 - Last updated - 2016-11-04 DO - http://dx.doi.org/10.1002/pon.3953 ER - TY - JOUR T1 - Absolute Measurement of Cardiac Injury-Induced microRNAs in Biofluids across Multiple Test Sites. AN - 1835684828; 27605421 AB - Extracellular microRNAs (miRNAs) represent a promising new source of toxicity biomarkers that are sensitive indicators of site of tissue injury. In order to establish reliable approaches for use in biomarker validation studies, the HESI technical committee on genomics initiated a multi-site study to assess sources of variance associated with quantitating levels of cardiac injury induced miRNAs in biofluids using RT-qPCR. Samples were generated at a central site using a model of acute cardiac injury induced in male Wistar rats by 0.5 mg/kg isoproterenol. Biofluid samples were sent to 11 sites for measurement of 3 cardiac enriched miRNAs (miR-1-3p, miR-208a-3p, and miR-499-5p) and 1 miRNA abundant in blood (miR-16-5p) or urine (miR-192-5p) by absolute quantification using calibration curves of synthetic miRNAs. The samples included serum and plasma prepared from blood collected at 4 h, urine collected from 6 to 24 h, and plasma prepared from blood collected at 24 h post subcutaneous injection. A 3 parameter logistic model was utilized to fit the calibration curve data and estimate levels of miRNAs in biofluid samples by inverse prediction. Most sites observed increased circulating levels of miR-1-3p and miR-208a-3p at 4 and 24 h after isoproterenol treatment, with no difference seen between serum and plasma. The biological differences in miRNA levels and sample type dominated as sources of variance, along with outlying performance by a few sites. The standard protocol established in this study was successfully implemented across multiple sites and provides a benchmark method for further improvements in quantitative assays for circulating miRNAs. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Thompson, Karol L AU - Boitier, Eric AU - Chen, Tao AU - Couttet, Philippe AU - Ellinger-Ziegelbauer, Heidrun AU - Goetschy, Manuela AU - Guillemain, Gregory AU - Kanki, Masayuki AU - Kelsall, Janet AU - Mariet, Claire AU - de La Moureyre-Spire, Catherine AU - Mouritzen, Peter AU - Nassirpour, Rounak AU - O'Lone, Raegan AU - Pine, P Scott AU - Rosenzweig, Barry A AU - Sharapova, Tatiana AU - Smith, Aaron AU - Uchiyama, Hidefumi AU - Yan, Jian AU - Yuen, Peter S AU - Wolfinger, Russ AD - Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993. ; Sanofi R&D, Disposition Safety and Animal Research, Vitry-Sur-Seine, France. ; Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arizona 72079. ; Novartis Pharma AG, Basel, CH 4057, Switzerland. ; Toxicology, Bayer Pharma, Wuppertal, AG 42096, Germany. ; Astellas Pharma Inc, Osaka 532-8514, Japan. ; AstraZeneca Ltd, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. ; Institut De Recherches Servier, 78290 Croissy Sur Seine, France. ; Exiqon, Vedbaek DK-2950, Denmark. ; Pfizer, Andover, Massachusetts 01810. ; ILSI Health and Environmental Sciences Institute, Washington, DC 20005 Rolone@hesiglobal.org. ; National Institute of Standards and Technology, Stanford, California 94305. ; AbbVie, Abbott Park, Illinois 60064. ; Eli Lilly, Indianapolis, Indiana 46285. ; Takeda Pharmaceutical Co Ltd, Fujisawa, Kanagawa 251-8555, Japan. ; NIH/NIDDK, Bethesda, Maryland 20892. ; SAS Institute Inc, Cary, North Carolina 27513. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 115 EP - 125 VL - 154 IS - 1 KW - biomarker KW - variance KW - microRNA KW - interlaboratory UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835684828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Absolute+Measurement+of+Cardiac+Injury-Induced+microRNAs+in+Biofluids+across+Multiple+Test+Sites.&rft.au=Thompson%2C+Karol+L%3BBoitier%2C+Eric%3BChen%2C+Tao%3BCouttet%2C+Philippe%3BEllinger-Ziegelbauer%2C+Heidrun%3BGoetschy%2C+Manuela%3BGuillemain%2C+Gregory%3BKanki%2C+Masayuki%3BKelsall%2C+Janet%3BMariet%2C+Claire%3Bde+La+Moureyre-Spire%2C+Catherine%3BMouritzen%2C+Peter%3BNassirpour%2C+Rounak%3BO%27Lone%2C+Raegan%3BPine%2C+P+Scott%3BRosenzweig%2C+Barry+A%3BSharapova%2C+Tatiana%3BSmith%2C+Aaron%3BUchiyama%2C+Hidefumi%3BYan%2C+Jian%3BYuen%2C+Peter+S%3BWolfinger%2C+Russ&rft.aulast=Thompson&rft.aufirst=Karol&rft.date=2016-11-01&rft.volume=154&rft.issue=1&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Pharmacogenomics and histone deacetylase inhibitors. AN - 1835522797; 27767376 AB - The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment. This review provides an overview of clinical studies on the effects of polymorphisms on the pharmacokinetics, efficacy or toxicities of HDIs including belinostat, romidepsin, vorinostat, panobinostat, VPA and a number of novel compounds currently being tested in Phase I and II trials. Although pharmacogenomic studies for HDIs are scarce, available data indicate that therapy with belinostat (UGT1A1), romidepsin (ABCB1), vorinostat (UGT2B17) or VPA (UGT1A6) could be optimized by upfront genotyping. JF - Pharmacogenomics AU - Goey, Andrew Kl AU - Sissung, Tristan M AU - Peer, Cody J AU - Figg, William D AD - Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1807 EP - 1815 VL - 17 IS - 16 KW - HDAC inhibitors KW - panobinostat KW - valproic acid KW - pharmacogenomics KW - romidepsin KW - vorinostat KW - UGT1A1 KW - belinostat UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835522797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Pharmacogenomics+and+histone+deacetylase+inhibitors.&rft.au=Goey%2C+Andrew+Kl%3BSissung%2C+Tristan+M%3BPeer%2C+Cody+J%3BFigg%2C+William+D&rft.aulast=Goey&rft.aufirst=Andrew&rft.date=2016-11-01&rft.volume=17&rft.issue=16&rft.spage=1807&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=1744-8042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients. AN - 1835518407; 27503091 AB - Studies have reported liver injury as a consequence of antipsychotic treatment. Very heavy alcohol drinking (ten or more drinks/day for men and eight for women) also causes liver injury. This study aims to evaluate liver injury with quetiapine extended release (XR) in very heavy drinking alcohol-dependent (AD) patients. Two hundred and eighteen AD patients, 18-65 years of age, received 12 weeks of quetiapine XR or placebo treatment in a dose-escalated manner reaching the full dose of 400 mg/day during week 4. Blood chemistry and hematology were assessed at baseline (W0), post-titration at the end of week 3 (W4), week 8 (W8), and end of week 12 (W13). Patients were further grouped as GR.1 (no liver injury, ALT ≤40) and GR.2 (pre-existing liver injury, ALT >40) within each treatment. Drinking history, fasting blood glucose concentration (FBG), and lipid panel were used as covariates in the analyses. Liver injury and total drinks and average drinking measures from the Timeline follow-back questionnaire (TLFB) were highly associated. No significant exacerbation in liver injury was observed in patients treated with quetiapine XR in GR.2. Liver injury as determined by elevated alanine aminotransaminase (ALT) was reported in a few patients in GR.1 who received quetiapine XR; however, the occurrence was low, and the level of liver injury was not significant. FBG and lipid measures showed some elevation, but did not show any significant association with liver injury. Quetiapine XR did not show any significant exacerbation of liver injury in very heavy drinking alcohol-dependent patients with pre-existing liver injury. Frequency and severity of new liver injury cases in quetiapine XR-treated patients without any pre-existing liver injury was also low. Study findings support medical management of AD patients with heavy drinking profile using quetiapine XR formulation. JF - Clinical drug investigation AU - Vatsalya, Vatsalya AU - Pandey, Akash AU - Schwandt, Melanie L AU - Cave, Matthew C AU - Barve, Shirish S AU - Ramchandani, Vijay A AU - McClain, Craig J AD - Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA. v0vats01@exchange.louisville.edu. ; Department of Pediatric Gastroenterology, Maria Fareri Children's Hospital - Westchester Medical Center, Valhalla, NY, USA. ; Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA. ; Laboratory of Clinical and Translational Studies, Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 935 EP - 944 VL - 36 IS - 11 KW - Antipsychotic Agents KW - 0 KW - Delayed-Action Preparations KW - Quetiapine Fumarate KW - 2S3PL1B6UJ KW - Index Medicus KW - Young Adult KW - Double-Blind Method KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Alcohol Drinking -- adverse effects KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Quetiapine Fumarate -- adverse effects KW - Chemical and Drug Induced Liver Injury -- etiology KW - Antipsychotic Agents -- adverse effects KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835518407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+drug+investigation&rft.atitle=Safety+Assessment+of+Liver+Injury+with+Quetiapine+Fumarate+XR+Management+in+Very+Heavy+Drinking+Alcohol-Dependent+Patients.&rft.au=Vatsalya%2C+Vatsalya%3BPandey%2C+Akash%3BSchwandt%2C+Melanie+L%3BCave%2C+Matthew+C%3BBarve%2C+Shirish+S%3BRamchandani%2C+Vijay+A%3BMcClain%2C+Craig+J&rft.aulast=Vatsalya&rft.aufirst=Vatsalya&rft.date=2016-11-01&rft.volume=36&rft.issue=11&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Clinical+drug+investigation&rft.issn=1179-1918&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-02 N1 - Date created - 2016-08-09 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 ER - TY - JOUR T1 - Adjuvant chemotherapy does not improve disease-free survival in FIGO stage IC ovarian granulosa cell tumors: The MITO-9 study. AN - 1835516319; 27597380 AB - Evidence-based management of granulosa cell tumors of the ovary (GCT) has been not yet standardized: surgery, including fertility-sparing procedures for young women, has been traditionally the standard treatment; on the other hand, chemotherapy has been used for treatment of advanced and/or recurrent disease. However, very limited experience, has been selectively focused on the role of adjuvant chemotherapy in stage IC patients. The objective of this retrospective study was to assess the efficacy of first line postoperative chemotherapy in patients with stage IC treated at the Italian Centers involved in the MITO (Multicenter Italian Trials in Ovarian cancer) Group. A retrospective multi-institutional review of patients with GCT of the ovary at FIGO stage IC treated or referred to MITO centers was conducted. Surgical outcome, pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors factors for disease free survival. A total of 40 patients with primary GCT of the ovary at FIGO stage IC were identified. The median follow-up period was 96months (range 7-300). At multivariate analysis, surgical treatment outside MITO centers and incomplete surgical staging were independent poor prognostic indicators for recurrence; adjuvant chemotherapy did not retain significant predictive value for recurrence. This study raises the question about the value of adjuvant chemotherapy in stage IC GCT: a comprehensive evaluation of a larger series is urgently needed in order to characterize stage IC substages who can be spared treatment toxicity. Copyright © 2016. Published by Elsevier Inc. JF - Gynecologic oncology AU - Mangili, G AU - Ottolina, J AU - Cormio, G AU - Loizzi, Vera AU - De Iaco, P AU - Pellegrini, D A AU - Candiani, M AU - Giorda, G AU - Scarfone, G AU - Cecere, S C AU - Frigerio, L AU - Gadducci, A AU - Marchetti, C AU - Ferrandina, G AD - Gynecology Department, San Raffaele Scientific Institute, Milan, Italy. Electronic address: mangili.giorgia@hsr.it. ; Gynecology Department, San Raffaele Scientific Institute, Milan, Italy. ; Department of Obstetrics and Gynecology, University of Bari, Bari, Italy. ; Department of Gynecologic Oncology, S. Orsola-Malpighi University Hospital, Bologna, Italy. ; Medical Oncology Division, National Cancer Institute Regina Elena, Rome, Italy. ; Gynecologic Oncology Department, Centro di riferimento Oncologico (CRO) National Cancer Institute, Aviano, Italy. ; Obstetrics and Gynecology Department, IRCCS Foundation Policlinico Mangiagalli Regina Elena Hospital, Milan, Italy. ; Uro-Gynecological Oncology, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. ; Gynecology Department, Riuniti di Bergamo Hospital, Bergamo, Italy. ; Division of Gynecology and Obstetrics, Department of Clinical and Experimental Medicine, Pisa University, Pisa, Italy. ; Department of Gynecology, Obstetrics and Urology, Umberto I, "Sapienza" University of Rome, Rome, Italy. ; Department of Health Sciences and Medicine, University of Molise, Campobasso/Gynecologic Oncology Unit, Policlinico Universitario "Agostino Gemelli", Rome, Italy. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 276 EP - 280 VL - 143 IS - 2 KW - Granulosa cell tumors of the ovary KW - Stage IC KW - Relapse KW - Adjuvant chemotherapy KW - Prognostic factors KW - MITO UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835516319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Adjuvant+chemotherapy+does+not+improve+disease-free+survival+in+FIGO+stage+IC+ovarian+granulosa+cell+tumors%3A+The+MITO-9+study.&rft.au=Mangili%2C+G%3BOttolina%2C+J%3BCormio%2C+G%3BLoizzi%2C+Vera%3BDe+Iaco%2C+P%3BPellegrini%2C+D+A%3BCandiani%2C+M%3BGiorda%2C+G%3BScarfone%2C+G%3BCecere%2C+S+C%3BFrigerio%2C+L%3BGadducci%2C+A%3BMarchetti%2C+C%3BFerrandina%2C+G&rft.aulast=Mangili&rft.aufirst=G&rft.date=2016-11-01&rft.volume=143&rft.issue=2&rft.spage=276&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=1095-6859&rft_id=info:doi/10.1016%2Fj.ygyno.2016.08.316 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ygyno.2016.08.316 ER - TY - JOUR T1 - A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-α-2b in patients with CEA-expressing carcinomas. AN - 1835488633; 27581603 AB - Prime-boost vaccination with recombinant (r) vaccinia(V)-CEA(6D)-TRICOM (triad of co-stimulatory molecules B7.1, ICAM-1 and LFA-3) and rFowlpox(F)-CEA(6D)-TRICOM infect antigen-presenting cells and direct expression of co-stimulatory molecules. We hypothesized that co-administration of vaccine with GM-CSF and interferon alpha (IFN-α) would have efficacy in CEA-expressing cancers. Patients with CEA-expressing cancers received the rV-CEA(6D)-TRICOM vaccine subcutaneously (s.c.) on day 1 followed by GM-CSF s.c. to the injection site on days 1-4. In Cycle 1, patients received thrice weekly s.c. injections of IFN-α-2b the week after rV-CEA(6D)-TRICOM. In Cycles 2-4, patients received thrice weekly s.c. injections of IFN-α-2b the same week that rF-CEA(6D)-TRICOM was given. The first cohort received no IFN followed by dose escalation of IFN-α in subsequent cohorts. Thirty-three patients were accrued (mean 59.8 years). Grade 3 toxicities included fatigue and hyperglycemia. Grade 4-5 adverse events (unrelated to treatment) were confusion (1), elevated aspartate transaminase (AST)/alanine transaminase (ALT) (1), and sudden death (1). No patients had a partial response, and eight patients exhibited stable disease of ≥3 months. Median progression-free survival and overall survival (OS) were 1.8 and 6.3 months, respectively. Significantly higher serum CD27 levels were observed after vaccine therapy (p = 0.006 post 1-2 cycles, p = 0.003 post 3 cycles, p = 0.03 post 4-7 cycles) and 42 % of patients assayed developed CEA-specific T cell responses. Pre-treatment levels of myeloid-derived suppressor cells correlated with overall survival (p = 0.04). Administration of IFN-α led to significantly increased OS (p = 0.02) compared to vaccine alone. While the vaccine regimen produced no clinical responses, IFN-α administration was associated with improved survival. JF - Cancer immunology, immunotherapy : CII AU - Duggan, Megan C AU - Jochems, Caroline AU - Donahue, Renee N AU - Richards, Jacob AU - Karpa, Volodymyr AU - Foust, Elizabeth AU - Paul, Bonnie AU - Brooks, Taylor AU - Tridandapani, Susheela AU - Olencki, Thomas AU - Pan, Xueliang AU - Lesinski, Gregory B AU - Schlom, Jeffrey AU - Carson Iii, William E AD - Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. ; National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA. ; Division of Medical Oncology, The Ohio State University, Columbus, OH, USA. ; Center for Biostatistics, The Ohio State University, Columbus, OH, USA. ; Division of Surgical Oncology, The Ohio State University, N924 Doan Hall, 410 W. 10th Avenue, Columbus, OH, 43210, USA. william.carson@osumc.edu. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1353 EP - 1364 VL - 65 IS - 11 KW - Immunotherapy KW - Colorectal cancer KW - Vaccines KW - Interferon alpha-2b KW - Carcinoembryonic antigen (CEA) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835488633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.atitle=A+phase+I+study+of+recombinant+%28r%29+vaccinia-CEA%286D%29-TRICOM+and+rFowlpox-CEA%286D%29-TRICOM+vaccines+with+GM-CSF+and+IFN-%CE%B1-2b+in+patients+with+CEA-expressing+carcinomas.&rft.au=Duggan%2C+Megan+C%3BJochems%2C+Caroline%3BDonahue%2C+Renee+N%3BRichards%2C+Jacob%3BKarpa%2C+Volodymyr%3BFoust%2C+Elizabeth%3BPaul%2C+Bonnie%3BBrooks%2C+Taylor%3BTridandapani%2C+Susheela%3BOlencki%2C+Thomas%3BPan%2C+Xueliang%3BLesinski%2C+Gregory+B%3BSchlom%2C+Jeffrey%3BCarson+Iii%2C+William+E&rft.aulast=Duggan&rft.aufirst=Megan&rft.date=2016-11-01&rft.volume=65&rft.issue=11&rft.spage=1353&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=1432-0851&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead. AN - 1835414538; 27742642 AB - There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Gumbo, Tawanda AU - Makhene, Mamodikoe K AU - Seddon, James A AD - Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa. ; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. ; Centre for International Child Health, Department of Paediatrics, Imperial College London, United Kingdom. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - S110 EP - S115 VL - 63 KW - tuberculosis KW - PK/PD KW - future KW - children KW - investment KW - hollow fiber UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835414538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Partnerships+to+Design+Novel+Regimens+to+Treat+Childhood+Tuberculosis%2C+Sui+Generis%3A+The+Road+Ahead.&rft.au=Gumbo%2C+Tawanda%3BMakhene%2C+Mamodikoe+K%3BSeddon%2C+James+A&rft.aulast=Gumbo&rft.aufirst=Tawanda&rft.date=2016-11-01&rft.volume=63&rft.issue=&rft.spage=S110&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The antiandrogen flutamide is a novel aryl hydrocarbon receptor ligand that disrupts bile acid homeostasis in mice through induction of Abcc4. AN - 1835391648; 27569425 AB - Flutamide (FLU), an oral, nonsteroidal antiandrogen drug used in the treatment of prostate cancer, is associated with idiosyncratic hepatotoxicity that sometimes causes severe liver damage, including cholestasis, jaundice, and liver necrosis. To understand the mechanism of toxicity, a combination of aryl hydrocarbon receptor (Ahr)-deficient (Ahr-/-) mice, primary hepatocytes, luciferase reporter gene assays, in silico ligand docking and ultra-performance chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics was used. A significant increase of liver weights, and liver and serum bile acid levels was observed after FLU treatment, indicating hepatomegaly and disrupted bile acid homeostasis. Expression of the AhR gene battery was markedly increased in livers of wild-type mice Ahr+/+ treated with FLU, while no change was noted in Ahr-/- mice. Messenger RNAs encoded by AhR target genes were induced in primary mouse hepatocytes cultured with FLU, which confirmed the in vivo results. Ligand-docking analysis further predicted that FLU is an AhR agonist ligand which was confirmed by luciferase reporter gene assays. Multivariate data analysis showed that bile acids were responsible for the separation of vehicle- and FLU-treated Ahr+/+ mice, while there was no separation in Ahr-/- mice. Expression of mRNA encoding the bile acid transporter ABCC4 was increased and farnesoid X receptor signaling was inhibited in the livers of Ahr+/+ mice, but not in Ahr-/- mice treated with FLU, in agreement with the observed downstream metabolic alterations. These findings provide new insights into the mechanism of liver injury caused by FLU treatment involving activation of AhR and the alterations of bile acid homeostasis, which could guide clinical application. Published by Elsevier Inc. JF - Biochemical pharmacology AU - Gao, Xiaoxia AU - Xie, Cen AU - Wang, Yuanyuan AU - Luo, Yuhong AU - Yagai, Tomoki AU - Sun, Dongxue AU - Qin, Xuemei AU - Krausz, Kristopher W AU - Gonzalez, Frank J AD - Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi 030006, China; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gaoxiaoxia@sxu.edu.cn. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: cen.xie@nih.gov. ; Bioscience Research Department, 875 Union Ave, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: ywang197@uthsc.edu. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: yuhong.luo@nih.gov. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tomoki.yagai@nih.gov. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address: dongxue.sun@nih.gov. ; Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi 030006, China. Electronic address: qinxm@sxu.edu.cn. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: krauszk@intra.nci.nih.gov. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: gonzalef@mail.nih.gov. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 93 EP - 104 VL - 119 KW - Bile acid homeostasis KW - Aryl hydrocarbon receptor KW - ABCC4 KW - Flutamide KW - Metabolomics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835391648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=The+antiandrogen+flutamide+is+a+novel+aryl+hydrocarbon+receptor+ligand+that+disrupts+bile+acid+homeostasis+in+mice+through+induction+of+Abcc4.&rft.au=Gao%2C+Xiaoxia%3BXie%2C+Cen%3BWang%2C+Yuanyuan%3BLuo%2C+Yuhong%3BYagai%2C+Tomoki%3BSun%2C+Dongxue%3BQin%2C+Xuemei%3BKrausz%2C+Kristopher+W%3BGonzalez%2C+Frank+J&rft.aulast=Gao&rft.aufirst=Xiaoxia&rft.date=2016-11-01&rft.volume=119&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=1873-2968&rft_id=info:doi/10.1016%2Fj.bcp.2016.08.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bcp.2016.08.021 ER - TY - JOUR T1 - Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F1 mice. AN - 1835384955; 27644598 AB - Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F1 mice were dosed with 3mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21mg/kg cumulative dose. DOX-treated male mice also had an increased number of γ-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27mg/kg cumulative dose and right atrium at 21 and 27mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Jenkins, G Ronald AU - Lee, Taewon AU - Moland, Carrie L AU - Vijay, Vikrant AU - Herman, Eugene H AU - Lewis, Sherry M AU - Davis, Kelly J AU - Muskhelishvili, Levan AU - Kerr, Susan AU - Fuscoe, James C AU - Desai, Varsha G AD - Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; Department of Mathematics, Korea University, Sejong, Republic of Korea. ; Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, Rockville, MD 20850-9734, United States. ; Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079, United States. ; Arkansas Heart Hospital, Little Rock, AR 72211, United States. ; Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. Electronic address: varsha.desai@fda.hhs.gov. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 159 EP - 174 VL - 310 KW - DNA damage KW - Apoptosis KW - Mouse model KW - Sex-based differences KW - Cardiotoxicity KW - Doxorubicin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835384955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Sources+of+polycyclic+aromatic+hydrocarbons+are+associated+with+gene-specific+promoter+methylation+in+women+with+breast+cancer.&rft.au=White%2C+Alexandra+J%3BChen%2C+Jia%3BTeitelbaum%2C+Susan+L%3BMcCullough%2C+Lauren+E%3BXu%2C+Xinran%3BHee+Cho%2C+Yoon%3BConway%2C+Kathleen%3BBeyea%2C+Jan%3BStellman%2C+Steven+D%3BSteck%2C+Susan+E%3BMordukhovich%2C+Irina%3BEng%2C+Sybil+M%3BBeth+Terry%2C+Mary%3BEngel%2C+Lawrence+S%3BHatch%2C+Maureen%3BNeugut%2C+Alfred+I%3BHibshoosh%2C+Hanina%3BSantella%2C+Regina+M%3BGammon%2C+Marilie+D&rft.aulast=White&rft.aufirst=Alexandra&rft.date=2016-02-01&rft.volume=145&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=1096-0953&rft_id=info:doi/10.1016%2Fj.envres.2015.11.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.09.012 ER - TY - JOUR T1 - Response to "Comment on 'Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures'". AN - 1834999165; 27801650 JF - Environmental health perspectives AU - Parks, Christine G AU - Hoppin, Jane A AU - De Roos, Anneclaire J AU - Costenbader, Karen H AU - Sandler, Dale P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 1 VL - 124 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834999165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Response+to+%22Comment+on+%27Rheumatoid+Arthritis+in+Agricultural+Health+Study+Spouses%3A+Associations+with+Pesticides+and+Other+Farm+Exposures%27%22.&rft.au=Parks%2C+Christine+G%3BHoppin%2C+Jane+A%3BDe+Roos%2C+Anneclaire+J%3BCostenbader%2C+Karen+H%3BSandler%2C+Dale+P&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2016-11-01&rft.volume=124&rft.issue=11&rft.spage=A197&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-11-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Attention bias modification for youth with social anxiety disorder AN - 1834802574 AB - Background Attention bias modification treatment (ABMT) targets threat-related attention biases in anxiety disorders. Most clinical trials of ABMT have focused on adults or small samples of youth. The current randomized controlled trial (RCT) examines ABMT efficacy in youth with social anxiety disorder (SAD) and tests possible moderators of treatment outcomes. Method Sixty-seven youth with SAD were randomly assigned to ABMT or attention control training (ACT) conditions. Anxiety severity was measured at baseline, posttreatment, and 3-month follow-up. ClinicalTrials.gov name and identifier: Attention bias modification treatment for children with social anxiety, NCT01397032; http://www.clinicaltrials.gov. Results Both ABMT and ACT induced significant reductions in clinician and self-rated social anxiety (ps < .001). An additional reduction was observed at the 3-month follow-up in clinician-rated anxiety symptoms (p = .03). Moderation effects were nonsignificant for the clinician-rated anxiety outcome, but age moderated self-reported anxiety. Older but not younger children, showed significant reduction in anxiety following ABMT relative to ACT (p < .001). Individual differences in attention control also moderated ABMT's effect on self-reported anxiety (p = .05). Children rated by their parents as lower on attention control benefited more from ABMT than those rated higher on attention control. Baseline attention bias did not moderate anxiety (p = .17). Conclusions Despite significant reductions in social anxiety, no specific evidence for ABMT was found relative to a control condition. Age and attention control moderated ABMT effects on self-reported SAD symptoms, with clinical effects for older relative to younger children and for those with lower attention control. These results highlight the need to consider developmental influences in the implementation of ABMT protocols. JF - Journal of Child Psychology and Psychiatry AU - Pergamin-Hight, Lee AU - Pine, Daniel S AU - Fox, Nathan A AU - Bar-Haim, Yair AD - School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel ; The Emotion and Development Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA ; The Department of Human Development and Quantitative Methodology, University of Maryland, College Park, MD, USA ; School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel ; School of Psychological Sciences, Tel-Aviv University, Tel-Aviv, Israel Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1317 EP - 1325 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 11 KW - Psychology KW - Modification KW - Moderation KW - Clinical trials KW - Older children KW - Clinical research KW - Efficacy KW - Severity KW - Moderators KW - Clinical outcomes KW - Randomized controlled trials KW - Selfassessment KW - Young people KW - Attentional bias KW - Individual differences KW - Social anxiety KW - Children UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834802574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Attention+bias+modification+for+youth+with+social+anxiety+disorder&rft.au=Pergamin-Hight%2C+Lee%3BPine%2C+Daniel+S%3BFox%2C+Nathan+A%3BBar-Haim%2C+Yair&rft.aulast=Pergamin-Hight&rft.aufirst=Lee&rft.date=2016-11-01&rft.volume=57&rft.issue=11&rft.spage=1317&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12599 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-11-02 DO - http://dx.doi.org/10.1111/jcpp.12599 ER - TY - JOUR T1 - Attentional bias training in girls at risk for depression AN - 1834802416 AB - Background This study examined, for the first time, whether attentional biases can be modified in adolescents at risk for depression. Methods The final sample consisted of 41 girls at familial risk for depression, who were randomly assigned to receive six sessions (864 trials) of real or sham attention bias training [Real attentional bias training (ABT) vs. Sham ABT]. Participants who received Real ABT completed a modified dot-probe task designed to train attention toward positive and away from negative facial expressions; in contrast, girls who received Sham ABT completed the standard dot-probe task. Attentional biases, self-reported mood, and psychophysiological responses to stress were measured at pre- and post-training assessments. Results As expected, girls who received Real ABT, but not those who received Sham ABT, exhibited significant increases from pre- to post-training in their attention toward happy faces and away from sad faces. Moreover, adolescents who received Real ABT were buffered against the negative outcomes experienced by adolescents who received Sham ABT. Specifically, only adolescents who received Sham ABT experienced an increase in negative mood and a pre- to post-training increase in heart rate in anticipation of the stressor. Conclusions The current findings provide the first experimental evidence that attentional biases can be modified in youth at risk for depression and further suggest that ABT modulates the heightened response to stress that is otherwise experienced by high-risk adolescents. JF - Journal of Child Psychology and Psychiatry AU - LeMoult, Joelle AU - Joormann, Jutta AU - Kircanski, Katharina AU - Gotlib, Ian H AD - Department of Psychology, Stanford University, California, CA, USA ; Department of Psychology, Yale University, New Haven, CT, USA ; Department of Health and Human Services, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA ; Department of Psychology, Stanford University, California, CA, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1326 EP - 1333 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 11 KW - Psychology KW - Bias KW - Teenagers KW - Heart rate KW - High risk KW - Psychophysiological aspects KW - Attentional bias KW - At risk KW - Facial expressions KW - Familial factors KW - Depression KW - First time KW - Adolescents KW - Girls UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834802416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Attentional+bias+training+in+girls+at+risk+for+depression&rft.au=LeMoult%2C+Joelle%3BJoormann%2C+Jutta%3BKircanski%2C+Katharina%3BGotlib%2C+Ian+H&rft.aulast=LeMoult&rft.aufirst=Joelle&rft.date=2016-11-01&rft.volume=57&rft.issue=11&rft.spage=1326&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12587 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1111/jcpp.12587 ER - TY - JOUR T1 - Genome-scale RNA interference screen identifies antizyme 1 (OAZ1) as a target for improvement of recombinant protein production in mammalian cells AN - 1827933714; PQ0003703761 AB - For the purpose of improving recombinant protein production from mammalian cells, an unbiased, high-throughput whole-genome RNA interference screen was conducted using human embryonic kidney 293 (HEK 293) cells expressing firefly luciferase. A 21,585 human genes were individually silenced with three different siRNAs for each gene. The screen identified 56 genes that led to the greatest improvement in luciferase expression. These genes were found to be included in several pathways involved in spliceosome formation and mRNA processing, transcription, metabolic processes, transport, and protein folding. The 10 genes that most enhanced protein expression when downregulated, were further confirmed by measuring the effect of their silencing on the expression of three additional recombinant proteins. Among the confirmed genes, OAZ1-the gene encoding the ornithine decarboxylase antizyme1-was selected for detailed investigation, since its silencing improved the reporter protein production without affecting cell viability. Silencing OAZ1 caused an increase of the ornithine decarboxylase enzyme and the cellular levels of putrescine and spermidine; an indication that increased cellular polyamines enhances luciferase expression without affecting its transcription. The study shows that OAZ1 is a novel target for improving expression of recombinant proteins. The genome-scale screening performed in this work can establish the foundation for targeted design of an efficient mammalian cell platform for various biotechnological applications. Biotechnol. Bioeng. 2016; 113: 2403-2415. Improving recombinant protein production from mammalian cells for research and therapeutic purposes is of major interest. For identifying unknown genes and pathways useful for improving protein expression, the effect of non-coding RNA, both miRNA and siRNA, on recombinant protein expression in 293HEK cells was investigated by applying large scale screening of miRNA and siRNA. Screening of 21,585 genes led to the selection of OAZ1, a gene that encodes ornithine decarboxylase antizyme, as a potential target since its silencing enhanced recombinant protein expression without affecting cell viability. Further studies revealed that silencing OAZ1was associated with increased concentration of polyamines. JF - Biotechnology and Bioengineering AU - Xiao, Su AU - Chen, Yu Chi AU - Buehler, Eugen AU - Mandal, Swati AU - Mandal, Ajeet AU - Betenbaugh, Michael AU - Park, Myung Hee AU - Martin, Scott AU - Shiloach, Joseph AD - Biotechnology Core Laboratory NIDDK, NIH, Bethesda, Maryland, 20892. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2403 EP - 2415 PB - Wiley Subscription Services VL - 113 IS - 11 SN - 0006-3592, 0006-3592 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Genomes KW - miRNA KW - Ornithine decarboxylase KW - non-coding RNA KW - Enzymes KW - Transcription KW - Therapeutic applications KW - Putrescine KW - Protein folding KW - siRNA KW - Mammalian cells KW - Spermidine KW - polyamines KW - RNA-mediated interference KW - Embryos KW - Spliceosomes KW - mRNA processing KW - Gene silencing KW - W 30925:Genetic Engineering KW - N 14830:RNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827933714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+and+Bioengineering&rft.atitle=Genome-scale+RNA+interference+screen+identifies+antizyme+1+%28OAZ1%29+as+a+target+for+improvement+of+recombinant+protein+production+in+mammalian+cells&rft.au=Xiao%2C+Su%3BChen%2C+Yu+Chi%3BBuehler%2C+Eugen%3BMandal%2C+Swati%3BMandal%2C+Ajeet%3BBetenbaugh%2C+Michael%3BPark%2C+Myung+Hee%3BMartin%2C+Scott%3BShiloach%2C+Joseph&rft.aulast=Xiao&rft.aufirst=Su&rft.date=2016-11-01&rft.volume=113&rft.issue=11&rft.spage=2403&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/10.1002%2Fbit.26017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Genomes; miRNA; non-coding RNA; Ornithine decarboxylase; Therapeutic applications; Transcription; Enzymes; Putrescine; Spermidine; Mammalian cells; siRNA; Protein folding; polyamines; RNA-mediated interference; Spliceosomes; Embryos; mRNA processing; Gene silencing DO - http://dx.doi.org/10.1002/bit.26017 ER - TY - JOUR T1 - Collaborating for Systems Change AN - 1826876509 AB - Environmental health researchers, government agencies, and community groups have endorsed long-term community-academic partnerships as an effective strategy to support science-based improvements in environmental health. Social sciences concepts, approaches, and methods are fundamental to these translational partnerships. However, appropriate roles for academic partners vary throughout the process of changing systems (policies, practices, programs, etc.). This can complicate planning, evaluating, and sustaining such partnerships. We set forth a conceptual framework for academic partners' roles at different stages of systems change. We apply this framework to three longstanding academic-community partnerships involving National Institute of Environmental Health Sciences Community Outreach and Engagement Cores. We conclude by discussing how the framework can help academic partners tap appropriate expertise, redefine their roles, and evaluate their contributions to community efforts to improve environmental health. JF - New Solutions : a Journal of Environmental and Occupational Health Policy : NS AU - Korfmacher, Katrina Smith AU - Pettibone, Kristianna Grass AU - Gray, Kathleen M AU - Newman, Ogonnaya Dotson AD - University of Rochester, NY, USA ; National Institute of Environmental Health Sciences, Morrisville, NC, USA ; University of North Carolina at Chapel Hill, USA ; WE ACT for Environmental Justice, Inc., New York, NY, USA ; University of Rochester, NY, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 429 EP - 457 CY - Thousand Oaks PB - SAGE PUBLICATIONS, INC. VL - 26 IS - 3 SN - 1048-2911 KW - Environmental Studies KW - environmental health KW - community partnerships KW - social science KW - systems change KW - Environmental Health KW - Social Sciences KW - Health Care Services Policy KW - Government Agencies KW - Planning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826876509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apais&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+Solutions+%3A+a+Journal+of+Environmental+and+Occupational+Health+Policy+%3A+NS&rft.atitle=Collaborating+for+Systems+Change&rft.au=Korfmacher%2C+Katrina+Smith%3BPettibone%2C+Kristianna+Grass%3BGray%2C+Kathleen+M%3BNewman%2C+Ogonnaya+Dotson&rft.aulast=Korfmacher&rft.aufirst=Katrina&rft.date=2016-11-01&rft.volume=26&rft.issue=3&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=New+Solutions+%3A+a+Journal+of+Environmental+and+Occupational+Health+Policy+%3A+NS&rft.issn=10482911&rft_id=info:doi/10.1177%2F1048291116662680 LA - English DB - PAIS Index N1 - Copyright - © The Author(s) 2016 N1 - Last updated - 2017-01-27 DO - http://dx.doi.org/10.1177/1048291116662680 ER - TY - JOUR T1 - Youth Violence AN - 1826876420 AB - Although research suggests gender differences in both forms and functions of aggressive behavior, there has been limited research into these types among African American early adolescents. This study examined the types and patterns of aggression in girls and boys in that group. Participants were 452 predominantly African American middle school youth (50.4% girls) aged 11 to 13 (M = 11.97) enrolled in three urban public schools. Students were invited to participate in a school-based intervention designed to prevent aggressive and deviant behaviors. Assessments occurred pre- and post-intervention. Surveys were analyzed to identify gender differences in the levels and types of aggressive behaviors, as well as differences in predictors of aggressive behaviors. Predictors were measured at baseline; aggressive behaviors at follow-up. There were significant gender differences in types of aggressive behaviors and their predictors indicating a need to develop and implement more suitable, gender-tailored prevention and treatment approaches. JF - Journal of Interpersonal Violence AU - Finigan-Carr, Nadine M AU - Gielen, Andrea AU - Haynie, Denise L AU - Cheng, Tina L AD - University of Maryland, Baltimore, MD, USA ; Johns Hopkins University, Baltimore, MD, USA ; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA ; University of Maryland, Baltimore, MD, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 3257 EP - 3281 CY - Thousand Oaks PB - SAGE PUBLICATIONS, INC. VL - 31 IS - 19 SN - 0886-2605 KW - Psychology KW - aggression KW - early adolescence KW - gender KW - urban KW - African American KW - Black Americans KW - Educational Attainment KW - Urban Areas KW - Sex Differences KW - Public Schools KW - Aggression KW - Age Differences KW - Youth KW - Prevention KW - Children KW - Adolescents KW - Schools KW - 2858:studies in violence; studies in violence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826876420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Interpersonal+Violence&rft.atitle=Youth+Violence&rft.au=Finigan-Carr%2C+Nadine+M%3BGielen%2C+Andrea%3BHaynie%2C+Denise+L%3BCheng%2C+Tina+L&rft.aulast=Finigan-Carr&rft.aufirst=Nadine&rft.date=2016-11-01&rft.volume=31&rft.issue=19&rft.spage=3257&rft.isbn=&rft.btitle=&rft.title=Journal+of+Interpersonal+Violence&rft.issn=08862605&rft_id=info:doi/10.1177%2F0886260515584348 LA - English DB - Social Services Abstracts; Sociological Abstracts N1 - Copyright - © The Author(s) 2015 N1 - Last updated - 2016-12-15 DO - http://dx.doi.org/10.1177/0886260515584348 ER - TY - JOUR T1 - The Pivotal Role of the Social Sciences in Environmental Health Sciences Research AN - 1826875781 AB - Environmental health sciences research seeks to elucidate environmental factors that put human health at risk. A primary aim is to develop strategies to prevent or reduce exposures and disease occurrence. Given this primary focus on prevention, environmental health sciences research focuses on the populations most at risk such as communities of color and/or low socioeconomic status. The National Institute of Environmental Health Sciences research programs incorporate the principles of Community-Based Participatory Research to study health disparities. These programs promote community engagement, culturally appropriate communications with a variety of stakeholders, and consideration of the social determinants of health that interact with environmental factors to increase risk. Multidisciplinary research teams that include social and behavioral scientists are essential to conduct this type of research. This article outlines the history of social and behavioral research funding at National Institute of Environmental Health Sciences and offers examples of National Institute of Environmental Health Sciences-funded projects that exemplify the value of social science to the environmental health sciences. JF - New Solutions : a Journal of Environmental and Occupational Health Policy : NS AU - Finn, Symma AU - Collman, Gwen AD - National Institute of Environmental Health Sciences, Durham, NC, USA ; National Institute of Environmental Health Sciences, Durham, NC, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 389 EP - 411 CY - Thousand Oaks PB - SAGE PUBLICATIONS, INC. VL - 26 IS - 3 SN - 1048-2911 KW - Environmental Studies KW - environmental health sciences KW - social sciences KW - anthropology KW - sociology KW - economics KW - Environmental Factors KW - Environmental Health KW - Social Sciences KW - Socioeconomic Status KW - Risk KW - Mental Health KW - Research KW - Prevention KW - Teams KW - Social Scientists KW - Health Education KW - Interest Groups UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826875781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apais&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+Solutions+%3A+a+Journal+of+Environmental+and+Occupational+Health+Policy+%3A+NS&rft.atitle=The+Pivotal+Role+of+the+Social+Sciences+in+Environmental+Health+Sciences+Research&rft.au=Finn%2C+Symma%3BCollman%2C+Gwen&rft.aulast=Finn&rft.aufirst=Symma&rft.date=2016-11-01&rft.volume=26&rft.issue=3&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=New+Solutions+%3A+a+Journal+of+Environmental+and+Occupational+Health+Policy+%3A+NS&rft.issn=10482911&rft_id=info:doi/10.1177%2F1048291116666485 LA - English DB - PAIS Index N1 - Name - National Institute of Environmental Health Sciences N1 - Copyright - © The Author(s) 2016 N1 - Last updated - 2017-01-27 DO - http://dx.doi.org/10.1177/1048291116666485 ER - TY - JOUR T1 - Influence of English-language Proficiency on the Cognitive Processing of Survey Questions AN - 1826875735 AB - When recruiting respondents for cognitive interviews testing translated survey questionnaires, researchers often recommend interviewing monolingual non-English speakers because they are the likely users of the translations. However, these individuals are hard to recruit, and there is no standard definition of monolingual. Using cognitive interview data collected from pretesting of Chinese and Korean translations of the American Community Survey Language Assistance Guide, we investigated whether there were differences in respondents' understanding of survey questions according to their level of English proficiency and if such differences remained after considering demographic characteristics. We found that the types of issues reported by monolingual speakers and partially bilingual speakers were similar and that differences seemed to be driven by different demographic characteristics and not necessarily by language proficiency. Our findings suggest the value of evaluating translated questionnaires with individuals having diverse demographic characteristics and recruiting both monolingual speakers and partially bilingual speakers as research participants. JF - Field Methods AU - Park, Hyunjoo AU - Sha, M Mandy AU - Willis, Gordon AD - RTI International, Center for Survey Methodology, Survey Research Division, San Francisco, CA, USA ; RTI International, Center for Survey Methodology, Survey Research Division, Chicago, IL, USA ; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA ; RTI International, Center for Survey Methodology, Survey Research Division, San Francisco, CA, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 415 EP - 430 CY - Thousand Oaks PB - SAGE PUBLICATIONS, INC. VL - 28 IS - 4 SN - 1525-822X KW - Anthropology KW - Surveys KW - Competence KW - Language Attitudes KW - Cognition KW - Asian Americans KW - English Language KW - Interviews KW - Sociodemographic Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826875735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Field+Methods&rft.atitle=Influence+of+English-language+Proficiency+on+the+Cognitive+Processing+of+Survey+Questions&rft.au=Park%2C+Hyunjoo%3BSha%2C+M+Mandy%3BWillis%2C+Gordon&rft.aulast=Park&rft.aufirst=Hyunjoo&rft.date=2016-11-01&rft.volume=28&rft.issue=4&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Field+Methods&rft.issn=1525822X&rft_id=info:doi/10.1177%2F1525822X16630262 LA - English DB - Sociological Abstracts N1 - Copyright - © The Author(s) 2016 N1 - Last updated - 2016-10-08 DO - http://dx.doi.org/10.1177/1525822X16630262 ER - TY - JOUR T1 - Development of a subset of forelimb muscles and their attachment sites requires the ulnar-mammary syndrome gene Tbx3. AN - 1826743242; 27491074 AB - In the vertebrate limb over 40 muscles are arranged in a precise pattern of attachment via muscle connective tissue and tendon to bone and provide an extensive range of motion. How the development of somite-derived muscle is coordinated with the development of lateral plate-derived muscle connective tissue, tendon and bone to assemble a functional limb musculoskeletal system is a long-standing question. Mutations in the T-box transcription factor, TBX3, have previously been identified as the genetic cause of ulnar-mammary syndrome (UMS), characterized by distinctive defects in posterior forelimb bones. Using conditional mutagenesis in mice, we now show that TBX3 has a broader role in limb musculoskeletal development. TBX3 is not only required for development of posterior forelimb bones (ulna and digits 4 and 5), but also for a subset of posterior muscles (lateral triceps and brachialis) and their bone eminence attachment sites. TBX3 specification of origin and insertion sites appears to be tightly linked with whether these particular muscles develop and may represent a newly discovered mechanism for specification of anatomical muscles. Re-examination of an individual with UMS reveals similar previously unrecognized muscle and bone eminence defects and indicates a conserved role for TBX3 in regulating musculoskeletal development. © 2016. Published by The Company of Biologists Ltd. JF - Disease models & mechanisms AU - Colasanto, Mary P AU - Eyal, Shai AU - Mohassel, Payam AU - Bamshad, Michael AU - Bonnemann, Carsten G AU - Zelzer, Elazar AU - Moon, Anne M AU - Kardon, Gabrielle AD - Department of Human Genetics, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA. ; Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel. ; Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institutes of Health, Building 35, Room 2A-116, MSC 3705, 35 Convent Drive, Bethesda, MD 20892-3705, USA. ; University of Washington School of Medicine, Department of Pediatrics, Division of Genetic Medicine, 1959 NE Pacific Street HSB I-607-F, Seattle, WA 98195-7371, USA. ; Weis Center for Research, Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17822, USA. ; Department of Human Genetics, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA gkardon@genetics.utah.edu. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 1257 EP - 1269 VL - 9 IS - 11 KW - Bone KW - UMS KW - Tbx3 KW - Muscle KW - Limb KW - Ulnar-mammary syndrome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826743242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Disease+models+%26+mechanisms&rft.atitle=Development+of+a+subset+of+forelimb+muscles+and+their+attachment+sites+requires+the+ulnar-mammary+syndrome+gene+Tbx3.&rft.au=Colasanto%2C+Mary+P%3BEyal%2C+Shai%3BMohassel%2C+Payam%3BBamshad%2C+Michael%3BBonnemann%2C+Carsten+G%3BZelzer%2C+Elazar%3BMoon%2C+Anne+M%3BKardon%2C+Gabrielle&rft.aulast=Colasanto&rft.aufirst=Mary&rft.date=2016-11-01&rft.volume=9&rft.issue=11&rft.spage=1257&rft.isbn=&rft.btitle=&rft.title=Disease+models+%26+mechanisms&rft.issn=1754-8411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation. AN - 1826703034; 27286794 AB - Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection. © Society for Leukocyte Biology. JF - Journal of leukocyte biology AU - Shaikh, Saame Raza AU - Fessler, Michael B AU - Gowdy, Kymberly M AD - Department of Biochemistry and Molecular Biology, East Carolina Diabetes and Obesity Institute, East Carolina Heart Institute, Brody School of Medicine, East Carolina University (ECU), Greenville, North Carolina, USA. ; Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health (NIEHS/NIH), Research Triangle Park, North Carolina, USA. ; Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA; gowdyk14@ecu.edu. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 985 EP - 997 VL - 100 IS - 5 KW - respiratory infections KW - n-3 PUFAs KW - oxidized phospholipids KW - immunity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826703034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Role+for+phospholipid+acyl+chains+and+cholesterol+in+pulmonary+infections+and+inflammation.&rft.au=Shaikh%2C+Saame+Raza%3BFessler%2C+Michael+B%3BGowdy%2C+Kymberly+M&rft.aulast=Shaikh&rft.aufirst=Saame&rft.date=2016-11-01&rft.volume=100&rft.issue=5&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=1938-3673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Ambient Air Pollution Exposures and Risk of Parkinson Disease. AN - 1826702958; 27285422 AB - Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (PD). We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 μm in diameter (PM10) and < 2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk. Our nested case-control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995-1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders. We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 vs. Q1 = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 vs. Q1 = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 vs. Q1 = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORQ5 vs. Q1 = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations. Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. Citation: Liu R, Young MT, Chen JC, Kaufman JD, Chen H. 2016. Ambient air pollution exposures and risk of Parkinson disease. Environ Health Perspect 124:1759-1765; http://dx.doi.org/10.1289/EHP135. JF - Environmental health perspectives AU - Liu, Rui AU - Young, Michael T AU - Chen, Jiu-Chiuan AU - Kaufman, Joel D AU - Chen, Honglei AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1759 EP - 1765 VL - 124 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826702958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Ambient+Air+Pollution+Exposures+and+Risk+of+Parkinson+Disease.&rft.au=Liu%2C+Rui%3BYoung%2C+Michael+T%3BChen%2C+Jiu-Chiuan%3BKaufman%2C+Joel+D%3BChen%2C+Honglei&rft.aulast=Liu&rft.aufirst=Rui&rft.date=2016-11-01&rft.volume=124&rft.issue=11&rft.spage=1759&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-27 N1 - Last updated - 2017-01-28 ER - TY - JOUR T1 - Nitrate from Drinking Water and Diet and Bladder Cancer Among Postmenopausal Women in Iowa. AN - 1826700831; 27258851 AB - Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 μg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed ≥ 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and ≥ 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue-Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751-1758; http://dx.doi.org/10.1289/EHP191. JF - Environmental health perspectives AU - Jones, Rena R AU - Weyer, Peter J AU - DellaValle, Curt T AU - Inoue-Choi, Maki AU - Anderson, Kristin E AU - Cantor, Kenneth P AU - Krasner, Stuart AU - Robien, Kim AU - Freeman, Laura E Beane AU - Silverman, Debra T AU - Ward, Mary H AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1751 EP - 1758 VL - 124 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826700831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Nitrate+from+Drinking+Water+and+Diet+and+Bladder+Cancer+Among+Postmenopausal+Women+in+Iowa.&rft.au=Jones%2C+Rena+R%3BWeyer%2C+Peter+J%3BDellaValle%2C+Curt+T%3BInoue-Choi%2C+Maki%3BAnderson%2C+Kristin+E%3BCantor%2C+Kenneth+P%3BKrasner%2C+Stuart%3BRobien%2C+Kim%3BFreeman%2C+Laura+E+Beane%3BSilverman%2C+Debra+T%3BWard%2C+Mary+H&rft.aulast=Jones&rft.aufirst=Rena&rft.date=2016-11-01&rft.volume=124&rft.issue=11&rft.spage=1751&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures. AN - 1826699916; 27285288 AB - Farming has been associated with rheumatoid arthritis (RA), but the role of pesticides is not known. We examined associations between RA and pesticides or other agricultural exposures among female spouses of licensed pesticide applicators in the Agricultural Health Study. Women were enrolled between 1993 and 1997 and followed through 2010. Cases (n = 275 total, 132 incident), confirmed by a physician or by self-reported use of disease modifying antirheumatic drugs, were compared with noncases (n = 24,018). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models adjusted for age, state, and smoking pack-years. Overall, women with RA were somewhat more likely to have reported lifetime use of any specific pesticide versus no pesticides (OR = 1.4; 95% CI: 1.0, 1.6). Of the 15 pesticides examined, maneb/mancozeb (OR = 3.3; 95% CI: 1.5, 7.1) and glyphosate (OR = 1.4; 95% CI: 1.0, 2.1) were associated with incident RA compared with no pesticide use. An elevated, but non-statistically significant association with incident RA was seen for DDT (OR = 1.9; 95% CI: 0.97, 3.6). Incident RA was also associated with the application of chemical fertilizers (OR = 1.7; 95% CI: 1.1, 2.7) and cleaning with solvents (OR = 1.6; 95% CI: 1.1, 2.4), but inversely associated with lifetime livestock exposure as a child and adult (OR = 0.48; 95% CI: 0.24, 0.97) compared with no livestock exposure. Our results suggest that specific agricultural pesticides, solvents, and chemical fertilizers may increase the risk of RA in women, while exposures involving animal contact may be protective. Citation: Parks CG, Hoppin JA, De Roos AJ, Costenbader KH, Alavanja MC, Sandler DP. 2016. Rheumatoid arthritis in Agricultural Health Study spouses: associations with pesticides and other farm exposures. Environ Health Perspect 124:1728-1734; http://dx.doi.org/10.1289/EHP129. JF - Environmental health perspectives AU - Parks, Christine G AU - Hoppin, Jane A AU - De Roos, Anneclaire J AU - Costenbader, Karen H AU - Alavanja, Michael C AU - Sandler, Dale P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1728 EP - 1734 VL - 124 IS - 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826699916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Rheumatoid+Arthritis+in+Agricultural+Health+Study+Spouses%3A+Associations+with+Pesticides+and+Other+Farm+Exposures.&rft.au=Parks%2C+Christine+G%3BHoppin%2C+Jane+A%3BDe+Roos%2C+Anneclaire+J%3BCostenbader%2C+Karen+H%3BAlavanja%2C+Michael+C%3BSandler%2C+Dale+P&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2016-11-01&rft.volume=124&rft.issue=11&rft.spage=1728&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - IRF2BP2 transcriptional repressor restrains naive CD4 T cell activation and clonal expansion induced by TCR triggering. AN - 1826698586; 27286791 AB - CD4 T cell activation and differentiation mechanisms constitute a complex and intricate signaling network involving several regulatory proteins. IRF2BP2 is a transcriptional repressor that is involved in gene-expression regulation in very diverse biologic contexts. Information regarding the IRF2BP2 regulatory function in CD4 T lymphocytes is very limited and suggests a role for this protein in repressing the expression of different cytokine genes. Here, we showed that Irf2bp2 gene expression was decreased in CD4 T cells upon activation. To investigate the possible regulatory roles for IRF2BP2 in CD4 T cell functions, this protein was ectopically expressed in murine primary-activated CD4 T lymphocytes through retroviral transduction. Interestingly, ectopic expression of IRF2BP2 led to a reduction in CD25 expression and STAT5 phosphorylation, along with an impaired proliferative capacity. The CD69 expression was also diminished in IRF2BP2-overexpressing cells, whereas CD44 and CD62L levels were not altered. In vivo, transferred, IRF2BP2-overexpressing, transduced cells displayed an impaired expansion capacity compared with controls. Furthermore, overexpression of IRF2BP2 in differentiated Th cells resulted in slightly reduced IL-4 and pro-TGF-β production in Th2 and iTregs but had no effect on IFN-γ or IL-17 expression in Th1 and Th17 cells, respectively. Taken together, our data suggest a role for IRF2BP2 in regulating CD4 T cell activation by repressing proliferation and the expression of CD25 and CD69 induced by TCR stimuli. © Society for Leukocyte Biology. JF - Journal of leukocyte biology AU - Sécca, Cristiane AU - Faget, Douglas V AU - Hanschke, Steffi C AU - Carneiro, Mayra S AU - Bonamino, Martin H AU - de-Araujo-Souza, Patricia S AU - Viola, João P B AD - Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil. ; Program of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil. ; Program of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil; jpviola@inca.gov.br. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1081 EP - 1091 VL - 100 IS - 5 KW - lymphocyte proliferation KW - survival KW - CD25 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826698586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=IRF2BP2+transcriptional+repressor+restrains+naive+CD4+T+cell+activation+and+clonal+expansion+induced+by+TCR+triggering.&rft.au=S%C3%A9cca%2C+Cristiane%3BFaget%2C+Douglas+V%3BHanschke%2C+Steffi+C%3BCarneiro%2C+Mayra+S%3BBonamino%2C+Martin+H%3Bde-Araujo-Souza%2C+Patricia+S%3BViola%2C+Jo%C3%A3o+P+B&rft.aulast=S%C3%A9cca&rft.aufirst=Cristiane&rft.date=2016-11-01&rft.volume=100&rft.issue=5&rft.spage=1081&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=1938-3673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Epidermal growth factor receptor derived peptide vaccination to prevent lung adenocarcinoma formation: An in vivo study in a murine model of EGFR mutant lung cancer. AN - 1826628062; 26346412 AB - The ability to prevent disease is the holy grail of medicine. For decades, efforts have been made to extend the successes seen with vaccination against infectious diseases to cancer. In some instances, preventive vaccination against viruses (prototypically HPV) has successfully prevented tumorigenesis and will make a major impact on public health in the decades to come. However, the majority of cancers that arise are a result of genetic mutation within the host, or non-viral environmental exposures. We present compelling evidence that vaccination against an overexpressed self-tumor oncoprotein has the potential to prevent tumor development. Vaccination against the Epidermal Growth Factor Receptor (EGFR) using a multipeptide vaccine in a preventive setting decreased EGFR-driven lung carcinogenesis by 76.4% in a mouse model of EGFR-driven lung cancer. We also demonstrate that anti-EGFR vaccination primes the development of a robust immune response in vivo. This study provides proof of concept for the first time that targeting tumor drivers in a preventive setting in lung cancer using peptide vaccination can inhibit tumorigenesis and may provide useful clinical insights into the development of strategies to vaccinate against EGFR in populations where EGFR-mutant disease is highly prevalent. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. JF - Molecular carcinogenesis AU - Ebben, Johnathan D AU - Lubet, Ronald A AU - Gad, Ekram AU - Disis, Mary L AU - You, Ming AD - Department of Pharmacology & Toxicology, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin. ; Division of Chemoprevention, National Cancer Institute, Bethesda, Maryland. ; Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, Washington. ; Department of Pharmacology & Toxicology, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin. myou@mcw.edu. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1517 EP - 1525 VL - 55 IS - 11 KW - lung cancer KW - cancer prevention KW - peptide vaccine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826628062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Epidermal+growth+factor+receptor+derived+peptide+vaccination+to+prevent+lung+adenocarcinoma+formation%3A+An+in+vivo+study+in+a+murine+model+of+EGFR+mutant+lung+cancer.&rft.au=Ebben%2C+Johnathan+D%3BLubet%2C+Ronald+A%3BGad%2C+Ekram%3BDisis%2C+Mary+L%3BYou%2C+Ming&rft.aulast=Ebben&rft.aufirst=Johnathan&rft.date=2016-11-01&rft.volume=55&rft.issue=11&rft.spage=1517&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=1098-2744&rft_id=info:doi/10.1002%2Fmc.22405 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2015-09-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/mc.22405 ER - TY - JOUR T1 - Cannabis effects on driving longitudinal control with and without alcohol. AN - 1824546867; 26889769 AB - Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis' effects on driving longitudinal control (with and without alcohol, drivers' most common drug combination) relative to psychoactive ∆(9) -tetrahydrocannabinol (THC) blood concentrations. Current occasional (≥1×/last 3 months, ≤3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving. We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC). In N=18 completing drivers, THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not. Neither was associated with altered longitudinal acceleration. A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers' tendency to drive faster with alcohol. Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd. JF - Journal of applied toxicology : JAT AU - Hartman, Rebecca L AU - Brown, Timothy L AU - Milavetz, Gary AU - Spurgin, Andrew AU - Pierce, Russell S AU - Gorelick, David A AU - Gaffney, Gary AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, 251 Bayview Boulevard Street, 200 Rm 05A721, Baltimore, MD, USA. ; National Advanced Driving Simulator, University of Iowa, 2401 Oakdale Boulevard, Iowa City, IA, USA. ; College of Pharmacy, University of Iowa, Iowa City, IA, USA. ; VariableSolutions, USA. ; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. ; Carver College of Medicine, University of Iowa, Iowa City, IA, USA. ; Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, 251 Bayview Boulevard Street, 200 Rm 05A721, Baltimore, MD, USA. mhuestis@intra.nida.nih.gov. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 1418 EP - 1429 VL - 36 IS - 11 KW - Index Medicus KW - cannabis KW - speed KW - alcohol KW - THC KW - driving KW - blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1824546867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+toxicology+%3A+JAT&rft.atitle=Cannabis+effects+on+driving+longitudinal+control+with+and+without+alcohol.&rft.au=Hartman%2C+Rebecca+L%3BBrown%2C+Timothy+L%3BMilavetz%2C+Gary%3BSpurgin%2C+Andrew%3BPierce%2C+Russell+S%3BGorelick%2C+David+A%3BGaffney%2C+Gary%3BHuestis%2C+Marilyn+A&rft.aulast=Hartman&rft.aufirst=Rebecca&rft.date=2016-11-01&rft.volume=36&rft.issue=11&rft.spage=1418&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=1099-1263&rft_id=info:doi/10.1002%2Fjat.3295 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/jat.3295 ER - TY - JOUR T1 - Disparities in achieving and sustaining viral suppression among a large cohort of HIV-infected persons in care - Washington, DC AN - 1818359827 AB - One goal of the HIV care continuum is achieving viral suppression (VS), yet disparities in suppression exist among subpopulations of HIV-infected persons. We sought to identify disparities in both the ability to achieve and sustain VS among an urban cohort of HIV-infected persons in care. Data from HIV-infected persons enrolled at the 13 DC Cohort study clinical sites between January 2011 and June 2014 were analyzed. Univariate and multivariate logistic regression were conducted to identify factors associated with achieving VS (viral load < 200 copies/ml) at least once, and Kaplan-Meier (KM) curves and Cox proportional hazards models were used to identify factors associated with sustaining VS and time to virologic failure (VL [greater than or equal to] 200 copies/ml after achievement of VS). Among the 4311 participants, 95.4% were either virally suppressed at study enrollment or able to achieve VS during the follow-up period. In multivariate analyses, achieving VS was significantly associated with age (aOR: 1.04; 95%CI: 1.03-1.06 per five-year increase) and having a higher CD4 (aOR: 1.05, 95% CI 1.04-1.06 per 100 cells/mm3). Patients infected through perinatal transmission were less likely to achieve VS compared to MSM patients (aOR: 0.63, 95% CI 0.51-0.79). Once achieved, most participants (74.4%) sustained VS during follow-up. Blacks and perinatally infected persons were less likely to have sustained VS in KM survival analysis (log rank chi-square p [less-than or equal to] .001 for both) compared to other races and risk groups. Earlier time to failure was observed among females, Blacks, publically insured, perinatally infected, those with longer standing HIV infection, and those with diagnoses of mental health issues or depression. Among this HIV-infected cohort, most people achieved and maintained VS; however, disparities exist with regard to patient age, race, HIV transmission risk, and co-morbid conditions. Identifying populations with disparate outcomes allows for appropriate targeting of resources to improve outcomes along the care continuum. JF - AIDS Care AU - Castel, Amanda D AU - Kalmin, Mariah M AU - Hart, Rachel L D AU - Young, Heather A AU - Hays, Harlen AU - Benator, Debra AU - Kumar, Princy AU - Elion, Richard AU - Parenti, David AU - Ruiz, Maria Elena AU - Wood, Angela AU - D'Angelo, Lawrence AU - Rakhmanina, Natella AU - Rana, Sohail AU - Bryant, Maya AU - Hebou, Annick AU - Fernández, Ricardo AU - Abbott, Stephen AU - Peterson, James AU - Wood, Kathy AU - Subramanian, Thilakavathy AU - Binkley, Jeffrey AU - Happ, Lindsey Powers AU - Kharfen, Michael AU - Masur, Henry AU - Greenberg, Alan E AD - Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health, Washington, DC, USA ; Cerner Corporation, Kansas City, MO, USA ; Veterans Affairs Medical Center, Washington, DC, USA ; Division of Infectious Diseases, Georgetown University, Washington, DC, USA ; Whitman-Walker Health, Washington, DC, USA ; Division of Infectious Disease, George Washington Medical Faculty Associates, Washington, DC, USA ; Division of Infectious Diseases, Department of Medicine, Washington Hospital Center, Washington, DC, USA ; Family and Medical Counseling Service, Washington, DC, USA ; Burgess Adolescent Clinic, Children's National Medical Center, Washington, DC, USA ; Special Immunology Service Pediatric Clinic Children's National Medical Center, Washington, DC, USA ; Department of Pediatric and Child Health, Howard University Hospital, Washington, DC, USA ; Howard University Hospital Adult Infectious Disease Clinic, Washington, DC, USA ; MetroHealth, Washington, DC, USA ; La Clinica Del Pueblo, Washington, DC, USA ; Unity Health Care, Washington, DC, USA ; Cerner Corporation, Vienna, VA, USA ; Cerner Corporation, Culver City, CA, USA ; District of Columbia Department of Health, HIV/AIDS, Hepatitis, Sexually Transmitted Diseases, Tuberculosis Administration (HAHSTA), Washington, DC, USA ; Department of Critical Care Medicine, National Institutes of Health, Bethesda, MD, USA ; Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health, Washington, DC, USA Y1 - 2016/11// PY - 2016 DA - Nov 2016 SP - 1355 EP - 1364 CY - London PB - Taylor & Francis Ltd. VL - 28 IS - 11 SN - 0954-0121 KW - Medical Sciences--Psychiatry And Neurology KW - Viral suppression KW - care continuum KW - HIV KW - disparities KW - cohort KW - Antiretroviral drugs KW - Human immunodeficiency virus--HIV KW - Survival analysis KW - In care KW - Immune response system KW - Suppression KW - Health inequalities KW - Mental health KW - Perinatal KW - Hazards KW - Clinical outcomes KW - Infection KW - Cohort analysis KW - Suppressed KW - Race KW - Enrollment KW - Fetal exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818359827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Care&rft.atitle=Disparities+in+achieving+and+sustaining+viral+suppression+among+a+large+cohort+of+HIV-infected+persons+in+care+-+Washington%2C+DC&rft.au=Castel%2C+Amanda+D%3BKalmin%2C+Mariah+M%3BHart%2C+Rachel+L+D%3BYoung%2C+Heather+A%3BHays%2C+Harlen%3BBenator%2C+Debra%3BKumar%2C+Princy%3BElion%2C+Richard%3BParenti%2C+David%3BRuiz%2C+Maria+Elena%3BWood%2C+Angela%3BD%27Angelo%2C+Lawrence%3BRakhmanina%2C+Natella%3BRana%2C+Sohail%3BBryant%2C+Maya%3BHebou%2C+Annick%3BFern%C3%A1ndez%2C+Ricardo%3BAbbott%2C+Stephen%3BPeterson%2C+James%3BWood%2C+Kathy%3BSubramanian%2C+Thilakavathy%3BBinkley%2C+Jeffrey%3BHapp%2C+Lindsey+Powers%3BKharfen%2C+Michael%3BMasur%2C+Henry%3BGreenberg%2C+Alan+E&rft.aulast=Castel&rft.aufirst=Amanda&rft.date=2016-11-01&rft.volume=28&rft.issue=11&rft.spage=1355&rft.isbn=&rft.btitle=&rft.title=AIDS+Care&rft.issn=09540121&rft_id=info:doi/10.1080%2F09540121.2016.1189496 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 Informa UK Limited, trading as Taylor & Francis Group N1 - Last updated - 2016-09-12 DO - http://dx.doi.org/10.1080/09540121.2016.1189496 ER - TY - JOUR T1 - Tumor-associated mesenchymal stem cells inhibit naive T cell expansion by blocking cysteine export from dendritic cells AN - 1815709833; PQ0003592965 AB - Mesenchymal stem cells (MSCs) represent an important cellular constituent of the tumor microenvironment, which along with tumor cells themselves, serve to regulate protective immune responses in support of progressive disease. We report that tumor MSCs prevent the ability of dendritic cells (DC) to promote naive CD4 super(+) and CD8 super(+) T cell expansion, interferon gamma secretion and cytotoxicity against tumor cells, which are critical to immune-mediated tumor eradication. Notably, tumor MSCs fail to prevent DC-mediated early T cell activation events or the ability of responder T cells to produce IL-2. The immunoregulatory activity of tumor MSCs is IL-10- and STAT3-dependent, with STAT3 repressing DC expression of cystathionase, a critical enzyme that converts methionine-to-cysteine. Under cysteine-deficient priming conditions, naive T cells exhibit defective cellular metabolism and proliferation. Bioinformatics analyses as well as in vitro observations suggest that STAT3 may directly bind to a GAS-like motif within the cystathionase promoter (-269 to -261) leading to IL-10-STAT3 mediated repression of cystathionase gene transcription. Our collective results provide evidence for a novel mechanism of tumor MSC-mediated T cell inhibition within tumor microenvironment. What's new? Mesenchymal stem cells (MSCs) within a tumor can suppress the immune response against that tumor. In this study, the authors discovered a pathway by which MSCs can block antigen-presenting cells (APCs) from stimulating cytotoxic T cells. This pathway inhibits an enzyme involved in the production of cysteine. Surprisingly, this cysteine deficiency doesn't suppress activation of the T cells, only their proliferation. These results suggest that targeting gene expression in MSCs may provide a useful therapeutic strategy to enhance the ability of T cells to eradicate tumors. JF - International Journal of Cancer AU - Ghosh, Tithi AU - Barik, Subhasis AU - Bhuniya, Avishek AU - Dhar, Jesmita AU - Dasgupta, Shayani AU - Ghosh, Sarbari AU - Sarkar, Madhurima AU - Guha, Ipsita AU - Sarkar, Koustav AU - Chakrabarti, Pinak AU - Saha, Bhaskar AU - Storkus, Walter J AU - Baral, Rathindranath AU - Bose, Anamika AD - Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata, West Bengal, 700026, India. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2068 EP - 2081 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 139 IS - 9 SN - 0020-7136, 0020-7136 KW - Immunology Abstracts; Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts KW - Immunoregulation KW - gamma -Interferon KW - Interleukin 2 KW - Tumor cells KW - Cell activation KW - Gene expression KW - Promoters KW - Dendritic cells KW - CD4 antigen KW - Stem cells KW - Lymphocytes T KW - Antigen-presenting cells KW - Mesenchyme KW - Stat3 protein KW - Transcription KW - Enzymes KW - CD8 antigen KW - Tumors KW - Cytotoxicity KW - Cysteine KW - Microenvironments KW - Bioinformatics KW - Cell proliferation KW - Metabolism KW - Gene silencing KW - B 26660:Miscellaneous Oncogenes & Growth Factors KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815709833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Tumor-associated+mesenchymal+stem+cells+inhibit+naive+T+cell+expansion+by+blocking+cysteine+export+from+dendritic+cells&rft.au=Ghosh%2C+Tithi%3BBarik%2C+Subhasis%3BBhuniya%2C+Avishek%3BDhar%2C+Jesmita%3BDasgupta%2C+Shayani%3BGhosh%2C+Sarbari%3BSarkar%2C+Madhurima%3BGuha%2C+Ipsita%3BSarkar%2C+Koustav%3BChakrabarti%2C+Pinak%3BSaha%2C+Bhaskar%3BStorkus%2C+Walter+J%3BBaral%2C+Rathindranath%3BBose%2C+Anamika&rft.aulast=Ghosh&rft.aufirst=Tithi&rft.date=2016-11-01&rft.volume=139&rft.issue=9&rft.spage=2068&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.30265 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - gamma -Interferon; Immunoregulation; Interleukin 2; Tumor cells; Cell activation; Gene expression; Dendritic cells; Promoters; Stem cells; CD4 antigen; Lymphocytes T; Antigen-presenting cells; Mesenchyme; Stat3 protein; Enzymes; Transcription; Tumors; CD8 antigen; Cytotoxicity; Cysteine; Microenvironments; Bioinformatics; Cell proliferation; Metabolism; Gene silencing DO - http://dx.doi.org/10.1002/ijc.30265 ER - TY - JOUR T1 - Genomic characterization of viral integration sites in HPV-related cancers. AN - 1812880280; 27343048 AB - Persistent infection with carcinogenic human papillomaviruses (HPV) causes the majority of anogenital cancers and a subset of head and neck cancers. The HPV genome is frequently found integrated into the host genome of invasive cancers. The mechanisms of how it may promote disease progression are not well understood. Thoroughly characterizing integration events can provide insights into HPV carcinogenesis. Individual studies have reported limited number of integration sites in cell lines and human samples. We performed a systematic review of published integration sites in HPV-related cancers and conducted a pooled analysis to formally test for integration hotspots and genomic features enriched in integration events using data from the Encyclopedia of DNA Elements (ENCODE). Over 1,500 integration sites were reported in the literature, of which 90.8% (N = 1,407) were in human tissues. We found 10 cytobands enriched for integration events, three previously reported ones (3q28, 8q24.21 and 13q22.1) and seven additional ones (2q22.3, 3p14.2, 8q24.22, 14q24.1, 17p11.1, 17q23.1 and 17q23.2). Cervical infections with HPV18 were more likely to have breakpoints in 8q24.21 (p = 7.68 × 10(-4) ) than those with HPV16. Overall, integration sites were more likely to be in gene regions than expected by chance (p = 6.93 × 10(-9) ). They were also significantly closer to CpG regions, fragile sites, transcriptionally active regions and enhancers. Few integration events occurred within 50 Kb of known cervical cancer driver genes. This suggests that HPV integrates in accessible regions of the genome, preferentially genes and enhancers, which may affect the expression of target genes. © 2016 UICC. JF - International journal of cancer AU - Bodelon, Clara AU - Untereiner, Michael E AU - Machiela, Mitchell J AU - Vinokurova, Svetlana AU - Wentzensen, Nicolas AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. ; Laboratory of Molecular Biology of Viruses, NN Blokhin Russian Cancer Research Center, Moscow, Russia. Y1 - 2016/11/01/ PY - 2016 DA - 2016 Nov 01 SP - 2001 EP - 2011 VL - 139 IS - 9 KW - Index Medicus KW - integration KW - HPV UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812880280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Genomic+characterization+of+viral+integration+sites+in+HPV-related+cancers.&rft.au=Bodelon%2C+Clara%3BUntereiner%2C+Michael+E%3BMachiela%2C+Mitchell+J%3BVinokurova%2C+Svetlana%3BWentzensen%2C+Nicolas&rft.aulast=Bodelon&rft.aufirst=Clara&rft.date=2016-11-01&rft.volume=139&rft.issue=9&rft.spage=2001&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.30243 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.30243 ER - TY - JOUR T1 - Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial. AN - 1804867863; 27187274 AB - To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. JF - Journal of cellular physiology AU - Pizzuti, Laura AU - Barba, Maddalena AU - Giannarelli, Diana AU - Sergi, Domenico AU - Botti, Claudio AU - Marchetti, Paolo AU - Anzà, Michele AU - Maugeri-Saccà, Marcello AU - Natoli, Clara AU - Di Filippo, Simona AU - Catenaro, Teresa AU - Tomao, Federica AU - Amodio, Antonella AU - Carpano, Silvia AU - Perracchio, Letizia AU - Mottolese, Marcella AU - Di Lauro, Luigi AU - Sanguineti, Giuseppe AU - Di Benedetto, Anna AU - Giordano, Antonio AU - Vici, Patrizia AD - Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy. ; Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy. ; Oncology Unit, Sant'Andrea Hospital, La Sapienza University of Rome, Rome, Italy. ; Department of Medical, Oral and Biotechnological Sciences and CeSI-MeT, G. d'Annunzio University, Chieti, Italy. ; Santa Maria Goretti, Hospital of Latina, Latina, Italy. ; Department of Gynecologic Oncology, University "Sapienza", Rome, Italy. ; Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome, Italy. ; Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania. Y1 - 2016/11// PY - 2016 DA - November 2016 SP - 2541 EP - 2547 VL - 231 IS - 11 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804867863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Neoadjuvant+Sequential+Docetaxel+Followed+by+High-Dose+Epirubicin+in+Combination+With+Cyclophosphamide+Administered+Concurrently+With+Trastuzumab.+The+DECT+Trial.&rft.au=Pizzuti%2C+Laura%3BBarba%2C+Maddalena%3BGiannarelli%2C+Diana%3BSergi%2C+Domenico%3BBotti%2C+Claudio%3BMarchetti%2C+Paolo%3BAnz%C3%A0%2C+Michele%3BMaugeri-Sacc%C3%A0%2C+Marcello%3BNatoli%2C+Clara%3BDi+Filippo%2C+Simona%3BCatenaro%2C+Teresa%3BTomao%2C+Federica%3BAmodio%2C+Antonella%3BCarpano%2C+Silvia%3BPerracchio%2C+Letizia%3BMottolese%2C+Marcella%3BDi+Lauro%2C+Luigi%3BSanguineti%2C+Giuseppe%3BDi+Benedetto%2C+Anna%3BGiordano%2C+Antonio%3BVici%2C+Patrizia&rft.aulast=Pizzuti&rft.aufirst=Laura&rft.date=2016-11-01&rft.volume=231&rft.issue=11&rft.spage=2541&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=1097-4652&rft_id=info:doi/10.1002%2Fjcp.25432 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/jcp.25432 ER - TY - JOUR T1 - Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers. AN - 1834996367; 27494631 AB - Gastrointestinal (GI) cancer taken together constitutes one of the most common cancers worldwide with a broad range of etiological mechanisms. In this review, we have examined the impact of nitric oxide (NO) on the etiology of colon, colorectal, gastric, esophageal, and liver cancers. Recent Advances: Despite differences in etiology, initiation, and progression, chronic inflammation has been shown to be a common element within these cancers showing interactions of numerous pathways. NO generated at the inflammatory site contributes to the initiation and progression of disease. The amount of NO generated, time, and site vary and are an important determinant of the biological effects initiated. Among the nitric oxide synthase enzymes, the inducible isoform has the most diverse range, participating in numerous carcinogenic processes. There is emerging evidence showing that inducible nitric oxide synthase (NOS2) plays a central role in the process of tumor initiation and/or development. Redox inflammation through NOS2 and cyclooxygenase-2 participates in driving the mechanisms of initiation and progression in GI cancers. Understanding the underlying mechanism involved in NOS2 activation can provide new insights into important prevention and treatment strategies. Antioxid. Redox Signal. 00, 000-000. JF - Antioxidants & redox signaling AU - de Oliveira, Graciele Almeida AU - Cheng, Robert Y S AU - Ridnour, Lisa A AU - Basudhar, Debashree AU - Somasundaram, Veena AU - McVicar, Daniel W AU - Monteiro, Hugo Pequeno AU - Wink, David A AD - 1 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland. ; 2 Laboratório de Sinalização Celular, Universidade Federal de São Paulo , São Paulo, Brazil . Y1 - 2016/10/31/ PY - 2016 DA - 2016 Oct 31 KW - nitric oxide KW - gastrointestinal cancer KW - liver UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834996367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antioxidants+%26+redox+signaling&rft.atitle=Inducible+Nitric+Oxide+Synthase+in+the+Carcinogenesis+of+Gastrointestinal+Cancers.&rft.au=de+Oliveira%2C+Graciele+Almeida%3BCheng%2C+Robert+Y+S%3BRidnour%2C+Lisa+A%3BBasudhar%2C+Debashree%3BSomasundaram%2C+Veena%3BMcVicar%2C+Daniel+W%3BMonteiro%2C+Hugo+Pequeno%3BWink%2C+David+A&rft.aulast=de+Oliveira&rft.aufirst=Graciele&rft.date=2016-10-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Antioxidants+%26+redox+signaling&rft.issn=1557-7716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Advancing Alternative Analysis: Integration of Decision Science. AN - 1835693591; 27791981 AB - Decision analysis-a systematic approach to solving complex problems-offers tools and frameworks to support decision making that are increasingly being applied to environmental challenges. Alternatives analysis is a method used in regulation and product design to identify, compare, and evaluate the safety and viability of potential substitutes for hazardous chemicals. Assess whether decision science may assist the alternatives analysis decision maker in comparing alternatives across a range of metrics. A workshop was convened that included representatives from government, academia, business, and civil society and included experts in toxicology, decision science, alternatives assessment, engineering, and law and policy. Participants were divided into two groups and prompted with targeted questions. Throughout the workshop, the groups periodically came together in plenary sessions to reflect on other groups' findings. We conclude the further incorporation of decision science into alternatives analysis would advance the ability of companies and regulators to select alternatives to harmful ingredients, and would also advance the science of decision analysis. We advance four recommendations: (1) engaging the systematic development and evaluation of decision approaches and tools; (2) using case studies to advance the integration of decision analysis into alternatives analysis; (3) supporting transdisciplinary research; and (4) supporting education and outreach efforts. JF - Environmental health perspectives AU - Malloy, Timothy F AU - Zaunbrecher, Virginia M AU - Batteate, Christina AU - Blake, Ann AU - Carroll, William F AU - Corbett, Charles J AU - Hansen, Steffen Foss AU - Lempert, Robert AU - Linkov, Igor AU - McFadden, Roger AU - Moran, Kelly D AU - Olivetti, Elsa AU - Ostrom, Nancy AU - Romero, Michelle AU - Schoenung, Julie AU - Seager, Thomas AU - Sinsheimer, Peter AU - Thayer, Kristina AD - School of Law, University of California, Los Angeles, Los Angeles, California, U.S.A. ; Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, U.S.A. ; Environmental and Public Health Consulting, Alameda, California, U.S.A. ; Department of Chemistry, Indiana University, Bloomington, Indiana, U.S.A. ; Anderson School of Management, University of California, Los Angeles, Los Angeles, California, U.S.A. ; Department of Environmental Engineering, Technical University of Denmark, Copenhagen, Denmark. ; RAND Corporation, Santa Monica, California, U.S.A. ; U.S. Army Engineer Research and Development Center, Concord, Massachusetts, U.S.A. ; McFadden and Associates, LLC, Oregon, U.S.A. ; TDC Environmental, LLC, San Mateo, California, U.S.A. ; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, U.S.A. ; Safer Products and Workplaces Program, Department of Toxic Substances Control, Sacramento, California, U.S.A. ; Henry Samueli School of Engineering, University of California, Irvine, Irvine, California, U.S.A. ; School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, Arizona, U.S.A. ; Office of Health Assessment and Translation, National Toxicology Program, National Institute of Environmental Health Sciences, Morrisville, North Carolina, U.S.A. Y1 - 2016/10/28/ PY - 2016 DA - 2016 Oct 28 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835693591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Advancing+Alternative+Analysis%3A+Integration+of+Decision+Science.&rft.au=Malloy%2C+Timothy+F%3BZaunbrecher%2C+Virginia+M%3BBatteate%2C+Christina%3BBlake%2C+Ann%3BCarroll%2C+William+F%3BCorbett%2C+Charles+J%3BHansen%2C+Steffen+Foss%3BLempert%2C+Robert%3BLinkov%2C+Igor%3BMcFadden%2C+Roger%3BMoran%2C+Kelly+D%3BOlivetti%2C+Elsa%3BOstrom%2C+Nancy%3BRomero%2C+Michelle%3BSchoenung%2C+Julie%3BSeager%2C+Thomas%3BSinsheimer%2C+Peter%3BThayer%2C+Kristina&rft.aulast=Malloy&rft.aufirst=Timothy&rft.date=2016-10-28&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - The biological fate of decabromodiphenyl ethane following oral, dermal or intravenous administration. AN - 1835533576; 27771980 AB - 1. It was important to investigate the disposition of decabromodiphenyl ethane (DBDPE) based on concerns over its structural similarities to decabromodiphenyl ether (decaBDE), high potential for environmental persistence and bioaccumulation, and high production volume. 2. In the present study, female Sprague Dawley rats were administered a single dose of [14C]-DBDPE by oral, topical or IV routes. Another set of rats were administered 10 daily oral doses of [14C]-DBDPE. Male B6C3F1/Tac mice were administered a single oral dose. 3. DBDPE was poorly absorbed following oral dosing, with 95% of administered [14C]-radioactivity recovered in the feces unchanged, 1% recovered in the urine and less than 3% in the tissues at 72 h. DBDPE excretion was similar in male mice and female rats. Accumulation of [14C]-DBDPE was observed in liver and the adrenal gland after 10 daily oral doses to rats. 4. Rat and human skin were used to assess potential dermal uptake of DBDPE. The dermis was a depot for dermally applied DBDPE; conservative estimates predict ∼14 ± 8% of DBDPE may be absorbed into human skin in vivo; ∼7 ± 4% of the parent chemical is expected to reach systemic circulation following continuous exposure (24 h). 5. Following intravenous administration, ∼70% of the dose remained in tissues after 72 h, with the highest concentrations found in lung (1223 ± 723 pmol-eq/g), spleen (1096 ± 369 pmol-eq/g) and liver (366 ± 98 pmol-eq/g); 5 ± 1% of the dose was recovered in urine and 26 ± 4% in the feces. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Knudsen, Gabriel A AU - Sanders, J Michael AU - Hughes, Michael F AU - Hull, Ethan P AU - Birnbaum, Linda S AD - a NCI Laboratory of Toxicology and Toxicokinetics , Research Triangle Park , NC , USA and. ; b Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park , NC , USA. Y1 - 2016/10/28/ PY - 2016 DA - 2016 Oct 28 SP - 1 EP - 9 KW - brominated flame retardant KW - lipophilic KW - ADME KW - persistent organic pollutant KW - bioaccumulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835533576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=The+biological+fate+of+decabromodiphenyl+ethane+following+oral%2C+dermal+or+intravenous+administration.&rft.au=Knudsen%2C+Gabriel+A%3BSanders%2C+J+Michael%3BHughes%2C+Michael+F%3BHull%2C+Ethan+P%3BBirnbaum%2C+Linda+S&rft.aulast=Knudsen&rft.aufirst=Gabriel&rft.date=2016-10-28&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=1366-5928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Pillar[5]arene-based amphiphilic supramolecular brush copolymer: fabrication, controllable self-assembly and application in self-imaging targeted drug delivery. AN - 1835003939; 27795740 AB - Supramolecular brush copolymers have attracted continuing interest due to their unusual architectures, fascinating properties, and potential applications in many fields involving smart stimuli-responsive drug delivery systems. Herein, the first pillararene-based amphiphilic supramolecular brush copolymer (P5-PEG-Biotin⊃PTPE) was constructed on the basis of the host-guest molecular recognition between a water-soluble pillar[5]arene (P5) and a viologen salt (M). P5-PEG-Biotin⊃PTPE self-assembled into supramolecular nanoparticles (SNPs), which were utilized as a self-imaging drug delivery vehicle by taking advantage of the aggregation-induced emission (AIE) effect. Encapsulation of anticancer drug doxorubicin (DOX) caused deactivation of the fluorescences of both the tetraphenylethene (TPE) and DOX chromophores due to the energy transfer relay (ETR) effect, mediated by Förster resonance energy transfer (FRET) and aggregation-caused quenching (ACQ). The release of loaded DOX molecules can be triggered by low pH and reductase, recovering the "silenced" fluorescence caused by the interruption of the ETR effect, achieving in situ visualization of the drug release process by observing the location and magnitude of the energy transfer-dependent fluorescence variation. The biotin ligands on the surfaces of the DOX-loaded SNPs act as targeting agents to deliver DOX preferentially to cancer cells over-expressing biotin receptor. In vitro studies demonstrated that the loading of DOX by this supramolecular nanomaterial exhibited selective cytotoxicity towards cancer cells over normal cells. The potency of this sophisticated supramolecular drug delivery system in cancer therapy was further evaluated in HeLa tumor-bearing mice. In vivo experiments confirmed that the DOX-loaded SNPs possess excellent antitumor efficacy with negligible systemic toxicity. JF - Polymer chemistry AU - Yu, Guocan AU - Zhao, Run AU - Wu, Dan AU - Zhang, Fuwu AU - Shao, Li AU - Zhou, Jiong AU - Yang, Jie AU - Tang, Guping AU - Chen, Xiaoyuan AU - Huang, Feihe AD - State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States. ; State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China. ; Department of Chemistry, Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310027, P. R. China. ; Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States. Y1 - 2016/10/28/ PY - 2016 DA - 2016 Oct 28 SP - 6178 EP - 6188 VL - 7 IS - 40 SN - 1759-9954, 1759-9954 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835003939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Polymer+chemistry&rft.atitle=Pillar%5B5%5Darene-based+amphiphilic+supramolecular+brush+copolymer%3A+fabrication%2C+controllable+self-assembly+and+application+in+self-imaging+targeted+drug+delivery.&rft.au=Yu%2C+Guocan%3BZhao%2C+Run%3BWu%2C+Dan%3BZhang%2C+Fuwu%3BShao%2C+Li%3BZhou%2C+Jiong%3BYang%2C+Jie%3BTang%2C+Guping%3BChen%2C+Xiaoyuan%3BHuang%2C+Feihe&rft.aulast=Yu&rft.aufirst=Guocan&rft.date=2016-10-28&rft.volume=7&rft.issue=40&rft.spage=6178&rft.isbn=&rft.btitle=&rft.title=Polymer+chemistry&rft.issn=17599954&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action AN - 1850786458; PQ0003837632 AB - Poly(ADP-ribose) polymerase (PARP) inhibitors are the first DNA damage response targeted agents approved for cancer therapy. Here, we focus on their molecular mechanism of action by PARP "trapping" and what this means for both clinical monotherapy and combination with chemotherapeutic agents. JF - Science Translational Medicine AU - Pommier, Yves AU - O'connor, Mark J AU - de Bono, Johann AD - Laboratory of Molecular Pharmacology and Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, pommier@nih.gov Y1 - 2016/10/26/ PY - 2016 DA - 2016 Oct 26 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 United States VL - 8 IS - 362 SN - 1946-6234, 1946-6234 KW - Biotechnology and Bioengineering Abstracts KW - Translation KW - Molecular modelling KW - DNA damage KW - Poly(ADP-ribose) polymerase KW - Chemotherapy KW - Trapping KW - Cancer KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850786458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+Translational+Medicine&rft.atitle=Laying+a+trap+to+kill+cancer+cells%3A+PARP+inhibitors+and+their+mechanisms+of+action&rft.au=Pommier%2C+Yves%3BO%27connor%2C+Mark+J%3Bde+Bono%2C+Johann&rft.aulast=Pommier&rft.aufirst=Yves&rft.date=2016-10-26&rft.volume=8&rft.issue=362&rft.spage=362ps17&rft.isbn=&rft.btitle=&rft.title=Science+Translational+Medicine&rft.issn=19466234&rft_id=info:doi/10.1126%2Fscitranslmed.aaf9246 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - DNA damage; Molecular modelling; Translation; Chemotherapy; Poly(ADP-ribose) polymerase; Trapping; Cancer DO - http://dx.doi.org/10.1126/scitranslmed.aaf9246 ER - TY - JOUR T1 - Serum biomarkers of polyomavirus infection and risk of lung cancer in never smokers. AN - 1835683938; 27632373 AB - Lung cancer in never smokers is a significant contributor of cancer mortality worldwide. In this analysis, we explored the role of nine human polyomaviruses, including JC virus (JCV), BK virus (BKV) and Merkel cell virus (MCV), in lung cancer development in never smokers as there are data to support that polyomaviruses are potentially carcinogenic in the human lung. We used multiplex serology to detect serum antibodies to polyomaviruses in a nested case-control design combining lung cancer cases and controls from four cohort studies - NYU Women's Health Study (NYU-WHS), Janus Serum Bank, Shanghai Women's Health Study and Singapore Chinese Health Study (SCHS). The final analyses included 511 cases and 508 controls. Seroprevalence for each polyomavirus showed significant heterogeneity by study, but overall there were no statistically significant differences between cases and controls. In total, 69.1% of the cases and 68.7% of the controls were seropositive for JCV VP1 antibody. Seropositivity for BKV was higher at 89.0% in cases and 89.8% in controls and lower for MCV at 59.3% in cases and 61.6% in controls. Similar results were obtained after adding an additional retrospective case-control study (Xuanwei study) to the analysis. Our results do not support the hypothesis that seropositivity for polyomaviruses is associated with increased lung cancer risk in never smokers. Future research to evaluate relationship between polyomavirus infection and lung carcinogenesis should focus more on evaluating the presence of virus or viral nucleic acids (DNA or RNA) in lung tumour samples. JF - British journal of cancer AU - Malhotra, Jyoti AU - Waterboer, Tim AU - Pawlita, Michael AU - Michel, Angelika AU - Cai, Qiuyin AU - Zheng, Wei AU - Gao, Yu-Tang AU - Lan, Qing AU - Rothman, Nathaniel AU - Langseth, Hilde AU - Grimsrud, Tom K AU - Yuan, Jian-Min AU - Koh, Woon-Puay AU - Wang, Renwei AU - Arslan, Alan A AU - Zeleniuch-Jacquotte, Anne AU - Boffetta, Paolo AD - Icahn School of Medicine at Mount Sinai, 17 East 102 St, Floor 4 West, Room 110, New York, NY, USA. ; German Cancer Research Center (DKFZ), Heidelberg, Germany. ; Vanderbilt University School of Medicine, Nashville, TN, USA. ; Shanghai Cancer Institute, Shanghai, China. ; National Cancer Institute, Rockville, MD, USA. ; Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway. ; University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. ; Duke-NUS Graduate Medical School Singapore, and Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore. ; New York University School of Medicine, New York, NY, USA. Y1 - 2016/10/25/ PY - 2016 DA - 2016 Oct 25 SP - 1131 EP - 1139 VL - 115 IS - 9 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835683938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Serum+biomarkers+of+polyomavirus+infection+and+risk+of+lung+cancer+in+never+smokers.&rft.au=Malhotra%2C+Jyoti%3BWaterboer%2C+Tim%3BPawlita%2C+Michael%3BMichel%2C+Angelika%3BCai%2C+Qiuyin%3BZheng%2C+Wei%3BGao%2C+Yu-Tang%3BLan%2C+Qing%3BRothman%2C+Nathaniel%3BLangseth%2C+Hilde%3BGrimsrud%2C+Tom+K%3BYuan%2C+Jian-Min%3BKoh%2C+Woon-Puay%3BWang%2C+Renwei%3BArslan%2C+Alan+A%3BZeleniuch-Jacquotte%2C+Anne%3BBoffetta%2C+Paolo&rft.aulast=Malhotra&rft.aufirst=Jyoti&rft.date=2016-10-25&rft.volume=115&rft.issue=9&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=1532-1827&rft_id=info:doi/10.1038%2Fbjc.2016.285 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/bjc.2016.285 ER - TY - JOUR T1 - Nlrp12 mutation causes C57BL/6J strain-specific defect in neutrophil recruitment. AN - 1835640515; 27779193 AB - The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12. These results demonstrate that C57BL/6J mice have a functional defect in NLRP12 and that macrophages require NLRP12 expression for effective recruitment of neutrophils to inflammatory sites. JF - Nature communications AU - Ulland, Tyler K AU - Jain, Nidhi AU - Hornick, Emma E AU - Elliott, Eric I AU - Clay, Gwendolyn M AU - Sadler, Jeffrey J AU - Mills, Kathleen A M AU - Janowski, Ann M AU - Volk, A Paige Davis AU - Wang, Kai AU - Legge, Kevin L AU - Gakhar, Lokesh AU - Bourdi, Mohammed AU - Ferguson, Polly J AU - Wilson, Mary E AU - Cassel, Suzanne L AU - Sutterwala, Fayyaz S AD - Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa 52242, USA. ; Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. ; Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. Y1 - 2016/10/25/ PY - 2016 DA - 2016 Oct 25 SP - 13180 VL - 7 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835640515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Nlrp12+mutation+causes+C57BL%2F6J+strain-specific+defect+in+neutrophil+recruitment.&rft.au=Ulland%2C+Tyler+K%3BJain%2C+Nidhi%3BHornick%2C+Emma+E%3BElliott%2C+Eric+I%3BClay%2C+Gwendolyn+M%3BSadler%2C+Jeffrey+J%3BMills%2C+Kathleen+A+M%3BJanowski%2C+Ann+M%3BVolk%2C+A+Paige+Davis%3BWang%2C+Kai%3BLegge%2C+Kevin+L%3BGakhar%2C+Lokesh%3BBourdi%2C+Mohammed%3BFerguson%2C+Polly+J%3BWilson%2C+Mary+E%3BCassel%2C+Suzanne+L%3BSutterwala%2C+Fayyaz+S&rft.aulast=Ulland&rft.aufirst=Tyler&rft.date=2016-10-25&rft.volume=7&rft.issue=&rft.spage=13180&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms13180 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms13180 ER - TY - JOUR T1 - Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti-programed death-ligand 1 (Avelumab). AN - 1826742978; 27490642 AB - The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans. JF - AIDS (London, England) AU - Gill, Amanda L AU - Green, Samantha A AU - Abdullah, Shahed AU - Le Saout, Cecile AU - Pittaluga, Stefania AU - Chen, Hui AU - Turnier, Refika AU - Lifson, Jeffrey AU - Godin, Steven AU - Qin, Jing AU - Sneller, Michael C AU - Cuillerot, Jean-Marie AU - Sabzevari, Helen AU - Lane, H Clifford AU - Catalfamo, Marta AD - aCMRS/Laboratory of Immunoregulation, NIAID bLaboratory of Pathology, NCI, NIH, Bethesda cClinical Support Laboratory, Leidos Biomedical Research, Inc. dAIDS and Cancer Virus Program, Retroviral Pathogenesis Section, Leidos Biomedical Research, Frederick National Laboratory, Frederick eSmithers Avanza Toxicology Services, Gaithersburg fBiostatistics Research Branch, DCR, NIAID, NIH, Bethesda, Maryland gEMD-Serono, Inc., Rockland hCompass Therapeutics, Cambridge, Massachusetts, USA. *Amanda L. Gill and Samantha A. Green contributed equally to the article. Y1 - 2016/10/23/ PY - 2016 DA - 2016 Oct 23 SP - 2487 EP - 2493 VL - 30 IS - 16 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826742978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Programed+death-1%2Fprogramed+death-ligand+1+expression+in+lymph+nodes+of+HIV+infected+patients%3A+results+of+a+pilot+safety+study+in+rhesus+macaques+using+anti-programed+death-ligand+1+%28Avelumab%29.&rft.au=Gill%2C+Amanda+L%3BGreen%2C+Samantha+A%3BAbdullah%2C+Shahed%3BLe+Saout%2C+Cecile%3BPittaluga%2C+Stefania%3BChen%2C+Hui%3BTurnier%2C+Refika%3BLifson%2C+Jeffrey%3BGodin%2C+Steven%3BQin%2C+Jing%3BSneller%2C+Michael+C%3BCuillerot%2C+Jean-Marie%3BSabzevari%2C+Helen%3BLane%2C+H+Clifford%3BCatalfamo%2C+Marta&rft.aulast=Gill&rft.aufirst=Amanda&rft.date=2016-10-23&rft.volume=30&rft.issue=16&rft.spage=2487&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=1473-5571&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex. AN - 1835441586; 27746017 AB - Caspase-8 activation can be triggered by death receptor-mediated formation of the death-inducing signaling complex (DISC) and by the inflammasome adaptor ASC. Caspase-8 assembles with FADD at the DISC and with ASC at the inflammasome through its tandem death effector domain (tDED), which is regulated by the tDED-containing cellular inhibitor cFLIP and the viral inhibitor MC159. Here we present the caspase-8 tDED filament structure determined by cryoelectron microscopy. Extensive assembly interfaces not predicted by the previously proposed linear DED chain model were uncovered, and were further confirmed by structure-based mutagenesis in filament formation in vitro and Fas-induced apoptosis and ASC-mediated caspase-8 recruitment in cells. Structurally, the two DEDs in caspase-8 use quasi-equivalent contacts to enable assembly. Using the tDED filament structure as a template, structural analyses reveal the interaction surfaces between FADD and caspase-8 and the distinct mechanisms of regulation by cFLIP and MC159 through comingling and capping, respectively. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Molecular cell AU - Fu, Tian-Min AU - Li, Yang AU - Lu, Alvin AU - Li, Zongli AU - Vajjhala, Parimala R AU - Cruz, Anthony C AU - Srivastava, Devendra B AU - DiMaio, Frank AU - Penczek, Pawel A AU - Siegel, Richard M AU - Stacey, Katryn J AU - Egelman, Edward H AU - Wu, Hao AD - Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. ; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia. ; Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. ; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX 77030, USA. ; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: wu@crystal.harvard.edu. Y1 - 2016/10/20/ PY - 2016 DA - 2016 Oct 20 SP - 236 EP - 250 VL - 64 IS - 2 KW - cFLIP KW - DISC KW - Fas KW - DED KW - MC159 KW - vFLIP KW - FADD KW - filament KW - death domain KW - caspase-8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835441586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cell&rft.atitle=Cryo-EM+Structure+of+Caspase-8+Tandem+DED+Filament+Reveals+Assembly+and+Regulation+Mechanisms+of+the+Death-Inducing+Signaling+Complex.&rft.au=Fu%2C+Tian-Min%3BLi%2C+Yang%3BLu%2C+Alvin%3BLi%2C+Zongli%3BVajjhala%2C+Parimala+R%3BCruz%2C+Anthony+C%3BSrivastava%2C+Devendra+B%3BDiMaio%2C+Frank%3BPenczek%2C+Pawel+A%3BSiegel%2C+Richard+M%3BStacey%2C+Katryn+J%3BEgelman%2C+Edward+H%3BWu%2C+Hao&rft.aulast=Fu&rft.aufirst=Tian-Min&rft.date=2016-10-20&rft.volume=64&rft.issue=2&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=1097-4164&rft_id=info:doi/10.1016%2Fj.molcel.2016.09.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.molcel.2016.09.009 ER - TY - JOUR T1 - Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer: innovation and implementation, June 16th and 17th 2016, Trondheim, Norway. AN - 1835495053; 27756323 AB - The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation and Implementation", was held June 16th and 17th 2016, at the Knowledge Center of the St. Olavs Hospital in Trondheim, Norway, under the auspices of the Norwegian University of Science and Technology (NTNU) and the HUNT biobank and research center. The Symposium attracted approximately 100 attendees and invited speakers from 12 countries and 4 continents. In this Symposium original research and overviews on diagnostic, predictive and prognostic cancer biomarkers in serum, plasma, urine, pleural fluid and tumor, circulating tumor cells and bioinformatics as well as how to implement biomarkers in clinical trials were presented. Senior researchers and young investigators presented, reviewed and vividly discussed important new developments in the field of clinical biomarkers of cancer, with the goal of accelerating biomarker research and implementation. The excerpts of this symposium aim to give a cutting-edge overview and insight on some highly important aspects of clinical cancer biomarkers to-date to connect molecular innovation with clinical implementation to eventually improve patient care. JF - Journal of translational medicine AU - Robles, Ana I AU - Olsen, Karina Standahl AU - Tsui, Dana W T AU - Georgoulias, Vassilis AU - Creaney, Jenette AU - Dobra, Katalin AU - Vyberg, Mogens AU - Minato, Nagahiro AU - Anders, Robert A AU - Børresen-Dale, Anne-Lise AU - Zhou, Jianwei AU - Sætrom, Pål AU - Nielsen, Boye Schnack AU - Kirschner, Michaela B AU - Krokan, Hans E AU - Papadimitrakopoulou, Vassiliki AU - Tsamardinos, Ioannis AU - Røe, Oluf D AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, USA. ; Department of Community Medicine, UiT The Artic University of Norway, Tromsø, Norway. ; Department of Pathology and Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, USA. ; Department of Medical Oncology, School of MedicineUniversity of Crete, Heraklion, Greece. ; National Centre for Asbestos Related Disease, University of Western Australia, Perth, Australia. ; Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. ; Department of Clinical Medicine, Institute of Pathology, Aalborg University Hospital, Aalborg University, Aalborg, Denmark. ; Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ; Department of Pathology, Johns Hopkins University, Baltimore, USA. ; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. ; Department of Molecular Cell Biology & Toxicology, Cancer Center School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. ; Department of Computer and Information Science, NTNU, Trondheim, Norway. ; Molecular Histology Bioneer A/S, Hørsholm, Denmark. ; Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland. ; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. ; Department of Thoracic/Head and Neck Medical Oncology, MD Anderson, Houston, USA. ; Department of Computer Science, University of Crete, Heraklion, Greece. ; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. oluf.roe@ntnu.no. Y1 - 2016/10/19/ PY - 2016 DA - 2016 Oct 19 SP - 295 VL - 14 IS - 1 KW - Early diagnosis KW - Circulating biomarkers KW - Bioinformatics KW - DNA repair KW - Circulating tumor cells KW - Early detection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835495053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+translational+medicine&rft.atitle=Excerpts+from+the+1st+international+NTNU+symposium+on+current+and+future+clinical+biomarkers+of+cancer%3A+innovation+and+implementation%2C+June+16th+and+17th+2016%2C+Trondheim%2C+Norway.&rft.au=Robles%2C+Ana+I%3BOlsen%2C+Karina+Standahl%3BTsui%2C+Dana+W+T%3BGeorgoulias%2C+Vassilis%3BCreaney%2C+Jenette%3BDobra%2C+Katalin%3BVyberg%2C+Mogens%3BMinato%2C+Nagahiro%3BAnders%2C+Robert+A%3BB%C3%B8rresen-Dale%2C+Anne-Lise%3BZhou%2C+Jianwei%3BS%C3%A6trom%2C+P%C3%A5l%3BNielsen%2C+Boye+Schnack%3BKirschner%2C+Michaela+B%3BKrokan%2C+Hans+E%3BPapadimitrakopoulou%2C+Vassiliki%3BTsamardinos%2C+Ioannis%3BR%C3%B8e%2C+Oluf+D&rft.aulast=Robles&rft.aufirst=Ana&rft.date=2016-10-19&rft.volume=14&rft.issue=1&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Journal+of+translational+medicine&rft.issn=1479-5876&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2. AN - 1835453279; 27752141 AB - Elevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site. Direct binding of HNF4α to Agxt2 promoter was confirmed by chromatin immunoprecipitation assay. siRNA-mediated knockdown of Hnf4a led to an almost 50% reduction in Agxt2 mRNA levels in Hepa 1-6 cells. Liver-specific Hnf4a knockout mice exhibited a 90% decrease in liver Agxt2 expression and activity, and elevated plasma levels of ADMA, SDMA and BAIB, compared to wild-type littermates. Thus we identified HNF4α as a major regulator of Agxt2 expression. Considering a strong association between human HNF4A polymorphisms and increased risk of type 2 diabetes our current findings suggest that downregulation of AGXT2 and subsequent impairment in metabolism of dimethylarginines and BAIB caused by HNF4α deficiency might contribute to development of cardiovascular complications in diabetic patients. JF - Scientific reports AU - Burdin, Dmitry V AU - Kolobov, Alexey A AU - Brocker, Chad AU - Soshnev, Alexey A AU - Samusik, Nikolay AU - Demyanov, Anton V AU - Brilloff, Silke AU - Jarzebska, Natalia AU - Martens-Lobenhoffer, Jens AU - Mieth, Maren AU - Maas, Renke AU - Bornstein, Stefan R AU - Bode-Böger, Stefanie M AU - Gonzalez, Frank AU - Weiss, Norbert AU - Rodionov, Roman N AD - Department of Physiology, Saint Petersburg State University, 199034 Saint Petersburg, Russia. ; Department of Biochemistry, Saint Petersburg State University, 199034 Saint Petersburg, Russia. ; National Cancer Institute, NIH, Bethesda, MD, 20892, USA. ; The Rockefeller University, New York, NY, 10065, USA. ; Stanford University School of Medicine, Stanford, CA, 94305, USA. ; Institute of Highly Pure Biopreparations, 197110 Saint Petersburg, Russia. ; University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany. ; Institute of Clinical Pharmacology, Otto-von-Guericke University, 39120 Magdeburg, Germany. ; Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany. ; Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany. Y1 - 2016/10/18/ PY - 2016 DA - 2016 Oct 18 SP - 35503 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835453279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Diabetes-linked+transcription+factor+HNF4%CE%B1+regulates+metabolism+of+endogenous+methylarginines+and+%CE%B2-aminoisobutyric+acid+by+controlling+expression+of+alanine-glyoxylate+aminotransferase+2.&rft.au=Burdin%2C+Dmitry+V%3BKolobov%2C+Alexey+A%3BBrocker%2C+Chad%3BSoshnev%2C+Alexey+A%3BSamusik%2C+Nikolay%3BDemyanov%2C+Anton+V%3BBrilloff%2C+Silke%3BJarzebska%2C+Natalia%3BMartens-Lobenhoffer%2C+Jens%3BMieth%2C+Maren%3BMaas%2C+Renke%3BBornstein%2C+Stefan+R%3BBode-B%C3%B6ger%2C+Stefanie+M%3BGonzalez%2C+Frank%3BWeiss%2C+Norbert%3BRodionov%2C+Roman+N&rft.aulast=Burdin&rft.aufirst=Dmitry&rft.date=2016-10-18&rft.volume=6&rft.issue=&rft.spage=35503&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep35503 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep35503 ER - TY - JOUR T1 - Metabolism disrupting chemicals and metabolic disorders. AN - 1835506017; 27760374 AB - The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations. Published by Elsevier Inc. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Heindel, Jerrold J AU - Blumberg, Bruce AU - Cave, Mathew AU - Machtinger, Ronit AU - Mantovani, Alberto AU - Mendez, Michelle A AU - Nadal, Angel AU - Palanza, Paola AU - Panzica, Giancarlo AU - Sargis, Robert AU - Vandenberg, Laura N AU - Vom Saal, Frederick AD - National Institute of Environmental Health Sciences, Division of Extramural Research and Training Research Triangle Park, NC, USA. Electronic address: heindelj@niehs.nih.gov. ; University of California, Department of Developmental and Cell Biology, Irvine CA, USA. ; University of Louisville, Division of Gastroenterology, Hepatology and Nutrition, Louisville KY, USA. ; Sheba Medical Center and Tel Aviv University, Tel Aviv, Israel. ; Instituto Superiore di Sanita, Rome, Italy. ; University of North Carolina at Chapel Hill, School of Public Health, Chapel Hill NC, USA. ; Institute of Bioengineering and CIBERDEM, Miguel Hernandez University of Elche, Elche, Alicante, Spain. ; University of Parma, Department of Neurosciences, Parma, Italy. ; University of Turin, Department of Neuroscience and Neuroscience Institute Cavalieri Ottolenghi (NICO), Turin, Italy. ; University of Chicago, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine Chicago, IL, USA. ; University of Massachusetts, Department of Environmental Health Sciences, School of Public Health & Health Sciences, Amherst, MA, USA. ; University of Missouri, Department of Biological Sciences, Columbia, MO, USA. Y1 - 2016/10/17/ PY - 2016 DA - 2016 Oct 17 KW - Obesity KW - Lipid disorders KW - Metabolism disruptors KW - Obesogens KW - Endocrine disruptors KW - Developmental origins of health and disease KW - Diabetes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835506017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Metabolism+disrupting+chemicals+and+metabolic+disorders.&rft.au=Heindel%2C+Jerrold+J%3BBlumberg%2C+Bruce%3BCave%2C+Mathew%3BMachtinger%2C+Ronit%3BMantovani%2C+Alberto%3BMendez%2C+Michelle+A%3BNadal%2C+Angel%3BPalanza%2C+Paola%3BPanzica%2C+Giancarlo%3BSargis%2C+Robert%3BVandenberg%2C+Laura+N%3BVom+Saal%2C+Frederick&rft.aulast=Heindel&rft.aufirst=Jerrold&rft.date=2016-10-17&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=1873-1708&rft_id=info:doi/10.1016%2Fj.reprotox.2016.10.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.reprotox.2016.10.001 ER - TY - JOUR T1 - Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease. AN - 1835437487; 27748623 AB - Rationale Lengthy multi-drug, toxic, and low efficacy regimens limit management of pulmonary nontuberculous mycobacterial (PNTM) disease. Objective This phase 2 study investigated efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory PNTM (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multi-drug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. Primary endpoint was change from baseline to day 84 on a semi-quantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute walk distance, and adverse events. Measurements and Main Results Modified intent-to-treat population included 89 (LAI=44; placebo=45) patients. Average age was 59 years, 88% were female, 92% were Caucasian; 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. Primary endpoint was not achieved (P=0.072); however, a greater proportion of the LAI group demonstrated ≥1 negative sputum cultures (32% [14/44] vs. 9% [4/45]; P=0.006) and improvement in 6-minute walk test (+20.6 vs. -25.0 meters; P=0.017) at day 84. Treatment effect was predominantly in patients without cystic fibrosis with MAC and was sustained 1 year post-LAI. Most adverse events were respiratory and in some patients led to drug discontinuation. Conclusions Although the primary endpoint was not reached, LAI added to a multi-drug regimen produced improvements in sputum conversion and 6-minute walk distance vs. placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research is needed. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01315236. JF - American journal of respiratory and critical care medicine AU - Olivier, Kenneth N AU - Griffith, David E AU - Eagle, Gina AU - McGinnis Ii, John P AU - Micioni, Liza AU - Liu, Keith AU - Daley, Charles L AU - Winthrop, Kevin L AU - Ruoss, Stephen AU - Addrizzo-Harris, Doreen J AU - Flume, Patrick A AU - Dorgan, Daniel AU - Salathe, Matthias AU - Brown-Elliott, Barbara A AU - Gupta, Renu AU - Wallace, Richard J AD - NHLBI, Cardiovascular and Pulmonary Branch, Bethesda, Maryland, United States ; olivierk@nhlbi.nih.gov. ; UTHC, Tyler, Texas, United States ; david.griffith@uthct.edu. ; Insmed Incorporated, Bridgewater, New Jersey, United States ; gina.eagle@insmed.com. ; Insmed Incorporated, Bridgewater, New Jersey, United States ; john.McGinnis@insmed.com. ; Insmed Incorporated, Bridgewater, New Jersey, United States ; liza.micioni@insmed.com. ; Insmed Incorporated, Bridgewater, New Jersey, United States ; keith.liu@insmed.com. ; National Jewish Health, Medicine, Denver, Colorado, United States ; daleyc@njhealth.org. ; Oregon Health & Sciences University, Infectious Diseases, Public Health and Preventive Medicine, Portland, Oregon, United States ; winthrop@ohsu.edu. ; Stanford University, Medicine, Stanford, California, United States ; ruoss@stanford.edu. ; NYU School of Medicine, New York, New York, United States ; Doreen.addrizzo@nyumc.org. ; Medical University of South Carolina, Medicine, Charleston, South Carolina, United States ; flumepa@musc.edu. ; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States ; daniel.dorgan@uphs.upenn.edu. ; University of Miami, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Miller School of Medicine, Miami, Florida, United States ; msalathe@med.miami.edu. ; The University of Texas Health Science Center at Tyler, Microbiology, BMR-2, Tyler, Texas, United States ; Barbara.Elliott@uthct.edu. ; Global Biopharma, Moorestown, New Jersey, United States ; renu.gupta@medstech.com. ; The University of Texas Healh Science Center at Tyler, Microbiology, Tyler, Texas, United States ; richard.wallace@uthct.edu. Y1 - 2016/10/17/ PY - 2016 DA - 2016 Oct 17 KW - Efficacy KW - Safety KW - Culture conversion KW - Phase 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835437487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+and+critical+care+medicine&rft.atitle=Randomized+Trial+of+Liposomal+Amikacin+for+Inhalation+in+Nontuberculous+Mycobacterial+Lung+Disease.&rft.au=Olivier%2C+Kenneth+N%3BGriffith%2C+David+E%3BEagle%2C+Gina%3BMcGinnis+Ii%2C+John+P%3BMicioni%2C+Liza%3BLiu%2C+Keith%3BDaley%2C+Charles+L%3BWinthrop%2C+Kevin+L%3BRuoss%2C+Stephen%3BAddrizzo-Harris%2C+Doreen+J%3BFlume%2C+Patrick+A%3BDorgan%2C+Daniel%3BSalathe%2C+Matthias%3BBrown-Elliott%2C+Barbara+A%3BGupta%2C+Renu%3BWallace%2C+Richard+J&rft.aulast=Olivier&rft.aufirst=Kenneth&rft.date=2016-10-17&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+and+critical+care+medicine&rft.issn=1535-4970&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Adrenocortical Cancer: A Molecularly Complex Disease Where Surgery Matters AN - 1837333100; PQ0003805948 AB - The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered adrenolytic, is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection. Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date, no targeted therapy has achieved meaningful outcomes. Consequently, first-line therapy for metastatic disease remains a combination regimen of etoposide, doxorubicin, and cisplatinum established in a randomized clinical trial. In addition to evaluating recent studies in adrenocortical cancer, we raise one critical clinical issuethe risk of peritoneal dissemination following laparoscopic resection of adrenocortical cancer. In a retrospective case series of 267 patients referred to the NCI for the treatment of recurrent or advanced adrenocortical cancer, we found extensive peritoneal dissemination in 25 of the 45 patients (55.6) who had undergone laparoscopic resection, compared with only 7 of the 222 patients (3) who had undergone an open resection (P < 0.0001). Although this has been debated in the literature, our data argue for an end to laparoscopic resection of adrenocortical cancers to avoid peritoneal dissemination, a complication of laparoscopy that is uniformly fatal. Clin Cancer Res; 22(20); 49895000. 2016 AACR. JF - Clinical Cancer Research AU - Payabyab, Eden C AU - Balasubramaniam, Sanjeeve AU - Edgerly, Maureen AU - Velarde, Margarita AU - Merino, Maria J AU - Venkatesan, Aradhana M AU - Leuva, Harshraj AU - Litman, Thomas AU - Bates, Susan E AU - Fojo, Tito AD - Surgery Branch and Thoracic & GI Oncology Branch, NCI, NIH, Bethesda, Maryland, atf2116@cumc.columbia.edu Y1 - 2016/10/15/ PY - 2016 DA - 2016 Oct 15 SP - 4989 EP - 5000 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 20 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Metastases KW - Data processing KW - Laparoscopy KW - Surgery KW - Peritoneum KW - Drug development KW - Adjuvants KW - Clinical trials KW - Etoposide KW - Cancer KW - Doxorubicin KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837333100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Adrenocortical+Cancer%3A+A+Molecularly+Complex+Disease+Where+Surgery+Matters&rft.au=Payabyab%2C+Eden+C%3BBalasubramaniam%2C+Sanjeeve%3BEdgerly%2C+Maureen%3BVelarde%2C+Margarita%3BMerino%2C+Maria+J%3BVenkatesan%2C+Aradhana+M%3BLeuva%2C+Harshraj%3BLitman%2C+Thomas%3BBates%2C+Susan+E%3BFojo%2C+Tito&rft.aulast=Payabyab&rft.aufirst=Eden&rft.date=2016-10-15&rft.volume=22&rft.issue=20&rft.spage=4989&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-1570 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Metastases; Data processing; Laparoscopy; Surgery; Peritoneum; Drug development; Adjuvants; Etoposide; Clinical trials; Doxorubicin; Cancer DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-1570 ER - TY - JOUR T1 - Progress in Endocrine Neoplasia AN - 1837329868; PQ0003805940 AB - Most endocrine tumors are benign, and afflicted patients usually seek medical advice because of symptoms caused by too much, or too little, native hormone secretion or the impingement of their tumor on a vital structure. Malignant endocrine tumors represent a more serious problem, and patient cure often depends on early diagnosis and treatment. The recent development of novel molecular therapeutics holds great promise for the treatment of patients with locally advanced or metastatic endocrine cancer. In this CCR Focus, expert clinical investigators describe the molecular characteristics of various endocrine tumors and discuss the current status of diagnosis and treatment. Clin Cancer Res; 22(20); 49818. 2016 AACR. JF - Clinical Cancer Research AU - Wells, Samuel A AD - Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Y1 - 2016/10/15/ PY - 2016 DA - 2016 Oct 15 SP - 4981 EP - 4988 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 20 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Metastases KW - Secretion KW - Tumors KW - Hormones KW - Cancer KW - Neoplasia KW - Benign KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837329868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Progress+in+Endocrine+Neoplasia&rft.au=Wells%2C+Samuel+A&rft.aulast=Wells&rft.aufirst=Samuel&rft.date=2016-10-15&rft.volume=22&rft.issue=20&rft.spage=4981&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0384 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Metastases; Secretion; Tumors; Hormones; Neoplasia; Cancer; Benign DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0384 ER - TY - JOUR T1 - Pheochromocytoma: The First Metabolic Endocrine Cancer AN - 1837312680; PQ0003805964 AB - Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics has allowed us to take a closer look at the metabolic changes present in pheochromocytomas (PHEO) and paragangliomas (PGL). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOsPGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies. Clin Cancer Res; 22(20); 500111. 2016 AACR. JF - Clinical Cancer Research AU - Jochmanova, Ivana AU - Pacak, Karel AD - First Department of Internal Medicine, Medical Faculty of P.J. afrik University in Koice, Koice, Slovakia, karel@mail.nih.gov Y1 - 2016/10/15/ PY - 2016 DA - 2016 Oct 15 SP - 5001 EP - 5011 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 20 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Cell survival KW - Invasiveness KW - Oxidative phosphorylation KW - Respiration KW - Tumorigenesis KW - Mitochondria KW - Enzymes KW - biomarkers KW - Pheochromocytoma KW - Cancer KW - Paraganglioma KW - Metabolic pathways KW - Cell proliferation KW - Tricarboxylic acid cycle KW - Glycolysis KW - Mutation KW - metabolomics KW - Neuroendocrine tumors KW - Signal transduction KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837312680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Pheochromocytoma%3A+The+First+Metabolic+Endocrine+Cancer&rft.au=Jochmanova%2C+Ivana%3BPacak%2C+Karel&rft.aulast=Jochmanova&rft.aufirst=Ivana&rft.date=2016-10-15&rft.volume=22&rft.issue=20&rft.spage=5001&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0606 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Cell survival; Invasiveness; Oxidative phosphorylation; Respiration; Tumorigenesis; Enzymes; Mitochondria; biomarkers; Cancer; Pheochromocytoma; Paraganglioma; Metabolic pathways; Tricarboxylic acid cycle; Cell proliferation; Mutation; Glycolysis; Neuroendocrine tumors; metabolomics; Signal transduction DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0606 ER - TY - JOUR T1 - Anthrax Toxin Protective Antigen Variants That Selectively Utilize either the CMG2 or TEM8 Receptors for Cellular Uptake and Tumor Targeting. AN - 1835416301; 27555325 AB - The protective antigen (PA) moiety of anthrax toxin binds to cellular receptors and mediates the translocation of the two enzymatic moieties of the toxin to the cytosol. Two PA receptors are known, with capillary morphogenesis protein 2 (CMG2) being the more important for pathogenesis and tumor endothelial marker 8 (TEM8) playing a minor role. The C-terminal PA domain 4 (PAD4) has extensive interactions with the receptors and is required for binding. Our previous study identified PAD4 variants having enhanced TEM8 binding specificity. To obtain PA variants that selectively bind to CMG2, here we performed phage display selections using magnetic beads having bound CMG2. We found that PA residue isoleucine 656 plays a critical role in PA binding to TEM8 but has a much lesser effect on PA binding to CMG2. We further characterized the role of residue 656 in distinguishing PA binding to CMG2 versus TEM8 by substituting it with the other 19 amino acids. Of the resulting variants, PA I656Q and PA I656V had significantly reduced activity on TEM8-expressing CHO cells but maintained their activity on CMG2-expressing CHO cells. The preference of these PA mutants for CMG2 over TEM8 was further demonstrated using mouse embryonic fibroblast cells and mice deficient in the CMG2 and/or the TEM8 receptors. The structural basis of the alterations in the receptor binding activities of these mutants is also discussed. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Chen, Kuang-Hua AU - Liu, Shihui AU - Leysath, Clinton E AU - Miller-Randolph, Sharmina AU - Zhang, Yi AU - Fattah, Rasem AU - Bugge, Thomas H AU - Leppla, Stephen H AD - From the Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892-3202 and. ; From the Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892-3202 and the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892. ; the Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892. ; From the Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892-3202 and sleppla@niaid.nih.gov. Y1 - 2016/10/14/ PY - 2016 DA - 2016 Oct 14 SP - 22021 EP - 22029 VL - 291 IS - 42 KW - TEM8 KW - mutagenesis in vitro KW - receptor KW - protective antigen KW - CMG2 KW - anthrax toxin KW - tumor therapy KW - phage display UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835416301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Anthrax+Toxin+Protective+Antigen+Variants+That+Selectively+Utilize+either+the+CMG2+or+TEM8+Receptors+for+Cellular+Uptake+and+Tumor+Targeting.&rft.au=Chen%2C+Kuang-Hua%3BLiu%2C+Shihui%3BLeysath%2C+Clinton+E%3BMiller-Randolph%2C+Sharmina%3BZhang%2C+Yi%3BFattah%2C+Rasem%3BBugge%2C+Thomas+H%3BLeppla%2C+Stephen+H&rft.aulast=Chen&rft.aufirst=Kuang-Hua&rft.date=2016-10-14&rft.volume=291&rft.issue=42&rft.spage=22021&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-24 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - 1TZN; PDB N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Are prenatal mercury levels associated with subsequent blood pressure in childhood and adolescence? The Avon prebirth cohort study. AN - 1835414344; 27742626 AB - There have been conflicting data suggesting that prenatal mercury exposure is associated with adverse cardiovascular measures in children. We therefore analysed a large prospective population study to investigate whether prenatal mercury exposure might influence offspring blood pressure (BP) and heart rate adversely. Prospective birth cohort. The Avon Longitudinal Study of Parents and Children (ALSPAC). Maternal whole blood collected in the first half of pregnancy was assayed for mercury and selenium. The offspring were followed throughout childhood and adolescence. Offspring resting BP and heart rates measured under standard conditions on six occasions between ages 7 and 17 years (numbers analysed: 1754 at 7 years to 1102 at 17). Statistical analyses took account of various factors present in pregnancy, including family adversity, maternal age, parity, smoking and alcohol intake. Unadjusted and adjusted regression analyses assessed the relationship between maternal prenatal mercury levels and offspring resting systolic and diastolic BP, and heart rates. A final set of analyses took account of selenium. Each analysis was carried out for all offspring, those whose mothers had, and those that had not, consumed fish during pregnancy. Further analysis for all offspring ascertained whether there were significant interaction effects between the sexes. There was little evidence to suggest that prenatal mercury exposure resulted in a clinically important increase in offspring BP in the whole group, since no effect size for an increase of 1 SD of blood mercury level was >0.3 mm Hg. Only 1 association was significant at p<0.05 and therefore likely due to chance. This study reveals no evidence to support the hypothesis that prenatal mercury exposure has adverse long-term effects on offspring BP or heart rates during childhood or adolescence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. JF - BMJ open AU - Gregory, Steve AU - Iles-Caven, Yasmin AU - Hibbeln, Joseph R AU - Taylor, Caroline M AU - Golding, Jean AD - Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol, UK. ; Department of Nutritional Neurosciences, LMBB, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/10/14/ PY - 2016 DA - 2016 Oct 14 SP - 1 VL - 6 IS - 10 KW - Selenium KW - Cardiovascular system KW - PUBLIC HEALTH KW - ALSPAC KW - Prenatal mercury KW - TOXICOLOGY UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835414344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMJ+open&rft.atitle=Are+prenatal+mercury+levels+associated+with+subsequent+blood+pressure+in+childhood+and+adolescence%3F+The+Avon+prebirth+cohort+study.&rft.au=Gregory%2C+Steve%3BIles-Caven%2C+Yasmin%3BHibbeln%2C+Joseph+R%3BTaylor%2C+Caroline+M%3BGolding%2C+Jean&rft.aulast=Gregory&rft.aufirst=Steve&rft.date=2016-10-14&rft.volume=6&rft.issue=10&rft.spage=e012425&rft.isbn=&rft.btitle=&rft.title=BMJ+open&rft.issn=2044-6055&rft_id=info:doi/10.1136%2Fbmjopen-2016-012425 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/bmjopen-2016-012425 ER - TY - JOUR T1 - Molecular signatures associated with ZIKV exposure in human cortical neural progenitors. AN - 1835413001; 27580721 AB - Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function is unclear. Here we systematically profiled transcriptomes of human neural progenitor cells exposed to Asian ZIKVC, African ZIKVM, and dengue virus (DENV). In contrast to the robust global transcriptome changes induced by DENV, ZIKV has a more selective and larger impact on expression of genes involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes and TP53. P53 inhibitors can block the apoptosis induced by both ZIKVC and ZIKVM in hNPCs, with higher potency against ZIKVC-induced apoptosis. Our analyses reveal virus- and strain-specific molecular signatures associated with ZIKV infection. These datasets will help to investigate ZIKV-host interactions and identify neurovirulence determinants of ZIKV. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. JF - Nucleic acids research AU - Zhang, Feiran AU - Hammack, Christy AU - Ogden, Sarah C AU - Cheng, Yichen AU - Lee, Emily M AU - Wen, Zhexing AU - Qian, Xuyu AU - Nguyen, Ha Nam AU - Li, Yujing AU - Yao, Bing AU - Xu, Miao AU - Xu, Tianlei AU - Chen, Li AU - Wang, Zhiqin AU - Feng, Hao AU - Huang, Wei-Kai AU - Yoon, Ki-Jun AU - Shan, Chao AU - Huang, Luoxiu AU - Qin, Zhaohui AU - Christian, Kimberly M AU - Shi, Pei-Yong AU - Xu, Mingjiang AU - Xia, Menghang AU - Zheng, Wei AU - Wu, Hao AU - Song, Hongjun AU - Tang, Hengli AU - Ming, Guo-Li AU - Jin, Peng AD - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. ; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Departments of Psychiatry and Behavioral Science, Cell Biology, and Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Biomedical Engineering Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892, USA. ; Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; Department of Biochemistry & Molecular Biology, Department of Pharmacology & Toxicology, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA. ; Sylvester Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA shongju1@jhmi.edu. ; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA tang@bio.fsu.edu. ; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA gming1@jhmi.edu. ; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA peng.jin@emory.edu. Y1 - 2016/10/14/ PY - 2016 DA - 2016 Oct 14 SP - 8610 EP - 8620 VL - 44 IS - 18 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835413001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Molecular+signatures+associated+with+ZIKV+exposure+in+human+cortical+neural+progenitors.&rft.au=Zhang%2C+Feiran%3BHammack%2C+Christy%3BOgden%2C+Sarah+C%3BCheng%2C+Yichen%3BLee%2C+Emily+M%3BWen%2C+Zhexing%3BQian%2C+Xuyu%3BNguyen%2C+Ha+Nam%3BLi%2C+Yujing%3BYao%2C+Bing%3BXu%2C+Miao%3BXu%2C+Tianlei%3BChen%2C+Li%3BWang%2C+Zhiqin%3BFeng%2C+Hao%3BHuang%2C+Wei-Kai%3BYoon%2C+Ki-Jun%3BShan%2C+Chao%3BHuang%2C+Luoxiu%3BQin%2C+Zhaohui%3BChristian%2C+Kimberly+M%3BShi%2C+Pei-Yong%3BXu%2C+Mingjiang%3BXia%2C+Menghang%3BZheng%2C+Wei%3BWu%2C+Hao%3BSong%2C+Hongjun%3BTang%2C+Hengli%3BMing%2C+Guo-Li%3BJin%2C+Peng&rft.aulast=Zhang&rft.aufirst=Feiran&rft.date=2016-10-14&rft.volume=44&rft.issue=18&rft.spage=8610&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 ER - TY - JOUR T1 - Evaluation of Chromane-Based Bryostatin Analogues Prepared via Hydrogen-Mediated C-C Bond Formation: Potency Does Not Confer Bryostatin-like Biology. AN - 1835418087; 27676096 AB - The synthesis and biological evaluation of chromane-containing bryostatin analogues WN-2-WN-7 and the previously reported salicylate-based analogue WN-8 are described. Analogues WN-2-WN-7 are prepared through convergent assembly of the chromane-containing fragment B-I with the "binding domain" fragment A-I or its C26-des-methyl congener, fragment A-II. The synthesis of fragment B-I features enantioselective double C-H allylation of 1,3-propanediol to form the C2-symmetric diol 3 and Heck cyclization of bromo-diene 5 to form the chromane core. The synthesis of salicylate WN-8 is accomplished through the union of fragments A-III and B-II. The highest binding affinities for PKCα are observed for the C26-des-methyl analogues WN-3 (Ki = 63.9 nM) and WN-7 (Ki = 63.1 nM). All analogues, WN-2-WN-8, inhibited growth of Toledo cells, with the most potent analogue being WN-7. This response, however, does not distinguish between phorbol ester-like and bryostatin-like behavior. In contrast, while many of the analogues contain a conserved C-ring in the binding domain and other features common to analogues with bryostatin-like properties, all analogues evaluated in the U937 proliferation and cell attachment assays displayed phorbol ester-like and/or toxic behavior, including WN-8, for which "bryostatin-like PKC modulatory activities" previously was suggested solely on the basis of PKC binding. These results underscore the importance of considering downstream biological effects, as tumor suppression cannot be inferred from potent PKC binding. JF - Journal of the American Chemical Society AU - Ketcham, John M AU - Volchkov, Ivan AU - Chen, Te-Yu AU - Blumberg, Peter M AU - Kedei, Noemi AU - Lewin, Nancy E AU - Krische, Michael J AD - Department of Chemistry and Biochemistry, University of Texas at Austin , Austin, Texas 78712, United States. ; Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892-4255, United States. Y1 - 2016/10/12/ PY - 2016 DA - 2016 Oct 12 SP - 13415 EP - 13423 VL - 138 IS - 40 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835418087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.atitle=Evaluation+of+Chromane-Based+Bryostatin+Analogues+Prepared+via+Hydrogen-Mediated+C-C+Bond+Formation%3A+Potency+Does+Not+Confer+Bryostatin-like+Biology.&rft.au=Ketcham%2C+John+M%3BVolchkov%2C+Ivan%3BChen%2C+Te-Yu%3BBlumberg%2C+Peter+M%3BKedei%2C+Noemi%3BLewin%2C+Nancy+E%3BKrische%2C+Michael+J&rft.aulast=Ketcham&rft.aufirst=John&rft.date=2016-10-12&rft.volume=138&rft.issue=40&rft.spage=13415&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=1520-5126&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression. AN - 1835406907; 27728804 AB - Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce their immune-mediated clearance to prevent tumor initiation, a process termed "senescence surveillance." However, senescent hepatocytes give rise to hepatocellular carcinomas (HCCs), if the senescence program is bypassed or if senescent cells are not cleared. Here, we show context-specific roles for CCR2+ myeloid cells in liver cancer. Senescence surveillance requires the recruitment and maturation of CCR2+ myeloid cells, and CCR2 ablation caused outgrowth of HCC. In contrast, HCC cells block the maturation of recruited myeloid precursors, which, through NK cell inhibition, promote growth of murine HCC and worsen the prognosis and survival of human HCC patients. Thus, while senescent hepatocyte-secreted chemokines suppress liver cancer initiation, they may accelerate the growth of fully established HCC. Published by Elsevier Inc. JF - Cancer cell AU - Eggert, Tobias AU - Wolter, Katharina AU - Ji, Juling AU - Ma, Chi AU - Yevsa, Tetyana AU - Klotz, Sabrina AU - Medina-Echeverz, José AU - Longerich, Thomas AU - Forgues, Marshonna AU - Reisinger, Florian AU - Heikenwalder, Mathias AU - Wang, Xin Wei AU - Zender, Lars AU - Greten, Tim F AD - Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Division of Gastrointestinal Oncology, Department of Internal Medicine I, University of Tübingen, 72076 Tübingen, Germany. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Institute of Pathology, University Hospital RWTH Aachen, 52074 Aachen, Germany. ; Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Division of Gastrointestinal Oncology, Department of Internal Medicine I, University of Tübingen, 72076 Tübingen, Germany; Translational Gastrointestinal Oncology Group within the German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: lars.zender@med.uni-tuebingen.de. ; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tim.greten@nih.gov. Y1 - 2016/10/10/ PY - 2016 DA - 2016 Oct 10 SP - 533 EP - 547 VL - 30 IS - 4 KW - myeloid cells KW - MDSC KW - CCL2 KW - NK cells KW - CCR2 KW - senescence KW - macrophages KW - liver cancer KW - hepatocellular carcinoma KW - HCC UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835406907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Serum+androgens+and+prostate+cancer+risk%3A+results+from+the+placebo+arm+of+the+Prostate+Cancer+Prevention+Trial.&rft.au=Schenk%2C+Jeannette+M%3BTill%2C+Cathee%3BHsing%2C+Ann+W%3BStanczyk%2C+Frank+Z%3BGong%2C+Zhihong%3BNeuhouser%2C+Marian+L%3BReichardt%2C+Juergen+K%3BHoque%2C+Ashraful+M%3BFigg%2C+William+D%3BGoodman%2C+Phyllis+J%3BTangen%2C+Catherine+M%3BThompson%2C+Ian+M&rft.aulast=Schenk&rft.aufirst=Jeannette&rft.date=2016-02-01&rft.volume=27&rft.issue=2&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=1573-7225&rft_id=info:doi/10.1007%2Fs10552-015-0695-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ccell.2016.09.003 ER - TY - JOUR T1 - Irreversible inhibition of Δ16HER2 is necessary to suppress Δ16HER2-positive breast carcinomas resistant to Lapatinib. AN - 1818336924; 27475932 AB - HER2 tyrosine kinase receptor is a validated target in breast cancer therapy. However, increasing evidence points to a major role of Δ16HER2 splice variant commonly coexpressed with HER2 and identified as a clinically important HER2 molecular alteration promoting aggressive metastatic breast cancer. Consistently, mice transgenic for the human Δ16HER2 isoform (Δ16HER2 mice) develop invasive mammary carcinomas with early onset and 100% penetrance. The present study provides preclinical evidence that Δ16HER2 expression confers de novo resistance to standard anti-HER2-therapies such as Lapatinib and acquired resistance to the selective Src inhibitor Saracatinib in breast cancer. Of note, Dacomitinib, an irreversible small molecule pan-HER inhibitor, was able to completely suppress Δ16HER2-driven breast carcinogenesis. Thus, only Dacomitinib may offer benefit in this molecularly defined patient subset by irreversibly inhibiting Δ16HER2 activation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Cancer letters AU - Tilio, Martina AU - Gambini, Valentina AU - Wang, Junbiao AU - Garulli, Chiara AU - Kalogris, Cristina AU - Andreani, Cristina AU - Bartolacci, Caterina AU - Elexpuru Zabaleta, Maria AU - Pietrella, Lucia AU - Hysi, Albana AU - Iezzi, Manuela AU - Belletti, Barbara AU - Orlando, Fiorenza AU - Provinciali, Mauro AU - Galeazzi, Roberta AU - Marchini, Cristina AU - Amici, Augusto AD - Department of Biosciences and Veterinary Medicine, University of Camerino, Camerino 62032, Italy. ; Aging Research Centre, G. d'Annunzio University, Chieti 66100, Italy. ; Division of Experimental Oncology 2, Centro di Riferimento Oncologico, National Cancer Institute, Aviano 33081, Italy. ; Advanced Technology Center for Aging Research, IRCCS-INRCA, Ancona 60121, Italy. ; Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona 60128, Italy. ; Department of Biosciences and Veterinary Medicine, University of Camerino, Camerino 62032, Italy. Electronic address: cristina.marchini@unicam.it. ; Department of Biosciences and Veterinary Medicine, University of Camerino, Camerino 62032, Italy. Electronic address: augusto.amici@unicam.it. Y1 - 2016/10/10/ PY - 2016 DA - 2016 Oct 10 SP - 76 EP - 84 VL - 381 IS - 1 KW - Index Medicus KW - Δ16HER2 mice KW - Breast cancer KW - Targeted therapies KW - HER2 isoform KW - Drug resistances UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818336924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Irreversible+inhibition+of+%CE%9416HER2+is+necessary+to+suppress+%CE%9416HER2-positive+breast+carcinomas+resistant+to+Lapatinib.&rft.au=Tilio%2C+Martina%3BGambini%2C+Valentina%3BWang%2C+Junbiao%3BGarulli%2C+Chiara%3BKalogris%2C+Cristina%3BAndreani%2C+Cristina%3BBartolacci%2C+Caterina%3BElexpuru+Zabaleta%2C+Maria%3BPietrella%2C+Lucia%3BHysi%2C+Albana%3BIezzi%2C+Manuela%3BBelletti%2C+Barbara%3BOrlando%2C+Fiorenza%3BProvinciali%2C+Mauro%3BGaleazzi%2C+Roberta%3BMarchini%2C+Cristina%3BAmici%2C+Augusto&rft.aulast=Tilio&rft.aufirst=Martina&rft.date=2016-10-10&rft.volume=381&rft.issue=1&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=1872-7980&rft_id=info:doi/10.1016%2Fj.canlet.2016.07.028 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.canlet.2016.07.028 ER - TY - JOUR T1 - Trastuzumab cardiotoxicity: from clinical trials to experimental studies. AN - 1835401094; 27714776 AB - Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20 to 25% of human breast cancers, which is associated with aggressive tumour growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumours. Although initial trials indicated high efficacy and a favourable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in earlier trials utilizing trastuzumab. There has been ongoing debate on the cardiac safety of trastuzumab ever since, initiating numerous clinical and preclinical investigations to better understand the background of trastuzumab cardiotoxicity and evaluate its effects on patient morbidity. Here, we have given a comprehensive overview of our current knowledge on the cardiotoxicity of trastuzumab, primarily focusing on data from clinical trials and highlighting the main molecular mechanisms proposed. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - British journal of pharmacology AU - Nemeth, Balazs T AU - Varga, Zoltan V AU - Wu, Wen Jin AU - Pacher, Pal AD - Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. ; Division of Biotechnology Research and Review 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA. Y1 - 2016/10/07/ PY - 2016 DA - 2016 Oct 07 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835401094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Trastuzumab+cardiotoxicity%3A+from+clinical+trials+to+experimental+studies.&rft.au=Nemeth%2C+Balazs+T%3BVarga%2C+Zoltan+V%3BWu%2C+Wen+Jin%3BPacher%2C+Pal&rft.aulast=Nemeth&rft.aufirst=Balazs&rft.date=2016-10-07&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=1476-5381&rft_id=info:doi/10.1111%2Fbph.13643 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/bph.13643 ER - TY - JOUR T1 - Customizing Functionality and Payload Delivery for Receptor-Engineered T Cells. AN - 1834994935; 27716501 AB - Adoptive immunotherapy using receptor engineering to achieve specific tumor targeting by T cells holds much promise for advancing cancer therapy. Here, two studies by Boice et al. and Roybal et al. provide distinct and potentially complimentary approaches to improve the efficacy and curb potential toxicities of this approach. Published by Elsevier Inc. JF - Cell AU - Klebanoff, Christopher A AU - Restifo, Nicholas P AD - Center for Cell Engineering and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: caklebanoff@gmail.com. ; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: restifo@nih.gov. Y1 - 2016/10/06/ PY - 2016 DA - 2016 Oct 06 SP - 304 EP - 306 VL - 167 IS - 2 KW - Receptors, Antigen, T-Cell KW - 0 KW - Index Medicus KW - Humans KW - Neoplasms -- therapy KW - T-Lymphocytes KW - Immunotherapy, Adoptive UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1834994935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Customizing+Functionality+and+Payload+Delivery+for+Receptor-Engineered+T+Cells.&rft.au=Klebanoff%2C+Christopher+A%3BRestifo%2C+Nicholas+P&rft.aulast=Klebanoff&rft.aufirst=Christopher&rft.date=2016-10-06&rft.volume=167&rft.issue=2&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=1097-4172&rft_id=info:doi/10.1016%2Fj.cell.2016.09.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-01 N1 - Date created - 2016-10-07 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Comment On: Cell. 2016 Oct 6;167(2):405-418.e13 [27693350] Cell. 2016 Oct 6;167(2):419-432.e16 [27693353] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cell.2016.09.033 ER - TY - JOUR T1 - Olfactomedin 4 deletion induces colon adenocarcinoma in ApcMin/+ mice. AN - 1826659884; 26973250 AB - Colon carcinogenesis is a multiple-step process involving the accumulation of a series of genetic and epigenetic alterations. The most commonly initiating event of intestinal carcinogenesis is mutation of the adenomatous polyposis coli (APC) gene, which leads to activation of the Wnt/β-catenin pathway. Olfactomedin 4 (OLFM4) has emerged as an intestinal stem-cell marker, but its biological function in the intestine remains to be determined. Here we show that Olfm4 deletion induced colon adenocarcinoma in the distal colon of ApcMin/+ mice. Mechanistically, we found that OLFM4 is a target gene of the Wnt/β-catenin pathway and can downregulate β-catenin signaling by competing with Wnt ligands for binding to Frizzled receptors, as well as by inhibition of the Akt-GSK-3β (Akt-glycogen synthase kinase-3β) pathway. We have shown that both Wnt and nuclear factor-κB (NF-κB) signaling were boosted in tumor tissues of Apc Olfm4 double-mutant mice. These data establish OLFM4 as a critical negative regulator of the Wnt/β-catenin and NF-κB pathways that inhibits colon-cancer development initiated by APC mutation. In addition, Olfm4 deletion significantly enhanced intestinal-crypt proliferation and inflammation induced by azoxymethane/dextran sodium sulfate. Thus, OLFM4 has an important role in the regulation of intestinal inflammation and tumorigenesis, and could be a potential therapeutic target for intestinal malignant tumors. Unlike the human colonic epithelium, the mouse colonic epithelium does not express OLFM4, but nevertheless, systemic OLFM4 deletion promotes colon tumorigenesis and that loss from mucosal neutrophils may have a role to play. JF - Oncogene AU - Liu, W AU - Li, H AU - Hong, S-H AU - Piszczek, G P AU - Chen, W AU - Rodgers, G P AD - Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. ; Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, Bethesda, MD, USA. ; Genomic Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. Y1 - 2016/10/06/ PY - 2016 DA - 2016 Oct 06 SP - 5237 EP - 5247 VL - 35 IS - 40 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826659884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Olfactomedin+4+deletion+induces+colon+adenocarcinoma+in+ApcMin%2F%2B+mice.&rft.au=Liu%2C+W%3BLi%2C+H%3BHong%2C+S-H%3BPiszczek%2C+G+P%3BChen%2C+W%3BRodgers%2C+G+P&rft.aulast=Liu&rft.aufirst=W&rft.date=2016-10-06&rft.volume=35&rft.issue=40&rft.spage=5237&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2016.58 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-03-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2016.58 ER - TY - JOUR T1 - New Generation of Gold Nanoshell-Coated Esophageal Stent: Preparation and Biomedical Applications. AN - 1835354994; 27684285 AB - Esophageal cancer is one of the six most common cancers in the world, constituting ∼7% of the gastrointestinal cancers. Esophageal stents can be inserted into the esophagus to open the pathway as a palliative treatment for advanced esophageal cancer. For the treatment of esophageal cancer, a series of anticancer drug-loaded stents such as paclitaxel or 5-fluorouracil/esophageal stent combinations have been prepared by covering a nitinol stent with a polymer or hydrogel shell. For the first time, we developed a gold nanoshell (AuNS)-coated stent with high photothermal efficiency and used in the repetitive photothermal therapy of esophageal cancer. The functionalized stent was prepared by using surface-coated polydopamine as the Au3+ anchor and template. The thickness of the AuNS can be easily adjusted by controlling the reaction time and amount of Au3+. The AuNS-coated stent efficiently increased the temperature of pork and porcine intestines irradiated with a near-infrared (NIR) laser. The deep penetration of the NIR laser and excellent stability of the stent provide opportunity for the clinical applications of the newly functionalized stent. In vitro toxicity experiments showed excellent biocompatibility and safety of this device. Compared with bare metal stent, AuNS-modified stent exhibits great potential to open the duct passageway and suppress tumor growth in future clinical applications. JF - ACS applied materials & interfaces AU - Song, Jibin AU - Hu, Hao AU - Jian, Chao AU - Wu, Kaichun AU - Chen, Xiaoyuan AD - Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health , Bethesda, Maryland 20892, United States. ; Sate Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an, China. Y1 - 2016/10/05/ PY - 2016 DA - 2016 Oct 05 KW - photothermal therapy KW - dopamine KW - NIR laser KW - gold nanoshell KW - stent KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835354994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+applied+materials+%26+interfaces&rft.atitle=New+Generation+of+Gold+Nanoshell-Coated+Esophageal+Stent%3A+Preparation+and+Biomedical+Applications.&rft.au=Song%2C+Jibin%3BHu%2C+Hao%3BJian%2C+Chao%3BWu%2C+Kaichun%3BChen%2C+Xiaoyuan&rft.aulast=Song&rft.aufirst=Jibin&rft.date=2016-10-05&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=ACS+applied+materials+%26+interfaces&rft.issn=1944-8252&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles AN - 1859495977; PQ0003988629 AB - Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential because of their ability to both self-renew and differentiate. It has been proposed that, given their unique properties, a small number of genetically modified HSPCs could accomplish lifelong, corrective reconstitution of the entire hematopoietic system in patients with various hematologic disorders. Scientists have demonstrated that gene addition therapies-targeted to HSPCs and using integrating retroviral vectors-possess clear clinical benefits in multiple diseases, among them immunodeficiencies, storage disorders, and hemoglobinopathies. Scientists attempting to develop clinically relevant gene therapy protocols have, however, encountered a number of unexpected hurdles because of their incomplete knowledge of target cells, genomic control, and gene transfer technologies. Targeted gene-editing technologies using engineered nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical promise, allowing for the site-specific correction of disease-causing mutations-a process with important applications in autosomal dominant or dominant-negative genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in particular, has sparked an exponential increase in the scientific community's interest in and use of these gene-editing technologies. In this minireview, we discuss the specific applications of gene-editing technologies in human HSPCs, as informed by prior experience with gene addition strategies. HSPCs are desirable but challenging targets; the specific mechanisms these cells evolved to protect themselves from DNA damage render them potentially more susceptible to oncogenesis, especially given their ability to self-renew and their long-term proliferative potential. We further review scientists' experience with gene-editing technologies to date, focusing on strategies to move these techniques toward implementation in safe and effective clinical trials. JF - Human Gene Therapy AU - Yu, Kyung-Rok AU - Natanson, Hannah AU - Dunbar, Cynthia E AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 729 EP - 740 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 United States VL - 27 IS - 10 SN - 1043-0342, 1043-0342 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859495977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Gene+Editing+of+Human+Hematopoietic+Stem+and+Progenitor+Cells%3A+Promise+and+Potential+Hurdles&rft.au=Yu%2C+Kyung-Rok%3BNatanson%2C+Hannah%3BDunbar%2C+Cynthia+E&rft.aulast=Yu&rft.aufirst=Kyung-Rok&rft.date=2016-10-01&rft.volume=27&rft.issue=10&rft.spage=729&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2Fhum.2016.107 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 71 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1089/hum.2016.107 ER - TY - JOUR T1 - Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study AN - 1850770955; PQ0003935476 AB - Hepcidin, the master regulator of bioavailable iron, is a key mediator of anemia and also plays a central role in host defense against infection. We hypothesized that measuring hepcidin levels in cord blood could provide an early indication of interindividual differences in iron regulation with quantifiable implications for anemia, malaria, and mortality-related risk. Hepcidin concentrations were measured in cord plasma from a birth cohort (N= 710), which was followed for up to 4 years in a region of perennial malaria transmission in Muheza, Tanzania (2002-2006). At the time of delivery, cord hepcidin levels were correlated with inflammatory mediators, iron markers, and maternal health conditions. Hepcidin levels were 30% (95% confidence interval [CI]: 12%, 44%) lower in children born to anemic mothers and 48% (95% CI: 11%, 97%) higher in placental malaria-exposed children. Relative to children in the lowest third, children in the highest third of cord hepcidin had on average 2.5 g/L (95% CI: 0.1, 4.8) lower hemoglobin levels over the duration of follow-up, increased risk of anemia and severe anemia (adjusted hazard ratio [HR] [95% CI]: 1.18 [1.03, 1.36] and 1.34 [1.08, 1.66], respectively), and decreased risk of malaria and all-cause mortality (adjusted HR [95% CI]: 0.78 [0.67, 0.91] and 0.34 [0.14, 0.84], respectively). Although longitudinal measurements of hepcidin and iron stores are required to strengthen causal inference, these results suggest that hepcidin may have utility as a biomarker indicating children's susceptibility to anemia and infection in early life. JF - American Journal of Tropical Medicine and Hygiene AU - Brickley, Elizabeth B AU - Spottiswoode, Natasha AU - Kabyemela, Edward AU - Morrison, Robert AU - Kurtis, Jonathan D AU - Wood, Angela M AU - Drakesmith, Hal AU - Fried, Michal AU - Duffy, Patrick E AD - Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, patrick.duffy@nih.gov Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 817 EP - 826 PB - American Society of Tropical Medicine and Hygiene, 60 Revere Drive, Suite 500 Northbrook IL 60062 United States VL - 95 IS - 4 SN - 0002-9637, 0002-9637 KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Health & Safety Science Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Bioindicators KW - Mortality KW - Human diseases KW - Parturition KW - Malaria KW - ISW, Tanzania KW - Biomarkers KW - Children KW - Infection KW - Disease transmission KW - Public health KW - Bioavailability KW - Blood KW - Anaemia KW - Tanzania, Tanga, Muheza KW - Hygiene KW - Iron KW - Mortality causes KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms KW - H 0500:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850770955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Cord+Blood+Hepcidin%3A+Cross-Sectional+Correlates+and+Associations+with+Anemia%2C+Malaria%2C+and+Mortality+in+a+Tanzanian+Birth+Cohort+Study&rft.au=Brickley%2C+Elizabeth+B%3BSpottiswoode%2C+Natasha%3BKabyemela%2C+Edward%3BMorrison%2C+Robert%3BKurtis%2C+Jonathan+D%3BWood%2C+Angela+M%3BDrakesmith%2C+Hal%3BFried%2C+Michal%3BDuffy%2C+Patrick+E&rft.aulast=Brickley&rft.aufirst=Elizabeth&rft.date=2016-10-01&rft.volume=95&rft.issue=4&rft.spage=817&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/10.4269%2Fajtmh.16-0218 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Blood; Human diseases; Anaemia; Parturition; Malaria; Biomarkers; Hygiene; Mortality causes; Public health; Bioindicators; Bioavailability; Mortality; Infection; Children; Iron; Disease transmission; Tanzania, Tanga, Muheza; ISW, Tanzania DO - http://dx.doi.org/10.4269/ajtmh.16-0218 ER - TY - JOUR T1 - Telomere content measurement in human hematopoietic cells: Comparative analysis of qPCR and Flow-FISH techniques AN - 1837337313; PQ0003760995 AB - Abnormal telomere lengths have been linked to cancer and other hematologic disorders. Determination of mean telomere content (MTC) is traditionally performed by Southern blotting and densitometry, giving a mean telomere restriction fragment (TRF) value for the total cell population studied. Here, we compared a quantitative Polymerase Chain Reaction approach (qPCR) and a flow cytometric approach, fluorescence in situ hybridization (Flow-FISH), to evaluate telomere content distribution in total patient peripheral blood mononuclear cells or specific cell populations. Flow-FISH is based on in situ hybridization using a fluorescein-labeled peptide nucleic acid (PNA) (CCCTAA) sub(3) probe and DNA staining with propidium iodide. We showed that both qPCR and Flow-FISH provide a robust measurement, with Flow-FISH measuring a relative content longer than qPCR at a single cell approach and that TRF2 fluorescence intensity did not correlate with MTC. Both methods showed comparable telomere content reduction with age, and the rate of relative telomere loss was similar. Published 2016 Wiley Periodicals Inc. This article is a US government work and, as such, is in the public domain in the United States of America. JF - Cytometry Part A AU - Wand, Taylor AU - Fang, Mike AU - Chen, Christina AU - Hardy, Nathan AU - McCoy, JPhilip AU - Dumitriu, Bogdan AU - Young, Neal S AU - Biancotto, Angelique AD - Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, Maryland, 28092. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 914 EP - 921 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 89 IS - 10 SN - 1552-4922, 1552-4922 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Southern blotting KW - Age KW - TRF2 protein KW - propidium iodide KW - Population studies KW - Cancer KW - Cytometry KW - peptide nucleic acids KW - Flow cytometry KW - Telomeres KW - Peripheral blood mononuclear cells KW - Hemopoiesis KW - Fluorescent indicators KW - Polymerase chain reaction KW - Telomere-binding protein KW - Fluorescence in situ hybridization KW - Densitometry KW - N 14820:DNA Metabolism & Structure KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837337313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytometry+Part+A&rft.atitle=Telomere+content+measurement+in+human+hematopoietic+cells%3A+Comparative+analysis+of+qPCR+and+Flow-FISH+techniques&rft.au=Wand%2C+Taylor%3BFang%2C+Mike%3BChen%2C+Christina%3BHardy%2C+Nathan%3BMcCoy%2C+JPhilip%3BDumitriu%2C+Bogdan%3BYoung%2C+Neal+S%3BBiancotto%2C+Angelique&rft.aulast=Wand&rft.aufirst=Taylor&rft.date=2016-10-01&rft.volume=89&rft.issue=10&rft.spage=914&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+A&rft.issn=15524922&rft_id=info:doi/10.1002%2Fcyto.a.22982 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Southern blotting; Age; TRF2 protein; propidium iodide; Population studies; Cytometry; Cancer; peptide nucleic acids; Flow cytometry; Telomeres; Peripheral blood mononuclear cells; Polymerase chain reaction; Fluorescent indicators; Hemopoiesis; Telomere-binding protein; Densitometry; Fluorescence in situ hybridization DO - http://dx.doi.org/10.1002/cyto.a.22982 ER - TY - JOUR T1 - Preconception perfluoroalkyl and polyfluoroalkyl substances and incident pregnancy loss, LIFE Study AN - 1837319536; PQ0003748399 AB - Equivocal findings are reported for perfluoroalkyl and polyfluoroalkyl substances (PFASs) and self-reported pregnancy loss. We prospectively assessed PFASs and pregnancy loss in a cohort comprising 501 couples recruited preconception and followed daily through 7 post-conception weeks. Seven PFASs were quantified: 2-N-ethyl-perfluorooctane sulfonamide acetate (Et-PFOSA-AcOH); 2-N-methyl-perfluorooctane sulfonamido acetate (Me-PFOSA-AcOH); perfluorodecanoate (PFDeA); perfluorononanoate (PFNA); perfluorooctane sulfonamide (PFOSA); perfluorooctane sulfonate (PFOS); and perfluorooctanoate (PFOA). Women used home pregnancy test kits. Loss denoted conversion from a positive to a negative pregnancy test, onset of menses or clinical confirmation (n=98; 28%). Chemicals were log transformed and rescaled by their standard deviations to estimate adjusted hazard ratios (HRs) and 95% confidence intervals. No significantly elevated HRs were observed for any PFASs suggesting no association with loss: Et-PFOSA-AcOH (1.04; 0.87, 1.23), Me-PFOSA-AcOH (0.79; 0.61, 1.00; p<0.05), PFDeA (0.83; 0.66, 1.04), PFNA (0.86; 0.70, 1.06), PFOSA (0.74; 0.50, 1.09), PFOS (0.81; 0.65, 1.00), and PFOA (0.93; 0.75, 1.16). JF - Reproductive Toxicology AU - Louis, Germaine MBuck AU - Sapra, Katherine J AU - Barr, Dana Boyd AU - Lu, Zhaohui AU - Sundaram, Rajeshwari AD - Office of the Director, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, United States Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 11 EP - 17 PB - Elsevier B.V., Box 882 New York NY 10159 United States VL - 65 SN - 0890-6238, 0890-6238 KW - Toxicology Abstracts KW - Cohort KW - Epidemiology KW - Miscarriage KW - Perfluoroalkyl KW - Perfluoroalkyl acids KW - Polyfluoroalkyl KW - Pregnancy loss KW - Reproductive toxicity KW - Standard deviation KW - Abortion KW - Sulfonamides KW - Acetic acid KW - Pregnancy KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837319536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Preconception+perfluoroalkyl+and+polyfluoroalkyl+substances+and+incident+pregnancy+loss%2C+LIFE+Study&rft.au=Louis%2C+Germaine+MBuck%3BSapra%2C+Katherine+J%3BBarr%2C+Dana+Boyd%3BLu%2C+Zhaohui%3BSundaram%2C+Rajeshwari&rft.aulast=Louis&rft.aufirst=Germaine&rft.date=2016-10-01&rft.volume=65&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2Fj.reprotox.2016.06.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Standard deviation; Abortion; Acetic acid; Sulfonamides; Pregnancy DO - http://dx.doi.org/10.1016/j.reprotox.2016.06.011 ER - TY - JOUR T1 - Mammalian Fe-S proteins: definition of a consensus motif recognized by the co-chaperone HSC20 AN - 1837299987; PQ0003746022 AB - Iron-sulfur (Fe-S) clusters are inorganic cofactors that are fundamental to several biological processes in all three kingdoms of life. In most organisms, Fe-S clusters are initially assembled on a scaffold protein, ISCU, and subsequently transferred to target proteins or to intermediate carriers by a dedicated chaperone/co-chaperone system. The delivery of assembled Fe-S clusters to recipient proteins is a crucial step in the biogenesis of Fe-S proteins, and, in mammals, it relies on the activity of a multiprotein transfer complex that contains the chaperone HSPA9, the co-chaperone HSC20 and the scaffold ISCU. How the transfer complex efficiently engages recipient Fe-S target proteins involves specific protein interactions that are not fully understood. This mini review focuses on recent insights into the molecular mechanism of amino acid motif recognition and discrimination by the co-chaperone HSC20, which guides Fe-S cluster delivery. JF - Metallomics AU - Maio, N AU - Rouault, T A AD - Molecular Medicine Program; Eunice Kennedy Shriver National Institute of Child Health and Human Development; 9000 Rockville Pike; 20892 Bethesda; MD; USA Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1032 EP - 1046 PB - Royal Society of Chemistry, c/o Springer-Verlag New York Inc. Secaucus New Jersey 07096 2485 United States VL - 8 IS - 10 SN - 1756-5901, 1756-5901 KW - Biotechnology and Bioengineering Abstracts KW - Molecular modelling KW - Amino acids KW - Cofactors KW - Reviews KW - Chaperones KW - scaffolds KW - Protein interaction KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837299987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Metallomics&rft.atitle=Mammalian+Fe-S+proteins%3A+definition+of+a+consensus+motif+recognized+by+the+co-chaperone+HSC20&rft.au=Maio%2C+N%3BRouault%2C+T+A&rft.aulast=Maio&rft.aufirst=N&rft.date=2016-10-01&rft.volume=8&rft.issue=10&rft.spage=1032&rft.isbn=&rft.btitle=&rft.title=Metallomics&rft.issn=17565901&rft_id=info:doi/10.1039%2Fc6mt00167j LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Number of references - 163 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Molecular modelling; Cofactors; Amino acids; Reviews; Chaperones; Protein interaction; scaffolds DO - http://dx.doi.org/10.1039/c6mt00167j ER - TY - JOUR T1 - Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models AN - 1837294563; PQ0003742174 AB - Scope Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models. Methods and results LDLR-KO mice were fed Western diet supplemented with 2% (w/w) of either LCMUFA concentrate, olive oil, or not (control) for 12 wk. LCMUFA, but not olive oil, significantly suppressed the development of atherosclerotic lesions and several plasma inflammatory cytokine levels, although there were no major differences in plasma lipids between the three groups. At higher doses 5% (w/w) LCMUFA supplementation was observed to reduce pro-atherogenic plasma lipoproteins and to also reduce atherosclerosis in ApoE-KO mice fed a Western diet. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from LDLR-K mice fed LCMUFA showed greater cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells. Conclusion Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway. To investigate the effect of long-chain monounsaturated fatty acid (LCMUFA) at least 20 carbons in length (i.e., C20:1 and C22:1 isomers combined) on atherosclerosis, a major cause of cardiovascular disease, two types of atherosclerotic mouse models were fed with LCMUFA-rich diet for three months. In ApoE-KO mice, 5% LCMUFA-supplemented diet decreased plasma cholesterol, and suppressed atherosclerosis. In LDLR-KO mice, a lower dose 2% LCMUFA also suppressed atherosclerosis and macrophage accumulation at aorta, although shorter-chain MUFA oleic acid (C18:1)-rich olive oil did not. JF - Molecular Nutrition & Food Research AU - Yang, Zhi-Hong AU - Bando, Masahiro AU - Sakurai, Toshihiro AU - Chen, Ye AU - Emma-Okon, Beatrice AU - Wilhite, Bree AU - Fukuda, Daiju AU - Vaisman, Boris AU - Pryor, Milton AU - Wakabayashi, Yoshiyuki AU - Sampson, Maureen AU - Yu, Zu-Xi AU - Sakurai, Akiko AU - Zarzour, Abdalrahman AU - Miyahara, Hiroko AU - Takeo, Jiro AU - Sakaue, Hiroshi AU - Sata, Masataka AU - Remaley, Alan T AD - Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 2208 EP - 2218 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 60 IS - 10 SN - 1613-4125, 1613-4125 KW - Biotechnology and Bioengineering Abstracts KW - Diets KW - Macrophages KW - Peroxisome proliferator-activated receptors KW - Lipids KW - Aorta KW - Animal models KW - Cell culture KW - Cholesterol KW - Arteriosclerosis KW - Olive oil KW - Fish oils KW - Isomers KW - Carbon KW - RNA KW - Lipoproteins KW - Fatty acids KW - Cytokines KW - Cardiovascular diseases KW - Signal transduction KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837294563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Nutrition+%26+Food+Research&rft.atitle=Long-chain+monounsaturated+fatty+acid-rich+fish+oil+attenuates+the+development+of+atherosclerosis+in+mouse+models&rft.au=Yang%2C+Zhi-Hong%3BBando%2C+Masahiro%3BSakurai%2C+Toshihiro%3BChen%2C+Ye%3BEmma-Okon%2C+Beatrice%3BWilhite%2C+Bree%3BFukuda%2C+Daiju%3BVaisman%2C+Boris%3BPryor%2C+Milton%3BWakabayashi%2C+Yoshiyuki%3BSampson%2C+Maureen%3BYu%2C+Zu-Xi%3BSakurai%2C+Akiko%3BZarzour%2C+Abdalrahman%3BMiyahara%2C+Hiroko%3BTakeo%2C+Jiro%3BSakaue%2C+Hiroshi%3BSata%2C+Masataka%3BRemaley%2C+Alan+T&rft.aulast=Yang&rft.aufirst=Zhi-Hong&rft.date=2016-10-01&rft.volume=60&rft.issue=10&rft.spage=2208&rft.isbn=&rft.btitle=&rft.title=Molecular+Nutrition+%26+Food+Research&rft.issn=16134125&rft_id=info:doi/10.1002%2Fmnfr.201600142 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Last updated - 2016-11-23 N1 - SubjectsTermNotLitGenreText - Macrophages; Diets; Peroxisome proliferator-activated receptors; Aorta; Lipids; Animal models; Cell culture; Arteriosclerosis; Cholesterol; Olive oil; Fish oils; Isomers; Carbon; RNA; Lipoproteins; Fatty acids; Cytokines; Cardiovascular diseases; Signal transduction DO - http://dx.doi.org/10.1002/mnfr.201600142 ER - TY - JOUR T1 - Botanicals and Their Bioactive Phytochemicals for Women's Health. AN - 1835531391; 27677719 AB - Botanical dietary supplements are increasingly popular for women's health, particularly for older women. The specific botanicals women take vary as a function of age. Younger women will use botanicals for urinary tract infections, especially Vaccinium macrocarpon (cranberry), where there is evidence for efficacy. Botanical dietary supplements for premenstrual syndrome (PMS) are less commonly used, and rigorous clinical trials have not been done. Some examples include Vitex agnus-castus (chasteberry), Angelica sinensis (dong quai), Viburnum opulus/prunifolium (cramp bark and black haw), and Zingiber officinale (ginger). Pregnant women have also used ginger for relief from nausea. Natural galactagogues for lactating women include Trigonella foenum-graecum (fenugreek) and Silybum marianum (milk thistle); however, rigorous safety and efficacy studies are lacking. Older women suffering menopausal symptoms are increasingly likely to use botanicals, especially since the Women's Health Initiative showed an increased risk for breast cancer associated with traditional hormone therapy. Serotonergic mechanisms similar to antidepressants have been proposed for Actaea/Cimicifuga racemosa (black cohosh) and Valeriana officinalis (valerian). Plant extracts with estrogenic activities for menopausal symptom relief include Glycine max (soy), Trifolium pratense (red clover), Pueraria lobata (kudzu), Humulus lupulus (hops), Glycyrrhiza species (licorice), Rheum rhaponticum (rhubarb), Vitex agnus-castus (chasteberry), Linum usitatissimum (flaxseed), Epimedium species (herba Epimedii, horny goat weed), and Medicago sativa (alfalfa). Some of the estrogenic botanicals have also been shown to have protective effects against osteoporosis. Several of these botanicals could have additional breast cancer preventive effects linked to hormonal, chemical, inflammatory, and/or epigenetic pathways. Finally, although botanicals are perceived as natural safe remedies, it is important for women and their healthcare providers to realize that they have not been rigorously tested for potential toxic effects and/or drug/botanical interactions. Understanding the mechanism of action of these supplements used for women's health will ultimately lead to standardized botanical products with higher efficacy, safety, and chemopreventive properties. Copyright © 2016 by The Author(s). JF - Pharmacological reviews AU - Dietz, Birgit M AU - Hajirahimkhan, Atieh AU - Dunlap, Tareisha L AU - Bolton, Judy L AD - University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois. ; University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois judy.bolton@uic.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1026 EP - 1073 VL - 68 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835531391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Botanicals+and+Their+Bioactive+Phytochemicals+for+Women%27s+Health.&rft.au=Dietz%2C+Birgit+M%3BHajirahimkhan%2C+Atieh%3BDunlap%2C+Tareisha+L%3BBolton%2C+Judy+L&rft.aulast=Dietz&rft.aufirst=Birgit&rft.date=2016-10-01&rft.volume=68&rft.issue=4&rft.spage=1026&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=1521-0081&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Partial splenic embolization to permit continuation of systemic chemotherapy. AN - 1835522354; 27611010 AB - Systemic chemotherapy treatments, commonly those that comprise oxaliplatin, have been linked to the appearance of distinctive liver lesions that evolves to portal hypertension, spleen enlargement, platelets sequestration, and thrombocytopenia. This outcome can interrupt treatment or force dosage reduction, decreasing efficiency of cancer therapy. We conducted a prospective phase II study for the evaluation of partial splenic embolization in patients with thrombocytopenia that impeded systemic chemotherapy continuation. From August 2014 through July 2015, 33 patients underwent partial splenic embolization to increase platelets count and allow their return to treatment. Primary endpoint was the accomplishment of a thrombocyte level superior to 130 × 109 /L and the secondary endpoints were the return to chemotherapy and toxicity. Partial splenic embolization was done 36 times in 33 patients. All patients presented gastrointestinal cancer and colorectal malignancy was the commonest primary site. An average of 6.4 cycles of chemotherapy was done before splenic embolization and the most common regimen was Folfox. Mean platelet count prior to embolization was 69 × 109 /L. A total of 94% of patients achieved primary endpoint. All patients in need reinitiated treatment and median time to chemotherapy return was 14 days. No grade 3 or above adverse events were identified. Aiming for a 50% to 70% infarction area may be sufficient to achieve success without the complications associated with more extensive infarction. Combined with the better safety profile, partial splenic embolization is an excellent option in the management of thrombocytopenia, enabling the resumption of systemic chemotherapy with minimal procedure-related morbidity. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. JF - Cancer medicine AU - Luz, Jose Hugo M AU - Luz, Paula M AU - Marchiori, Edson AU - Rodrigues, Leonardo A AU - Gouveia, Hugo R AU - Martin, Henrique S AU - Faria, Igor M AU - Souza, Roberto R AU - Gil, Roberto de Almeida AU - Palladino, Alexandre de M AU - Pimenta, Karina B AU - de Souza, Henrique S AD - Department of Interventional Radiology, Radiology Division, National Cancer Institute, INCA, Rio de Janeiro, Brazil. jhugoluz@gmail.com. ; National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. ; Department of Radiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. ; Department of Interventional Radiology, Radiology Division, National Cancer Institute, INCA, Rio de Janeiro, Brazil. ; Department of Clinical Oncology, National Cancer Institute, INCA, Rio de Janeiro, Brazil. ; Department of Anesthesiology, National Cancer Institute, INCA, Rio de Janeiro, Brazil. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 2715 EP - 2720 VL - 5 IS - 10 KW - interventional Radiology KW - thrombocytopenia KW - systemic chemotherapy KW - spleen KW - oxaliplatin KW - Cancer KW - partial splenic embolization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835522354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+medicine&rft.atitle=Partial+splenic+embolization+to+permit+continuation+of+systemic+chemotherapy.&rft.au=Luz%2C+Jose+Hugo+M%3BLuz%2C+Paula+M%3BMarchiori%2C+Edson%3BRodrigues%2C+Leonardo+A%3BGouveia%2C+Hugo+R%3BMartin%2C+Henrique+S%3BFaria%2C+Igor+M%3BSouza%2C+Roberto+R%3BGil%2C+Roberto+de+Almeida%3BPalladino%2C+Alexandre+de+M%3BPimenta%2C+Karina+B%3Bde+Souza%2C+Henrique+S&rft.aulast=Luz&rft.aufirst=Jose+Hugo&rft.date=2016-10-01&rft.volume=5&rft.issue=10&rft.spage=2715&rft.isbn=&rft.btitle=&rft.title=Cancer+medicine&rft.issn=2045-7634&rft_id=info:doi/10.1002%2Fcam4.856 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cam4.856 ER - TY - JOUR T1 - Effects of occupational exposure to carbon black on peripheral white blood cell counts and lymphocyte subsets. AN - 1835423490; 27671983 AB - The International Agency for Research on Cancer has classified carbon black (CB) as a possible (Group 2B) human carcinogen. Given that most CB manufacturing processes result in the emission of various types of chemicals, it is uncertain if the adverse health effects that have been observed in CB-exposed workers are related to CB specifically or are due to other exposures. To address this issue, we conducted a cross-sectional molecular epidemiology study in China of 106 male factory workers who were occupationally exposed to pure CB and 112 unexposed male workers frequency-matched by age and smoking status from the same geographic region. Repeated personal exposure measurements were taken in workers before biological sample collection. Peripheral blood from all workers was used for the complete blood cell count and lymphocyte subsets analysis. Compared to unexposed workers, eosinophil counts in workers exposed to CB were increased by 30.8% (P = 0.07) after adjusting for potential confounders. When stratified by smoking status, statistically significant differences in eosinophils between CB exposed and unexposed workers were only present among never smokers (P = 0.040). Smoking is associated with alterations in various cell counts; however, no significant interaction between CB exposure and smoking status for any cell counts was observed. Given that inflammation, characterized in part by elevated eosinophils in peripheral blood, may be associated with increased cancer risk, our findings provide new biologic insights into the potential relationship between CB exposure and lung carcinogenesis. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Environmental and molecular mutagenesis AU - Dai, Yufei AU - Niu, Yong AU - Duan, Huawei AU - Bassig, Bryan A AU - Ye, Meng AU - Zhang, Xiao AU - Meng, Tao AU - Bin, Ping AU - Jia, Xiaowei AU - Shen, Meili AU - Zhang, Rong AU - Hu, Wei AU - Yang, Xiaofa AU - Vermeulen, Roel AU - Silverman, Debra AU - Rothman, Nathaniel AU - Lan, Qing AU - Yu, Shanfa AU - Zheng, Yuxin AD - Key Laboratory, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China. ; Occupational and Environmental Epidemiology Branch, National Cancer Institute, Rockville, Maryland. ; Jiao Zuo Center for Disease Control and Prevention, Jiaozuo, China. ; Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands. ; Occupational and Environmental Epidemiology Branch, National Cancer Institute, Rockville, Maryland. zhengyx@chinacdc.cn. ; Henan Provincial Institute for Occupational Health, Zhengzhou, China. yu-shanfa@163.com. ; Key Laboratory, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China. qingl@mail.nih.gov. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 615 EP - 622 VL - 57 IS - 8 KW - inflammation KW - carbon black KW - immunotoxicity KW - occupational exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835423490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Effects+of+occupational+exposure+to+carbon+black+on+peripheral+white+blood+cell+counts+and+lymphocyte+subsets.&rft.au=Dai%2C+Yufei%3BNiu%2C+Yong%3BDuan%2C+Huawei%3BBassig%2C+Bryan+A%3BYe%2C+Meng%3BZhang%2C+Xiao%3BMeng%2C+Tao%3BBin%2C+Ping%3BJia%2C+Xiaowei%3BShen%2C+Meili%3BZhang%2C+Rong%3BHu%2C+Wei%3BYang%2C+Xiaofa%3BVermeulen%2C+Roel%3BSilverman%2C+Debra%3BRothman%2C+Nathaniel%3BLan%2C+Qing%3BYu%2C+Shanfa%3BZheng%2C+Yuxin&rft.aulast=Dai&rft.aufirst=Yufei&rft.date=2016-10-01&rft.volume=57&rft.issue=8&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=1098-2280&rft_id=info:doi/10.1002%2Fem.22036 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/em.22036 ER - TY - JOUR T1 - Remembering Heinrich Malling. AN - 1835371117; 27696552 JF - Environmental and molecular mutagenesis AU - Hoffmann, George R AU - Shelby, Michael D AU - Zeiger, Errol AD - Department of Biology, College of the Holy Cross, Worcester, Massachusetts, 01610. ghoffmann@holycross.edu. ; National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709. ; Errol Zeiger Consulting, Chapel Hill, North Carolina, 27514. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 575 EP - 578 VL - 57 IS - 8 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835371117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+molecular+mutagenesis&rft.atitle=Remembering+Heinrich+Malling.&rft.au=Hoffmann%2C+George+R%3BShelby%2C+Michael+D%3BZeiger%2C+Errol&rft.aulast=Hoffmann&rft.aufirst=George&rft.date=2016-10-01&rft.volume=57&rft.issue=8&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=1098-2280&rft_id=info:doi/10.1002%2Fem.22056 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-10-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/em.22056 ER - TY - JOUR T1 - Effects of Sex, Drinking History, and Omega-3 and Omega-6 Fatty Acids Dysregulation on the Onset of Liver Injury in Very Heavy Drinking Alcohol-Dependent Patients. AN - 1835364157; 27589090 AB - Heavy alcohol consumption frequently causes liver inflammation/injury, and certain fatty acids (FAs) may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking and the changes in the FA levels involved in the ω-6 (pro-inflammatory) and ω-3 (anti-inflammatory) state in alcohol-dependent (AD) patients who had no clinical manifestations of liver injury. We aimed to identify sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. A total of 114 heavy drinking AD female and male patients aged 21 to 65 years without clinical manifestations of liver injury, who were admitted to an alcohol dependence treatment program, were grouped by the alanine aminotransferase (ALT) levels: ≤40 IU/l, as no liver injury (GR.1), and >40 IU/l, as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic panel, comprehensive FA panel, and drinking history data were evaluated. Elevated ALT and aspartate aminotransferase (AST) showed close association with markers of heavy alcohol intake. In the patients with mild biochemical liver injury (GR.2), females showed significantly higher AST level than males. Significant association of AST and total drinks in past 90 days (TD90) in females, and AST and heavy drinking days in past 90 days (HDD90) in males was observed. The ω-6:ω-3 ratio showed a significant pro-inflammatory response only in females with mild liver injury (GR.2) when adjusted by drinking history marker, TD90. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased in males with liver injury, while females did not show any comparable rise in EPA; and DHA levels were lower. Measures of heavy drinking, TD90 and HDD90, predicted changes in liver injury. Changes in the ω-3 and ω-6 FA levels and the ω-6:ω-3 ratio showed a pro-inflammatory shift in patients with biochemical liver injury with a significant effect in females. Changes in FAs involved in the inflammatory state may represent one mechanism for liver inflammation/injury in response to heavy alcohol drinking. Copyright © 2016 by the Research Society on Alcoholism. JF - Alcoholism, clinical and experimental research AU - Vatsalya, Vatsalya AU - Song, Ming AU - Schwandt, Melanie L AU - Cave, Matthew C AU - Barve, Shirish S AU - George, David T AU - Ramchandani, Vijay A AU - McClain, Craig J AD - Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky. vatsalya.vatsalya@louisville.edu. ; Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky. ; Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 2085 EP - 2093 VL - 40 IS - 10 KW - Alcohol KW - Fatty Acids KW - Liver Injury KW - Heavy Drinking Markers KW - Sex UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835364157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Effects+of+Sex%2C+Drinking+History%2C+and+Omega-3+and+Omega-6+Fatty+Acids+Dysregulation+on+the+Onset+of+Liver+Injury+in+Very+Heavy+Drinking+Alcohol-Dependent+Patients.&rft.au=Vatsalya%2C+Vatsalya%3BSong%2C+Ming%3BSchwandt%2C+Melanie+L%3BCave%2C+Matthew+C%3BBarve%2C+Shirish+S%3BGeorge%2C+David+T%3BRamchandani%2C+Vijay+A%3BMcClain%2C+Craig+J&rft.aulast=Vatsalya&rft.aufirst=Vatsalya&rft.date=2016-10-01&rft.volume=40&rft.issue=10&rft.spage=2085&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=1530-0277&rft_id=info:doi/10.1111%2Facer.13197 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-12 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/acer.13197 ER - TY - JOUR T1 - Total Synthesis of the Complete Protective Antigen of Vibrio cholerae O139 AN - 1832247335; PQ0003703631 AB - The first chemical synthesis of the complete protective O-antigen of a human-disease-causing pathogenic bacterium is described. The synthesis involved a protecting-group strategy that facilitated the regioselectivity of the key transformations, stereoselective glycosylation reactions, and enabled the one-step global deprotection of the completely assembled, fully protected, phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final amino-group-functionalized, linker-equipped antigen was obtained in a form ready for conjugation to suitable carriers, for example, proteins, to yield immunogens. The whole shebang: The protective O-antigen (see structure) of a human-disease-causing pathogenic bacterium was synthesized by a route involving a protecting-group strategy that enabled one-step global deprotection of the completely assembled phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final antigen was obtained with a linker functionalized for conjugation to suitable carriers, such as proteins, to yield immunogens. JF - Angewandte Chemie (International Edition) AU - Soliman, Sameh E AU - Kovac, Pavol AD - NIDDK, LBC, Section on Carbohydrates, National Institutes of Health (NIH), Bethesda, MD, 20892-0815, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 12850 EP - 12853 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 55 IS - 41 SN - 1433-7851, 1433-7851 KW - Microbiology Abstracts B: Bacteriology KW - Transformation KW - Vibrio cholerae KW - protective antigen KW - Hydrogenation KW - Glycosylation KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1832247335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Angewandte+Chemie+%28International+Edition%29&rft.atitle=Total+Synthesis+of+the+Complete+Protective+Antigen+of+Vibrio+cholerae+O139&rft.au=Soliman%2C+Sameh+E%3BKovac%2C+Pavol&rft.aulast=Soliman&rft.aufirst=Sameh&rft.date=2016-10-01&rft.volume=55&rft.issue=41&rft.spage=12850&rft.isbn=&rft.btitle=&rft.title=Angewandte+Chemie+%28International+Edition%29&rft.issn=14337851&rft_id=info:doi/10.1002%2Fanie.201606116 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-11-09 N1 - SubjectsTermNotLitGenreText - Transformation; protective antigen; Glycosylation; Hydrogenation; Vibrio cholerae DO - http://dx.doi.org/10.1002/anie.201606116 ER - TY - JOUR T1 - Total Synthesis of the Complete Protective Antigen of Vibrio cholerae O139 AN - 1832245728; PQ0003703597 AB - The first chemical synthesis of the complete protective O-antigen of a human-disease-causing pathogenic bacterium is described. The synthesis involved a protecting-group strategy that facilitated the regioselectivity of the key transformations, stereoselective glycosylation reactions, and enabled the one-step global deprotection of the completely assembled, fully protected, phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final amino-group-functionalized, linker-equipped antigen was obtained in a form ready for conjugation to suitable carriers, for example, proteins, to yield immunogens.Original Abstract: Das schuetzende O-Antigen (siehe Struktur) eines humanpathogenen Bakteriums wurde durch eine Schutzgruppenstrategie synthetisiert, welche die einstufige globale Entschuetzung des vollstaendigen, phosphorylierten Hexasaccharids durch Hydrierung/Hydrogenolyse ermoglichte. Das finale Antigen enthaelt einen funktionalisierten Linker fuer die Konjugation molekularer Frachten wie Proteine, um Immunogene zu erzeugen. JF - Angewandte Chemie (English Edition) AU - Soliman, Sameh E AU - Kovac, Pavol AD - NIDDK, LBC, Section on Carbohydrates, National Institutes of Health (NIH), Bethesda, MD, 20892-0815, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 13042 EP - 13045 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 128 IS - 41 SN - 0044-8249, 0044-8249 KW - Microbiology Abstracts B: Bacteriology KW - Transformation KW - Vibrio cholerae KW - protective antigen KW - Glycosylation KW - Hydrogenation KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1832245728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Angewandte+Chemie+%28English+Edition%29&rft.atitle=Total+Synthesis+of+the+Complete+Protective+Antigen+of+Vibrio+cholerae+O139&rft.au=Soliman%2C+Sameh+E%3BKovac%2C+Pavol&rft.aulast=Soliman&rft.aufirst=Sameh&rft.date=2016-10-01&rft.volume=128&rft.issue=41&rft.spage=13042&rft.isbn=&rft.btitle=&rft.title=Angewandte+Chemie+%28English+Edition%29&rft.issn=00448249&rft_id=info:doi/10.1002%2Fange.201606116 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-11-09 N1 - SubjectsTermNotLitGenreText - Transformation; protective antigen; Hydrogenation; Glycosylation; Vibrio cholerae DO - http://dx.doi.org/10.1002/ange.201606116 ER - TY - JOUR T1 - Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer AN - 1827925299; PQ0003641406 AB - Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40-42 degree C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/- heat), free docetaxel (+/- heat), and LTSL docetaxel (+/- heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200-300 mm super(3). Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/- heat n=3-5) was performed to determine molecular mechanism responsible for tumor cell killing. LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion. This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment. JF - Pharmaceutical Research AU - Ranjan, Ashish AU - Benjamin, Compton J AU - Negussie, Ayele H AU - Chokshi, Saurin AU - Chung, Paul H AU - Volkin, Dmitry AU - Yeram, Nitin AU - Linehan, WMarston AU - Dreher, Matthew R AU - Pinto, Peter A AU - Wood, Bradford J AD - Center for Interventional Oncology, Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, MSC 1182- building 10- room 1c -341, 10 Center Drive, Bethesda, Maryland, 20892, USA, bwood@cc.nih.gov Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 2459 EP - 2469 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 33 IS - 10 SN - 0724-8741, 0724-8741 KW - Biotechnology and Bioengineering Abstracts KW - Temperature effects KW - Molecular modelling KW - Translation KW - Hyperthermia KW - Perfusion KW - Apoptosis KW - Animal models KW - Tumors KW - Tumor cells KW - Liposomes KW - Leg KW - Veins KW - Prostate cancer KW - Body weight KW - Heat KW - Caspase-3 KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827925299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmaceutical+Research&rft.atitle=Biodistribution+and+Efficacy+of+Low+Temperature-Sensitive+Liposome+Encapsulated+Docetaxel+Combined+with+Mild+Hyperthermia+in+a+Mouse+Model+of+Prostate+Cancer&rft.au=Ranjan%2C+Ashish%3BBenjamin%2C+Compton+J%3BNegussie%2C+Ayele+H%3BChokshi%2C+Saurin%3BChung%2C+Paul+H%3BVolkin%2C+Dmitry%3BYeram%2C+Nitin%3BLinehan%2C+WMarston%3BDreher%2C+Matthew+R%3BPinto%2C+Peter+A%3BWood%2C+Bradford+J&rft.aulast=Ranjan&rft.aufirst=Ashish&rft.date=2016-10-01&rft.volume=33&rft.issue=10&rft.spage=2459&rft.isbn=&rft.btitle=&rft.title=Pharmaceutical+Research&rft.issn=07248741&rft_id=info:doi/10.1007%2Fs11095-016-1971-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 46 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Temperature effects; Translation; Molecular modelling; Hyperthermia; Apoptosis; Perfusion; Animal models; Tumors; Liposomes; Tumor cells; Leg; Prostate cancer; Veins; Body weight; Heat; Caspase-3 DO - http://dx.doi.org/10.1007/s11095-016-1971-8 ER - TY - JOUR T1 - Pharmacokinetic Properties and Human Use Characteristics of an FDA-Approved Intranasal Naloxone Product for the Treatment of Opioid Overdose AN - 1827912822; PQ0003696360 AB - Parenteral naloxone has been approved to treat opiate overdose for over 4 decades. Intranasal naloxone, administered "off label" using improvised devices, has been widely used by both first responders and the lay public to treat overdose. However, these improvised devices require training for effective use, and the recommended volumes (2 to 4 mL) exceed those considered optimum for intranasal administration. The present study compared the pharmacokinetic properties of intranasal naloxone (2 to 8 mg) delivered in low volumes (0.1 to 0.2 mL) using an Aptar Unit-Dose device to an approved (0.4 mg) intramuscular dose. A parallel study assessed the ease of use of this device in a simulated overdose situation. All doses of intranasal naloxone resulted in plasma concentrations and areas under the curve greater than those observed following the intramuscular dose; the time to reach maximum plasma concentrations was not different following intranasal and intramuscular administration. Plasma concentrations of naloxone were dose proportional between 2 and 8 mg and independent of whether drug was administered to 1 or both nostrils. In a study using individuals representative of the general population, >90% were able to perform both critical tasks (inserting nozzle into a nostril and pressing plunger) needed to deliver a simulated dose of naloxone without prior training. Based on both pharmacokinetic and human use studies, a 4-mg dose delivered in a single device (0.1 mL) was selected as the final product. This product can be used by first responders and the lay public, providing an important and potentially life-saving intervention for victims of an opioid overdose. JF - Journal of Clinical Pharmacology AU - Krieter, Philip AU - Chiang, Nora AU - Gyaw, Shwe AU - Skolnick, Phil AU - Crystal, Roger AU - Keegan, Fintan AU - Aker, Julie AU - Beck, Melissa AU - Harris, Jennifer AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1243 EP - 1253 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 56 IS - 10 SN - 0091-2700, 0091-2700 KW - Toxicology Abstracts KW - Overdose KW - Intranasal administration KW - Opiates KW - Opioids KW - Drugs KW - Pharmacokinetics KW - Naloxone KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827912822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Pharmacology&rft.atitle=Pharmacokinetic+Properties+and+Human+Use+Characteristics+of+an+FDA-Approved+Intranasal+Naloxone+Product+for+the+Treatment+of+Opioid+Overdose&rft.au=Krieter%2C+Philip%3BChiang%2C+Nora%3BGyaw%2C+Shwe%3BSkolnick%2C+Phil%3BCrystal%2C+Roger%3BKeegan%2C+Fintan%3BAker%2C+Julie%3BBeck%2C+Melissa%3BHarris%2C+Jennifer&rft.aulast=Krieter&rft.aufirst=Philip&rft.date=2016-10-01&rft.volume=56&rft.issue=10&rft.spage=1243&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Pharmacology&rft.issn=00912700&rft_id=info:doi/10.1002%2Fjcph.759 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Overdose; Opiates; Intranasal administration; Opioids; Drugs; Pharmacokinetics; Naloxone DO - http://dx.doi.org/10.1002/jcph.759 ER - TY - JOUR T1 - Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer AN - 1827906444; PQ0003710750 AB - The detection of cancer biomarkers freely circulating in blood offers new opportunities for cancer early diagnosis, patient follow-up, and therapy efficacy assessment based on liquid biopsy. In particular, circulating cell-free nucleic acids released from tumor cells have recently attracted great attention also because they become detectable in blood before the appearance of other circulating biomarkers, such as circulating tumor cells. The detection of circulating nucleic acids poses several technical challenges that arise from their low concentration and relatively small size. Here, possibilities offered by innovative biosensing approaches for the detection of circulating DNA in peripheral blood and blood-derived products such as plasma and serum blood are discussed. Different transduction principles are used to detect circulating DNAs and great advantages are derived from the combined use of nanostructured materials. JF - Analytical and Bioanalytical Chemistry AU - Bellassai, Noemi AU - Spoto, Giuseppe AD - Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici, c/o Dipartimento di Scienze Chimiche, Universita di Catania, Viale Andrea Doria 6, Catania, Italy, spotog@unict.it Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 7255 EP - 7264 PB - Springer Science+Business Media, Berlin/Heidelberg Germany VL - 408 IS - 26 SN - 1618-2642, 1618-2642 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Biosensors KW - nucleic acids KW - DNA KW - Biopsy KW - Peripheral blood KW - Tumor cells KW - biomarkers KW - Cancer KW - W 30955:Biosensors KW - N 14845:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827906444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+and+Bioanalytical+Chemistry&rft.atitle=Biosensors+for+liquid+biopsy%3A+circulating+nucleic+acids+to+diagnose+and+treat+cancer&rft.au=Bellassai%2C+Noemi%3BSpoto%2C+Giuseppe&rft.aulast=Bellassai&rft.aufirst=Noemi&rft.date=2016-10-01&rft.volume=408&rft.issue=26&rft.spage=7255&rft.isbn=&rft.btitle=&rft.title=Analytical+and+Bioanalytical+Chemistry&rft.issn=16182642&rft_id=info:doi/10.1007%2Fs00216-016-9806-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 101 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Biosensors; nucleic acids; DNA; Peripheral blood; Biopsy; biomarkers; Tumor cells; Cancer DO - http://dx.doi.org/10.1007/s00216-016-9806-3 ER - TY - JOUR T1 - Mediterranean diet and mortality risk in metabolically healthy obese and metabolically unhealthy obese phenotypes AN - 1827894971; PQ0003725500 AB - Background: The Mediterranean diet has been consistently associated with reduced mortality risk. Few prospective studies have examined whether the benefits from a Mediterranean diet are equally shared by obese individuals with varying metabolic health. Objective: The objective of this study was to investigate the association between Mediterranean diet, metabolic phenotypes and mortality risk in a representative obese US population. Methods: Data from 1739 adults aged 20-88 years were analyzed from participants of the National Health and Nutrition Examination Survey III, 1988-1994 followed up for deaths until 31 December 2011 in a prospective cohort analysis. Mediterranean Diet Scores (MDS) were created to assess the adherence to Mediterranean diet. Participants were classified as metabolically healthy obese (MHO) phenotype (0 or 1 metabolic abnormality) or metabolically unhealthy obese (MUO) phenotype (two or more metabolic abnormalities), based on high glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein and low high-density lipoprotein cholesterol. Results: The MHO phenotype (n=598) was observed in 34.8% (s.e., 1.7%) of those who were obese (mean body mass index was 33.4 and 34.8 in MHO and MUO phenotypes, respectively). During a median follow-up of 18.5 years, there were 77 (12.9%) and 309 (27.1%) deaths in MHO and MUO individuals, respectively. In MHO individuals, the multivariable-adjusted hazard ratio (HR) of all-cause mortality in the highest tertile compared with the first tertile of MDS was 0.44 (95% confidence interval (CI), 0.26-0.75; P for trend <0.001), after adjustment for potential confounders. A five-point (1 s.d.) increment in the adherence to MDS was associated with a 41% reduction in the risk of all-cause mortality (HR, 0.59; 95% CI, 0.37-0.94). Similar findings were obtained when we restricted our analyses to those with or without prevalent diabetes mellitus and hypertension. We did not observe mortality risk reduction in either individuals with MUO phenotype or all obese participants combined. Conclusions: Adherence to a Mediterranean dietary pattern appears to reduce mortality in the MHO phenotype, but not among the MUO phenotype in an obese population. JF - International Journal of Obesity AU - Park, Y-M AU - Steck, S E AU - Fung, T T AU - Zhang, J AU - Hazlett, L J AU - Han, K AU - Merchant, A T AD - Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1541 EP - 1549 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 40 IS - 10 SN - 0307-0565, 0307-0565 KW - Physical Education Index; Health & Safety Science Abstracts KW - Risk assessment KW - Death KW - Body mass KW - Lipids KW - Compliance KW - Glucose KW - Health KW - Risk reduction KW - Adults KW - Nutrition KW - Blood pressure KW - Insulin KW - Diets KW - Mortality KW - Obesity KW - Cholesterol KW - Diabetes mellitus KW - MED KW - Analysis KW - Proteins KW - Diet KW - Hypertension KW - H 12000:Epidemiology and Public Health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827894971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=Mediterranean+diet+and+mortality+risk+in+metabolically+healthy+obese+and+metabolically+unhealthy+obese+phenotypes&rft.au=Park%2C+Y-M%3BSteck%2C+S+E%3BFung%2C+T+T%3BZhang%2C+J%3BHazlett%2C+L+J%3BHan%2C+K%3BMerchant%2C+A+T&rft.aulast=Park&rft.aufirst=Y-M&rft.date=2016-10-01&rft.volume=40&rft.issue=10&rft.spage=1541&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.114 LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Obesity; Death; Lipids; Analysis; Compliance; Health; Adults; Diet; Nutrition; Diets; Risk assessment; Mortality; Body mass; Glucose; Risk reduction; Cholesterol; Insulin; Blood pressure; Diabetes mellitus; Proteins; Hypertension; MED DO - http://dx.doi.org/10.1038/ijo.2016.114 ER - TY - JOUR T1 - Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat AN - 1827885113; PQ0003710094 AB - There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo -p -dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. JF - Toxicologic Pathology AU - Filgo, Adam J AU - Foley, Julie F AU - Puvanesarajah, Samantha AU - Borde, Aditi R AU - Midkiff, Bentley R AU - Reed, Casey E AU - Chappell, Vesna A AU - Alexander, Lydia B AU - Borde, Pretish R AU - Troester, Melissa A AU - Bouknight, Schantel AHayes AU - Fenton, Suzanne E AD - 1 .Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA, fentonse@niehs.nih.gov Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1034 EP - 1058 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 7 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - mammary gland KW - atlas KW - HSD KW - rat KW - developmental exposure KW - steroid receptor KW - histology KW - whole mount KW - Estrogens KW - Data processing KW - Progesterone KW - Mammary gland KW - Endocrine disruptors KW - Animal models KW - Toxicity KW - Androgen receptors KW - Gestation KW - Embryos KW - Progeny KW - Diethylstilbestrol KW - Sex KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827885113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Mammary+Gland+Evaluation+in+Juvenile+Toxicity+Studies%3A+Temporal+Developmental+Patterns+in+the+Male+and+Female+Harlan+Sprague-Dawley+Rat&rft.au=Filgo%2C+Adam+J%3BFoley%2C+Julie+F%3BPuvanesarajah%2C+Samantha%3BBorde%2C+Aditi+R%3BMidkiff%2C+Bentley+R%3BReed%2C+Casey+E%3BChappell%2C+Vesna+A%3BAlexander%2C+Lydia+B%3BBorde%2C+Pretish+R%3BTroester%2C+Melissa+A%3BBouknight%2C+Schantel+AHayes%3BFenton%2C+Suzanne+E&rft.aulast=Filgo&rft.aufirst=Adam&rft.date=2016-10-01&rft.volume=44&rft.issue=7&rft.spage=1034&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316663864 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 73 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Estrogens; Data processing; Progesterone; Mammary gland; Endocrine disruptors; Animal models; Toxicity; Androgen receptors; Gestation; Progeny; Embryos; Diethylstilbestrol; Sex DO - http://dx.doi.org/10.1177/0192623316663864 ER - TY - JOUR T1 - Preparation of High-quality Hematoxylin and Eosin-stained Sections from Rodent Mammary Gland Whole Mounts for Histopathologic Review AN - 1827884688; PQ0003710098 AB - Identifying environmental exposures that cause adverse mammary gland outcomes in rodents is a first step in disease prevention in humans and domestic pets. "Whole mounts" are an easy and inexpensive tissue preparation method that can elucidate typical or abnormal mammary gland morphology in rodent studies. Here, we propose procedures to facilitate the use of whole mounts for histological identification of grossly noted tissue alterations. We noted lesions in mammary whole mounts from 14-month-old CD-1 mice that were not found in the contralateral gland hematoxylin and eosin (H&E)-stained section. Whole mounts were removed from the slide and carefully processed to produce high-quality histological sections that mirrored the quality of the original H&E-stained section in order to properly diagnose the unidentified gross abnormalities. Incorporation of this method into testing protocols that focus on human relevant chemical and endocrine disruptors exposure will increase the chances of identifying lesions in the gland and reduce the risk of false negative findings. This method can be especially invaluable when lesions are not always palpable during the course of the study or visible at necropsy, or when a single cross section of the mammary gland is otherwise used for detecting lesions. JF - Toxicologic Pathology AU - Tucker, Deirdre K AU - Foley, Julie F AU - Hayes-Bouknight, Schantel A AU - Fenton, Suzanne E AD - 1 .University of North Carolina at Chapel Hill, Curriculum in Toxicology, Chapel Hill, North Carolina, USA, fentonse@niehs.nih.gov Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1059 EP - 1064 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 7 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - mammary gland KW - whole mount KW - contralateral KW - development KW - breast KW - pathology KW - Autopsy KW - Pets KW - Mammary gland KW - Reviews KW - Endocrine disruptors KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827884688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Preparation+of+High-quality+Hematoxylin+and+Eosin-stained+Sections+from+Rodent+Mammary+Gland+Whole+Mounts+for+Histopathologic+Review&rft.au=Tucker%2C+Deirdre+K%3BFoley%2C+Julie+F%3BHayes-Bouknight%2C+Schantel+A%3BFenton%2C+Suzanne+E&rft.aulast=Tucker&rft.aufirst=Deirdre&rft.date=2016-10-01&rft.volume=44&rft.issue=7&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316660769 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 10 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Autopsy; Pets; Mammary gland; Endocrine disruptors; Reviews DO - http://dx.doi.org/10.1177/0192623316660769 ER - TY - JOUR T1 - Indoor concentrations of nitrogen dioxide and sulfur dioxide from burning solid fuels for cooking and heating in Yunnan Province, China AN - 1827880729; PQ0003704351 AB - The Chinese national pollution census has indicated that the domestic burning of solid fuels is an important contributor to nitrogen dioxide (NO sub(2)) and sulfur dioxide (SO sub(2)) emissions in China. To characterize indoor NO sub(2) and SO sub(2) air concentrations in relation to solid fuel use and stove ventilation in the rural counties of Xuanwei and Fuyuan, in Yunnan Province, China, which have among the highest lung cancer rates in the nation, a total of 163 participants in 30 selected villages were enrolled. Indoor 24-h NO sub(2) and SO sub(2) samples were collected in each household over two consecutive days. Compared to smoky coal, smokeless coal use was associated with higher NO sub(2) concentrations [geometric mean (GM) = 132 mu g/m super(3) for smokeless coal and 111 mu g/m super(3) for smoky coal, P = 0.065] and SO sub(2) [limit of detection = 24 mu g/m super(3); percentage detected (%Detect) = 86% for smokeless coal and 40% for smoky coal, P < 0.001]. Among smoky coal users, significant variation of NO sub(2) and SO sub(2) air concentrations was observed across different stove designs and smoky coal sources in both counties. Model construction indicated that the measurements of both pollutants were influenced by stove design. This exposure assessment study has identified high levels of NO sub(2) and SO sub(2) as a result of burning solid fuels for cooking and heating. JF - Indoor Air AU - Seow, W J AU - Downward, G S AU - Wei, H AU - Rothman, N AU - Reiss, B AU - Xu, J AU - Bassig, BA AU - Li, J AU - He, J AU - Hosgood, H D AU - Wu, G AU - Chapman, R S AU - Tian, L AU - Wei, F AU - Caporaso, N E AU - Vermeulen, R AU - Lan, Q AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 776 EP - 783 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 26 IS - 5 SN - 0905-6947, 0905-6947 KW - Pollution Abstracts; Toxicology Abstracts; Environment Abstracts KW - Ventilation KW - Fuels KW - Coal KW - Models KW - Nitrogen dioxide KW - Sulfur dioxide KW - Pollutants KW - Cooking KW - Emissions KW - Pollution KW - Lung cancer KW - Cancer KW - China, People's Rep., Yunnan Prov. KW - Villages KW - Households KW - Census KW - Burning KW - Indoor environments KW - Rural areas KW - P 0000:AIR POLLUTION KW - X 24350:Industrial Chemicals KW - ENA 01:Air Pollution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827880729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indoor+Air&rft.atitle=Indoor+concentrations+of+nitrogen+dioxide+and+sulfur+dioxide+from+burning+solid+fuels+for+cooking+and+heating+in+Yunnan+Province%2C+China&rft.au=Seow%2C+W+J%3BDownward%2C+G+S%3BWei%2C+H%3BRothman%2C+N%3BReiss%2C+B%3BXu%2C+J%3BBassig%2C+BA%3BLi%2C+J%3BHe%2C+J%3BHosgood%2C+H+D%3BWu%2C+G%3BChapman%2C+R+S%3BTian%2C+L%3BWei%2C+F%3BCaporaso%2C+N+E%3BVermeulen%2C+R%3BLan%2C+Q&rft.aulast=Seow&rft.aufirst=W&rft.date=2016-10-01&rft.volume=26&rft.issue=5&rft.spage=776&rft.isbn=&rft.btitle=&rft.title=Indoor+Air&rft.issn=09056947&rft_id=info:doi/10.1111%2Fina.12251 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Nitrogen dioxide; Sulfur dioxide; Ventilation; Pollutants; Fuels; Cooking; Census; Burning; Coal; Pollution; Lung cancer; Models; Cancer; Villages; Households; Emissions; Indoor environments; Rural areas; China, People's Rep., Yunnan Prov. DO - http://dx.doi.org/10.1111/ina.12251 ER - TY - JOUR T1 - Exploring stigma as a barrier to cancer service engagement with breast cancer survivors in Kampala, Uganda AN - 1825767518 AB - Objective To understand the role of stigma in the delay of cancer service engagement by women with breast cancer in Kampala, Uganda. Background Women in Sub-Saharan African countries are twice as likely to die from cancer as women in high-income countries, which is largely attributable to late diagnosis. While breast cancer-related stigma has been identified in Sub-Saharan Africa, limited research focuses on how stigma impacts the behavior of breast cancer patients in Uganda. Methods This qualitative study used a grounded theory approach to examine illness narratives from 20 breast cancer survivors in Uganda, gathered through semistructured interviews. Results Thematic analysis showed that perceived and internalized stigma associated with breast cancer influenced care engagement throughout illness, delaying engagement and inhibiting treatment completion. Women identified key factors for overcoming stigma including acceptance of diagnosis, social support, and understanding of breast cancer. Conclusion The growing burden of mortality associated with breast cancer in Uganda can be mitigated by improving early detection and treatment engagement through interventions which account for key psychosocial barriers such as stigma. JF - Psycho-Oncology AU - Meacham, Elizabeth AU - Orem, Jackson AU - Nakigudde, Gertrude AU - Zujewski, Jo Anne AU - Rao, Deepa AD - Department of Global Health, University of Washington, Seattle, WA, USA ; Uganda Cancer Institute, Kampala, Uganda ; Uganda Women's Cancer Support Organization (UWOCASO), Kampala, Uganda ; National Cancer Institute, Rockville, MD, USA ; Department of Global Health, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA ; Department of Global Health, University of Washington, Seattle, WA, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 1206 EP - 1211 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 25 IS - 10 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Breast cancer KW - Stigma KW - Women KW - Early intervention programmes KW - Mortality KW - Semistructured interviews KW - Survivors KW - Early warnings KW - Stigmatization KW - Clinical outcomes KW - Grounded theory KW - Narratives KW - Internalization KW - Diagnosis KW - Detection KW - Psychosocial factors KW - Social support KW - Kampala Uganda KW - Uganda UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1825767518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=Exploring+stigma+as+a+barrier+to+cancer+service+engagement+with+breast+cancer+survivors+in+Kampala%2C+Uganda&rft.au=Meacham%2C+Elizabeth%3BOrem%2C+Jackson%3BNakigudde%2C+Gertrude%3BZujewski%2C+Jo+Anne%3BRao%2C+Deepa&rft.aulast=Meacham&rft.aufirst=Elizabeth&rft.date=2016-10-01&rft.volume=25&rft.issue=10&rft.spage=1206&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.4215 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 John Wiley & Sons, Ltd. N1 - Last updated - 2016-10-05 N1 - SubjectsTermNotLitGenreText - Uganda; Kampala Uganda DO - http://dx.doi.org/10.1002/pon.4215 ER - TY - JOUR T1 - Estimating and testing interactions when explanatory variables are subject to non-classical measurement error AN - 1825333844 AB - Assessing interactions in linear regression models when covariates have measurement error (ME) is complex. We previously described regression calibration (RC) methods that yield consistent estimators and standard errors for interaction coefficients of normally distributed covariates having classical ME. Here we extend normal based RC (NBRC) and linear RC (LRC) methods to a non-classical ME model, and describe more efficient versions that combine estimates from the main study and internal sub-study. We apply these methods to data from the Observing Protein and Energy Nutrition (OPEN) study. Using simulations we show that (i) for normally distributed covariates efficient NBRC and LRC were nearly unbiased and performed well with sub-study size ≥200; (ii) efficient NBRC had lower MSE than efficient LRC; (iii) the naïve test for a single interaction had type I error probability close to the nominal significance level, whereas efficient NBRC and LRC were slightly anti-conservative but more powerful; (iv) for markedly non-normal covariates, efficient LRC yielded less biased estimators with smaller variance than efficient NBRC. Our simulations suggest that it is preferable to use: (i) efficient NBRC for estimating and testing interaction effects of normally distributed covariates and (ii) efficient LRC for estimating and testing interactions for markedly non-normal covariates. JF - Statistical Methods in Medical Research AU - Murad, Havi AU - Kipnis, Victor AU - Freedman, Laurence S AD - Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel-Hashomer, Israel ; Biometry Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA ; Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel-Hashomer, Israel Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 1991 EP - 2013 CY - London PB - Sage Publications Ltd. VL - 25 IS - 5 SN - 0962-2802 KW - Medical Sciences KW - measurement error (ME) KW - errors in variables KW - interaction KW - regression calibration (RC) KW - linear regression calibration KW - efficient regression calibration KW - type I error probability KW - power KW - Economic models KW - Measurement KW - Nutrition KW - Bias KW - Standard errors KW - Estimators UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1825333844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistical+Methods+in+Medical+Research&rft.atitle=Estimating+and+testing+interactions+when+explanatory+variables+are+subject+to+non-classical+measurement+error&rft.au=Murad%2C+Havi%3BKipnis%2C+Victor%3BFreedman%2C+Laurence+S&rft.aulast=Murad&rft.aufirst=Havi&rft.date=2016-10-01&rft.volume=25&rft.issue=5&rft.spage=1991&rft.isbn=&rft.btitle=&rft.title=Statistical+Methods+in+Medical+Research&rft.issn=09622802&rft_id=info:doi/10.1177%2F0962280213509720 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2013 N1 - Last updated - 2016-10-04 DO - http://dx.doi.org/10.1177/0962280213509720 ER - TY - JOUR T1 - Influence of Aspergillus fumigatus conidia viability on murine pulmonary microRNA and mRNA expression following subchronic inhalation exposure. AN - 1825217970; 27473664 AB - Personal exposure to fungal bioaerosols derived from contaminated building materials or agricultural commodities may induce or exacerbate a variety of adverse health effects. The genomic mechanisms that underlie pulmonary immune responses to fungal bioaerosols have remained unclear. The impact of fungal viability on the pulmonary microRNA and messenger RNA profiles that regulate murine immune responses was evaluated following subchronic inhalation exposure to Aspergillus fumigatus conidia. Three groups of naïve B6C3F1/N mice were exposed via nose-only inhalation to A. fumigatus viable conidia, heat-inactivated conidia (HIC), or HEPA-filtered air twice a week for 13 weeks. Total RNA was isolated from whole lung 24 and 48 h postfinal exposure and was further processed for gene expression and microRNA array analysis. The molecular network pathways between viable and HIC groups were evaluated. Comparison of data sets revealed increased Il4, Il13 and Il33 expression in mice exposed to viable vs. HIC. Of 415 microRNAs detected, approximately 50% were altered in mice exposed to viable vs. HIC 48 h postexposure. Significantly down-regulated (P ≤ 0.05) miR-29a-3p was predicted to regulate TGF-β3 and Clec7a, genes involved in innate responses to viable A. fumigatus. Also significantly down-regulated (P ≤ 0.05), miR-23b-3p regulates genes involved in pulmonary IL-13 and IL-33 responses and SMAD2, downstream of TGF-β signalling. Using Ingenuity Pathway Analysis, a novel interaction was identified between viable conidia and SMAD2/3. Examination of the pulmonary genetic profiles revealed differentially expressed genes and microRNAs following subchronic inhalation exposure to A. fumigatus. MicroRNAs regulating genes involved in the pulmonary immune responses were those with the greatest fold change. Specifically, germinating A. fumigatus conidia were associated with Clec7a and were predicted to interact with Il13 and Il33. Furthermore, altered microRNAs may serve as potential biomarkers to evaluate fungal exposure. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology AU - Croston, T L AU - Nayak, A P AU - Lemons, A R AU - Goldsmith, W T AU - Gu, J K AU - Germolec, D R AU - Beezhold, D H AU - Green, B J AD - Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV, USA. xzu9@cdc.gov. ; Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV, USA. ; Engineering and Control Technology Branch, Health Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV, USA. ; Biostatistics and Epidemiology Branch, Health Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV, USA. ; Toxicology Branch, DNTP/NIEHS, Research Triangle Park, NC, USA. ; Office of the Director, Health Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1315 EP - 1327 VL - 46 IS - 10 KW - Index Medicus KW - genetics KW - allergens and epitopes KW - animal models UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1825217970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+experimental+allergy+%3A+journal+of+the+British+Society+for+Allergy+and+Clinical+Immunology&rft.atitle=Influence+of+Aspergillus+fumigatus+conidia+viability+on+murine+pulmonary+microRNA+and+mRNA+expression+following+subchronic+inhalation+exposure.&rft.au=Croston%2C+T+L%3BNayak%2C+A+P%3BLemons%2C+A+R%3BGoldsmith%2C+W+T%3BGu%2C+J+K%3BGermolec%2C+D+R%3BBeezhold%2C+D+H%3BGreen%2C+B+J&rft.aulast=Croston&rft.aufirst=T&rft.date=2016-10-01&rft.volume=46&rft.issue=10&rft.spage=1315&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+allergy+%3A+journal+of+the+British+Society+for+Allergy+and+Clinical+Immunology&rft.issn=1365-2222&rft_id=info:doi/10.1111%2Fcea.12783 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cea.12783 ER - TY - JOUR T1 - Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date. AN - 1825214177; 27688118 AB - Oral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk. We identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world-wide between January, 2000 and February, 2016 using a combined keyword search on PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI were considered for full review. The majority of eligible studies that explored candidate gene associations for OPMD were small (N<200 cases), limiting their scope to provide strong inference for any SNP identified to date in any population. Commonly studied SNPs were genes of carcinogen metabolism (n=18 studies), DNA repair (n=11 studies), cell cycle control (n=8 studies), extra-cellular matrix alteration (n=8 studies) and immune-inflammatory (n=6 studies) pathways. Based on significant associations as reported by two or more studies, suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171; promotor region), TNFα (-308; rs800629), XPD (codon 751) and Gemin3 (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal or greater number of studies reported null or mixed associations for SNPs in GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null) and CYP1A1m1 (MspI site). Candidate gene association studies have not yielded consistent data on risk loci for OPMD. High-throughput genotyping approaches for OPMD, with concurrent efforts for oral cancer, could prove useful in identifying robust risk-loci to help understand early disease course susceptibility for oral cancer. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved. JF - Oral oncology AU - Shridhar, Krithiga AU - Aggarwal, Aastha AU - Walia, Gagandeep Kaur AU - Gulati, Smriti AU - Geetha, A V AU - Prabhakaran, D AU - Dhillon, Preet K AU - Rajaraman, Preetha AD - Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India. Electronic address: g.krithiga@phfi.org. ; Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India. Electronic address: aastha.aggrawal@phfi.org. ; Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India. Electronic address: gagandeep.k.walia@phfi.org. ; Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India. Electronic address: smriti5gulati@gmail.com. ; Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India. Electronic address: geetha.nambiar@phfi.org. ; Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India; Centre for Chronic Disease Control, Haryana, India; London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: dprabakaran@ccdcindia.org. ; Centre for Chronic Conditions and Injuries, Public Health Foundation of India, Haryana, India. Electronic address: preet.dhillon@phfi.org. ; Centre for Global Health, National Cancer Institute, Bethesda, USA. Electronic address: rajarama@mail.nih.gov. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 146 EP - 151 VL - 61 KW - Index Medicus KW - Polymorphisms KW - SNP KW - Oral potentially malignant disorders KW - Susceptibility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1825214177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oral+oncology&rft.atitle=Single+nucleotide+polymorphisms+as+markers+of+genetic+susceptibility+for+oral+potentially+malignant+disorders+risk%3A+Review+of+evidence+to+date.&rft.au=Shridhar%2C+Krithiga%3BAggarwal%2C+Aastha%3BWalia%2C+Gagandeep+Kaur%3BGulati%2C+Smriti%3BGeetha%2C+A+V%3BPrabhakaran%2C+D%3BDhillon%2C+Preet+K%3BRajaraman%2C+Preetha&rft.aulast=Shridhar&rft.aufirst=Krithiga&rft.date=2016-10-01&rft.volume=61&rft.issue=&rft.spage=146&rft.isbn=&rft.btitle=&rft.title=Oral+oncology&rft.issn=1879-0593&rft_id=info:doi/10.1016%2Fj.oraloncology.2016.08.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.oraloncology.2016.08.005 ER - TY - JOUR T1 - Association of P16-RBSP3 inactivation with phosphorylated RB1 overexpression in basal-parabasal layers of normal cervix unchanged during CACX development. AN - 1824545035; 27458253 AB - To understand the molecular mechanism of RB1 phosphorylation in basal-parabasal layers of normal cervix and during cervical cancer (CACX) development, we analyzed the alterations (expression/methylation/deletion/mutation) of RB1/phosphorylated RB1 (p-RB1) (ser807/811 and ser567) and two RB1 phosphorylation inhibitors, P16 and RBSP3, in disease-free normal cervical epithelium (n = 9), adjacent normal cervical epithelium of tumors (n = 70), cervical intraepithelial neoplasia (CIN; n = 28), CACX (n = 102) samples and two CACX cell lines. Immunohistochemical analysis revealed high/medium expression of RB1/p-RB1 (ser807/811 and ser567) and low expression of P16 and RBSP3 in proliferating basal-parabasal layers of majority of normal cervical epitheliums, irrespective of HPV16 infection. Interestingly, 35-52% samples showed high/medium expression of P16 in basal-parabasal layers of normal and had significant association with deleterious non-synonimous SNPs of P16. Methylation of P16 and RBSP3 in basal-parabasal layers of normal cervix (32 and 62%, respectively) showed concordance with their respective expressions in basal-parabasal layers. The methylation frequency of P16 and RBSP3 in basal-parabasal layers of normal did not change significantly in CIN and CACX. The deletion frequency of P16 and RB1 increased significantly with CACX progression. While, deletion of RBSP3 was high in CIN and comparable during CACX progression. P16 showed scattered and infrequent mutation in CACX. The alteration of P16 and RBSP3 was synergistic and showed association with overexpression of p-RB1 in tumors and associated with poor prognosis of patients. Thus, our data suggest that overexpression of p-RB1 in basal-parabasal layers of normal cervical epithelium was due to methylation/low functional-linked non-synonimous SNPs of P16 and RBSP3. This pattern was maintained during cervical carcinogenesis by additional deletion/mutation. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. JF - The Biochemical journal AU - Chakraborty, Chandraditya AU - Roychowdhury, Anirban AU - Samadder, Sudip AU - Roy, Anup AU - Mandal, Ranajit Kumar AU - Basu, Partha AU - Roychoudhury, Susanta AU - Panda, Chinmay Kumar AD - Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, West Bengal, India. ; North Bengal Medical College and Hospital, Siliguri, West Bengal, India. ; Department of Gynecologic Oncology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, West Bengal, India. ; Saroj Gupta Cancer Centre & Research Institute, MG Road, Thakurpukur, Kolkata, India. Y1 - 2016/10/01/ PY - 2016 DA - 2016 Oct 01 SP - 3221 EP - 3236 VL - 473 IS - 19 KW - Index Medicus KW - RB1 phosphorylation KW - HPV KW - basal–parabasal layers KW - CACX progression UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1824545035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Association+of+P16-RBSP3+inactivation+with+phosphorylated+RB1+overexpression+in+basal-parabasal+layers+of+normal+cervix+unchanged+during+CACX+development.&rft.au=Chakraborty%2C+Chandraditya%3BRoychowdhury%2C+Anirban%3BSamadder%2C+Sudip%3BRoy%2C+Anup%3BMandal%2C+Ranajit+Kumar%3BBasu%2C+Partha%3BRoychoudhury%2C+Susanta%3BPanda%2C+Chinmay+Kumar&rft.aulast=Chakraborty&rft.aufirst=Chandraditya&rft.date=2016-10-01&rft.volume=473&rft.issue=19&rft.spage=3221&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=1470-8728&rft_id=info:doi/10.1042%2FBCJ20160323 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1042/BCJ20160323 ER - TY - JOUR T1 - Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies. AN - 1823908570; 27619199 AB - Pre-clinical data in non-M3 AML supports the use of differentiation therapy, but clinical activity has been limited. Myeloid growth factors can enhance anti-leukemic activity of differentiating agents in vitro. We conducted companion phase II trials investigating sargramostim (GM-CSF) 125μg/m(2)/day plus 1) bexarotene (BEX) 300mg/m(2)/day or 2) entinostat (ENT) 4-8mg/m(2)/week in patients with MDS or relapsed/refractory AML. Primary endpoints were response after at least two treatment cycles and toxicity. 26 patients enrolled on the BEX trial had a median of 2 prior treatments and 24 enrolled on the ENT trial had a median of 1. Of 13 response-evaluable patients treated with BEX, the best response noted was hematologic improvement in neutrophils (HI-N) seen in 4 (31%) patients; none achieved complete (CR) or partial remission (PR). Of 10 treated with ENT, there was 1 (10%) partial remission (PR) and 2 (20%) with HI-N. The secondary endpoint responses of HI-N with each combination were accompanied by a numerical increase in ANC (BEX: 524 to 931 cells/mm(3), p=0.096; ENT: 578 to 1 137 cells/mm(3), p=0.15) without increasing marrow blasts. Shared grade 3-4 non-hematologic toxicities included febrile neutropenia, bone pain, fatigue, and dyspnea. GM-CSF plus either BEX or ENT are well tolerated in resistant and refractory MDS and AML and showed modest clinical and biologic activity, most commonly HI-N. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Leukemia research AU - Norsworthy, Kelly J AU - Cho, Eunpi AU - Arora, Jyoti AU - Kowalski, Jeanne AU - Tsai, Hua-Ling AU - Warlick, Erica AU - Showel, Margaret AU - Pratz, Keith W AU - Sutherland, Lesley A AU - Gore, Steven D AU - Ferguson, Anna AU - Sakoian, Sarah AU - Greer, Jackie AU - Espinoza-Delgado, Igor AU - Jones, Richard J AU - Matsui, William H AU - Smith, B Douglas AD - Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States. ; Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute of Emory University, Atlanta, GA, United States. ; Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD, United States. ; Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States. Electronic address: bdsmith@jhmi.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 90 EP - 97 VL - 49 KW - Index Medicus KW - Myelodysplastic syndrome KW - Differentiation KW - Entinostat KW - Bexarotene KW - Acute myeloid leukemia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823908570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+research&rft.atitle=Differentiation+therapy+in+poor+risk+myeloid+malignancies%3A+Results+of+companion+phase+II+studies.&rft.au=Norsworthy%2C+Kelly+J%3BCho%2C+Eunpi%3BArora%2C+Jyoti%3BKowalski%2C+Jeanne%3BTsai%2C+Hua-Ling%3BWarlick%2C+Erica%3BShowel%2C+Margaret%3BPratz%2C+Keith+W%3BSutherland%2C+Lesley+A%3BGore%2C+Steven+D%3BFerguson%2C+Anna%3BSakoian%2C+Sarah%3BGreer%2C+Jackie%3BEspinoza-Delgado%2C+Igor%3BJones%2C+Richard+J%3BMatsui%2C+William+H%3BSmith%2C+B+Douglas&rft.aulast=Norsworthy&rft.aufirst=Kelly&rft.date=2016-10-01&rft.volume=49&rft.issue=&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Leukemia+research&rft.issn=1873-5835&rft_id=info:doi/10.1016%2Fj.leukres.2016.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.leukres.2016.09.003 ER - TY - JOUR T1 - Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing AN - 1823846573 AB - Background Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and volume-based measures. This study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence. Methods Structural MRI scans were obtained from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused adolescents (ages 13-20). Abuse was operationalized using dichotomous and continuous measures. We examined associations between abuse and brain structure in several a priori-defined regions, controlling for parental education, age, sex, race, and total brain volume for subcortical GMV. Significance was evaluated at p < .05 with a false discovery rate correction. Results Child abuse exposure and severity were associated with reduced thickness in ventromedial prefrontal cortex (PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right middle, and right superior temporal gyri. Neither abuse measure predicted cortical surface area or subcortical GMV. Bilateral PHG thickness was inversely related to externalizing symptoms. Conclusions Child abuse, an experience characterized by a high degree of threat, is associated with reduced cortical thickness in ventromedial and ventrolateral PFC and medial and lateral temporal cortex in adolescence. Reduced PHG thickness may be a mediator linking abuse with externalizing psychopathology, although prospective research is needed to evaluate this possibility. JF - Journal of Child Psychology and Psychiatry AU - Gold, Andrea L AU - Sheridan, Margaret A AU - Peverill, Matthew AU - Busso, Daniel S AU - Lambert, Hilary K AU - Alves, Sonia AU - Pine, Daniel S AU - McLaughlin, Katie A AD - National Institutes of Health, Bethesda, MD, USA ; The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA ; University of Washington, Seattle, WA, USA ; Harvard Graduate School of Education, Cambridge, MA, USA ; National Institutes of Health, Bethesda, MD, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 1154 EP - 1164 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 10 KW - Psychology KW - Childhood abuse KW - Emotion recognition KW - Cortex KW - Parents KW - Discovery KW - Severity KW - Emotional abuse KW - Ventromedial prefrontal cortex KW - Abused children KW - Brain structure KW - Child abuse KW - Magnetic resonance imaging KW - Race KW - Sexual abuse KW - Psychopathology KW - Adolescents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823846573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Childhood+abuse+and+reduced+cortical+thickness+in+brain+regions+involved+in+emotional+processing&rft.au=Gold%2C+Andrea+L%3BSheridan%2C+Margaret+A%3BPeverill%2C+Matthew%3BBusso%2C+Daniel+S%3BLambert%2C+Hilary+K%3BAlves%2C+Sonia%3BPine%2C+Daniel+S%3BMcLaughlin%2C+Katie+A&rft.aulast=Gold&rft.aufirst=Andrea&rft.date=2016-10-01&rft.volume=57&rft.issue=10&rft.spage=1154&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12630 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-09-28 DO - http://dx.doi.org/10.1111/jcpp.12630 ER - TY - JOUR T1 - mTOR inhibition prevents rapid-onset of carcinogen-induced malignancies in a novel inducible HPV-16 E6/E7 mouse model. AN - 1823456305; 27538837 AB - The rising incidence of human papillomavirus (HPV)-associated malignancies, especially for oropharyngeal cancers, has highlighted the urgent need to understand how the interplay between high-risk HPV oncogenes and carcinogenic exposure results in squamous cell carcinoma (SCC) development. Here, we describe an inducible mouse model expressing high risk HPV-16 E6/E7 oncoproteins in adults, bypassing the impact of these viral genes during development. HPV-16 E6/E7 genes were targeted to the basal squamous epithelia in transgenic mice using a doxycycline inducible cytokeratin 5 promoter (cK5-rtTA) system. After doxycycline induction, both E6 and E7 were highly expressed, resulting in rapid epidermal hyperplasia with a remarkable expansion of the proliferative cell compartment to the suprabasal layers. Surprisingly, in spite of the massive growth of epithelial cells and their stem cell progenitors, HPV-E6/E7 expression was not sufficient to trigger mTOR activation, a key oncogenic driver in HPV-associated malignancies, and malignant progression to SCC. However, these mice develop SCC rapidly after a single exposure to a skin carcinogen, DMBA, which was increased by the prolonged exposure to a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Thus, only few oncogenic hits may be sufficient to induce cancer in E6/E7 expressing cells. All HPV-E6/E7 expressing SCC lesions exhibited increased mTOR activation. Remarkably, rapamycin, an mTOR inhibitor, abolished tumor development when administered to HPV-E6/E7 mice prior to DMBA exposure. Our findings revealed that mTOR inhibition protects HPV-E6/E7 expressing tissues form SCC development upon carcinogen exposure, thus supporting the potential clinical use of mTOR inhibitors as a molecular targeted approach for prevention of HPV-associated malignancies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. JF - Carcinogenesis AU - Callejas-Valera, Juan Luis AU - Iglesias-Bartolome, Ramiro AU - Amornphimoltham, Panomwat AU - Palacios-Garcia, Julia AU - Martin, Daniel AU - Califano, Joseph A AU - Molinolo, Alfredo A AU - Gutkind, J Silvio AD - Developmental Skin Biology Section (HNB-254), NIH/NIAMS Building 50., Bethesda, MD 20814-4340, USA. ; Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, 28049 Spain and. ; Oral and Pharyngeal Cancer Branch, NIH/NIDCR, Building 30, Bethesda, MD 20892-2190, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1014 EP - 1025 VL - 37 IS - 10 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823456305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=mTOR+inhibition+prevents+rapid-onset+of+carcinogen-induced+malignancies+in+a+novel+inducible+HPV-16+E6%2FE7+mouse+model.&rft.au=Callejas-Valera%2C+Juan+Luis%3BIglesias-Bartolome%2C+Ramiro%3BAmornphimoltham%2C+Panomwat%3BPalacios-Garcia%2C+Julia%3BMartin%2C+Daniel%3BCalifano%2C+Joseph+A%3BMolinolo%2C+Alfredo+A%3BGutkind%2C+J+Silvio&rft.aulast=Callejas-Valera&rft.aufirst=Juan&rft.date=2016-10-01&rft.volume=37&rft.issue=10&rft.spage=1014&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=1460-2180&rft_id=info:doi/10.1093%2Fcarcin%2Fbgw086 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/carcin/bgw086 ER - TY - JOUR T1 - Gender differences in cancer susceptibility: role of oxidative stress. AN - 1823452462; 27481070 AB - Cancer is a leading cause of death worldwide and environmental factors, including chemicals, have been suggested as major etiological incitements. Cancer statistics indicates that men get more cancer than women. However, differences in the known risk factors including life style or occupational exposure only offer partial explanation. Using a text mining tool, we have investigated the scientific literature concerning male- and female-specific rat carcinogens that induced tumors only in one gender in NTP 2-year cancer bioassay. Our evaluation shows that oxidative stress, although frequently reported for both male- and female-specific rat carcinogens, was mentioned significantly more in literature concerning male-specific rat carcinogens. Literature analysis of testosterone and estradiol showed the same pattern. Tox21 high-throughput assay results, although showing only weak association of oxidative stress-related processes for male- and female-specific rat carcinogens, provide additional support. We also analyzed the literature concerning 26 established human carcinogens (IARC group 1). Oxidative stress was more frequently reported for the majority of these carcinogens, and the Tox21 data resembled that of male-specific rat carcinogens. Thus, our data, based on about 600000 scientific abstracts and Tox21 screening assays, suggest a link between male-specific carcinogens, testosterone and oxidative stress. This implies that a different cellular response to oxidative stress in men and women may be a critical factor in explaining the greater cancer susceptibility observed in men. Although the IARC carcinogens are classified as human carcinogens, their classification largely based on epidemiological evidence from male cohorts, which raises the question whether carcinogen classifications should be gender specific. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. JF - Carcinogenesis AU - Ali, Imran AU - Högberg, Johan AU - Hsieh, Jui-Hua AU - Auerbach, Scott AU - Korhonen, Anna AU - Stenius, Ulla AU - Silins, Ilona AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA and. ; Department of Theoretical and Applied Linguistics, University of Cambridge, Cambridge CB3 9DA, UK. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 985 EP - 992 VL - 37 IS - 10 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823452462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Gender+differences+in+cancer+susceptibility%3A+role+of+oxidative+stress.&rft.au=Ali%2C+Imran%3BH%C3%B6gberg%2C+Johan%3BHsieh%2C+Jui-Hua%3BAuerbach%2C+Scott%3BKorhonen%2C+Anna%3BStenius%2C+Ulla%3BSilins%2C+Ilona&rft.aulast=Ali&rft.aufirst=Imran&rft.date=2016-10-01&rft.volume=37&rft.issue=10&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=1460-2180&rft_id=info:doi/10.1093%2Fcarcin%2Fbgw076 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/carcin/bgw076 ER - TY - JOUR T1 - Identification of Novel Plasmodium falciparum Hexokinase Inhibitors with Antiparasitic Activity. AN - 1823035124; 27458230 AB - Plasmodium falciparum, the deadliest species of malaria parasites, is dependent on glycolysis for the generation of ATP during the pathogenic red blood cell stage. Hexokinase (HK) catalyzes the first step in glycolysis, transferring the γ-phosphoryl group of ATP to glucose to yield glucose-6-phosphate. Here, we describe the validation of a high-throughput assay for screening small-molecule collections to identify inhibitors of the P. falciparum HK (PfHK). The assay, which employed an ADP-Glo reporter system in a 1,536-well-plate format, was robust with a signal-to-background ratio of 3.4 ± 1.2, a coefficient of variation of 6.8% ± 2.9%, and a Z'-factor of 0.75 ± 0.08. Using this assay, we screened 57,654 molecules from multiple small-molecule collections. Confirmed hits were resolved into four clusters on the basis of structural relatedness. Multiple singleton hits were also identified. The most potent inhibitors had 50% inhibitory concentrations as low as ∼1 μM, and several were found to have low-micromolar 50% effective concentrations against asexual intraerythrocytic-stage P. falciparum parasites. These molecules additionally demonstrated limited toxicity against a panel of mammalian cells. The identification of PfHK inhibitors with antiparasitic activity using this validated screening assay is encouraging, as it justifies additional HTS campaigns with more structurally amenable libraries for the identification of potential leads for future therapeutic development. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Antimicrobial agents and chemotherapy AU - Davis, Mindy I AU - Patrick, Stephen L AU - Blanding, Walker M AU - Dwivedi, Varun AU - Suryadi, Jimmy AU - Golden, Jennifer E AU - Coussens, Nathan P AU - Lee, Olivia W AU - Shen, Min AU - Boxer, Matthew B AU - Hall, Matthew D AU - Sharlow, Elizabeth R AU - Drew, Mark E AU - Morris, James C AD - National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, Maryland, USA. ; Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA. ; Departments of Microbial Infection and Immunity and Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus, Ohio, USA. ; School of Pharmacy, Department of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA. ; Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA. ; Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA jmorri2@clemson.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 6023 EP - 6033 VL - 60 IS - 10 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823035124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Identification+of+Novel+Plasmodium+falciparum+Hexokinase+Inhibitors+with+Antiparasitic+Activity.&rft.au=Davis%2C+Mindy+I%3BPatrick%2C+Stephen+L%3BBlanding%2C+Walker+M%3BDwivedi%2C+Varun%3BSuryadi%2C+Jimmy%3BGolden%2C+Jennifer+E%3BCoussens%2C+Nathan+P%3BLee%2C+Olivia+W%3BShen%2C+Min%3BBoxer%2C+Matthew+B%3BHall%2C+Matthew+D%3BSharlow%2C+Elizabeth+R%3BDrew%2C+Mark+E%3BMorris%2C+James+C&rft.aulast=Davis&rft.aufirst=Mindy&rft.date=2016-10-01&rft.volume=60&rft.issue=10&rft.spage=6023&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=1098-6596&rft_id=info:doi/10.1128%2FAAC.00914-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1128/AAC.00914-16 ER - TY - JOUR T1 - Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice. AN - 1823032636; 27359351 AB - Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α-hydroxylase (Cyp7a1) and sterol 12α-hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and altered bile acid composition, with the α/β-muricholic acid proportion in bile increased by 2.6-fold and taurocholic acid (TCA) level reduced by 71%. Overexpression of Cyp8b1 or concurrent overexpression of Cyp7a1 and Cyp8b1 normalizes TCA level, bile acid composition, and intestinal cholesterol absorption. Activation of FXR inhibits intestinal cholesterol absorption by modulation of bile acid pool size and composition, thus leading to increased RCT. Targeting hepatic FXR and/or bile acids may be useful for boosting RCT and preventing the development of atherosclerosis. (Hepatology 2016;64:1072-1085). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Xu, Yang AU - Li, Fei AU - Zalzala, Munaf AU - Xu, Jiesi AU - Gonzalez, Frank J AU - Adorini, Luciano AU - Lee, Yoon-Kwang AU - Yin, Liya AU - Zhang, Yanqiao AD - Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD. ; Intercept Pharmaceuticals, New York, NY. ; Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH. lyin@neomed.edu. ; Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH. yzhang@neomed.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1072 EP - 1085 VL - 64 IS - 4 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823032636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Farnesoid+X+receptor+activation+increases+reverse+cholesterol+transport+by+modulating+bile+acid+composition+and+cholesterol+absorption+in+mice.&rft.au=Xu%2C+Yang%3BLi%2C+Fei%3BZalzala%2C+Munaf%3BXu%2C+Jiesi%3BGonzalez%2C+Frank+J%3BAdorini%2C+Luciano%3BLee%2C+Yoon-Kwang%3BYin%2C+Liya%3BZhang%2C+Yanqiao&rft.aulast=Xu&rft.aufirst=Yang&rft.date=2016-10-01&rft.volume=64&rft.issue=4&rft.spage=1072&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28712 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28712 ER - TY - JOUR T1 - Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure. AN - 1823028740; 27613105 AB - The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland (MG) development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ MG development was assessed in females of the Harlan Sprague-Dawley (Hsd:SD), Charles River Sprague-Dawley (Crl:SD), and Charles River Long-Evans (Crl:LE) rat strains at postnatal days 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Although body weight (BW) was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre- and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in the rate of MG development across commonly used strains, which is independent of BW and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. © The Author(s) 2016. JF - Toxicologic pathology AU - Stanko, Jason P AU - Kissling, Grace E AU - Chappell, Vesna A AU - Fenton, Suzanne E AD - National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. ; Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. ; National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA fentonse@niehs.nih.gov. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1021 EP - 1033 VL - 44 IS - 7 KW - Index Medicus KW - female reproduction KW - development KW - carcinogenesis KW - animal models KW - mammary gland KW - rat. KW - epithelium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1823028740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Differences+in+the+Rate+of+in+Situ+Mammary+Gland+Development+and+Other+Developmental+Endpoints+in+Three+Strains+of+Female+Rat+Commonly+Used+in+Mammary+Carcinogenesis+Studies%3A+Implications+for+Timing+of+Carcinogen+Exposure.&rft.au=Stanko%2C+Jason+P%3BKissling%2C+Grace+E%3BChappell%2C+Vesna+A%3BFenton%2C+Suzanne+E&rft.aulast=Stanko&rft.aufirst=Jason&rft.date=2016-10-01&rft.volume=44&rft.issue=7&rft.spage=1021&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=1533-1601&rft_id=info:doi/10.1177%2F0192623316655222 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0192623316655222 ER - TY - JOUR T1 - Ranking Differential Drug Activities from Dose-Response Synthetic Lethality Screens. AN - 1822468381; 27112173 AB - Synthetic lethal screens are used to discover new combination treatments for cancer. In traditional high-throughput synthetic lethal screens, compounds are tested at a single dose, and hit selection is based on threshold activity values from the variance of the efficacy of the compounds tested. The limitation of the single-dose screening for synthetic lethal screens is that it does not allow for the robust detection of differential activities from compound collections with a broad range of potencies and efficacies. There is therefore a need to develop screening approaches that enable the identification of compounds with synthetic lethal effects based on changes in both potency and efficacy. Here we describe the implementation of a dose response-based synthetic lethal screen to find drugs that enhance or mitigate the cytotoxic effect of an immunotoxin protein (HA22). We developed a data analysis framework for the selection of compounds with enhancing or mitigating cytotoxic activities based on the use of dose-response parameters. The data analysis framework includes an ensemble ranking approach that allows the use of multiple dose-response parameters in a nonparametric fashion. Quantitative high-throughput screening (HTS) enables the identification of compounds with synthetic lethal activity not identified by single-dose HTS. © 2016 Society for Laboratory Automation and Screening. JF - Journal of biomolecular screening AU - Guha, Rajarshi AU - Mathews Griner, Lesley A AU - Keller, Jonathan M AU - Zhang, Xiaohu AU - Fitzgerald, David AU - Antignani, Antonella AU - Pastan, Ira AU - Thomas, Craig J AU - Ferrer, Marc AD - Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA. ; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA ferrerm@mail.nih.gov. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 942 EP - 955 VL - 21 IS - 9 KW - Index Medicus KW - synthetic lethal screen KW - qHTS KW - immunotoxin KW - ranking UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1822468381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biomolecular+screening&rft.atitle=Ranking+Differential+Drug+Activities+from+Dose-Response+Synthetic+Lethality+Screens.&rft.au=Guha%2C+Rajarshi%3BMathews+Griner%2C+Lesley+A%3BKeller%2C+Jonathan+M%3BZhang%2C+Xiaohu%3BFitzgerald%2C+David%3BAntignani%2C+Antonella%3BPastan%2C+Ira%3BThomas%2C+Craig+J%3BFerrer%2C+Marc&rft.aulast=Guha&rft.aufirst=Rajarshi&rft.date=2016-10-01&rft.volume=21&rft.issue=9&rft.spage=942&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomolecular+screening&rft.issn=1552-454X&rft_id=info:doi/10.1177%2F1087057116644890 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/1087057116644890 ER - TY - JOUR T1 - Cocaine attenuates blood flow but not neuronal responses to stimulation while preserving neurovascular coupling for resting brain activity. AN - 1821790226; 26666202 AB - Cocaine affects neuronal activity and constricts cerebral blood vessels, making it difficult to determine whether cocaine-induced changes in cerebral blood flow (CBF) reflect neuronal activation or its vasoactive effects. Here we assessed the effects of acute cocaine on both resting-state and stimulation responses to investigate cocaine's effects on neurovascular coupling and to differentiate its effects on neuronal activity from its vasoactive actions. We concurrently measured cortical field potentials via thinned-skull electroencephalography recordings and CBF with laser Doppler flowmetry in the rat's somatosensory cortex for both resting state and forepaw stimulation before and following cocaine administration (1 mg kg(-1), intravenously). Results show both resting-state field potentials and CBF were depressed after cocaine administration (19.8±4.7% and 52.1±13.4%, respectively) and these changes were strongly correlated with each other (r=0.81, P<0.001), indicating that cocaine did not affect neurovascular coupling at rest and that the reduction in resting CBF reflected reduction in synchronized spontaneous neuronal activity rather than vasoconstriction. In contrast, the forepaw stimulation-evoked neuronal activity was not changed by cocaine (P=0.244), whereas the CBF to the stimulation was reduced 49.9±2.6% (P=0.028) gradually recovering ∼20 min after cocaine injection, indicating that neurovascular coupling during stimulation was temporarily disrupted by cocaine. Neurovascular uncoupling by cocaine during stimulation but not during rest indicates that distinct processes might underlie neurovascular regulation for both stimulation and spontaneous activity. The greater reductions by cocaine to the stimulation-induced CBF increases than to the background CBF should be considered when interpreting functional MRI studies comparing activation responses between controls and cocaine abusers. Neurovascular uncoupling could contribute to cocaine's neurotoxicity, particularly for stimulation conditions when CBF might be insufficient to cover for the energetic demands of neuronal tissue. JF - Molecular psychiatry AU - Chen, W AU - Liu, P AU - Volkow, N D AU - Pan, Y AU - Du, C AD - Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA. ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1408 EP - 1416 VL - 21 IS - 10 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1821790226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+psychiatry&rft.atitle=Cocaine+attenuates+blood+flow+but+not+neuronal+responses+to+stimulation+while+preserving+neurovascular+coupling+for+resting+brain+activity.&rft.au=Chen%2C+W%3BLiu%2C+P%3BVolkow%2C+N+D%3BPan%2C+Y%3BDu%2C+C&rft.aulast=Chen&rft.aufirst=W&rft.date=2016-10-01&rft.volume=21&rft.issue=10&rft.spage=1408&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=1476-5578&rft_id=info:doi/10.1038%2Fmp.2015.185 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/mp.2015.185 ER - TY - JOUR T1 - Preemptive Bone Marrow Transplantation and Event-Free Survival in Fanconi Anemia. AN - 1821097821; 27345141 AB - Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome associated with high risks of severe bone marrow failure (BMF), acute myeloid leukemia (AML), and solid tumors (ST). Bone marrow transplantation (BMT) provides a theoretical cure for hematologic risks (BMF, AML), but it introduces uncertain risks of transplantation-related mortality (TRM) and carcinogenicity. We developed a mathematical (Markov) decision model to estimate event-free survival (EFS) conditional on age based on per-year cause-specific hazard rates. We assumed that preemptive (PE) BMT eliminates the risks of BMF and AML, but it may introduce independent risks of TRM or influence the trajectory to ST. Our model suggested that the expected mean EFS in FA is higher for PE-BMT at young ages, with minimal risk of TRM and with little carcinogenicity. PE-BMT in adults decreased expected EFS because of the greater competing risk of ST in adulthood. Estimates of EFS conditioned on attained age may be used in shared decision-making when clinicians must counsel patients using limited data. Our methods may be used to model early transplantation in other blood disorders for which hematopoietic stem cell transplantation mitigates some but not all of the risks. Published by Elsevier Inc. JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Khan, Nicholas E AU - Rosenberg, Philip S AU - Alter, Blanche P AD - Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Electronic address: alterb@mail.nih.gov. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1888 EP - 1892 VL - 22 IS - 10 KW - Index Medicus KW - Markov model KW - Preemptive transplantation KW - Fanconi anemia KW - Decision analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1821097821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=Preemptive+Bone+Marrow+Transplantation+and+Event-Free+Survival+in+Fanconi+Anemia.&rft.au=Khan%2C+Nicholas+E%3BRosenberg%2C+Philip+S%3BAlter%2C+Blanche+P&rft.aulast=Khan&rft.aufirst=Nicholas&rft.date=2016-10-01&rft.volume=22&rft.issue=10&rft.spage=1888&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=1523-6536&rft_id=info:doi/10.1016%2Fj.bbmt.2016.06.018 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bbmt.2016.06.018 ER - TY - JOUR T1 - Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin fusion protein for lung cancer therapy. AN - 1820603458; 27507537 AB - Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non-specific toxicity. To overcome both obstacles we developed RG7787, a de-immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24). Reactivity of RG7787 with sera from immunotoxin-treated patients was >1000 fold reduced. In vitro RG7787 inhibited cell viability of lung cancer cell lines with picomolar potency. The pharmacokinetic properties of RG7787 in rodents were comparable to SS1P, yet it was tolerated up to 10 fold better without causing severe vascular leak syndrome or hepatotoxicity. A pharmacokinetic/pharmacodynamic model developed based on NCI-H596 xenograft studies showed that for RG7787 and SS1P, their in vitro and in vivo potencies closely correlate. At optimal doses of 2-3 mg/kg RG7787 is more efficacious than SS1P. Even large, well established tumors (600 mm(3)) underwent remission during three treatment cycles with RG7787. Also in two patient-derived lung cancer xenograft models, Lu7336 and Lu7187, RG7787 showed anti-tumor efficacy. In monotherapy two treatment cycles were moderately efficacious in the Lu7336 model but showed good anti-tumor activity in the KRAS mutant Lu7187 model (26% and 80% tumor growth inhibition, respectively). Combination of RG7787 with standard chemotherapies further enhanced efficacy in both models achieving near complete eradication of Lu7187 tumors. Copyright © 2016 Federation of European Biochemical Societies. All rights reserved. JF - Molecular oncology AU - Bauss, Frieder AU - Lechmann, Martin AU - Krippendorff, Ben-Fillippo AU - Staack, Roland AU - Herting, Frank AU - Festag, Matthias AU - Imhof-Jung, Sabine AU - Hesse, Friederike AU - Pompiati, Marc AU - Kollmorgen, Gwendlyn AU - da Silva Mateus Seidl, Rita AU - Bossenmaier, Birgit AU - Lau, Wilma AU - Schantz, Christian AU - Stracke, Jan O AU - Brinkmann, Ulrich AU - Onda, Masanori AU - Pastan, Ira AU - Bosslet, Klaus AU - Niederfellner, Gerhard AD - Roche Pharma Research & Early Development (pRED), Discovery Oncology, Innovation Center Munich, Roche Diagnostics GmbH Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany. ; Roche Pharma Research & Early Development (pRED), Pharmaceutical Sciences, Innovation Center Munich, Roche Diagnostics GmbH Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany. ; Roche pRED Innovation Center Basel, Pharmaceutical Sciences, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland. ; Roche Pharma Research & Early Development (pRED), Large Molecule Research, Innovation Center Munich, Roche Diagnostics GmbH Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany. ; Roche Pharma Research & Early Development (pRED), Large Molecule Research, Innovation Center Munich, Roche Diagnostics GmbH Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany; Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland. ; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; Roche Pharma Research & Early Development (pRED), Discovery Oncology, Innovation Center Munich, Roche Diagnostics GmbH Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany. Electronic address: gerhard.niederfellner@roche.com. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1317 EP - 1329 VL - 10 IS - 8 KW - Index Medicus KW - Targeted therapy KW - De-immunization KW - Patient-derived xenografts KW - Pharmacokinetics KW - Immunotoxin KW - Lung cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1820603458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+oncology&rft.atitle=Characterization+of+a+re-engineered%2C+mesothelin-targeted+Pseudomonas+exotoxin+fusion+protein+for+lung+cancer+therapy.&rft.au=Bauss%2C+Frieder%3BLechmann%2C+Martin%3BKrippendorff%2C+Ben-Fillippo%3BStaack%2C+Roland%3BHerting%2C+Frank%3BFestag%2C+Matthias%3BImhof-Jung%2C+Sabine%3BHesse%2C+Friederike%3BPompiati%2C+Marc%3BKollmorgen%2C+Gwendlyn%3Bda+Silva+Mateus+Seidl%2C+Rita%3BBossenmaier%2C+Birgit%3BLau%2C+Wilma%3BSchantz%2C+Christian%3BStracke%2C+Jan+O%3BBrinkmann%2C+Ulrich%3BOnda%2C+Masanori%3BPastan%2C+Ira%3BBosslet%2C+Klaus%3BNiederfellner%2C+Gerhard&rft.aulast=Bauss&rft.aufirst=Frieder&rft.date=2016-10-01&rft.volume=10&rft.issue=8&rft.spage=1317&rft.isbn=&rft.btitle=&rft.title=Molecular+oncology&rft.issn=1878-0261&rft_id=info:doi/10.1016%2Fj.molonc.2016.07.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.molonc.2016.07.003 ER - TY - JOUR T1 - Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines. AN - 1820601293; 27474751 AB - The UDP-glucuronosyltransferase (UGT) 2B enzymes are important in the detoxification of a variety of endogenous and exogenous compounds, including many hormones, drugs, and carcinogens. Identifying novel mechanisms governing their expression is important in understanding patient-specific response to drugs and cancer risk factors. In silico prediction algorithm programs were used to screen for microRNAs (miRNAs) as potential regulators of UGT2B enzymes, with miR-216b-5p identified as a potential candidate. Luciferase data suggested the presence of a functional miR-216b-5p binding motif within the 3' untranslated regions of UGTs 2B7, 2B4, and 2B10. Overexpression of miR-216b-5p mimics significantly repressed UGT2B7 (P < 0.001) and UGT2B10 (P = 0.0018) mRNA levels in HuH-7 cells and UGT2B4 (P < 0.001) and UGT2B10 (P = 0.018) mRNA in Hep3B cells. UGT2B7 protein levels were repressed in both HuH-7 and Hep3B cells in the presence of increasing miR-216b-5p concentrations, corresponding with significant (P < 0.001 and P = 0.011, respectively) decreases in glucuronidation activity against the UGT2B7-specific substrate epirubicin. Inhibition of endogenous miR-216b-5p levels significantly increased UGT2B7 mRNA levels in HuH-7 (P = 0.021) and Hep3B (P = 0.0068) cells, and increased epirubicin glucuronidation by 85% (P = 0.057) and 50% (P = 0.012) for HuH-7 and Hep3B cells, respectively. UGT2B4 activity against codeine and UGT2B10 activity against nicotine were significantly decreased in both HuH-7 and Hep3B cells (P < 0.001 and P = 0.0048, and P = 0.017 and P = 0.043, respectively) after overexpression of miR-216b-5p mimic. This is the first evidence that miRNAs regulate UGT 2B7, 2B4, and 2B10 expression, and that miR-216b-5p regulation of UGT2B proteins may be important in regulating the metabolism of UGT2B substrates. Copyright © 2016 by The Author(s). JF - The Journal of pharmacology and experimental therapeutics AU - Dluzen, Douglas F AU - Sutliff, Aimee K AU - Chen, Gang AU - Watson, Christy J W AU - Ishmael, Faoud T AU - Lazarus, Philip AD - National Institute on Aging, National Institutes of Health, Baltimore, Maryland (D.F.D.); Department of Pulmonary Medicine, Penn State University College of Medicine, Hershey, Pennsylvania (F.T.I.); and Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington (A.K.S., G.C., C.W., P.L.). ; National Institute on Aging, National Institutes of Health, Baltimore, Maryland (D.F.D.); Department of Pulmonary Medicine, Penn State University College of Medicine, Hershey, Pennsylvania (F.T.I.); and Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington (A.K.S., G.C., C.W., P.L.) phil.lazarus@wsu.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 182 EP - 193 VL - 359 IS - 1 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1820601293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Regulation+of+UGT2B+Expression+and+Activity+by+miR-216b-5p+in+Liver+Cancer+Cell+Lines.&rft.au=Dluzen%2C+Douglas+F%3BSutliff%2C+Aimee+K%3BChen%2C+Gang%3BWatson%2C+Christy+J+W%3BIshmael%2C+Faoud+T%3BLazarus%2C+Philip&rft.aulast=Dluzen&rft.aufirst=Douglas&rft.date=2016-10-01&rft.volume=359&rft.issue=1&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=1521-0103&rft_id=info:doi/10.1124%2Fjpet.116.235044 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/jpet.116.235044 ER - TY - JOUR T1 - Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4+ T Cell Responses in Coincident Filarial Infection. AN - 1820600969; 27566825 AB - Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10-induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite- and allergen-specific CD4(+) T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil](+)allergy [A](+)) were compared with the responses to three appropriate control groups (Fil(-)A(-) [n = 13], Fil(-)A(+) [n = 12], Fil(+)A(-) [n = 11]). The most important findings revealed that Fil(+)A(+) had marked (p < 0.0001 for all cytokines) increases in parasite Ag-driven Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), and the regulatory (IL-10) cytokines when compared with Fil(+)A(-) Moreover, using multiparameter flow cytometry, filarial parasite Ag induced a marked increase in not only the frequency of CD4(+) T cells producing IL-4, IL-5, IL-2, and TNF-α in Fil(+)A(+) when compared with Fil(+)A(-) patients, but also in the frequencies of polyfunctional Th2-like (CD4(+)IL-4(+)IL-5(+) and CD4(+)IL-2(+)IL-4(+)IL-5(+)TNF-α(+)) cells. The Th2-associated responses seen in the Fil(+)A(+) group were correlated with serum IgE levels (p < 0.01, r = 0.5165 for IL-4; p < 0.001, r = 0.5544 for IL-5; and p < 0.001, r = 0.4901 for IL-13) and levels of circulating eosinophils (p < 0.0116, r = 0.5656) and their degranulation/activation products (major basic protein [p < 0.001, r = 0.7353] and eosinophil-derived neurotoxin [p < 0.01, r = 0.7059]). CD4(+) responses to allergen were not different (to a large extent) among the groups. Taken together, our data suggest that allergic sensitization coincident with filarial infection drives parasite Ag-specific T cell hyperresponsiveness, which is characterized largely by an augmented Th2-dominated immune response. Copyright © 2016 by The American Association of Immunologists, Inc. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Gazzinelli-Guimarães, Pedro H AU - Bonne-Année, Sandra AU - Fujiwara, Ricardo T AU - Santiago, Helton C AU - Nutman, Thomas B AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; and. ; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ; Department of Parasitology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; and. ; Department of Immunology and Biochemistry, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil. ; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; tnutman@niaid.nih.gov. Y1 - 2016/10/01/ PY - 2016 DA - 2016 Oct 01 SP - 2772 EP - 2779 VL - 197 IS - 7 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1820600969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Allergic+Sensitization+Underlies+Hyperreactive+Antigen-Specific+CD4%2B+T+Cell+Responses+in+Coincident+Filarial+Infection.&rft.au=Gazzinelli-Guimar%C3%A3es%2C+Pedro+H%3BBonne-Ann%C3%A9e%2C+Sandra%3BFujiwara%2C+Ricardo+T%3BSantiago%2C+Helton+C%3BNutman%2C+Thomas+B&rft.aulast=Gazzinelli-Guimar%C3%A3es&rft.aufirst=Pedro&rft.date=2016-10-01&rft.volume=197&rft.issue=7&rft.spage=2772&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=1550-6606&rft_id=info:doi/10.4049%2Fjimmunol.1600829 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.4049/jimmunol.1600829 ER - TY - JOUR T1 - Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer. AN - 1819905486; 26780387 AB - To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone. Eligible patients with metastatic castration-resistant prostate cancer enrolled in this open-label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m(2) ) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3-week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy. A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events (AEs) being haematological, and were ascertained by weekly blood counts. Twenty-nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non-haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of >30, >50 and >90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively. With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis-generating data would require randomized trials to confirm the findings. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - BJU international AU - Madan, Ravi A AU - Karzai, Fatima H AU - Ning, Yang-Min AU - Adesunloye, Bamidele A AU - Huang, Xuan AU - Harold, Nancy AU - Couvillon, Anna AU - Chun, Guinevere AU - Cordes, Lisa AU - Sissung, Tristan AU - Beedie, Shaunna L AU - Dawson, Nancy A AU - Theoret, Marc R AU - McLeod, David G AU - Rosner, Inger AU - Trepel, Jane B AU - Lee, Min-Jung AU - Tomita, Yusuke AU - Lee, Sunmin AU - Chen, Clara AU - Steinberg, Seth M AU - Arlen, Philip M AU - Gulley, James L AU - Figg, William D AU - Dahut, William L AD - Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA. ; Center for Prostate Disease Research, Walter Reed National Military Medical Center, Bethesda, MD, USA. ; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; Radiology and Imaging Sciences, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. wdfigg@helix.nih.gov. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 590 EP - 597 VL - 118 IS - 4 KW - Index Medicus KW - combinationation therapy KW - docetaxel coimbination KW - metastatic castration resistant prostate cancer KW - angiogenesis inhibition KW - prostate cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819905486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BJU+international&rft.atitle=Phase+II+trial+of+docetaxel%2C+bevacizumab%2C+lenalidomide+and+prednisone+in+patients+with+metastatic+castration-resistant+prostate+cancer.&rft.au=Madan%2C+Ravi+A%3BKarzai%2C+Fatima+H%3BNing%2C+Yang-Min%3BAdesunloye%2C+Bamidele+A%3BHuang%2C+Xuan%3BHarold%2C+Nancy%3BCouvillon%2C+Anna%3BChun%2C+Guinevere%3BCordes%2C+Lisa%3BSissung%2C+Tristan%3BBeedie%2C+Shaunna+L%3BDawson%2C+Nancy+A%3BTheoret%2C+Marc+R%3BMcLeod%2C+David+G%3BRosner%2C+Inger%3BTrepel%2C+Jane+B%3BLee%2C+Min-Jung%3BTomita%2C+Yusuke%3BLee%2C+Sunmin%3BChen%2C+Clara%3BSteinberg%2C+Seth+M%3BArlen%2C+Philip+M%3BGulley%2C+James+L%3BFigg%2C+William+D%3BDahut%2C+William+L&rft.aulast=Madan&rft.aufirst=Ravi&rft.date=2016-10-01&rft.volume=118&rft.issue=4&rft.spage=590&rft.isbn=&rft.btitle=&rft.title=BJU+international&rft.issn=1464-410X&rft_id=info:doi/10.1111%2Fbju.13412 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/bju.13412 ER - TY - JOUR T1 - Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry. AN - 1819431182; 27380242 AB - MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology. JF - Human genetics AU - Qian, Frank AU - Feng, Ye AU - Zheng, Yonglan AU - Ogundiran, Temidayo O AU - Ojengbede, Oladosu AU - Zheng, Wei AU - Blot, William AU - Ambrosone, Christine B AU - John, Esther M AU - Bernstein, Leslie AU - Hu, Jennifer J AU - Ziegler, Regina G AU - Nyante, Sarah AU - Bandera, Elisa V AU - Ingles, Sue A AU - Press, Michael F AU - Nathanson, Katherine L AU - Hennis, Anselm AU - Nemesure, Barbara AU - Ambs, Stefan AU - Kolonel, Laurence N AU - Olopade, Olufunmilayo I AU - Haiman, Christopher A AU - Huo, Dezheng AD - Department of Medicine, University of Chicago, Chicago, IL, USA. ; Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. ; Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria. ; Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria. ; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. ; Roswell Park Cancer Institute, Buffalo, NY, USA. ; Cancer Prevention Institute of California, Fremont, CA, USA. ; Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, Duarte, CA, USA. ; Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL, USA. ; Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, DC, USA. ; Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. ; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. ; Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. ; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ; Chronic Disease Research Centre and Tropical Medicine Research Institute, University of the West Indies, Bridgetown, Barbados. ; Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA. ; Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. ; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. ; Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave., MC 2007, Chicago, IL, 60637, USA. dhuo@health.bsd.uchicago.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1145 EP - 1159 VL - 135 IS - 10 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819431182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+genetics&rft.atitle=Genetic+variants+in+microRNA+and+microRNA+biogenesis+pathway+genes+and+breast+cancer+risk+among+women+of+African+ancestry.&rft.au=Qian%2C+Frank%3BFeng%2C+Ye%3BZheng%2C+Yonglan%3BOgundiran%2C+Temidayo+O%3BOjengbede%2C+Oladosu%3BZheng%2C+Wei%3BBlot%2C+William%3BAmbrosone%2C+Christine+B%3BJohn%2C+Esther+M%3BBernstein%2C+Leslie%3BHu%2C+Jennifer+J%3BZiegler%2C+Regina+G%3BNyante%2C+Sarah%3BBandera%2C+Elisa+V%3BIngles%2C+Sue+A%3BPress%2C+Michael+F%3BNathanson%2C+Katherine+L%3BHennis%2C+Anselm%3BNemesure%2C+Barbara%3BAmbs%2C+Stefan%3BKolonel%2C+Laurence+N%3BOlopade%2C+Olufunmilayo+I%3BHaiman%2C+Christopher+A%3BHuo%2C+Dezheng&rft.aulast=Qian&rft.aufirst=Frank&rft.date=2016-10-01&rft.volume=135&rft.issue=10&rft.spage=1145&rft.isbn=&rft.btitle=&rft.title=Human+genetics&rft.issn=1432-1203&rft_id=info:doi/10.1007%2Fs00439-016-1707-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00439-016-1707-1 ER - TY - JOUR T1 - Increased Risk of Nasopharyngeal Carcinoma with Increasing Levels of Diet-Associated Inflammation in an Italian Case-Control Study. AN - 1819429124; 27564524 AB - Components of diet can modulate inflammation and therefore may have an important role in the development of nasopharyngeal carcinoma (NPC). Little is known about the inflammatory potential of diet in relation to nasopharyngeal carcinogenesis. Data from an Italian multicenter case-control study conducted between 1992 and 2008 and including 198 cases with incident, histologically confirmed NPC, and 594 controls hospitalized for acute nonneoplastic diseases were used to estimate the relation between a dietary inflammatory index (DII) and the risk of NPC. The DII was computed based on the intake of selected dietary factors assessed by a validated 78-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) adjusted for study center, place of living, sex, age, year of interview, education, tobacco smoking, alcohol drinking, and energy intake using the residual method. Subjects with higher DII scores had an increased risk of NPC, with each DII point increasing risk by nearly 20% [OR: 1.19; 95% confidence interval (CI): 1.05-1.36]. Compared to subjects in the lowest DII tertile, those in the highest tertile had >60% higher risk of NPC (OR: 1.64; 95% CI: 1.06-2.55; Ptrend = 0.04). These results indicate that inflammatory potential of diet plays a role in NPC. JF - Nutrition and cancer AU - Shivappa, Nitin AU - Hébert, James R AU - Zucchetto, Antonella AU - Montella, Maurizio AU - Libra, Massimo AU - Garavello, Werner AU - Rossi, Marta AU - La Vecchia, Carlo AU - Serraino, Diego AD - a South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina , Columbia , South Carolina , USA. ; d Epidemiology and Biostatistics Unit, CRO Aviano National Cancer Institute , Aviano , Italy. ; e Department of Epidemiology , 'Fondazione G. Pascale', Istituto Nazionale Tumori , Naples , Italy. ; f Department of Biomedical and Biotechnological Sciences , University of Catania , Catania , Italy. ; g Department of Surgery and Translational Medicine , University of Milano-Bicocca , Milan , Italy. ; h Department of Clinical Sciences and Community Health , Università degli Studi di Milano , Milan , Italy. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1123 EP - 1130 VL - 68 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819429124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Increased+Risk+of+Nasopharyngeal+Carcinoma+with+Increasing+Levels+of+Diet-Associated+Inflammation+in+an+Italian+Case-Control+Study.&rft.au=Shivappa%2C+Nitin%3BH%C3%A9bert%2C+James+R%3BZucchetto%2C+Antonella%3BMontella%2C+Maurizio%3BLibra%2C+Massimo%3BGaravello%2C+Werner%3BRossi%2C+Marta%3BLa+Vecchia%2C+Carlo%3BSerraino%2C+Diego&rft.aulast=Shivappa&rft.aufirst=Nitin&rft.date=2016-10-01&rft.volume=68&rft.issue=7&rft.spage=1123&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=1532-7914&rft_id=info:doi/10.1080%2F01635581.2016.1216137 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/01635581.2016.1216137 ER - TY - JOUR T1 - Efficient production and enhanced tumor delivery of engineered extracellular vesicles AN - 1819136210; PQ0003631271 AB - Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles. We have used a hollow-fiber bioreactor for the efficient production of bioactive EV bearing the heterodimeric cytokine complex Interleukin-15:Interleukin-15 receptor alpha. Bioreactor culture yielded 40-fold more EV per mL conditioned medium, as compared to conventional cell culture. Biophysical analysis and comparative proteomics suggested a more diverse population of EV in the bioreactor preparations, while serum protein contaminants were detectable only in conventional culture EV preparations. We also identified the Scavenger Receptor Class A family (SR-A) as a novel monocyte/macrophage uptake receptor for EV. In vivo blockade of SR-A with dextran sulfate dramatically decreased EV liver clearance in mice, while enhancing tumor accumulation. These findings facilitate development of EV therapeutic methods. JF - Biomaterials AU - Watson, Dionysios C AU - Bayik, Defne AU - Srivatsan, Avinash AU - Bergamaschi, Cristina AU - Valentin, Antonio AU - Niu, Gang AU - Bear, Jenifer AU - Monninger, Mitchell AU - Sun, Mei AU - Morales-Kastresana, Aizea AU - Jones, Jennifer C AU - Felber, Barbara K AU - Chen, Xiaoyuan AU - Gursel, Ihsan AU - Pavlakis, George N AD - Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 195 EP - 205 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 105 SN - 0142-9612, 0142-9612 KW - Biotechnology and Bioengineering Abstracts KW - Exosomes KW - Drug delivery KW - Biodistribution KW - Scavenger receptor KW - Reticuloendothelial system KW - Dextran sulfate KW - Macrophages KW - exosomes KW - Drug development KW - Cell culture KW - Tumors KW - Serum proteins KW - siRNA KW - Bioreactors KW - Liver KW - Vesicles KW - Monocytes KW - proteomics KW - Contaminants KW - Intercellular signalling KW - Drugs KW - scavenger receptors KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819136210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biomaterials&rft.atitle=Efficient+production+and+enhanced+tumor+delivery+of+engineered+extracellular+vesicles&rft.au=Watson%2C+Dionysios+C%3BBayik%2C+Defne%3BSrivatsan%2C+Avinash%3BBergamaschi%2C+Cristina%3BValentin%2C+Antonio%3BNiu%2C+Gang%3BBear%2C+Jenifer%3BMonninger%2C+Mitchell%3BSun%2C+Mei%3BMorales-Kastresana%2C+Aizea%3BJones%2C+Jennifer+C%3BFelber%2C+Barbara+K%3BChen%2C+Xiaoyuan%3BGursel%2C+Ihsan%3BPavlakis%2C+George+N&rft.aulast=Watson&rft.aufirst=Dionysios&rft.date=2016-10-01&rft.volume=105&rft.issue=&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Biomaterials&rft.issn=01429612&rft_id=info:doi/10.1016%2Fj.biomaterials.2016.07.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-09-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Macrophages; exosomes; Cell culture; Drug development; Tumors; Serum proteins; Dextran sulfate; siRNA; Bioreactors; Liver; Vesicles; proteomics; Monocytes; Contaminants; Drugs; Intercellular signalling; scavenger receptors DO - http://dx.doi.org/10.1016/j.biomaterials.2016.07.003 ER - TY - JOUR T1 - Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency. AN - 1819122390; 27539235 AB - The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency. JF - Journal of clinical immunology AU - John, Tami AU - Walter, Jolan E AU - Schuetz, Catherina AU - Chen, Karin AU - Abraham, Roshini S AU - Bonfim, Carmem AU - Boyce, Thomas G AU - Joshi, Avni Y AU - Kang, Elizabeth AU - Carvalho, Beatriz Tavares Costa AU - Mahajerin, Arash AU - Nugent, Diane AU - Puthenveetil, Geetha AU - Soni, Amit AU - Su, Helen AU - Cowan, Morton J AU - Notarangelo, Luigi AU - Buchbinder, David AD - Division of Hematology/Oncology, CHOC Children's Hospital, 1201 W. La Veta Avenue, Orange, CA, 92868, USA. tamidjohn@gmail.com. ; Division of Immunology, MassGeneral Hospital for Children, 55 Fruit Street, Boston, MA, 02114, USA. ; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany. ; Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Utah School of Medicine, 81 Mario Capecchi Drive, Salt Lake City, UT, USA. ; Allergy and Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. ; Bone Marrow Transplantation Unit, Federal University of Paraná, Rua XV de Novembro, 1299 - Centro, Curitiba, PR, 80060-000, Brazil. ; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. ; NIAID, National Institutes of Health, Building 10CRC, Room 5-3940, 10 Center Drive, MSC 1456, Bethesda, MD, 20892-9806, USA. ; Disciplina de Alergia, Imunologia Clínica e Reumatologia - UNIFESP, Sao Paulo, Brazil. ; Division of Hematology, CHOC Children's Hospital, 1201 W. La Veta Avenue, Orange, CA, 92868, USA. ; Department of Pediatrics, University of California, San Francisco, Box 1278, UCSF, San Francisco, CA, 94143, USA. ; Division of Immunology, Children's Hospital Boston, Karp Building, Room 10217, 1 Blackfan Circle, Boston, MA, 02115, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 725 EP - 732 VL - 36 IS - 7 KW - Index Medicus KW - primary immunodeficiency KW - bone marrow transplantation KW - RAG deficiency KW - immune dysregulation KW - autoimmunity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819122390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+immunology&rft.atitle=Unrelated+Hematopoietic+Cell+Transplantation+in+a+Patient+with+Combined+Immunodeficiency+with+Granulomatous+Disease+and+Autoimmunity+Secondary+to+RAG+Deficiency.&rft.au=John%2C+Tami%3BWalter%2C+Jolan+E%3BSchuetz%2C+Catherina%3BChen%2C+Karin%3BAbraham%2C+Roshini+S%3BBonfim%2C+Carmem%3BBoyce%2C+Thomas+G%3BJoshi%2C+Avni+Y%3BKang%2C+Elizabeth%3BCarvalho%2C+Beatriz+Tavares+Costa%3BMahajerin%2C+Arash%3BNugent%2C+Diane%3BPuthenveetil%2C+Geetha%3BSoni%2C+Amit%3BSu%2C+Helen%3BCowan%2C+Morton+J%3BNotarangelo%2C+Luigi%3BBuchbinder%2C+David&rft.aulast=John&rft.aufirst=Tami&rft.date=2016-10-01&rft.volume=36&rft.issue=7&rft.spage=725&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+immunology&rft.issn=1573-2592&rft_id=info:doi/10.1007%2Fs10875-016-0326-x LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10875-016-0326-x ER - TY - JOUR T1 - The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in aging mice. AN - 1818678465; 27498053 AB - Human immunodeficiency virus 1 and its envelope protein gp120 reduce synaptodendritic complexity. However, the mechanisms contributing to this pathological feature are still not understood. The proneurotrophin brain-derived neurotrophic factor promotes synaptic simplification through the activation of the p75 neurotrophin receptor (p75NTR). Here, we have used gp120 transgenic (gp120tg) mice to investigate whether p75NTR has a role in gp120-mediated neurotoxicity. Old (∼10 months) gp120tg mice exhibited an increase in proneurotrophin brain-derived neurotrophic factor levels in the hippocampus as well as a decrease in the number of dendritic spines when compared to age-matched wild type. These effects were not observed in 3- or 6-month-old mice. To test if the reduction in spine density and morphology is caused by the activation of p75NTR, we crossed gp120tg mice with p75NTR null mice. We found that deletion of only 1 copy of the p75NTR gene in gp120tg mice is sufficient to normalize the number of hippocampal spines, strongly suggesting that the neurotoxic effect of gp120 is mediated by p75NTR. These data indicate that p75NTR antagonists could provide an adjunct therapy against synaptic simplification caused by human immunodeficiency virus 1. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Neurobiology of aging AU - Bachis, Alessia AU - Wenzel, Erin AU - Boelk, Allyssia AU - Becker, Jodi AU - Mocchetti, Italo AD - Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. ; Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA; Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA. ; Center for Cancer Research, National Cancer Institute, Frederick, MD, USA. ; Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: moccheti@georgetown.edu. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 160 EP - 168 VL - 46 KW - Index Medicus KW - Hippocampus KW - Aging KW - proBDNF KW - HIV KW - p75NTR KW - TrkB UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818678465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+aging&rft.atitle=The+neurotrophin+receptor+p75+mediates+gp120-induced+loss+of+synaptic+spines+in+aging+mice.&rft.au=Bachis%2C+Alessia%3BWenzel%2C+Erin%3BBoelk%2C+Allyssia%3BBecker%2C+Jodi%3BMocchetti%2C+Italo&rft.aulast=Bachis&rft.aufirst=Alessia&rft.date=2016-10-01&rft.volume=46&rft.issue=&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+aging&rft.issn=1558-1497&rft_id=info:doi/10.1016%2Fj.neurobiolaging.2016.07.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-11 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1016/j.neurobiolaging.2016.07.001 ER - TY - JOUR T1 - Early Adolescents' Unique Perspectives of Maternal and Paternal Rejection: Examining Their Across-Dyad Generalizability and Relations with Adjustment 1 Year Later AN - 1818655538 AB - Parental rejection is linked to deep and enduring adjustment problems during adolescence. This study aims to further clarify this relation by demonstrating what has long been posited by parental acceptance/rejection theory but never validated empirically--namely that adolescents' unique or subjective experience of parental rejection independently informs their future adjustment. Among a longitudinal, multi-informant sample of 161 families (early adolescents were 47 % female and 40 % European American) this study utilized a multitrait-multimethod confirmatory factor analysis to isolate for each early adolescent-parent dyad, the adolescent's distinct view of parental rejection (i.e., the adolescent unique perspective) from the portion of his or her view that overlaps with his or her parent's view. The findings indicated that adolescents' unique perspectives of maternal rejection were not differentiated from their unique perspectives of paternal rejection. Also, consistent with parental acceptance-rejection theory, early adolescents' unique perspectives of parental rejection were associated with worse adjustment (internalizing and externalizing) 1 year later. This study further demonstrates the utility and validity of the multitrait-multimethod confirmatory factor analysis approach for identifying and examining adolescent unique perspectives. Both conceptually and analytically, this study also integrates research focused on unique perspectives with a distinct but related line of research focused on discrepancies in perspectives. JF - Journal of Youth and Adolescence AU - Jager, Justin AU - Mahler, Alissa AU - An, Danming AU - Putnick, Diane L AU - Bornstein, Marc H AU - Lansford, Jennifer E AU - Dodge, Kenneth A AU - Skinner, Ann T AU - Deater-deckard, Kirby AD - T. Denny Sanford School of Social and Family Dynamics, Arizona State University, PO Box 873701, Tempe, AZ, USA ; Department of Psychology and Social Behavior, University of California, Irvine, CA, USA ; Child and Family Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA ; Center for Child and Family Policy, Duke University, Box 90545, Durham, NC, USA ; Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, USA ; T. Denny Sanford School of Social and Family Dynamics, Arizona State University, PO Box 873701, Tempe, AZ, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 2108 EP - 2124 CY - New York PB - Springer Science & Business Media VL - 45 IS - 10 SN - 0047-2891 KW - Psychology KW - Unique perspectives KW - Parental rejection KW - Internalizing KW - Externalizing KW - Early adolescence KW - Adjustment KW - Factor Analysis KW - Parents KW - Adolescents KW - Mothers KW - Social Acceptance KW - 1939:the family and socialization; adolescence & youth UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818655538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Youth+and+Adolescence&rft.atitle=Early+Adolescents%27+Unique+Perspectives+of+Maternal+and+Paternal+Rejection%3A+Examining+Their+Across-Dyad+Generalizability+and+Relations+with+Adjustment+1+Year+Later&rft.au=Jager%2C+Justin%3BMahler%2C+Alissa%3BAn%2C+Danming%3BPutnick%2C+Diane+L%3BBornstein%2C+Marc+H%3BLansford%2C+Jennifer+E%3BDodge%2C+Kenneth+A%3BSkinner%2C+Ann+T%3BDeater-deckard%2C+Kirby&rft.aulast=Jager&rft.aufirst=Justin&rft.date=2016-10-01&rft.volume=45&rft.issue=10&rft.spage=2108&rft.isbn=&rft.btitle=&rft.title=Journal+of+Youth+and+Adolescence&rft.issn=00472891&rft_id=info:doi/10.1007%2Fs10964-016-0509-z LA - English DB - Sociological Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-12-13 DO - http://dx.doi.org/10.1007/s10964-016-0509-z ER - TY - JOUR T1 - LTβR signalling preferentially accelerates oncogenic AKT-initiated liver tumours. AN - 1818337559; 26206664 AB - The relative contributions of inflammatory signalling and sequential oncogenic dysregulation driving liver cancer pathogenesis remain incompletely understood. Lymphotoxin-β receptor (LTβR) signalling is critically involved in hepatitis and liver tumorigenesis. Therefore, we explored the interdependence of inflammatory lymphotoxin signalling and specific oncogenic pathways in the progression of hepatic cancer. Pathologically distinct liver tumours were initiated by hydrodynamic transfection of oncogenic V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT)/β-catenin or AKT/Notch expressing plasmids. To investigate the relationship of LTβR signalling and specific oncogenic pathways, LTβR antagonist (LTβR-Fc) or agonist (anti-LTβR) were administered post oncogene transfection. Initiated livers/tumours were investigated for changes in oncogene expression, tumour proliferation, progression, latency and pathology. Moreover, specific LTβR-mediated molecular events were investigated in human liver cancer cell lines and through transcriptional analyses of samples from patients with intrahepatic cholangiocarcinoma (ICC). AKT/β-catenin-transfected livers displayed increased expression of LTβ and LTβR, with antagonism of LTβR signalling reducing tumour progression and enhancing survival. Conversely, enforced LTβR-activation of AKT/β-catenin-initiated tumours induced robust increases in proliferation and progression of hepatic tumour phenotypes in an AKT-dependent manner. LTβR-activation also rapidly accelerated ICC progression initiated by AKT/Notch, but not Notch alone. Moreover, LTβR-accelerated development coincides with increases of Notch, Hes1, c-MYC, pAKT and β-catenin. We further demonstrate LTβR signalling in human liver cancer cell lines to be a regulator of Notch, pAKTser473 and β-catenin. Transcriptome analysis of samples from patients with ICC links increased LTβR network expression with poor patient survival, increased Notch1 expression and Notch and AKT/PI3K signalling. Our findings link LTβR and oncogenic AKT signalling in the development of ICC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ JF - Gut AU - Scarzello, Anthony J AU - Jiang, Qun AU - Back, Timothy AU - Dang, Hien AU - Hodge, Deborah AU - Hanson, Charlotte AU - Subleski, Jeffrey AU - Weiss, Jonathan M AU - Stauffer, Jimmy K AU - Chaisaingmongkol, Jitti AU - Rabibhadana, Siritida AU - Ruchirawat, Mathuros AU - Ortaldo, John AU - Wang, Xin Wei AU - Norris, Paula S AU - Ware, Carl F AU - Wiltrout, Robert H AD - Cancer and Inflamation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. ; Chulabhorn Research Institute, Bangkok, Thailand. ; Infectious and Inflammatory Diseases Research Center, Sanford Burnham Medical Research Institute, La Jolla, California, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1765 EP - 1775 VL - 65 IS - 10 KW - Abridged Index Medicus KW - Index Medicus KW - CANCER IMMUNOBIOLOGY UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818337559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=LT%CE%B2R+signalling+preferentially+accelerates+oncogenic+AKT-initiated+liver+tumours.&rft.au=Scarzello%2C+Anthony+J%3BJiang%2C+Qun%3BBack%2C+Timothy%3BDang%2C+Hien%3BHodge%2C+Deborah%3BHanson%2C+Charlotte%3BSubleski%2C+Jeffrey%3BWeiss%2C+Jonathan+M%3BStauffer%2C+Jimmy+K%3BChaisaingmongkol%2C+Jitti%3BRabibhadana%2C+Siritida%3BRuchirawat%2C+Mathuros%3BOrtaldo%2C+John%3BWang%2C+Xin+Wei%3BNorris%2C+Paula+S%3BWare%2C+Carl+F%3BWiltrout%2C+Robert+H&rft.aulast=Scarzello&rft.aufirst=Anthony&rft.date=2016-10-01&rft.volume=65&rft.issue=10&rft.spage=1765&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2014-308810 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/gutjnl-2014-308810 ER - TY - JOUR T1 - Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours. AN - 1818337406; 26129866 AB - Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10(-12)) and non-cardia cancers (p=2.42×10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ JF - Gut AU - Hu, Nan AU - Wang, Zhaoming AU - Song, Xin AU - Wei, Lixuan AU - Kim, Byung Sik AU - Freedman, Neal D AU - Baek, Jiwon AU - Burdette, Laurie AU - Chang, Jiang AU - Chung, Charles AU - Dawsey, Sanford M AU - Ding, Ti AU - Gao, Yu-Tang AU - Giffen, Carol AU - Han, Yaling AU - Hong, Myunghee AU - Huang, Jia AU - Kim, Hee Sung AU - Koh, Woon-Puay AU - Liao, Linda M AU - Mao, Yi Min AU - Qiao, You-Lin AU - Shu, Xiao-Ou AU - Tan, Wen AU - Wang, Chaoyu AU - Wu, Chen AU - Wu, Min-Jie AU - Xiang, Yong-Bing AU - Yeager, Meredith AU - Yook, Jeong Hwan AU - Yuan, Jian-Min AU - Zhang, Peng AU - Zhao, Xue-Ke AU - Zheng, Wei AU - Song, Kyuyoung AU - Wang, Li-Dong AU - Lin, Dongxin AU - Chanock, Stephen J AU - Goldstein, Alisa M AU - Taylor, Philip R AU - Abnet, Christian C AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China. ; Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. ; Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. ; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Cancer Genome Research Laboratory, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland, USA. ; Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China. ; Shanghai Cancer Institute, Shanghai, People's Republic of China. ; Information Management Services Inc., Silver Spring, Maryland, USA. ; Duke-NUS Graduate Medical School Singapore, Singapore, Singapore. ; Department of Epidemiology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China. ; Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA. ; Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China. ; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1611 EP - 1618 VL - 65 IS - 10 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818337406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=Genome-wide+association+study+of+gastric+adenocarcinoma+in+Asia%3A+a+comparison+of+associations+between+cardia+and+non-cardia+tumours.&rft.au=Hu%2C+Nan%3BWang%2C+Zhaoming%3BSong%2C+Xin%3BWei%2C+Lixuan%3BKim%2C+Byung+Sik%3BFreedman%2C+Neal+D%3BBaek%2C+Jiwon%3BBurdette%2C+Laurie%3BChang%2C+Jiang%3BChung%2C+Charles%3BDawsey%2C+Sanford+M%3BDing%2C+Ti%3BGao%2C+Yu-Tang%3BGiffen%2C+Carol%3BHan%2C+Yaling%3BHong%2C+Myunghee%3BHuang%2C+Jia%3BKim%2C+Hee+Sung%3BKoh%2C+Woon-Puay%3BLiao%2C+Linda+M%3BMao%2C+Yi+Min%3BQiao%2C+You-Lin%3BShu%2C+Xiao-Ou%3BTan%2C+Wen%3BWang%2C+Chaoyu%3BWu%2C+Chen%3BWu%2C+Min-Jie%3BXiang%2C+Yong-Bing%3BYeager%2C+Meredith%3BYook%2C+Jeong+Hwan%3BYuan%2C+Jian-Min%3BZhang%2C+Peng%3BZhao%2C+Xue-Ke%3BZheng%2C+Wei%3BSong%2C+Kyuyoung%3BWang%2C+Li-Dong%3BLin%2C+Dongxin%3BChanock%2C+Stephen+J%3BGoldstein%2C+Alisa+M%3BTaylor%2C+Philip+R%3BAbnet%2C+Christian+C&rft.aulast=Hu&rft.aufirst=Nan&rft.date=2016-10-01&rft.volume=65&rft.issue=10&rft.spage=1611&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2015-309340 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/gutjnl-2015-309340 ER - TY - JOUR T1 - Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials. AN - 1817848274; 27478165 AB - With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms "partial breast irradiation" OR "intraoperative radiotherapy" OR "IMRT" OR ("accelerated" AND "radiation") AND "randomised/randomized," as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non-breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), -0.7 to +0.7]; P=.999). Non-breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, -2.1% to -0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, -2.5% to 0.0%]; P=.05). Use of PBI instead of WBI in selected patients results in a lower 5-year non-breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when breast-conserving therapy is proposed to a patient. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved. JF - International journal of radiation oncology, biology, physics AU - Vaidya, Jayant S AU - Bulsara, Max AU - Wenz, Frederik AU - Coombs, Nathan AU - Singer, Julian AU - Ebbs, Stephen AU - Massarut, Samuele AU - Saunders, Christobel AU - Douek, Michael AU - Williams, Norman R AU - Joseph, David AU - Tobias, Jeffrey S AU - Baum, Michael AD - Division of Surgery and Interventional Science, University College London, London, UK; Department of Surgery, Royal Free Hospital, London, UK; Department of Surgery, Whittington Health, London, UK. Electronic address: jayant.vaidya@ucl.ac.uk. ; Department of Biostatistics, University of Notre Dame, Fremantle, WA, Australia. ; Department of Radiation Oncology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany. ; Department of Surgery, Great Western Hospital, Swindon, UK. ; Department of Clinical Oncology, The Princess Alexandra Hospital, Harlow, UK. ; Croydon University Hospital, Croydon, UK. ; National Cancer Institute, Centro di Riferimento Oncologico, Aviano, Italy. ; School of Surgery, University of Western Australia, Perth, WA, Australia. ; Department of Surgery, Kings College London, London, UK. ; Division of Surgery and Interventional Science, University College London, London, UK. ; Departments of Radiation Oncology, and Surgery, Sir Charles Gairdner Hospital, Perth, WA, Australia. ; Department of Clinical Oncology, University College London Hospitals, London, UK. Y1 - 2016/10/01/ PY - 2016 DA - 2016 Oct 01 SP - 259 EP - 265 VL - 96 IS - 2 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1817848274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Reduced+Mortality+With+Partial-Breast+Irradiation+for+Early+Breast+Cancer%3A+A%C2%A0Meta-Analysis+of+Randomized+Trials.&rft.au=Vaidya%2C+Jayant+S%3BBulsara%2C+Max%3BWenz%2C+Frederik%3BCoombs%2C+Nathan%3BSinger%2C+Julian%3BEbbs%2C+Stephen%3BMassarut%2C+Samuele%3BSaunders%2C+Christobel%3BDouek%2C+Michael%3BWilliams%2C+Norman+R%3BJoseph%2C+David%3BTobias%2C+Jeffrey+S%3BBaum%2C+Michael&rft.aulast=Vaidya&rft.aufirst=Jayant&rft.date=2016-10-01&rft.volume=96&rft.issue=2&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=1879-355X&rft_id=info:doi/10.1016%2Fj.ijrobp.2016.05.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ijrobp.2016.05.008 ER - TY - JOUR T1 - Safety analysis, association with response and previous treatments of everolimus and exemestane in 181 metastatic breast cancer patients: A multicenter Italian experience. AN - 1817833116; 27476084 AB - The everolimus and exemestane combination represents a treatment option for the endocrine sensitive metastatic breast cancer (MBC) patients. The toxicity profile reported in the Bolero 2 trial showed the feasibility in the selected patients. Few data are available for the unselected population. In order to evaluate the safety in the unselected population of the clinical practice and to evaluate a possible association of toxicities with previous treatments, clinical data from 181 consecutive patients were retrospectively collected. Due to toxic events, everolimus dosage was reduced to 5 mg in 27% of patients. No association was found in the analysis between toxicity and number of prior therapies, neither between toxicity and response. In the multivariate analysis the previous exposure to anthracyclines for advanced disease represents the only predictive factor of developing grade ≥2 toxicity (OR = 2.85 CI 95% 1.07-7.59, p = 0.036). The association of everolimus and exemestane has confirmed to be a safe and effective treatment for endocrine sensitive MBC patients even in routine clinical practice. The rate of treatment discontinuation due to toxicity is low and none association between previous number of treatments and response or between toxicity and response was found. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Breast (Edinburgh, Scotland) AU - Moscetti, L AU - Vici, P AU - Gamucci, T AU - Natoli, C AU - Cortesi, E AU - Marchetti, P AU - Santini, D AU - Giuliani, R AU - Sperduti, I AU - Mauri, M AU - Pizzuti, L AU - Mancini, M L AU - Fabbri, M A AU - Magri, V AU - Iezzi, L AU - Sini, V AU - D'Onofrio, L AU - Mentuccia, L AU - Vaccaro, A AU - Ramponi, S AU - Roma, C L AU - Ruggeri, E M AD - Division of Oncology, Complesso Ospedaliero Belcolle, AUSL Viterbo, Viterbo, Italy; Department of Oncology and Haematology, Azienda Ospedaliera Policlinico, Modena, Italy. Electronic address: moscetti.luca@policlinico.mo.it. ; Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: patrizia.vici@ifo.gov.it. ; Medical Oncology Unit, ASL Frosinone, Frosinone, Italy. Electronic address: t.gamucci@libero.it. ; Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio, Chieti, Italy. Electronic address: natoli@unich.it. ; Medical Oncology Unit, Department of Radiological Oncological and Pathological Sciences, Sapienza, University of Rome, Italy. Electronic address: enrico.cortesi@uniroma1.it. ; Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy; Oncology Unit, IDI - I.R.C.C.S., Rome, Italy. Electronic address: paolo.marchetti@hotmail.it. ; Medical Oncology, Policlinico Universitario Campus Bio-Medico, Roma, Italy. Electronic address: d.santini@unicampus.it. ; Department of Medical Oncology, San Camillo and Forlanini Hospitals Rome, Italy. Electronic address: rosagiuliani@gmail.com. ; Biostatistics, Regina Elena National Cancer Institute, Roma, Italy. Electronic address: isperduti@yahoo.it. ; Division of Oncology, San Giovanni Hospital, Rome, Italy. Electronic address: mariella.mauri@libero.it. ; Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: pizzuti8@hotmail.com. ; Medical Oncology Unit, Department of Radiological Oncological and Pathological Sciences, Sapienza, University of Rome, Italy. Electronic address: marialaura.mancini@yahoo.it. ; Division of Oncology, Complesso Ospedaliero Belcolle, AUSL Viterbo, Viterbo, Italy. Electronic address: agnese.fabbri@yahoo.it. ; Medical Oncology Unit, Department of Radiological Oncological and Pathological Sciences, Sapienza, University of Rome, Italy. Electronic address: magri.vi@hotmail.it. ; Medical Oncology Unit, SS. Annunziata Hospital, Chieti, Italy. Electronic address: iezzilau@gmail.com. ; Oncology Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy; Oncology Unit, IDI - I.R.C.C.S., Rome, Italy. Electronic address: sini_valentina@libero.it. ; Medical Oncology, Policlinico Universitario Campus Bio-Medico, Roma, Italy. Electronic address: l.donofrio@unicampus.it. ; Medical Oncology Unit, ASL Frosinone, Frosinone, Italy. Electronic address: lucia.mentuccia@gmail.com. ; Medical Oncology Unit, ASL Frosinone, Frosinone, Italy. Electronic address: angelavaccaro64@gmail.com. ; Division of Oncology, Sandro Pertini Hospital, Rome, Italy. Electronic address: sara.ramponi@aslromab.it. ; Division of Oncology, San Giovanni Hospital, Rome, Italy. Electronic address: carmineluigiroma@yahoo.it. ; Division of Oncology, Complesso Ospedaliero Belcolle, AUSL Viterbo, Viterbo, Italy. Electronic address: ruggeriem@gmail.com. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 96 EP - 101 VL - 29 KW - Index Medicus KW - Everolimus KW - Metastatic breast cancer KW - Exemestane UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1817833116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+%28Edinburgh%2C+Scotland%29&rft.atitle=Safety+analysis%2C+association+with+response+and+previous+treatments+of+everolimus+and+exemestane+in+181+metastatic+breast+cancer+patients%3A+A+multicenter+Italian+experience.&rft.au=Moscetti%2C+L%3BVici%2C+P%3BGamucci%2C+T%3BNatoli%2C+C%3BCortesi%2C+E%3BMarchetti%2C+P%3BSantini%2C+D%3BGiuliani%2C+R%3BSperduti%2C+I%3BMauri%2C+M%3BPizzuti%2C+L%3BMancini%2C+M+L%3BFabbri%2C+M+A%3BMagri%2C+V%3BIezzi%2C+L%3BSini%2C+V%3BD%27Onofrio%2C+L%3BMentuccia%2C+L%3BVaccaro%2C+A%3BRamponi%2C+S%3BRoma%2C+C+L%3BRuggeri%2C+E+M&rft.aulast=Moscetti&rft.aufirst=L&rft.date=2016-10-01&rft.volume=29&rft.issue=&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=Breast+%28Edinburgh%2C+Scotland%29&rft.issn=1532-3080&rft_id=info:doi/10.1016%2Fj.breast.2016.07.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.breast.2016.07.005 ER - TY - JOUR T1 - Diagnosis lost: Differences between children who had and who currently have an autism spectrum disorder diagnosis AN - 1817564956 AB - Autism spectrum disorder diagnoses sometimes change due to misdiagnosis, maturation, or treatment. This study uses a probability-based national survey--the Survey of Pathways to Diagnosis and Services--to compare currently diagnosed (n = 1420) and previously diagnosed (n = 187) children aged 6-17 years based on retrospective parental reports of early concerns about their children's development, responses to those concerns by doctors and other healthcare providers, the type of provider who made the first autism spectrum disorder diagnosis, and the autism spectrum disorder subtype diagnoses received (if any). Propensity score matching was used to control for differences between the groups on children's current level of functioning and other current characteristics that may have been related to diagnosis loss. Approximately 13% of the children ever diagnosed with autism spectrum disorder were estimated to have lost the diagnosis, and parents of 74% of them believed it was changed due to new information. Previously diagnosed children were less likely to have parents with early concerns about verbal skills, nonverbal communication, learning, and unusual gestures or movements. They were also less likely to have been referred to and diagnosed by a specialist. Previously diagnosed children were less likely to have ever received a diagnosis of Asperger's disorder or autistic disorder. JF - Autism AU - Blumberg, Stephen J AU - Zablotsky, Benjamin AU - Avila, Rosa M AU - Colpe, Lisa J AU - Pringle, Beverly A AU - Kogan, Michael D AD - Centers for Disease Control and Prevention, USA ; University of Washington, USA ; National Institutes of Health, USA ; Health Resources and Services Administration, USA ; Centers for Disease Control and Prevention, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 783 EP - 795 CY - London PB - SAGE PUBLICATIONS, INC. VL - 20 IS - 7 SN - 1362-3613 KW - Psychology KW - autism spectrum disorder KW - diagnosis KW - epidemiology KW - national surveys KW - Health care KW - Maturation KW - Autistic spectrum disorders KW - Misdiagnosis KW - Autistic children KW - National surveys KW - Doctors KW - Learning KW - Asperger's syndrome KW - Child development KW - Gestures KW - Nonverbal communication KW - Diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1817564956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Autism&rft.atitle=Diagnosis+lost%3A+Differences+between+children+who+had+and+who+currently+have+an+autism+spectrum+disorder+diagnosis&rft.au=Blumberg%2C+Stephen+J%3BZablotsky%2C+Benjamin%3BAvila%2C+Rosa+M%3BColpe%2C+Lisa+J%3BPringle%2C+Beverly+A%3BKogan%2C+Michael+D&rft.aulast=Blumberg&rft.aufirst=Stephen&rft.date=2016-10-01&rft.volume=20&rft.issue=7&rft.spage=783&rft.isbn=&rft.btitle=&rft.title=Autism&rft.issn=13623613&rft_id=info:doi/10.1177%2F1362361315607724 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2015 N1 - Last updated - 2016-09-08 DO - http://dx.doi.org/10.1177/1362361315607724 ER - TY - JOUR T1 - Nonverbal and paraverbal behavior in (simulated) medical visits related to genomics and weight: a role for emotion and race AN - 1817066962 AB - It is crucial to examine patient reactions to genomics-informed approaches to weight management within a clinical context, and understand the influence of patient characteristics (here, emotion and race). Examining nonverbal reactions offers a window into patients' implicit cognitive, attitudinal and affective processes related to clinical encounters. We simulated a weight management clinical interaction with a virtual reality-based physician, and experimentally manipulated patient emotional state (anger/fear) and whether the physician made genomic or personal behavior attributions for weight. Participants were 190 overweight females who racially identified as either Black or White. Participants made less visual contact when receiving genomic information in the anger condition, and Black participants exhibited lowered voice pitch when receiving genomic information. Black participants also increased their interpersonal distance when receiving genomic information in the anger condition. By studying non-conscious nonverbal behavior, we can better understand the nuances of these interactions. Trial registry clinicaltrials.gov NCT01888913. JF - Journal of Behavioral Medicine AU - Persky, Susan AU - Ferrer, Rebecca A AU - Klein, William M; P AD - Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA ; Basic Biobehavioral and Psychological Sciences Branch, Behavioral Research Program, National Cancer Institute, Bethesda, MD, USA ; Behavioral Research Program, National Cancer Institute, Bethesda, MD, USA ; Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 804 EP - 814 CY - New York PB - Springer Science & Business Media VL - 39 IS - 5 SN - 0160-7715 KW - Psychology KW - Nonverbal behavior KW - Paraverbal behavior KW - Physician-patient interaction KW - Genomics KW - Emotion KW - Obesity KW - Race KW - Anger KW - Attributions KW - Fear KW - Nonverbal behaviour KW - Virtual reality KW - Weight loss KW - Pitch UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1817066962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Behavioral+Medicine&rft.atitle=Nonverbal+and+paraverbal+behavior+in+%28simulated%29+medical+visits+related+to+genomics+and+weight%3A+a+role+for+emotion+and+race&rft.au=Persky%2C+Susan%3BFerrer%2C+Rebecca+A%3BKlein%2C+William+M%3B+P&rft.aulast=Persky&rft.aufirst=Susan&rft.date=2016-10-01&rft.volume=39&rft.issue=5&rft.spage=804&rft.isbn=&rft.btitle=&rft.title=Journal+of+Behavioral+Medicine&rft.issn=01607715&rft_id=info:doi/10.1007%2Fs10865-016-9747-5 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-09-07 DO - http://dx.doi.org/10.1007/s10865-016-9747-5 ER - TY - JOUR T1 - Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine. AN - 1815971415; 27493274 AB - Illicit drug preparations often include more than one pharmacologically active compound. For example, cocaine and synthetic cathinones [e.g., 3,4-methylenedioxypyrovalerone (MDPV)] are often mixed with caffeine before sale. Caffeine is likely added to these preparations because it is inexpensive and legal; however, caffeine might also mimic or enhance some of the effects of cocaine or MDPV. In these studies, male Sprague-Dawley rats were trained to discriminate 10 mg/kg cocaine from saline, and the discriminative stimulus effects of cocaine, caffeine, and MDPV were evaluated alone and as binary mixtures (cocaine and caffeine, MDPV and caffeine, and cocaine and MDPV) at fixed-dose ratios of 3:1, 1:1, and 1:3 relative to the dose of each drug that produced 50% cocaine-appropriate responding. Dose-addition analyses were used to determine the nature of the drug-drug interactions for each mixture (e.g., additive, supra-additive, or subadditive). Although additive interactions were observed for most mixtures, supra-additive interactions were observed at the 50% effect level for the 1:1 mixture of cocaine and caffeine and at the 80% effect level for all three mixtures of cocaine and caffeine, as well as for the 3:1 and 1:3 mixtures of cocaine and MDPV. These results demonstrate that with respect to cocaine-like discriminative stimulus effects, caffeine can function as a substitute in drug preparations containing either cocaine or MDPV, with enhancements of cocaine-like effects possible under certain conditions. Further research is needed to determine whether similar interactions exist for other abuse-related or toxic effects of drug preparations, including cocaine, synthetic cathinones, and caffeine. U.S. Government work not protected by U.S. copyright. JF - The Journal of pharmacology and experimental therapeutics AU - Collins, Gregory T AU - Abbott, Megan AU - Galindo, Kayla AU - Rush, Elise L AU - Rice, Kenner C AU - France, Charles P AD - Departments of Pharmacology (G.T.C., M.A., K.G., E.L.R., C.P.F.) and Psychiatry (C.P.F.), University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System (G.T.C.), San Antonio, Texas; and Chemical Biology Research Branch, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.) collinsg@uthscsa.edu. ; Departments of Pharmacology (G.T.C., M.A., K.G., E.L.R., C.P.F.) and Psychiatry (C.P.F.), University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System (G.T.C.), San Antonio, Texas; and Chemical Biology Research Branch, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (K.C.R.). Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1 EP - 10 VL - 359 IS - 1 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815971415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Discriminative+Stimulus+Effects+of+Binary+Drug+Mixtures%3A+Studies+with+Cocaine%2C+MDPV%2C+and+Caffeine.&rft.au=Collins%2C+Gregory+T%3BAbbott%2C+Megan%3BGalindo%2C+Kayla%3BRush%2C+Elise+L%3BRice%2C+Kenner+C%3BFrance%2C+Charles+P&rft.aulast=Collins&rft.aufirst=Gregory&rft.date=2016-10-01&rft.volume=359&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=1521-0103&rft_id=info:doi/10.1124%2Fjpet.116.234252 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/jpet.116.234252 ER - TY - JOUR T1 - Mothers', fathers' and children's perceptions of parents' expectations about children's family obligations in nine countries AN - 1815816025 AB - Children's family obligations involve assistance and respect that children are expected to provide to immediate and extended family members and reflect beliefs related to family life that may differ across cultural groups. Mothers, fathers and children (N = 1432 families) in 13 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand and United States) reported on their expectations regarding children's family obligations and parenting attitudes and behaviours. Within families, mothers and fathers had more concordant expectations regarding children's family obligations than did parents and children. Parenting behaviours that were warmer, less neglectful and more controlling as well as parenting attitudes that were more authoritarian were related to higher expectations regarding children's family obligations between families within cultures as well as between cultures. These international findings advance understanding of children's family obligations by contextualising them both within families and across a number of diverse cultural groups in 9 countries. JF - International Journal of Psychology. Journal International de Psychologie AU - Lansford, Jennifer E AU - Godwin, Jennifer AU - Alampay, Liane Peña AU - Uribe Tirado, Liliana Maria AU - Zelli, Arnaldo AU - Al-Hassan, Suha M AU - Bacchini, Dario AU - Bombi, Anna Silvia AU - Bornstein, Marc H AU - Chang, Lei AU - Deater-Deckard, Kirby AU - Di Giunta, Laura AU - Dodge, Kenneth A AU - Malone, Patrick S AU - Oburu, Paul AU - Pastorelli, Concetta AU - Skinner, Ann T AU - Sorbring, Emma AU - Tapanya, Sombat AD - Center for Child and Family Policy, Duke University, Durham, NC, USA ; Department of Psychology, Ateneo de Manila University, Quezon City, Philippines ; Consultorio Psicológico Popular, Universidad San Buenaventura, Medellín, Colombia ; Department of Education Sciences, University of Rome "Foro Italico", Rome, Italy ; Queen Rania Faculty for Childhood, Hashemite University, Zarqa, Jordan, and Health and Special Education Division, Emirates College for Advanced Education, Abu Dhabi, UAE ; Department of Psychology, Second University of Naples, Caserta, Italy ; Faculty of Psychology, Università di Roma "La Sapienza", Rome, Italy ; Child and Family Research Program in Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA ; Department of Psychological Studies, Hong Kong Institute of Education, Hong Kong, China ; Department of Psychology, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA ; Department of Education Psychology, Maseno University, Maseno, Kenya ; Department of Psychology, University West, Trollhättan, Sweden ; Department of Psychiatry, Chiang Mai University, Chiang Mai, Thailand ; Center for Child and Family Policy, Duke University, Durham, NC, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 366 EP - 374 CY - Paris PB - Taylor & Francis Ltd. VL - 51 IS - 5 SN - 0020-7594 KW - Psychology KW - Families & family life KW - Children & youth KW - Mothers KW - Parenting KW - Parental control KW - Family life KW - Parents KW - Attitudes KW - Relatives KW - Children UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815816025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Psychology.+Journal+International+de+Psychologie&rft.atitle=Mothers%27%2C+fathers%27+and+children%27s+perceptions+of+parents%27+expectations+about+children%27s+family+obligations+in+nine+countries&rft.au=Lansford%2C+Jennifer+E%3BGodwin%2C+Jennifer%3BAlampay%2C+Liane+Pe%C3%B1a%3BUribe+Tirado%2C+Liliana+Maria%3BZelli%2C+Arnaldo%3BAl-Hassan%2C+Suha+M%3BBacchini%2C+Dario%3BBombi%2C+Anna+Silvia%3BBornstein%2C+Marc+H%3BChang%2C+Lei%3BDeater-Deckard%2C+Kirby%3BDi+Giunta%2C+Laura%3BDodge%2C+Kenneth+A%3BMalone%2C+Patrick+S%3BOburu%2C+Paul%3BPastorelli%2C+Concetta%3BSkinner%2C+Ann+T%3BSorbring%2C+Emma%3BTapanya%2C+Sombat&rft.aulast=Lansford&rft.aufirst=Jennifer&rft.date=2016-10-01&rft.volume=51&rft.issue=5&rft.spage=366&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Psychology.+Journal+International+de+Psychologie&rft.issn=00207594&rft_id=info:doi/10.1002%2Fijop.12185 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 International Union of Psychological Science N1 - Last updated - 2016-09-01 DO - http://dx.doi.org/10.1002/ijop.12185 ER - TY - JOUR T1 - Power of Food Scale in association with weight outcomes and dieting in a nationally representative cohort of U.S. young adults AN - 1815706979; PQ0003566567 AB - Food reward sensitivity may influence susceptibility to overeating in a permissive food environment, contributing to unintended weight gain and intentional weight loss behavior. This study examined associations of food reward sensitivity, assessed by the Power of Food Scale (PFS), with weight outcomes and dieting in a nationally representative cohort of U.S. emerging adults. Wave 5 (W5, 5th year of follow-up) respondents from the NEXT Generation Health Study were included (N = 2202, W5 age = 20.3 plus or minus 0.02 years). Baseline and W5 BMI, W5 weight status (normal weight = 18.5 less than or equal to BMI < 25, overweight = 25 less than or equal to BMI < 30, obese = BMI greater than or equal to 30), BMI change (W5-baseline BMI) and onset of overweight or obesity (OWOB) were calculated from self-reported height and weight. PFS (aggregate and 3 domain scores: food available, present, and tasted) and dieting for weight-loss were assessed at W5. Adjusted linear regressions estimated associations of PFS with W5 BMI and BMI change. Log-binomial regressions estimated associations of high W5 BMI ( greater than or equal to 25), OWOB onset and dieting with PFS. Post hoc analyses estimated associations of PFS with W5 perceived weight status (overweight vs. about right or underweight). W5 BMI = 25.73 plus or minus 0.32 kg/m2, and OWOB onset occurred in 27.7% of participants. The PFS-food available score was associated with BMI change, beta plus or minus SE = 0.41 plus or minus 0.19. Other PFS scores were not associated with weight outcomes. Dieting prevalence was higher in participants with high versus low W5 BMI (61% versus 32%), and was positively associated with all PFS scores except the PFS-food tasted score, e.g., relative risk (RR) of dieting for PFS-aggregate = 1.13, 95%CI [1.01-1.26]. Post-hoc analyses indicated perceived overweight was positively associated with PFS-food available, 1.12, [1.01-1.24], and PFS-food present, 1.13, [1.03-1.24]. PFS was positively related to dieting and perceived overweight, but not concurrent or change in weight status in a representative cohort of U.S. emerging adults. JF - Appetite AU - Lipsky, L M AU - Nansel, T R AU - Haynie, D L AU - Liu, D AU - Eisenberg, M H AU - Simons-Morton, B AD - Health Behavior Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, North Bethesda, MD, United States Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 385 EP - 391 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 105 SN - 0195-6663, 0195-6663 KW - Biotechnology and Bioengineering Abstracts KW - Adolescent KW - Young adult KW - Body mass index KW - Obesity KW - Overweight KW - Cohort studies KW - PFS Power of Food Scale KW - fMRI functional magnetic resonance imaging KW - OWOB overweight and obesity KW - %ile percentile KW - CDC Centers for Disease Control and Prevention KW - W5 wave 5 KW - Risk assessment KW - Body weight loss KW - Age KW - Body weight KW - Food KW - Reinforcement KW - Food availability KW - Underweight KW - Waves KW - Body weight gain KW - W 30935:Food Biotechnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815706979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Appetite&rft.atitle=Power+of+Food+Scale+in+association+with+weight+outcomes+and+dieting+in+a+nationally+representative+cohort+of+U.S.+young+adults&rft.au=Lipsky%2C+L+M%3BNansel%2C+T+R%3BHaynie%2C+D+L%3BLiu%2C+D%3BEisenberg%2C+M+H%3BSimons-Morton%2C+B&rft.aulast=Lipsky&rft.aufirst=L&rft.date=2016-10-01&rft.volume=105&rft.issue=&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Appetite&rft.issn=01956663&rft_id=info:doi/10.1016%2Fj.appet.2016.06.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Body weight loss; Risk assessment; Obesity; Age; Body weight; Food; Reinforcement; Waves; Underweight; Food availability; Body weight gain DO - http://dx.doi.org/10.1016/j.appet.2016.06.012 ER - TY - JOUR T1 - Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer AN - 1808715047; PQ0003484656 AB - The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose-limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m super(2) biweekly. Efficacy was evaluated in 15 patients with irinotecan-refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre- and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and posttherapy tumor biopsies penetration of the ASO into the site of metastasis. What's new? Antisense technologies offer a number of potential advantages over more traditional therapeutic approaches, including improved specificity. Here the authors treated individuals afflicted with chemo-refractory colorectal cancer with an antisense oligonucleotide (ASO) against eIF4E, a critical translational factor often dysregulated in malignant tumors. Treatment was performed in combination with the chemotherapeutic irinotecan and halted disease progression in less than half of the treated individuals. The authors speculate based on detection of the ASO in tumor biopsies that stromal binding may reduce intracellular penetrance and lower effectiveness of the treatment. JF - International Journal of Cancer AU - Duffy, A G AU - Makarova-Rusher, O V AU - Ulahannan, S V AU - Rahma, O E AU - Fioravanti, S AU - Walker, M AU - Abdullah, S AU - Raffeld, M AU - Anderson, V AU - Abi-Jaoudeh, N AU - Levy, E AU - Wood, B J AU - Lee, S AU - Tomita, Y AU - Trepel, J B AU - Steinberg, S M AU - Revenko, A S AU - MacLeod, A R AU - Peer, C J AU - Figg, W D AU - Greten, T F AD - Gastrointestinal Malignancies Section, Thoracic-GI Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 1648 EP - 1657 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 139 IS - 7 SN - 0020-7136, 0020-7136 KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts KW - Translation KW - Data processing KW - Solid tumors KW - Translation initiation KW - Irinotecan KW - Colorectal cancer KW - Disease control KW - Peripheral blood KW - Biopsy KW - Toxicity KW - Tumors KW - Clinical trials KW - Initiation factor eIF-4E KW - Pharmacokinetics KW - Gene expression KW - Metastases KW - Antisense oligonucleotides KW - Oncogenes KW - Carcinogenesis KW - Computed tomography KW - Colorectal carcinoma KW - Cell proliferation KW - W 30910:Imaging KW - B 26680:Metastasis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808715047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Modulation+of+tumor+eIF4E+by+antisense+inhibition%3A+A+phase+I%2FII+translational+clinical+trial+of+ISIS+183750-an+antisense+oligonucleotide+against+eIF4E-in+combination+with+irinotecan+in+solid+tumors+and+irinotecan-refractory+colorectal+cancer&rft.au=Duffy%2C+A+G%3BMakarova-Rusher%2C+O+V%3BUlahannan%2C+S+V%3BRahma%2C+O+E%3BFioravanti%2C+S%3BWalker%2C+M%3BAbdullah%2C+S%3BRaffeld%2C+M%3BAnderson%2C+V%3BAbi-Jaoudeh%2C+N%3BLevy%2C+E%3BWood%2C+B+J%3BLee%2C+S%3BTomita%2C+Y%3BTrepel%2C+J+B%3BSteinberg%2C+S+M%3BRevenko%2C+A+S%3BMacLeod%2C+A+R%3BPeer%2C+C+J%3BFigg%2C+W+D%3BGreten%2C+T+F&rft.aulast=Duffy&rft.aufirst=A&rft.date=2016-10-01&rft.volume=139&rft.issue=7&rft.spage=1648&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.30199 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-11-23 N1 - SubjectsTermNotLitGenreText - Translation; Data processing; Translation initiation; Solid tumors; Irinotecan; Disease control; Colorectal cancer; Biopsy; Peripheral blood; Tumors; Toxicity; Clinical trials; Pharmacokinetics; Initiation factor eIF-4E; Metastases; Gene expression; Antisense oligonucleotides; Oncogenes; Computed tomography; Carcinogenesis; Colorectal carcinoma; Cell proliferation DO - http://dx.doi.org/10.1002/ijc.30199 ER - TY - JOUR T1 - B-IGEV (bortezomib plus IGEV) versus IGEV before high-dose chemotherapy followed by autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: a randomized, phase II trial of the Fondazione Italiana Linfomi (FIL). AN - 1808374630; 26879066 AB - This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m(2)) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p < 0.001). Toxicity was overall similar with the two regimens. The addition of bortezomib to IGEV does not improve response in relapsed/refractory HL patients. However, its favorable therapeutic and safety profile, and the prognostic role of pre-transplant PET negativity in patients receiving IGEV-based regimens are confirmed. JF - Leukemia & lymphoma AU - Balzarotti, Monica AU - Brusamolino, Ercole AU - Angelucci, Emanuele AU - Carella, Angelo Michele AU - Vitolo, Umberto AU - Russo, Eleonora AU - Congiu, Angelagiovanna AU - Gotti, Manuel AU - Massidda, Stefania AU - Botto, Barbara AU - Annechini, Giorgia AU - Spina, Michele AU - Re, Alessandro AU - Zilioli, Vittorio Ruggero AU - Merli, Francesco AU - Salvi, Flavia AU - Stelitano, Caterina AU - Bonfichi, Maurizio AU - Rodari, Marcello AU - Murru, Roberta AU - Magagnoli, Massimo AU - Anastasia, Antonella AU - Mazza, Rita AU - Giordano, Laura AU - Santoro, Armando AD - a Humanitas Cancer Center , Rozzano , Milan , Italy ; ; c U.O. Ematologia E Centro Trapianti Midollo Osseo. "Armando Businco" Hospital , Cagliari , Italy ; ; d IRCCS AOU San Martino-IST , Genoa , Italy ; ; e AO Città Della Salute E Della Scienza , Turin , Italy ; ; f Department of Biotechnology and Hematology, University La Sapienza , Rome , Italy ; ; b San Matteo Hospital , Pavia , Italy ; ; g National Cancer Institute , Aviano , PN , Italy ; ; h Spedali Civili , Brescia , Italy ; ; i Niguarda Ca' Granda Hospital , Milan , Italy ; ; j Arcispedale S. Maria Nuova Hospital , Reggio Emilia , Italy ; ; k SS Antonio E Biagio E Cesare Arrigo Hospital , Alessandria , Italy ; ; l Bianchi, Melacrino, Morelli Hospital , Reggio Calabria , Italy ; Y1 - 2016/10// PY - 2016 DA - October 2016 SP - 2375 EP - 2381 VL - 57 IS - 10 KW - Index Medicus KW - clinical results KW - lymphoma and Hodgkin lymphoma KW - Chemotherapeutic approaches UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808374630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=B-IGEV+%28bortezomib+plus+IGEV%29+versus+IGEV+before+high-dose+chemotherapy+followed+by+autologous+stem+cell+transplantation+in+relapsed+or+refractory+Hodgkin+lymphoma%3A+a+randomized%2C+phase+II+trial+of+the+Fondazione+Italiana+Linfomi+%28FIL%29.&rft.au=Balzarotti%2C+Monica%3BBrusamolino%2C+Ercole%3BAngelucci%2C+Emanuele%3BCarella%2C+Angelo+Michele%3BVitolo%2C+Umberto%3BRusso%2C+Eleonora%3BCongiu%2C+Angelagiovanna%3BGotti%2C+Manuel%3BMassidda%2C+Stefania%3BBotto%2C+Barbara%3BAnnechini%2C+Giorgia%3BSpina%2C+Michele%3BRe%2C+Alessandro%3BZilioli%2C+Vittorio+Ruggero%3BMerli%2C+Francesco%3BSalvi%2C+Flavia%3BStelitano%2C+Caterina%3BBonfichi%2C+Maurizio%3BRodari%2C+Marcello%3BMurru%2C+Roberta%3BMagagnoli%2C+Massimo%3BAnastasia%2C+Antonella%3BMazza%2C+Rita%3BGiordano%2C+Laura%3BSantoro%2C+Armando&rft.aulast=Balzarotti&rft.aufirst=Monica&rft.date=2016-10-01&rft.volume=57&rft.issue=10&rft.spage=2375&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=1029-2403&rft_id=info:doi/10.3109%2F10428194.2016.1140161 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.3109/10428194.2016.1140161 ER - TY - JOUR T1 - Bilingual mothers' language choice in child-directed speech: continuity and change AN - 1804218695 AB - An important aspect of Family Language Policy in bilingual families is parental language choice. Little is known about the continuity in parental language choice and the factors affecting it. This longitudinal study explores maternal language choice over time. Thirty-one bilingual mothers provided reports of what language(s) they spoke with their children. Mother-child interactions were videotaped when children were pre-verbal (5M), producing words in two languages (20M), and fluent speakers (53M). All children had heard two languages from birth in the home. Most mothers reported addressing children in the same single language. Observational data confirmed mothers' use of mainly a single language in interactions with their children, but also showed the occasional use of the other language in over half the sample when children were 20 months. Once children were 53 months mothers again used only the same language they reported speaking to children. These findings reveal a possible effect of children's overall level of language development and demonstrate the difficulty of adhering to a strict 'one person, one language' policy. The fact that there was longitudinal continuity in the language most mothers mainly spoke with children provided children with cumulative language input learning opportunities. JF - Journal of Multilingual and Multicultural Development AU - De Houwer, Annick AU - Bornstein, Marc H AD - Linguistics, Erfurt University, Erfurt, Germany ; Child and Family Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2016/10// PY - 2016 DA - Oct 2016 SP - 680 EP - 693 CY - Abingdon PB - Taylor & Francis Ltd. VL - 37 IS - 7 SN - 0143-4632 KW - Linguistics KW - Mothers KW - language choice KW - bilingual families KW - Bilingual First Language Acquisition KW - Dutch KW - French KW - Language Acquisition KW - Bilingualism KW - Child Directed Speech KW - Families KW - Parents KW - Longitudinal Studies KW - Maternal Speech KW - Language Use KW - Parent Child Interaction KW - 5612:sociolinguistics; language usage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804218695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Multilingual+and+Multicultural+Development&rft.atitle=Bilingual+mothers%26amp%3Bapos%3B+language+choice+in+child-directed+speech%3A+continuity+and+change&rft.au=De+Houwer%2C+Annick%3BBornstein%2C+Marc+H&rft.aulast=De+Houwer&rft.aufirst=Annick&rft.date=2016-10-01&rft.volume=37&rft.issue=7&rft.spage=680&rft.isbn=&rft.btitle=&rft.title=Journal+of+Multilingual+and+Multicultural+Development&rft.issn=01434632&rft_id=info:doi/10.1080%2F01434632.2015.1127929 LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Copyright - © 2016 Informa UK Limited, trading as Taylor & Francis Group N1 - Last updated - 2016-08-17 DO - http://dx.doi.org/10.1080/01434632.2015.1127929 ER - TY - JOUR T1 - Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma. AN - 1835395816; 27667400 AB - Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer. JF - Scientific reports AU - Zhang, Yi-Fan AU - Ho, Mitchell AD - Antibody Therapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States. Y1 - 2016/09/26/ PY - 2016 DA - 2016 Sep 26 SP - 33878 VL - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835395816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Humanization+of+high-affinity+antibodies+targeting+glypican-3+in+hepatocellular+carcinoma.&rft.au=Zhang%2C+Yi-Fan%3BHo%2C+Mitchell&rft.aulast=Zhang&rft.aufirst=Yi-Fan&rft.date=2016-09-26&rft.volume=6&rft.issue=&rft.spage=33878&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep33878 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep33878 ER - TY - JOUR T1 - Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer. AN - 1859720122; 27663600 AB - Our preclinical studies showed that the PARP inhibitor, olaparib, prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence-specific pharmacokinetic and pharmacodynamic effects, safety, and activity of the combination. Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200 mg twice daily, days 1-7) in a 3 + 3 dose escalation with carboplatin AUC4 or 5 every 21 days, up to eight cycles, followed by olaparib 300 mg twice daily maintenance. Patients were randomly assigned to starting schedule: cohort A (olaparib days 1-7, carboplatin on day 8) or B (carboplatin on day 1, olaparib days 2-8) during cycle 1. Patients received the reversed scheme in cycle 2. Blood was collected for olaparib pharmacokinetics, platinum-DNA adducts, comet assay, and PAR concentrations. The primary objectives were to examine schedule-dependent effects on olaparib pharmacokinetics and platinum-DNA adducts. A total of 77 (60 ovarian, 14 breast, and 3 uterine cancer) patients were treated. Dose-limiting toxicity was thrombocytopenia and neutropenia, defining olaparib 200 mg twice daily + carboplatin AUC4 as the MTD. Olaparib clearance was increased approximately 50% when carboplatin was given 24 hours before olaparib. In vitro experiments demonstrated carboplatin preexposure increased olaparib clearance due to intracellular olaparib uptake. Quantities of platinum-DNA adducts were not different as a function of the order of drug administration. Responses included 2 CRs and 31 PRs (46%) with a higher RR in BRCA mutation carriers compared with nonmutation carriers (68% vs. 19%). Tablet olaparib with carboplatin is a safe and active combination. Carboplatin preexposure causes intracellular olaparib accumulation reducing bioavailable olaparib, suggesting carboplatin should be administered prior to olaparib. Clin Cancer Res; 1-10. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Lee, Jung-Min AU - Peer, Cody J AU - Yu, Minshu AU - Amable, Lauren AU - Gordon, Nicolas AU - Annunziata, Christina M AU - Houston, Nicole AU - Goey, Andrew K L AU - Sissung, Tristan M AU - Parker, Bernard AU - Minasian, Lori AU - Chiou, Victoria L AU - Murphy, Robert F AU - Widemann, Brigitte C AU - Figg, William D AU - Kohn, Elise C AD - Women's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, Maryland. leej6@mail.nih.gov. ; Clinical Pharmacology Program, Center for Cancer Research, NCI, Bethesda, Maryland. ; Women's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, Maryland. ; National Institute on Minority Health and Health Disparities, Bethesda, Maryland. ; Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. Y1 - 2016/09/23/ PY - 2016 DA - 2016 Sep 23 SN - 1078-0432, 1078-0432 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859720122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Sequence-Specific+Pharmacokinetic+and+Pharmacodynamic+Phase+I%2FIb+Study+of+Olaparib+Tablets+and+Carboplatin+in+Women%27s+Cancer.&rft.au=Lee%2C+Jung-Min%3BPeer%2C+Cody+J%3BYu%2C+Minshu%3BAmable%2C+Lauren%3BGordon%2C+Nicolas%3BAnnunziata%2C+Christina+M%3BHouston%2C+Nicole%3BGoey%2C+Andrew+K+L%3BSissung%2C+Tristan+M%3BParker%2C+Bernard%3BMinasian%2C+Lori%3BChiou%2C+Victoria+L%3BMurphy%2C+Robert+F%3BWidemann%2C+Brigitte+C%3BFigg%2C+William+D%3BKohn%2C+Elise+C&rft.aulast=Lee&rft.aufirst=Jung-Min&rft.date=2016-09-23&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-1546 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-24 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-1546 ER - TY - JOUR T1 - Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach. AN - 1822115111; 27477586 AB - Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers. With the use of liquid chromatography-mass spectrometry-time-of-flight analysis (LC-MS-TOF), we developed a workflow for the identification of metabolites for the 8:2 FTOH and 8:2 diPAP. Analysis of serum and urine of dosed rats indicated the 8:2 FTOH-sulfate and the 8:2 diPAP as potential biomarkers. These compounds, as well as 25 other fluorinated compounds and metabolites, were analyzed in human serum and urine samples from the general population (n = 100) and office workers (n = 30). The 8:2 FTOH-sulfate was measured for the first time in human samples in 5 to 10% of the serum samples, ranging from 50 to 80 pg/mL. The 8:2 diPAP was measured in 58% of the samples, ranging from 100 to 800 pg/mL. This study indicates the FTOH-sulfate conjugate as a biomarker of exposure to FTOHs and PAPs in humans. JF - Environmental science & technology AU - Dagnino, Sonia AU - Strynar, Mark J AU - McMahen, Rebecca L AU - Lau, Christopher S AU - Ball, Carol AU - Garantziotis, Stavros AU - Webster, Thomas F AU - McClean, Michael D AU - Lindstrom, Andrew B AD - Oak Ridge Associated Universities, ORISE Program , Oak Ridge, Tennessee 37831, United States. ; Agilent Technologies, Inc. , 13000 Weston Parkway, Cary, North Carolina 27510, United States. ; Clinical Research Program and Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709, United States. ; Department of Environmental Health, Boston University School of Public Health , 715 Albany Street, T4W, Boston, Massachusetts 02118, United States. Y1 - 2016/09/20/ PY - 2016 DA - 2016 Sep 20 SP - 10216 EP - 10225 VL - 50 IS - 18 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1822115111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+science+%26+technology&rft.atitle=Identification+of+Biomarkers+of+Exposure+to+FTOHs+and+PAPs+in+Humans+Using+a+Targeted+and+Nontargeted+Analysis+Approach.&rft.au=Dagnino%2C+Sonia%3BStrynar%2C+Mark+J%3BMcMahen%2C+Rebecca+L%3BLau%2C+Christopher+S%3BBall%2C+Carol%3BGarantziotis%2C+Stavros%3BWebster%2C+Thomas+F%3BMcClean%2C+Michael+D%3BLindstrom%2C+Andrew+B&rft.aulast=Dagnino&rft.aufirst=Sonia&rft.date=2016-09-20&rft.volume=50&rft.issue=18&rft.spage=10216&rft.isbn=&rft.btitle=&rft.title=Environmental+science+%26+technology&rft.issn=1520-5851&rft_id=info:doi/10.1021%2Facs.est.6b01170 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.est.6b01170 ER - TY - JOUR T1 - Smokers in Brazil: who are they? AN - 1815711067; PQ0003597379 AB - BackgroundBrazil has experienced a large decline in smoking prevalence due to several tobacco control policies that were implemented in the past 25years. Previous population-wide studies found a consistent reduction over time in daily cigarette consumption among all socioeconomic groups.ObjectiveTo examine changes between 2008 and 2013 in tobacco behaviours and health-related conditions of smokers.MethodsWe used data obtained from two nationally-representative surveys conducted in 2008 and 2013 to estimate the prevalence of self-reported psychological and physical morbidity, and nicotine dependence markers, stratified by gender and sociodemographic groups. Generalised linear models were used to understand whether absolute differences in prevalence rates over time differed by categories of selected variables.ResultsFor both genders, as smoking prevalence declined in Brazil, there has been an increase in the proportion of ever smokers who have quit. In addition, remaining smokers seem to be making more quitting attempts. Among men with low educational level or younger than 25years-old, as compared to their counterparts, cessation rate showed an even greater increase over time. Moreover, the proportion of light smokers, which represent the vast majority of smokers, did not decrease. The percentage of poor health-conditions among remaining smokers nevertheless increased, particularly among women, which can make future cessation more challenging.ConclusionsIn Brazil, quitting rate is increasing, thus suggesting that tobacco control interventions implemented in Brazil in the past years seem to be effectively reaching the smoking population. This is strong evidence against the 'hardening hypothesis', which posits that remaining smokers decrease their willingness and ability to quit. JF - Tobacco Control AU - Szklo, Andre Salem AU - de Souza, Mirian Carvalho AU - Szklo, Moysees AU - de Almeida, Liz Maria AD - Division of Epidemiology, Brazilian National Cancer Institute (INCA), , Rio de Janeiro, Brazil Y1 - 2016/09/20/ PY - 2016 DA - 2016 Sep 20 SP - 564 EP - 570 PB - BMJ Publishing Group Ltd. VL - 25 IS - 5 SN - 0964-4563, 0964-4563 KW - Toxicology Abstracts KW - Addiction KW - Disparities KW - Surveillance and monitoring KW - Cessation KW - Smoking KW - Drug dependence KW - Socio-economic aspects KW - Data processing KW - Cigarettes KW - Tobacco KW - Morbidity KW - Models KW - Light effects KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815711067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+Control&rft.atitle=Smokers+in+Brazil%3A+who+are+they%3F&rft.au=Szklo%2C+Andre+Salem%3Bde+Souza%2C+Mirian+Carvalho%3BSzklo%2C+Moysees%3Bde+Almeida%2C+Liz+Maria&rft.aulast=Szklo&rft.aufirst=Andre&rft.date=2016-09-20&rft.volume=25&rft.issue=5&rft.spage=564&rft.isbn=&rft.btitle=&rft.title=Tobacco+Control&rft.issn=09644563&rft_id=info:doi/10.1136%2Ftobaccocontrol-2015-052324 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Socio-economic aspects; Drug dependence; Smoking; Data processing; Cigarettes; Tobacco; Morbidity; Light effects; Models DO - http://dx.doi.org/10.1136/tobaccocontrol-2015-052324 ER - TY - JOUR T1 - Silencing KRAS Overexpression in Cadmium-Transformed Prostate Epithelial Cells Mitigates Malignant Phenotype. AN - 1821791210; 27510461 AB - Cadmium (Cd) is a potential human prostate carcinogen. Chronic Cd exposure malignantly transforms RWPE-1 human prostate epithelial cells into CTPE cells by an unclear mechanism. Previous studies show that RWPE-1 can also be malignantly transformed by arsenic, and KRAS activation is key to causation and maintenance of this phenotype. Although Cd and arsenic can both transform prostate epithelial cells, it is uncertain whether their mechanisms are similar. Thus, here we determined whether KRAS activation is critical in causing and maintaining Cd-induced malignant transformation in CTPE cells. Expression of KRAS, miRNAs, and other genes of interest was analyzed by Western blot and RT-PCR. Following stable KRAS knockdown (KD) by RNA interference using shRNAmir, the malignant phenotype was assessed by various physical and genetic parameters. CTPE cells greatly overexpressed KRAS by 20-fold, indicating a likely role in Cd transformation. Thus, we attempted to reverse the malignant phenotype via KRAS KD. Two weeks after shRNAmir transduction, KRAS protein was undetectable in CTPE KD cells, confirming stable KD. KRAS KD reduced stimulated RAS/ERK and PI3K/AKT signaling pathways and markedly mitigated multiple physical and molecular malignant cell characteristics including: hypersecretion of MMP-2, colony formation, cell survival, and expression of cancer-relevant genes (reduced proliferation and cell cycle-related genes; activated tumor suppressor PTEN). However, KRAS KD did not reverse miRNA expression originally down-regulated by Cd transformation. These data strongly suggest KRAS is a key gene in development and maintenance of the Cd-induced malignant phenotype, at least in the prostate. It is not, however, the only genetic factor sustaining this phenotype. JF - Chemical research in toxicology AU - Ngalame, Ntube N O AU - Waalkes, Michael P AU - Tokar, Erik J AD - Stem Cell Toxicology Group, National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709, United States. Y1 - 2016/09/19/ PY - 2016 DA - 2016 Sep 19 SP - 1458 EP - 1467 VL - 29 IS - 9 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1821791210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Silencing+KRAS+Overexpression+in+Cadmium-Transformed+Prostate+Epithelial+Cells+Mitigates+Malignant+Phenotype.&rft.au=Ngalame%2C+Ntube+N+O%3BWaalkes%2C+Michael+P%3BTokar%2C+Erik+J&rft.aulast=Ngalame&rft.aufirst=Ntube+N&rft.date=2016-09-19&rft.volume=29&rft.issue=9&rft.spage=1458&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=1520-5010&rft_id=info:doi/10.1021%2Facs.chemrestox.6b00137 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.chemrestox.6b00137 ER - TY - JOUR T1 - Differential Activation of a Mouse Estrogen Receptor β Isoform (mERβ2) with Endocrine-Disrupting Chemicals (EDCs). AN - 1859740562; 27634370 AB - Endocrine disrupting compounds (EDCs) are suspected of altering estrogenic signaling through estrogen receptor (ER) α or β (mERβ1 in mice). Several EDC effects have been reported in animal studies and extrapolated to human studies. Unlike humans, rodents express a novel isoform of ERβ (mERβ2) with a modified ligand binding domain sequence. EDC activity through this isoform remains uncharacterized. We identified the expression pattern of mERβ2 in mouse tissues and assessed the estrogenic activity of EDCs through mERβ2. mERβ2 mRNA expression was measured in mouse tissues. HepG2 cells were used to assess the transactivation activity of mERβ isoforms with EDCs and ER coactivators. 293A cells transiently transfected with mER isoforms were used to detect EDC-mediated changes in endogenous ER target gene expression. Expression of mERβ2 mRNA was detected in mouse reproductive tissues (ovary, testis, and prostate) and lung and colon tissues from both female and male mice. Five (E2, DES, DPN, BPAF, Coum, 1-BP) of sixteen compounds tested by reporter assay had estrogenic activity through mERβ2. mERβ2 had a compound-specifc negative effect on ERβ/ligand-mediated activity and ER target genes when co-expressed with mERβ1. mERβ2 recruited coactivators SRC2 or SRC3 in the presence of EDCs, but showed less recruitment than mERβ1. mERβ2 showed weaker estrogenic activity than mERβ1 in our in vitro system, and can dampen mERβ1 activity. In vivo models of EDC activity and ER-mediated toxicity should consider the role of mERβ2, as rodent tissue responses involving mERβ2 may not be reproduced in human biology. JF - Environmental health perspectives AU - Donoghue, Lauren J AU - Neufeld, Thomas I AU - Li, Yin AU - Arao, Yukitomo AU - Coons, Laurel A AU - Korach, Kenneth S AD - Receptor Biology Section, Reproductive and Developmental Biology Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/09/16/ PY - 2016 DA - 2016 Sep 16 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859740562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Differential+Activation+of+a+Mouse+Estrogen+Receptor+%CE%B2+Isoform+%28mER%CE%B22%29+with+Endocrine-Disrupting+Chemicals+%28EDCs%29.&rft.au=Donoghue%2C+Lauren+J%3BNeufeld%2C+Thomas+I%3BLi%2C+Yin%3BArao%2C+Yukitomo%3BCoons%2C+Laurel+A%3BKorach%2C+Kenneth+S&rft.aulast=Donoghue&rft.aufirst=Lauren&rft.date=2016-09-16&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats. AN - 1859726004; 27638505 AB - N,N-dimethyl-p-toluidine (DMPT), an accelerant for methyl methacrylate monomers in medical devices, was a liver carcinogen in male and female F344/N rats and B6C3F1 mice in a 2-year oral exposure study. p-Toluidine, a structurally related chemical, was a liver carcinogen in mice but not in rats in an 18-month feed exposure study. In this current study, liver transcriptomic data were used to characterize mechanisms in DMPT and p-toluidine liver toxicity and for conducting benchmark dose (BMD) analysis. Male F344/N rats were exposed orally to DMPT or p-toluidine (0, 1, 6, 20, 60 or 120 mg/kg/day) for 5 days. The liver was examined for lesions and transcriptomic alterations. Both chemicals caused mild hepatic toxicity at 60 and 120 mg/kg and dose-related transcriptomic alterations in the liver. There were 511 liver transcripts differentially expressed for DMPT and 354 for p-toluidine at 120 mg/kg/day (false discovery rate threshold of 5 %). The liver transcriptomic alterations were characteristic of an anti-oxidative damage response (activation of the Nrf2 pathway) and hepatic toxicity. The top cellular processes in gene ontology (GO) categories altered in livers exposed to DMPT or p-toluidine were used for BMD calculations. The lower confidence bound benchmark doses for these chemicals were 2 mg/kg/day for DMPT and 7 mg/kg/day for p-toluidine. These studies show the promise of using 5-day target organ transcriptomic data to identify chemical-induced molecular changes that can serve as markers for preliminary toxicity risk assessment. JF - Archives of toxicology AU - Dunnick, June K AU - Shockley, Keith R AU - Morgan, Daniel L AU - Brix, Amy AU - Travlos, Gregory S AU - Gerrish, Kevin AU - Michael Sanders, J AU - Ton, T V AU - Pandiri, Arun R AD - Toxicology Branch, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. dunnickj@niehs.nih.gov. ; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. ; NTP Laboratory, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. ; Experimental Pathology Laboratories, Inc., National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. ; Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. ; Molecular Genomics Core, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. ; National Cancer Institute at NIEHS, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709, USA. Y1 - 2016/09/16/ PY - 2016 DA - 2016 Sep 16 KW - p-Toluidine KW - N,N-dimethyl-p-toluidine KW - Molecular markers KW - Liver toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859726004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=Hepatic+transcriptomic+alterations+for+N%2CN-dimethyl-p-toluidine+%28DMPT%29+and+p-toluidine+after+5-day+exposure+in+rats.&rft.au=Dunnick%2C+June+K%3BShockley%2C+Keith+R%3BMorgan%2C+Daniel+L%3BBrix%2C+Amy%3BTravlos%2C+Gregory+S%3BGerrish%2C+Kevin%3BMichael+Sanders%2C+J%3BTon%2C+T+V%3BPandiri%2C+Arun+R&rft.aulast=Dunnick&rft.aufirst=June&rft.date=2016-09-16&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=1432-0738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Structural Insights into Substrate Recognition and Catalysis in Outer Membrane Protein B (OmpB) by Protein-lysine Methyltransferases from Rickettsia. AN - 1820602900; 27474738 AB - Rickettsia belong to a family of Gram-negative obligate intracellular infectious bacteria that are the causative agents of typhus and spotted fever. Outer membrane protein B (OmpB) occurs in all rickettsial species, serves as a protective envelope, mediates host cell adhesion and invasion, and is a major immunodominant antigen. OmpBs from virulent strains contain multiple trimethylated lysine residues, whereas the avirulent strain contains mainly monomethyllysine. Two protein-lysine methyltransferases (PKMTs) that catalyze methylation of recombinant OmpB at multiple sites with varying sequences have been identified and overexpressed. PKMT1 catalyzes predominantly monomethylation, whereas PKMT2 catalyzes mainly trimethylation. Rickettsial PKMT1 and PKMT2 are unusual in that their primary substrate appears to be limited to OmpB, and both are capable of methylating multiple lysyl residues with broad sequence specificity. Here we report the crystal structures of PKMT1 from Rickettsia prowazekii and PKMT2 from Rickettsia typhi, both the apo form and in complex with its cofactor S-adenosylmethionine or S-adenosylhomocysteine. The structure of PKMT1 in complex with S-adenosylhomocysteine is solved to a resolution of 1.9 Å. Both enzymes are dimeric with each monomer containing an S-adenosylmethionine binding domain with a core Rossmann fold, a dimerization domain, a middle domain, a C-terminal domain, and a centrally located open cavity. Based on the crystal structures, residues involved in catalysis, cofactor binding, and substrate interactions were examined using site-directed mutagenesis followed by steady state kinetic analysis to ascertain their catalytic functions in solution. Together, our data reveal new structural and mechanistic insights into how rickettsial methyltransferases catalyze OmpB methylation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Abeykoon, Amila H AU - Noinaj, Nicholas AU - Choi, Bok-Eum AU - Wise, Lindsay AU - He, Yi AU - Chao, Chien-Chung AU - Wang, Guanghui AU - Gucek, Marjan AU - Ching, Wei-Mei AU - Chock, P Boon AU - Buchanan, Susan K AU - Yang, David C H AD - From the Department of Chemistry, Georgetown University, Washington, D. C. 20057. ; Markey Center for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, nnoinaj@purdue.edu. ; Laboratory of Biochemistry and. ; Viral and Rickettsial Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, Maryland 20910. ; Proteomics Core Facility, NHLBI and. ; Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, and. ; From the Department of Chemistry, Georgetown University, Washington, D. C. 20057, yangdc@georgetown.edu. Y1 - 2016/09/16/ PY - 2016 DA - 2016 Sep 16 SP - 19962 EP - 19974 VL - 291 IS - 38 KW - Index Medicus KW - enzyme catalysis KW - virulence factor KW - protein methylation KW - bacteria KW - enzyme structure KW - cell surface protein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1820602900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Structural+Insights+into+Substrate+Recognition+and+Catalysis+in+Outer+Membrane+Protein+B+%28OmpB%29+by+Protein-lysine+Methyltransferases+from+Rickettsia.&rft.au=Abeykoon%2C+Amila+H%3BNoinaj%2C+Nicholas%3BChoi%2C+Bok-Eum%3BWise%2C+Lindsay%3BHe%2C+Yi%3BChao%2C+Chien-Chung%3BWang%2C+Guanghui%3BGucek%2C+Marjan%3BChing%2C+Wei-Mei%3BChock%2C+P+Boon%3BBuchanan%2C+Susan+K%3BYang%2C+David+C+H&rft.aulast=Abeykoon&rft.aufirst=Amila&rft.date=2016-09-16&rft.volume=291&rft.issue=38&rft.spage=19962&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/10.1074%2Fjbc.M116.723460 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1074/jbc.M116.723460 ER - TY - JOUR T1 - CDK1 phosphorylates WRN at collapsed replication forks. AN - 1820599936; 27634057 AB - Regulation of end-processing is critical for accurate repair and to switch between homologous recombination (HR) and non-homologous end joining (NHEJ). End resection is a two-stage process but very little is known about regulation of the long-range resection, especially in humans. WRN participates in one of the two alternative long-range resection pathways mediated by DNA2 or EXO1. Here we demonstrate that phosphorylation of WRN by CDK1 is essential to perform DNA2-dependent end resection at replication-related DSBs, promoting HR, replication recovery and chromosome stability. Mechanistically, S1133 phosphorylation of WRN is dispensable for relocalization in foci but is involved in the interaction with the MRE11 complex. Loss of WRN phosphorylation negatively affects MRE11 foci formation and acts in a dominant negative manner to prevent long-range resection altogether, thereby licensing NHEJ at collapsed forks. Collectively, we unveil a CDK1-dependent regulation of the WRN-DNA2-mediated resection and identify an undescribed function of WRN as a DSB repair pathway switch. JF - Nature communications AU - Palermo, Valentina AU - Rinalducci, Sara AU - Sanchez, Massimo AU - Grillini, Francesca AU - Sommers, Joshua A AU - Brosh, Robert M AU - Zolla, Lello AU - Franchitto, Annapaola AU - Pichierri, Pietro AD - Section of Experimental and Computational Carcinogenesis, Department of Environment and Health, Istituto Superiore di Sanità, Rome 00161, Italy. ; Proteomics Lab, Department of Ecology and Biology, Università della Tuscia, 01100 Viterbo, Italy. ; Section of Gene and Cell Therapy, Department of Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy. ; Laboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, Baltimore, Maryland 21224, USA. ; Section of Molecular Epidemiology, Department of Environment and Health, Istituto Superiore di Sanità, 00161 Rome, Italy. Y1 - 2016/09/16/ PY - 2016 DA - 2016 Sep 16 SP - 12880 VL - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1820599936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=CDK1+phosphorylates+WRN+at+collapsed+replication+forks.&rft.au=Palermo%2C+Valentina%3BRinalducci%2C+Sara%3BSanchez%2C+Massimo%3BGrillini%2C+Francesca%3BSommers%2C+Joshua+A%3BBrosh%2C+Robert+M%3BZolla%2C+Lello%3BFranchitto%2C+Annapaola%3BPichierri%2C+Pietro&rft.aulast=Palermo&rft.aufirst=Valentina&rft.date=2016-09-16&rft.volume=7&rft.issue=&rft.spage=12880&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms12880 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms12880 ER - TY - JOUR T1 - MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer. AN - 1819903883; 27624283 AB - Two functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk. Recently, a third SNP (SNP55C > T; rs2870820) was also reported to affect Sp1 binding and MDM2 transcription. In this large population based case-control study, we genotyped MDM2 SNP55 in 10,779 Caucasian individuals, previously genotyped for SNP309 and SNP285, including cases of colon (n = 1,524), lung (n = 1,323), breast (n = 1,709) and prostate cancer (n = 2,488) and 3,735 non-cancer controls, as well as 299 healthy African-Americans. Applying the dominant model, we found an elevated risk of colon cancer among individuals harbouring SNP55TT/CT genotypes compared to the SNP55CC genotype (OR = 1.15; 95% CI = 1.01-1.30). The risk was found to be highest for left-sided colon cancer (OR = 1.21; 95% CI = 1.00-1.45) and among females (OR = 1.32; 95% CI = 1.01-1.74). Assessing combined genotypes, we found the highest risk of colon cancer among individuals harbouring the SNP55TT or CT together with the SNP309TG genotype (OR = 1.21; 95% CI = 1.00-1.46). Supporting the conclusions from the risk estimates, we found colon cancer cases carrying the SNP55TT/CT genotypes to be diagnosed at younger age as compared to SNP55CC (p = 0.053), in particular among patients carrying the SNP309TG/TT genotypes (p = 0.009). JF - Scientific reports AU - Helwa, Reham AU - Gansmo, Liv B AU - Romundstad, Pål AU - Hveem, Kristian AU - Vatten, Lars AU - Ryan, Bríd M AU - Harris, Curtis C AU - Lønning, Per E AU - Knappskog, Stian AD - Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway. ; Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA. Y1 - 2016/09/14/ PY - 2016 DA - 2016 Sep 14 SP - 33153 VL - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819903883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=MDM2+promoter+SNP55+%28rs2870820%29+affects+risk+of+colon+cancer+but+not+breast-%2C+lung-%2C+or+prostate+cancer.&rft.au=Helwa%2C+Reham%3BGansmo%2C+Liv+B%3BRomundstad%2C+P%C3%A5l%3BHveem%2C+Kristian%3BVatten%2C+Lars%3BRyan%2C+Br%C3%ADd+M%3BHarris%2C+Curtis+C%3BL%C3%B8nning%2C+Per+E%3BKnappskog%2C+Stian&rft.aulast=Helwa&rft.aufirst=Reham&rft.date=2016-09-14&rft.volume=6&rft.issue=&rft.spage=33153&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep33153 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep33153 ER - TY - JOUR T1 - Cellular Delivery of RNA Nanoparticles. AN - 1819122171; 27509068 AB - RNA nanostructures can be programmed to exhibit defined sizes, shapes and stoichiometries from naturally occurring or de novo designed RNA motifs. These constructs can be used as scaffolds to attach functional moieties, such as ligand binding motifs or gene expression regulators, for nanobiology applications. This review is focused on four areas of importance to RNA nanotechnology: the types of RNAs of particular interest for nanobiology, the assembly of RNA nanoconstructs, the challenges of cellular delivery of RNAs in vivo, and the delivery carriers that aid in the matter. The available strategies for the design of nucleic acid nanostructures, as well as for formulation of their carriers, make RNA nanotechnology an important tool in both basic research and applied biomedical science. JF - ACS combinatorial science AU - Parlea, Lorena AU - Puri, Anu AU - Kasprzak, Wojciech AU - Bindewald, Eckart AU - Zakrevsky, Paul AU - Satterwhite, Emily AU - Joseph, Kenya AU - Afonin, Kirill A AU - Shapiro, Bruce A AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States. ; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702, United States. ; Department of Chemistry, University of North Carolina at Charlotte , Charlotte, North Carolina 28223, United States. Y1 - 2016/09/12/ PY - 2016 DA - 2016 Sep 12 SP - 527 EP - 547 VL - 18 IS - 9 KW - Index Medicus KW - self-assembly KW - therapeutics KW - RNA KW - RNA nanoparticle KW - delivery KW - nanoconstruct UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819122171?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+combinatorial+science&rft.atitle=Cellular+Delivery+of+RNA+Nanoparticles.&rft.au=Parlea%2C+Lorena%3BPuri%2C+Anu%3BKasprzak%2C+Wojciech%3BBindewald%2C+Eckart%3BZakrevsky%2C+Paul%3BSatterwhite%2C+Emily%3BJoseph%2C+Kenya%3BAfonin%2C+Kirill+A%3BShapiro%2C+Bruce+A&rft.aulast=Parlea&rft.aufirst=Lorena&rft.date=2016-09-12&rft.volume=18&rft.issue=9&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=ACS+combinatorial+science&rft.issn=2156-8944&rft_id=info:doi/10.1021%2Facscombsci.6b00073 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acscombsci.6b00073 ER - TY - JOUR T1 - Krüppel-like Factor 13 Is a Major Mediator of Glucocorticoid Receptor Signaling in Cardiomyocytes and Protects These Cells from DNA Damage and Death. AN - 1818339374; 27451392 AB - Glucocorticoid receptor (GR) signaling has recently been shown to play a direct role in the regulation of cardiomyocyte function. In this study, we investigated the potential role of KLF13 as a downstream effector of GR action utilizing both in vivo and in vitro approaches. Our data show that KLF13 mRNA and protein levels are significantly diminished in the hearts of mice lacking GR in cardiomyocytes. Glucocorticoid administration up-regulated Klf13 mRNA in the mouse heart, in isolated primary cardiomyocytes, and in immortal cardiomyocyte cell lines. Glucocorticoid Klf13 gene expression was abolished by treatment with a GR antagonist (RU486) or by knockdown of GR in cardiomyocytes. Moreover, glucocorticoid induction of Klf13 mRNA was resistant to de novo protein synthesis inhibition, demonstrating that Klf13 is a direct glucocorticoid receptor gene target. A glucocorticoid responsive element (GRE) was identified in the Klf13 gene and its function was verified by chromatin immunoprecipitation in HL-1 cells and mouse hearts. Functional studies showed that GR regulation of Klf13 is critical to protect cardiomyocytes from DNA damage and cell death induced by cobalt(II) chloride hexahydrate (CoCl2·6H2O) and the antineoplastic drug doxorubicin. These results established a novel role for GR and KLF13 signaling in adult cardiomyocytes with potential clinical implications for the prevention of cardiotoxicity induced heart failure. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Cruz-Topete, Diana AU - He, Bo AU - Xu, Xiaojiang AU - Cidlowski, John A AD - From the Laboratory of Signal Transduction and. ; Integrative Bioinformatics, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709. ; From the Laboratory of Signal Transduction and cidlows1@niehs.nih.gov. Y1 - 2016/09/09/ PY - 2016 DA - 2016 Sep 09 SP - 19374 EP - 19386 VL - 291 IS - 37 KW - Index Medicus KW - Kruppel-like factor (KLF) KW - cardiomyocyte KW - gene regulation KW - hypoxia KW - glucocorticoid receptor UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1818339374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Kr%C3%BCppel-like+Factor+13+Is+a+Major+Mediator+of+Glucocorticoid+Receptor+Signaling+in+Cardiomyocytes+and+Protects+These+Cells+from+DNA+Damage+and+Death.&rft.au=Cruz-Topete%2C+Diana%3BHe%2C+Bo%3BXu%2C+Xiaojiang%3BCidlowski%2C+John+A&rft.aulast=Cruz-Topete&rft.aufirst=Diana&rft.date=2016-09-09&rft.volume=291&rft.issue=37&rft.spage=19374&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/10.1074%2Fjbc.M116.725903 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1074/jbc.M116.725903 ER - TY - JOUR T1 - Nitric Oxide Synthase-2-Derived Nitric Oxide Drives Multiple Pathways of Breast Cancer Progression. AN - 1826736693; 27464521 AB - Breast cancer is the second leading cause of cancer-related deaths among women in the United States. Development and progression of malignancy are associated with diverse cell signaling pathways that control cell proliferation, survival, motility, invasion, and metastasis. An increasing number of clinical studies have implicated a strong relationship between elevated tumor nitric oxide synthase-2 (NOS2) expression and poor patient survival. Herein, we review what we believe to be key mechanisms in the role(s) of NOS2-derived nitric oxide (NO) as a driver of breast cancer disease progression. High NO increases cyclooxygenase-2 activity, hypoxia inducible factor-1 alpha protein stabilization, and activation of important cell signaling pathways, including phosphoinositide 3-kinase/protein kinase B, mitogen-activated protein kinase, epidermal growth factor receptor, and Ras, through post-translational protein modifications. Moreover, dysregulated NO flux within the tumor microenvironment has other important roles, including the promotion of angiogenesis and modulation of matrix metalloproteinase/tissue inhibitor matrix metalloproteinase associated with tumor progression. The elucidation of these and other NO-driven pathways implicates NOS2 as a key driver of breast cancer disease progression and provides a new perspective in the identification of novel targets that may be therapeutically beneficial in the treatment of estrogen receptor-negative disease. Antioxid. Redox Signal. 00, 000-000. JF - Antioxidants & redox signaling AU - Basudhar, Debashree AU - Somasundaram, Veena AU - de Oliveira, Graciele Almeida AU - Kesarwala, Aparna AU - Heinecke, Julie L AU - Cheng, Robert Y AU - Glynn, Sharon A AU - Ambs, Stefan AU - Wink, David A AU - Ridnour, Lisa A AD - 1 Cancer and Inflammation Program, National Cancer Institute-Frederick , Frederick, Maryland. ; 2 Radiation Oncology Branch, National Cancer Institute , Bethesda, Maryland. ; 3 Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland , Galway, Ireland . ; 4 Laboratory of Human Carcinogenesis, National Cancer Institute , Bethesda, Maryland. Y1 - 2016/09/07/ PY - 2016 DA - 2016 Sep 07 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826736693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antioxidants+%26+redox+signaling&rft.atitle=Nitric+Oxide+Synthase-2-Derived+Nitric+Oxide+Drives+Multiple+Pathways+of+Breast+Cancer+Progression.&rft.au=Basudhar%2C+Debashree%3BSomasundaram%2C+Veena%3Bde+Oliveira%2C+Graciele+Almeida%3BKesarwala%2C+Aparna%3BHeinecke%2C+Julie+L%3BCheng%2C+Robert+Y%3BGlynn%2C+Sharon+A%3BAmbs%2C+Stefan%3BWink%2C+David+A%3BRidnour%2C+Lisa+A&rft.aulast=Basudhar&rft.aufirst=Debashree&rft.date=2016-09-07&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Antioxidants+%26+redox+signaling&rft.issn=1557-7716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Collateral Damage and Critical Turning Points: Public Health Implications of HPV Vaccine News Coverage for Boys and Men in 2011 AN - 1851151959 AB - In 2009, the Food and Drug Administration (FDA) officially expanded approval of the Gardasil vaccine to include human papillomavirus (HPV) vaccination for boys and men, and in 2011, the Centers for Disease Control and Prevention (CDC) issued a formal recommendation for routine vaccination for this population. Despite these efforts, HPV vaccination rates for boys and men continue to fall short of public health targets. While news was breaking about the benefits of the HPV vaccine for boys and men, public attention shifted as a result of political debates concerning the vaccine. This study examines a pivotal time period for public health in which the vaccine became officially recommended for boys and men and at the same time became the center of political controversies in the lead-up to the 2012 presidential campaign. The current study extends previous research and presents a content analysis of newspaper articles (N = 154) about the HPV vaccine for the year 2011. Results indicate that the lack of comprehensive coverage of HPV and the HPV vaccine found in previous studies continued in this year. Results shed light on key political events that may have functioned to overshadow the recommendation of the HPV vaccine for boys and men. The implications of this pattern of news coverage can inform public health efforts to address low rates of HPV vaccination uptake among boys and men in present day. JF - Health Communication AU - Krakow, Melinda AU - Rogers, Brian AD - Cancer Prevention Fellowship Program National Cancer Institute ; Department of Communication University of Utah ; Cancer Prevention Fellowship Program National Cancer Institute Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 1081 EP - 1088 CY - Mahwah PB - Taylor & Francis Ltd. VL - 31 IS - 9 SN - 1041-0236 KW - Public Health And Safety KW - Men KW - Presidential elections KW - Human papillomaviruses KW - Uptake KW - Immunization KW - Public health KW - Coverage KW - Healthy food KW - Boys KW - Campaigns KW - Content analysis KW - Turning points KW - News UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1851151959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Communication&rft.atitle=Collateral+Damage+and+Critical+Turning+Points%3A+Public+Health+Implications+of+HPV+Vaccine+News+Coverage+for+Boys+and+Men+in+2011&rft.au=Krakow%2C+Melinda%3BRogers%2C+Brian&rft.aulast=Krakow&rft.aufirst=Melinda&rft.date=2016-09-01&rft.volume=31&rft.issue=9&rft.spage=1081&rft.isbn=&rft.btitle=&rft.title=Health+Communication&rft.issn=10410236&rft_id=info:doi/10.1080%2F10410236.2015.1038773 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 Taylor & Francis N1 - Last updated - 2017-01-06 DO - http://dx.doi.org/10.1080/10410236.2015.1038773 ER - TY - JOUR T1 - Surface flow measurements from drones AN - 1832729630; 2016-090269 AB - Drones are transforming the way we sense and interact with the environment. However, despite their increased capabilities, the use of drones in geophysical sciences usually focuses on image acquisition for generating high-resolution maps. Motivated by the increasing demand for innovative and high performance geophysical observational methodologies, we posit the integration of drone technology and optical sensing toward a quantitative characterization of surface flow phenomena. We demonstrate that a recreational drone can be used to yield accurate surface flow maps of sub-meter water bodies. Specifically, drone's vibrations do not hinder surface flow observations, and velocity measurements are in agreement with traditional techniques. This first instance of quantitative water flow sensing from a flying drone paves the way to novel observations of the environment. JF - Journal of Hydrology AU - Tauro, Flavia AU - Porfiri, Maurizio AU - Grimaldi, Salvatore Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 240 EP - 245 PB - Elsevier, Amsterdam VL - 540 SN - 0022-1694, 0022-1694 KW - high-resolution methods KW - imagery KW - monitoring KW - surface water KW - rivers and streams KW - data processing KW - channels KW - mapping KW - measurement KW - drones KW - unmanned aerial vehicles KW - streamflow KW - fluvial features KW - drainage basins KW - accuracy KW - remote sensing KW - airborne methods KW - 21:Hydrogeology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1832729630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Hydrology&rft.atitle=Surface+flow+measurements+from+drones&rft.au=Tauro%2C+Flavia%3BPorfiri%2C+Maurizio%3BGrimaldi%2C+Salvatore&rft.aulast=Tauro&rft.aufirst=Flavia&rft.date=2016-09-01&rft.volume=540&rft.issue=&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Journal+of+Hydrology&rft.issn=00221694&rft_id=info:doi/10.1016%2Fj.jhydrol.2016.06.012 L2 - http://www.sciencedirect.com/science/journal/00221694 LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2016, American Geosciences Institute. Reference includes data from CAPCAS, Elsevier Scientific Publishers, Amsterdam, Netherlands N1 - Date revised - 2016-01-01 N1 - Number of references - 47 N1 - Document feature - illus. incl. 1 table N1 - Last updated - 2016-10-27 N1 - CODEN - JHYDA7 N1 - SubjectsTermNotLitGenreText - accuracy; airborne methods; channels; data processing; drainage basins; drones; fluvial features; high-resolution methods; imagery; mapping; measurement; monitoring; remote sensing; rivers and streams; streamflow; surface water; unmanned aerial vehicles DO - http://dx.doi.org/10.1016/j.jhydrol.2016.06.012 ER - TY - JOUR T1 - Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus AN - 1827931751; PQ0003606407 AB - Cells use the post-translational modification ADP-ribosylation to control a host of biological activities. In some pathogenic bacteria, an operon-encoded mono-ADP-ribosylation cycle mediates response to host-induced oxidative stress. In this system, reversible mono ADP-ribosylation of a lipoylated target protein represses oxidative stress response. An NAD super(+)-dependent sirtuin catalyzes the single ADP-ribose (ADPr) addition, while a linked macrodomain-containing protein removes the ADPr. Here we report the crystal structure of the sitruin-linked macrodomain protein from Staphylococcus aureus, SauMacro (also known as SAV0325) to 1.75-Aa resolution. The monomeric SauMacro bears a previously unidentified Zn super(2+)-binding site that putatively aids in substrate recognition and catalysis. An amino-terminal three-helix bundle motif unique to this class of macrodomain proteins provides a structural scaffold for the Zn super(2+) site. Structural features of the enzyme further indicate a cleft proximal to the Zn super(2+) binding site appears well suited for ADPr binding, while a deep hydrophobic channel in the protein core is suitable for binding the lipoate of the lipoylated protein target. JF - Protein Science AU - Appel, CDenise AU - Feld, Geoffrey K AU - Wallace, Bret D AU - Williams, RScott AD - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, US National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, 27709. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1682 EP - 1691 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 25 IS - 9 SN - 0961-8368, 0961-8368 KW - Microbiology Abstracts B: Bacteriology KW - Post-translation KW - Oxidative stress KW - Zinc KW - Sirtuins KW - Crystal structure KW - Enzymes KW - Hydrophobicity KW - Staphylococcus aureus KW - ADP-ribosylation KW - scaffolds KW - Catalysis KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827931751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Science&rft.atitle=Structure+of+the+sirtuin-linked+macrodomain+SAV0325+from+Staphylococcus+aureus&rft.au=Appel%2C+CDenise%3BFeld%2C+Geoffrey+K%3BWallace%2C+Bret+D%3BWilliams%2C+RScott&rft.aulast=Appel&rft.aufirst=CDenise&rft.date=2016-09-01&rft.volume=25&rft.issue=9&rft.spage=1682&rft.isbn=&rft.btitle=&rft.title=Protein+Science&rft.issn=09618368&rft_id=info:doi/10.1002%2Fpro.2974 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Post-translation; Oxidative stress; Zinc; Crystal structure; Sirtuins; Enzymes; Hydrophobicity; ADP-ribosylation; scaffolds; Catalysis; Staphylococcus aureus DO - http://dx.doi.org/10.1002/pro.2974 ER - TY - JOUR T1 - Simultaneous quantification of 11 cannabinoids and metabolites in human urine by liquid chromatography tandem mass spectrometry using WAX-S tips AN - 1827930274; PQ0003688194 AB - A comprehensive cannabinoid urine quantification method may improve clinical and forensic result interpretation and is necessary to support our clinical research. A liquid chromatography tandem mass spectrometry quantification method for Delta super(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), Delta super(9)-tetrahydrocannabinolic acid (THCAA), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), Delta super(9)-tetrahydrocannabivarin (THCV), 11-nor-9-carboxy-THCV (THCVCOOH), THC-glucuronide (THC-gluc), and THCCOOH-glucuronide (THCCOOH-gluc) in urine was developed and validated according to the Scientific Working Group on Toxicology guidelines. Sample preparation consisted of disposable pipette extraction (WAX-S) of 200 mu L urine. Separation was achieved on a Kinetex C18 column using gradient elution with flow rate 0.5 mL/min, mobile phase A (10 mM ammonium acetate in water), and mobile phase B (15 % methanol in acetonitrile). Total run time was 14 min. Analytes were monitored in both positive and negative ionization modes by scheduled multiple reaction monitoring. Linear ranges were 0.5-100 mu g/L for THC and THCCOOH; 0.5-50 mu g/L for 11-OH-THC, CBD, CBN, THCAA, and THC-gluc; 1-100 mu g/L for CBG, THCV, and THCVCOOH; and 5-500 mu g/L for THCCOOH-gluc (R super(2)>0.99). Analytical biases were 88.3-113.7 %, imprecisions 3.3-14.3 %, extraction efficiencies 42.4-81.5 %, and matrix effect -10 to 32.5 %. We developed and validated a comprehensive, simple, and rapid LC-MS/MS cannabinoid urine method for quantification of 11 cannabinoids and metabolites. This method is being used in a controlled cannabis administration study, investigating urine cannabinoid markers documenting recent cannabis use, chronic frequent smoking, or route of drug administration and potentially improving urine cannabinoid result interpretation. JF - Analytical and Bioanalytical Chemistry AU - Andersson, Maria AU - Scheidweiler, Karl B AU - Sempio, Cristina AU - Barnes, Allan J AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA, kscheidweiler@intra.nida.nih.gov Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 6461 EP - 6471 PB - Springer Science+Business Media, Berlin/Heidelberg Germany VL - 408 IS - 23 SN - 1618-2642, 1618-2642 KW - Biotechnology and Bioengineering Abstracts KW - Methanol KW - Metabolites KW - Drug abuse KW - Ammonium acetate KW - Mass spectroscopy KW - Tetrahydrocannabinol KW - Smoking KW - Cannabinoids KW - Liquid chromatography KW - Urine KW - Forensic science KW - Cannabis KW - Acetonitrile KW - Ionization KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827930274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+and+Bioanalytical+Chemistry&rft.atitle=Simultaneous+quantification+of+11+cannabinoids+and+metabolites+in+human+urine+by+liquid+chromatography+tandem+mass+spectrometry+using+WAX-S+tips&rft.au=Andersson%2C+Maria%3BScheidweiler%2C+Karl+B%3BSempio%2C+Cristina%3BBarnes%2C+Allan+J%3BHuestis%2C+Marilyn+A&rft.aulast=Andersson&rft.aufirst=Maria&rft.date=2016-09-01&rft.volume=408&rft.issue=23&rft.spage=6461&rft.isbn=&rft.btitle=&rft.title=Analytical+and+Bioanalytical+Chemistry&rft.issn=16182642&rft_id=info:doi/10.1007%2Fs00216-016-9765-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 35 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Methanol; Metabolites; Drug abuse; Ammonium acetate; Mass spectroscopy; Tetrahydrocannabinol; Smoking; Cannabinoids; Urine; Liquid chromatography; Cannabis; Forensic science; Acetonitrile; Ionization DO - http://dx.doi.org/10.1007/s00216-016-9765-8 ER - TY - JOUR T1 - Product Development Under FDA's Animal Rule: Understanding FDA's Expectations and Potential Implications for Traditional Development Programs AN - 1827928671; PQ0003637383 AB - In 2002 the US Food and Drug Administration (FDA) established a regulatory pathway for drug and biological products targeting indications for which human efficacy studies are not feasible or ethical. These regulations (21 CFR 314.600 for drugs and 21 CFR 601.90 for biologics), commonly referred to as the "Animal Rule," were the result of many years of thinking about how to make such products available to people who might need them. A handful of products have been approved under the Animal Rule, and several others are in development. This article reviews how different products met the requirements for licensure under the Animal Rule, based on information publicly available on FDA's website. The primary aim of this manuscript is to offer an understanding of FDA's interpretation of relevant regulations and guidances in the context of this licensure pathway. Some of the methods used for Animal Rule approvals may also have potential application in more traditional development programs. Thus, this article may also offer insight into methods for accelerating product development in general. JF - Therapeutic Innovation & Regulatory Science AU - Allio, Theresa AD - 1 .Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, theresa.allio@nih.gov Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 660 EP - 670 PB - Sage Publications, Inc. VL - 50 IS - 5 SN - 2168-4790, 2168-4790 KW - Biotechnology and Bioengineering Abstracts KW - Animal Rule KW - data extrapolation KW - efficacy KW - pharmacokinetics KW - dose selection KW - Ethics KW - W 30935:Food Biotechnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827928671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapeutic+Innovation+%26+Regulatory+Science&rft.atitle=Product+Development+Under+FDA%27s+Animal+Rule%3A+Understanding+FDA%27s+Expectations+and+Potential+Implications+for+Traditional+Development+Programs&rft.au=Allio%2C+Theresa&rft.aulast=Allio&rft.aufirst=Theresa&rft.date=2016-09-01&rft.volume=50&rft.issue=5&rft.spage=660&rft.isbn=&rft.btitle=&rft.title=Therapeutic+Innovation+%26+Regulatory+Science&rft.issn=21684790&rft_id=info:doi/10.1177%2F2168479016641717 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 34 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Ethics DO - http://dx.doi.org/10.1177/2168479016641717 ER - TY - JOUR T1 - Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption AN - 1827927237; PQ0003681734 AB - Background/ Objectives: Prader-Willi syndrome (PWS) is a type of human genetic obesity that may give us information regarding the physiology of non-syndromic obesity. The objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison with healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings.Subjects/ Methods: This study compared the central effects of food consumption in nine individuals with PWS (7 men, 2 women; body fat 35.3 plus or minus 10.0%) and seven controls (7 men; body fat 28.8 plus or minus 7.6%), matched for percentage body fat. H sub(2) super(15)O-PET (positron emission tomography) scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity. Results: Compared with obese controls, PWS showed altered (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls, DLPFC rCBF tended to remain unchanged. In more liberal analyses (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.005), rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, Delta rCBF of the right OFC was associated with changes in appetite ratings. Conclusions: The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal-induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior. JF - International Journal of Obesity AU - Reinhardt, M AU - Parigi, A D AU - Chen, K AU - Reiman, E M AU - Thiyyagura, P AU - Krakoff, J AU - Hohenadel, M G AU - Le, D S N T AU - Weise, C M AD - Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, USA; Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1360 EP - 1368 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 40 IS - 9 SN - 0307-0565, 0307-0565 KW - CSA Neurosciences Abstracts; Health & Safety Science Abstracts KW - Hunger KW - Obesity KW - Satiety KW - Physiology KW - Brain KW - Prader-Willi syndrome KW - Ingestion KW - Appetite KW - Blood KW - Food consumption KW - Emissions KW - Positron emission tomography KW - Body fat KW - Standards KW - Deactivation KW - Cortex (prefrontal) KW - Cerebral blood flow KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - N3 11023:Neurogenetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827927237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=Deactivation+of+the+left+dorsolateral+prefrontal+cortex+in+Prader-Willi+syndrome+after+meal+consumption&rft.au=Reinhardt%2C+M%3BParigi%2C+A+D%3BChen%2C+K%3BReiman%2C+E+M%3BThiyyagura%2C+P%3BKrakoff%2C+J%3BHohenadel%2C+M+G%3BLe%2C+D+S+N+T%3BWeise%2C+C+M&rft.aulast=Reinhardt&rft.aufirst=M&rft.date=2016-09-01&rft.volume=40&rft.issue=9&rft.spage=1360&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.75 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Hunger; Food consumption; Obesity; Satiety; Positron emission tomography; Brain; Prader-Willi syndrome; Body fat; Deactivation; Appetite; Cerebral blood flow; Cortex (prefrontal); Blood; Physiology; Emissions; Standards; Ingestion DO - http://dx.doi.org/10.1038/ijo.2016.75 ER - TY - JOUR T1 - Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor- Kappa B Signaling for Cancer Treatment AN - 1827921964; PQ0003664699 AB - The NF- Kappa B signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation. Cytoplasmic signaling to activate NF- Kappa B can occur as part of the DNA damage response or in response to a large variety of activators, including viruses, inflammation, and cell death. NF- Kappa B transcription factors play a fundamental role in tumorigenesis and are implicated in the origination and propagation of both hematologic and solid tumor types, including melanoma, breast, prostate, ovarian, pancreatic, colon, lung, and thyroid cancers. On the other hand, NF- Kappa B signaling is key to immune function and is likely necessary for antitumor immunity. This presents a dilemma when designing therapeutic approaches to target NF- Kappa B. There is growing interest in identifying novel modulators to inhibit NF- Kappa B activity as impeding different steps of the NF- Kappa B pathway has potential to slow tumor growth, progression, and resistance to chemotherapy. Despite significant advances in our understanding of this pathway, our ability to effectively clinically block key targets for cancer therapy remains limited due to on-target effects in normal tissues. Tumor specificity is critical to developing therapeutic strategies targeting this antiapoptotic signaling pathway to maintain antitumor immune surveillance when applying such therapy to patients. Clin Cancer Res; 22(17); 4302-8. copyright 2016 AACR. JF - Clinical Cancer Research AU - Zeligs, Kristen P AU - Neuman, Monica K AU - Annunziata, Christina M AD - Department of Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, Maryland, annunzic@mail.nih.gov Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 4302 EP - 4308 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 17 SN - 1078-0432, 1078-0432 KW - Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Cell survival KW - Solid tumors KW - Pancreas KW - Chemotherapy KW - Tumorigenesis KW - Immunity KW - Melanoma KW - NF- Kappa B protein KW - Inflammation KW - DNA damage KW - Cell death KW - Colon KW - Lung KW - Immunosurveillance KW - Transcription factors KW - thyroid cancer KW - Immune response KW - Prostate KW - Signal transduction KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827921964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Molecular+Pathways%3A+The+Balance+between+Cancer+and+the+Immune+System+Challenges+the+Therapeutic+Specificity+of+Targeting+Nuclear+Factor-+Kappa+B+Signaling+for+Cancer+Treatment&rft.au=Zeligs%2C+Kristen+P%3BNeuman%2C+Monica+K%3BAnnunziata%2C+Christina+M&rft.aulast=Zeligs&rft.aufirst=Kristen&rft.date=2016-09-01&rft.volume=22&rft.issue=17&rft.spage=4302&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-1374 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Cell survival; Solid tumors; Chemotherapy; Pancreas; Tumorigenesis; Immunity; Inflammation; NF- Kappa B protein; Melanoma; DNA damage; Cell death; Colon; Immunosurveillance; Lung; Transcription factors; thyroid cancer; Immune response; Prostate; Signal transduction DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-1374 ER - TY - JOUR T1 - Female breast cancer in Central and South America AN - 1827920505; PQ0003716824 AB - Rationale and objective The burden of breast cancer has increased worldwide. Breast cancer mortality has been increasing in Central and South America (CSA) in the last few decades. We describe the current burden of breast cancer in CSA and review the current status of disease control. Methods We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence and mortality rates per 100,000 person-years for 2003-2007 and the estimated annual percentage change to describe time trends. Results In the most recent 5-year period, Argentina, Brazil, and Uruguay had the highest incidence rates (67.7-71.9) and Bolivia and El Salvador had the lowest (7.9-12.7). For most countries, mortality rates were less than or equal to 12.3, except in Uruguay, Argentina and Cuba (14.9-20.5). Age-specific rates increased after the age of 40-50 years and reached a maximum after age 65 years (mean age at diagnosis 56-62 years). Most countries have developed national screening guidelines; however, there is limited capacity for screening. Conclusion The geographic variation of breast cancer rates may be explained by differences in the prevalence of reproductive patterns, lifestyle factors, early detection, and healthcare access. Extending early-detection programs is challenging because of inequalities in healthcare access and coverage, limited funding, and inadequate infrastructure, and thus it may not be feasible. Given the current status of breast cancer in CSA, data generated by population-based cancer registries is urgently needed for effective planning for cancer control. JF - Cancer Epidemiology AU - Di Sibio, Alejandro AU - Abriata, Graciela AU - Forman, David AU - Sierra, Monica S AD - National Cancer Institute, Argentina Y1 - 2016/09// PY - 2016 DA - September 2016 SP - S110 EP - S120 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 44 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - Breast KW - Neoplasm KW - Screening KW - Central and South America KW - Mortality KW - Databases KW - Age KW - Data processing KW - Reviews KW - Disease control KW - Breast cancer KW - Geographical variations KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827920505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Female+breast+cancer+in+Central+and+South+America&rft.au=Di+Sibio%2C+Alejandro%3BAbriata%2C+Graciela%3BForman%2C+David%3BSierra%2C+Monica+S&rft.aulast=Di+Sibio&rft.aufirst=Alejandro&rft.date=2016-09-01&rft.volume=44&rft.issue=&rft.spage=S110&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.08.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 104 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Databases; Mortality; Age; Data processing; Reviews; Disease control; Breast cancer; Geographical variations DO - http://dx.doi.org/10.1016/j.canep.2016.08.010 ER - TY - JOUR T1 - Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers AN - 1827920094; PQ0003664716 AB - Purpose: Epithelial-to-mesenchymal transition (EMT) is important in cancer progression and metastasis. We and others have previously reported that lysyl oxidase (LOX) is overexpressed in aggressive cancers, is associated with increased mortality, and regulates EMT. However, the mechanism by which LOX mediates EMT is unknown. In this study, we investigated the effect of LOX on mediators of EMT.Experimental Design: We used chromatin immunoprecipitation and promoter luciferase assays to determine the target gene of LOX. To determine the effects of SNAI2 in vivo, we used our metastatic anaplastic thyroid cancer (ATC) mouse model. To investigate the effects of LOX and SNAI2 on MMPs and TIMPs, protein arrays were used. Primary tumors from patients with metastatic, breast and colon cancer, and tissue array for thyroid cancer were assessed for SNAI2 and TIMP4 expression by immunohistochemistry.Results: We found that LOX knockdown decreases SNAI2 expression in cancer cell lines. Furthermore, knockdown of LOX reduced SNAI2 expression in a metastatic mouse model of thyroid cancer. We also demonstrated that LOX binds and transactivates the SNAI2 promoter. We found a direct correlation in thyroid and breast cancer samples between LOX and SNAI2 expression. To understand how LOX/SNAI2 axis mediates these effects, we performed a comprehensive analysis of MMPs/TIMPs. LOX and SNAI2 depletion reduced TIMP4 secretion. Analysis of SNAI2 and TIMP4 expression showed overexpression of both proteins in aggressive thyroid, colon, and breast tumors.Conclusions: Our findings provide new evidence that LOX regulates SNAI2 expression and that SNAI2-mediated TIMP4 secretion plays a role in cancer progression. Clin Cancer Res; 22(17); 4491-504. copyright 2016 AACR. JF - Clinical Cancer Research AU - Boufraqech, Myriem AU - Zhang, Lisa AU - Nilubol, Naris AU - Sadowski, Samira M AU - Kotian, Shweta AU - Quezado, Martha AU - Kebebew, Electron AD - Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, kebebewe@mail.nih.gov Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 4491 EP - 4504 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 17 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Mortality KW - Chromatin KW - Immunoprecipitation KW - Animal models KW - Transcription KW - Tissue inhibitor of metalloproteinases KW - Tumors KW - Colon cancer KW - Metastases KW - Promoters KW - Tumor cell lines KW - Lysyl oxidase KW - Tissue inhibitor of metalloproteinase 4 KW - snail protein KW - thyroid cancer KW - Protein arrays KW - Breast cancer KW - W 30945:Fermentation & Cell Culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827920094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Lysyl+Oxidase+%28LOX%29+Transcriptionally+Regulates+SNAI2+Expression+and+TIMP4+Secretion+in+Human+Cancers&rft.au=Boufraqech%2C+Myriem%3BZhang%2C+Lisa%3BNilubol%2C+Naris%3BSadowski%2C+Samira+M%3BKotian%2C+Shweta%3BQuezado%2C+Martha%3BKebebew%2C+Electron&rft.aulast=Boufraqech&rft.aufirst=Myriem&rft.date=2016-09-01&rft.volume=22&rft.issue=17&rft.spage=4491&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2461 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Mortality; Chromatin; Animal models; Immunoprecipitation; Transcription; Colon cancer; Tumors; Tissue inhibitor of metalloproteinases; Metastases; Promoters; Tumor cell lines; Lysyl oxidase; Tissue inhibitor of metalloproteinase 4; snail protein; Protein arrays; thyroid cancer; Breast cancer DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2461 ER - TY - JOUR T1 - Comparison of analytical techniques for the identification of bioactive compounds from natural products AN - 1827909714; PQ0003722305 AB - Covering: 2000 to 2016 Natural product extracts are a rich source of bioactive compounds. As a result, the screening of natural products for the identification of novel biologically active metabolites has been an essential part of several drug discovery programs. It is estimated that more than 70% of all drugs approved from 1981 and 2006, were either derived from or structurally similar to nature based compounds indicating the necessity for the development of a rapid method for the identification of novel compounds from plant extracts. The screening of biological matrices for the identification of novel modulators is nevertheless still challenging. In this review we discuss current techniques in phytochemical analysis and the identification of biologically active components. JF - Natural Product Reports AU - Ciesla, Lukasz AU - Moaddel, Ruin AD - Laboratory of Clinical Investigation; Biomedical Research Center, 8C232; National Institute on Aging; National Institutes of Health; 251 Bayview Boulevard; Baltimore; Maryland 21224; USA; +1-410-558-8294 Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1131 EP - 1145 PB - Royal Society of Chemistry VL - 33 IS - 10 SN - 0265-0568, 0265-0568 KW - Biotechnology and Bioengineering Abstracts KW - Drug discovery KW - natural products KW - Drug development KW - Metabolites KW - Plant extracts KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827909714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Natural+Product+Reports&rft.atitle=Comparison+of+analytical+techniques+for+the+identification+of+bioactive+compounds+from+natural+products&rft.au=Ciesla%2C+Lukasz%3BMoaddel%2C+Ruin&rft.aulast=Ciesla&rft.aufirst=Lukasz&rft.date=2016-09-01&rft.volume=33&rft.issue=10&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=Natural+Product+Reports&rft.issn=02650568&rft_id=info:doi/10.1039%2Fc6np00016a LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 94 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Drug discovery; Metabolites; Drug development; natural products; Plant extracts DO - http://dx.doi.org/10.1039/c6np00016a ER - TY - JOUR T1 - Differential Utilization of Basic Proline-Rich Glycoproteins during Growth of Oral Bacteria in Saliva AN - 1827909276; PQ0003647346 AB - Although saliva is widely recognized as a primary source of carbon and nitrogen for growth of the dental plaque biofilm community, little is known about how different oral bacteria utilize specific salivary components. To address this question, 32 strains representing 16 genera commonly isolated from early plaque biofilms were compared for growth over two transfers in stimulated (by chewing Parafilm) whole saliva that was stabilized by heat treatment and dialysis. The cell densities, measured by quantitative PCR (qPCR), ranged from similar to 1 106 to 1 107/ml for strains of Streptococcus gordonii, Streptococcus oralis, and Streptococcus mitis and one strain of Streptococcus sanguinis. Strains of Streptococcus mutans, Gemella haemolysans, and Granulicatella adiacens reached similar to 1 105 to 1 106/ml. In contrast, little or no growth was noted for three other strains of S. sanguinis, as well as for strains of Streptococcus parasanguinis, Streptococcus salivarius, Streptococcus vestibularis, Streptococcus sobrinus, Actinomyces spp., Abiotrophia defectiva, and Rothia dentocariosa. SDS-PAGE, lectin blotting, and two-dimensional gel electrophoresis of saliva from cultures of S. gordonii, S. oralis, and S. mitis revealed species-specific differences in the degradation of basic proline-rich glycoproteins (PRG). In contrast, saliva from cultures of other bacteria was indistinguishable from control saliva. Species-dependent differences in the utilization of individual host sugars were minor. Thus, differences in salivary glycan foraging between oral species may be important to cross-feeding and cooperation between organisms in dental plaque biofilm development. IMPORTANCE Bacteria in the mouth use saliva for nutrition. How each of the many types of bacteria uses saliva is not clear. We show that a major protein in saliva, called PRG, is an important nutrition source for certain bacteria but not for others. PRG has many sugar molecules linked in chains, but the sugar is not available for bacteria until the chains are degraded. The bacteria that can grow by digesting this protein break the sugar chains into parts which not only support their own growth but could also be available to support the growth of those bacteria that cannot use the intact protein. JF - Antimicrobial Agents & Chemotherapy AU - Zhou, Yuan AU - Yang, Jinghua AU - Zhang, Luxia AU - Zhou, Xuedong AU - Cisar, John O AU - Palmer, Robert J, Jr AD - << + $0, rjpalmer@dir.nidcr.nih.gov. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 5249 EP - 5258 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 82 IS - 17 SN - 0099-2240, 0099-2240 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Cell density KW - Cell culture KW - Development KW - Polysaccharides KW - Nutrition KW - Carbon KW - Streptococcus gordonii KW - Streptococcus sanguinis KW - Syntrophism KW - Polymerase chain reaction KW - Streptococcus salivarius KW - Glycoproteins KW - Biofilms KW - Streptococcus mutans KW - Mouth KW - Streptococcus mitis KW - Actinomyces KW - Streptococcus oralis KW - Bacteria KW - Sugar KW - Dialysis KW - Chewing KW - Streptococcus sobrinus KW - Streptococcus parasanguinis KW - Lectins KW - Dental plaque KW - Abiotrophia defectiva KW - Granulicatella adiacens KW - Saliva KW - Heat treatments KW - Rothia dentocariosa KW - Nitrogen KW - A 01340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827909276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Differential+Utilization+of+Basic+Proline-Rich+Glycoproteins+during+Growth+of+Oral+Bacteria+in+Saliva&rft.au=Zhou%2C+Yuan%3BYang%2C+Jinghua%3BZhang%2C+Luxia%3BZhou%2C+Xuedong%3BCisar%2C+John+O%3BPalmer%2C+Robert+J%2C+Jr&rft.aulast=Zhou&rft.aufirst=Yuan&rft.date=2016-09-01&rft.volume=82&rft.issue=17&rft.spage=5249&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00992240&rft_id=info:doi/10.1128%2FAEM.01111-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 39 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Sugar; Dialysis; Chewing; Cell density; Cell culture; Lectins; Development; Polysaccharides; Dental plaque; Nutrition; Carbon; Syntrophism; Polymerase chain reaction; Saliva; Biofilms; Glycoproteins; Mouth; Heat treatments; Nitrogen; Bacteria; Streptococcus parasanguinis; Streptococcus sobrinus; Abiotrophia defectiva; Streptococcus gordonii; Granulicatella adiacens; Streptococcus sanguinis; Streptococcus salivarius; Streptococcus mutans; Rothia dentocariosa; Streptococcus mitis; Actinomyces; Streptococcus oralis DO - http://dx.doi.org/10.1128/AEM.01111-16 ER - TY - JOUR T1 - The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B AN - 1827909219; PQ0003647292 AB - Drug resistance studies have played an important role in the validation of antibiotic targets. In the case of the polyene antibiotic amphotericin B (AmB), such studies have demonstrated the essential role that depletion of ergosterol plays in the development of AmB-resistant (AmB-R) organisms. However, AmB-R strains also occur in fungi and parasitic protozoa that maintain a normal level of ergosterol at the plasma membrane. Here, I review evidence that shows not only that there is increased protection against the deleterious consequences of AmB-induced ion leakage across the membrane in these resistant pathogens but also that a set of events are activated that block the cell signaling responses that trigger the oxidative damage produced by the antibiotic. Such signaling events appear to be the consequence of a membrane-thinning effect that is exerted upon lipid-anchored Ras proteins by the aqueous pores formed by AmB. A similar membrane disturbance effect may also explain the activity of AmB on mammalian cells containing Toll-like receptors. These resistance mechanisms expand our current understanding of the role that the formation of AmB aqueous pores plays in triggering signal transduction responses in both pathogens and host immune cells. JF - Antimicrobial Agents & Chemotherapy AU - Cohen, B Eleazar Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 5122 EP - 5129 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 60 IS - 9 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Ras protein KW - Amphotericin B KW - Leakage KW - Fungi KW - Drug resistance KW - Antibiotics KW - Pathogens KW - Pores KW - Mammalian cells KW - polyenes KW - Protozoa KW - Plasma membranes KW - Reviews KW - Ergosterol KW - Toll-like receptors KW - Signal transduction KW - A 01340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827909219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=The+Role+of+Signaling+via+Aqueous+Pore+Formation+in+Resistance+Responses+to+Amphotericin+B&rft.au=Cohen%2C+B+Eleazar&rft.aulast=Cohen&rft.aufirst=B&rft.date=2016-09-01&rft.volume=60&rft.issue=9&rft.spage=5122&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/10.1128%2FAAC.00878-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 97 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Ras protein; Amphotericin B; Leakage; Drug resistance; Fungi; Antibiotics; Pathogens; Pores; Plasma membranes; Protozoa; polyenes; Mammalian cells; Reviews; Ergosterol; Toll-like receptors; Signal transduction DO - http://dx.doi.org/10.1128/AAC.00878-16 ER - TY - JOUR T1 - Case-control data analysis for randomly pooled biomarkers AN - 1827907323; PQ0003648764 AB - Pooled study designs, where individual biospecimens are combined prior to measurement via a laboratory assay, can reduce lab costs while maintaining statistical efficiency. Analysis of the resulting pooled measurements, however, often requires specialized techniques. Existing methods can effectively estimate the relation between a binary outcome and a continuous pooled exposure when pools are matched on disease status. When pools are of mixed disease status, however, the existing methods may not be applicable. By exploiting characteristics of the gamma distribution, we propose a flexible method for estimating odds ratios from pooled measurements of mixed and matched status. We use simulation studies to compare consistency and efficiency of risk effect estimates from our proposed methods to existing methods. We then demonstrate the efficacy of our method applied to an analysis of pregnancy outcomes and pooled cytokine concentrations. Our proposed approach contributes to the toolkit of available methods for analyzing odds ratios of a pooled exposure, without restricting pools to be matched on a specific outcome. JF - Biometrical Journal AU - Perkins, Neil J AU - Mitchell, Emily M AU - Lyles, Robert H AU - Schisterman, Enrique F AD - Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, Bethesda, MD, 20892, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1007 EP - 1020 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 58 IS - 5 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Statistics KW - Data processing KW - Cytokines KW - Biometrics KW - biomarkers KW - Pregnancy KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827907323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrical+Journal&rft.atitle=Case-control+data+analysis+for+randomly+pooled+biomarkers&rft.au=Perkins%2C+Neil+J%3BMitchell%2C+Emily+M%3BLyles%2C+Robert+H%3BSchisterman%2C+Enrique+F&rft.aulast=Perkins&rft.aufirst=Neil&rft.date=2016-09-01&rft.volume=58&rft.issue=5&rft.spage=1007&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.201500010 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Data processing; Statistics; Cytokines; Biometrics; biomarkers; Pregnancy DO - http://dx.doi.org/10.1002/bimj.201500010 ER - TY - JOUR T1 - Effect of charge localization on the in vivo optical imaging properties of near-infrared cyanine dye/monoclonal antibody conjugates AN - 1827906167; PQ0003695551 AB - Near-infrared (NIR) fluorophores show superior in vivo imaging properties than visible-light fluorophores because of the increased light penetration in tissue and lower autofluorescence of these wavelengths. We have recently reported that new NIR cyanine dyes containing a novel C4'-O-alkyl linker exhibit greater chemical stability and excellent optical properties relative to existing C4'-O-aryl variants. In this study, we synthesized two NIR cyanine dyes with the same core structure and charge but different indolenine substituents: FNIR-Z-759 bearing a combination of two sulfonates and two quaternary ammonium cations, and FNIR-G-765 bearing a combination of two sulfonates and two guanidines, resulting in zwitterionic charge with distinct cationic moieties. In this study, we compare the in vitro and in vivo optical imaging properties of monoclonal antibody (mAb) conjugates of FNIR-Z-759 and FNIR-G-765 with panitumumab (pan) at antibody-to-dye ratios of 1 : 2 or 1 : 5. One-to-five conjugation of pan-to-FNIR-G-765 was not successful due to aggregate formation during the conjugation reaction. Conjugates of both dyes to pan (2 : 1) demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. However, FNIR-Z-759 conjugates showed significantly lower accumulation in the mouse liver, resulting in higher tumor-to-liver ratio. Thus, FNIR-Z-759 conjugates appear to have superior in vivo imaging characteristics compared with FNIR-G-765 conjugates, especially in the abdominal region. Moreover, from a chemistry point of view, mAb conjugation with FNIR-Z-759 has an advantage over FNIR-G-765, because it does not form aggregates at high dye-to-mAb ratio. These results suggest that zwitterionic cyanine dyes are a superior class of fluorophores for conjugating with mAbs for fluorescence imaging applications due to improving target-to-background contrast in vivo. However, zwitterionic cyanine dyes should be designed carefully, as small changes to the structure can alter in vivo pharmacokinetics of mAb-dye conjugates. JF - Molecular BioSystems AU - Sato, Kazuhide AU - Gorka, Alexander P AU - Nagaya, Tadanobu AU - Michie, Megan S AU - Nakamura, Yuko AU - Nani, Roger R AU - Coble, Vince L AU - Vasalatiy, Olga V AU - Swenson, Rolf E AU - Choyke, Peter L AU - Schnermann, Martin J AU - Kobayashi, Hisataka AD - Molecular Imaging Program; Center for Cancer Research; National Cancer Institute; USA; +1 301-402-3191; +1 301-435-4086 Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 3046 EP - 3056 PB - Royal Society of Chemistry VL - 12 IS - 10 SN - 1742-206X, 1742-206X KW - Biotechnology and Bioengineering Abstracts KW - Ammonium KW - Fluorescence KW - I.R. radiation KW - Brightness KW - Monoclonal antibodies KW - Optical properties KW - Guanidine KW - fluorophores KW - imaging KW - Pharmacokinetics KW - Cations KW - Dyes KW - Liver KW - Light penetration KW - Wavelength KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827906167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+BioSystems&rft.atitle=Effect+of+charge+localization+on+the+in+vivo+optical+imaging+properties+of+near-infrared+cyanine+dye%2Fmonoclonal+antibody+conjugates&rft.au=Sato%2C+Kazuhide%3BGorka%2C+Alexander+P%3BNagaya%2C+Tadanobu%3BMichie%2C+Megan+S%3BNakamura%2C+Yuko%3BNani%2C+Roger+R%3BCoble%2C+Vince+L%3BVasalatiy%2C+Olga+V%3BSwenson%2C+Rolf+E%3BChoyke%2C+Peter+L%3BSchnermann%2C+Martin+J%3BKobayashi%2C+Hisataka&rft.aulast=Sato&rft.aufirst=Kazuhide&rft.date=2016-09-01&rft.volume=12&rft.issue=10&rft.spage=3046&rft.isbn=&rft.btitle=&rft.title=Molecular+BioSystems&rft.issn=1742206X&rft_id=info:doi/10.1039%2Fc6mb00371k LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 25 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Ammonium; I.R. radiation; Fluorescence; Monoclonal antibodies; Brightness; Optical properties; Guanidine; fluorophores; imaging; Pharmacokinetics; Dyes; Cations; Liver; Light penetration; Wavelength DO - http://dx.doi.org/10.1039/c6mb00371k ER - TY - JOUR T1 - O10-4Ionizing radiation exposure and risks of cancer and circulatory disease in technologists performing nuclear medicine procedures AN - 1827895480; PQ0003697114 AB - The number of nuclear medicine procedures performed has increased substantially over the past several decades, resulting in potentially greater radiation exposure to the technologists who perform them. However, there have been no epidemiologic studies of cancer or other serious health effects in these workers. Using data from the U.S. Radiologic Technologists (USRT) Study (1994-1998), we prospectively examined risks of cancer and circulatory disease (incidence through 2005 and mortality through 2008) associated with reported performance of nuclear medicine and brachytherapy procedures. Although risks for most outcomes examined were not elevated, we observed increased risks for squamous cell carcinoma of the skin (HR = 1.29, 95% CI: 1.01-1.66) with ever performing diagnostic radionuclide procedures, for myocardial infarction incidence (HR = 1.37, 95% CI: 1.10-1.70), all-cause mortality (HR = 1.10, 95% CI: 1.00-1.20) and all-cancer mortality (HR = 1.20, 95% CI: 1.01-1.43) with ever performing brachytherapy; also mortality from all causes (HR = 1.14, 95% CI: 1.01-1.30), breast cancer (HR = 2.68, 95% CI: 1.10-6.51), and myocardial infarction (HR = 1.76, 95% CI: 1.02-3.04) were associated with ever performing other radionuclide therapy procedures; higher risks were also observed with greater frequency of performing these procedures before 1980. For a sample of 4,406 technologists in USRT who completed a detailed work history survey in 2013-14, we described trends over the past six decades in nuclear medicine work history practices. We found that the frequency of most diagnostic nuclear medicine procedures performed by technologists increased over time, particularly for cardiac and positron emission tomography (PET) scans, while the frequency of therapeutic procedures performed remained stable. Although adherence to most radiation protection practices increased, lead apron use sharply declined. Estimation of organ-specific occupational radiation doses for individual technologists using these data (in progress) will be used in comprehensive retrospective and prospective investigations of radiogenic cancer and other serious disease risks. A study evaluating nuclear medicine work history practices and associated doses in a sample of U.S. technologists who are more recently trained and primarily certified in nuclear medicine technology is currently underway. JF - Occupational and Environmental Medicine AU - Kitahara, Cari AU - Doody, Michele AU - Dyke, Miriam Van AU - Drozdovitch, Vladimir AU - Simon, Steven AU - Lim, Hyeyeun AU - Preston, Dale AU - Miller, Jeremy AU - Brill, Aaron AU - Bolus, Norman AU - Little, Mark AU - Freedman, D Michal AU - Rajaraman, Preetha AU - Alexander, Bruce AU - Linet, Martha AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A21 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Historical account KW - Workers KW - Radiation KW - Risk factors KW - Emissions KW - Positron emission tomography KW - Occupational exposure KW - Heart KW - Mortality KW - Skin KW - Data processing KW - squamous cell carcinoma KW - Cancer KW - Myocardial infarction KW - Health risks KW - Brachytherapy KW - Radioisotopes KW - Breast cancer KW - Nuclear medicine KW - Technology KW - X 24390:Radioactive Materials KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827895480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O10-4Ionizing+radiation+exposure+and+risks+of+cancer+and+circulatory+disease+in+technologists+performing+nuclear+medicine+procedures&rft.au=Kitahara%2C+Cari%3BDoody%2C+Michele%3BDyke%2C+Miriam+Van%3BDrozdovitch%2C+Vladimir%3BSimon%2C+Steven%3BLim%2C+Hyeyeun%3BPreston%2C+Dale%3BMiller%2C+Jeremy%3BBrill%2C+Aaron%3BBolus%2C+Norman%3BLittle%2C+Mark%3BFreedman%2C+D+Michal%3BRajaraman%2C+Preetha%3BAlexander%2C+Bruce%3BLinet%2C+Martha&rft.aulast=Kitahara&rft.aufirst=Cari&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A21&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.55 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Heart; Mortality; Data processing; Skin; squamous cell carcinoma; Myocardial infarction; Workers; Brachytherapy; Radiation; Risk factors; Positron emission tomography; Radioisotopes; Nuclear medicine; Breast cancer; Historical account; Health risks; Emissions; Occupational exposure; Cancer; Technology DO - http://dx.doi.org/10.1136/oemed-2016-103951.55 ER - TY - JOUR T1 - S13-1Pesticides and cancer epidemiology in the agricultural health study AN - 1827891642; PQ0003696851 AB - BackgroundPesticides, which encompass a wide range of chemicals, are used extensively worldwide to control weeds, insects and other pests, both agriculturally, and in other settings, and have been linked to numerous adverse health outcomes, including cancer. Use has increased dramatically in the last several decades, but establishing a link between specific pesticide active ingredients and disease can be challenging.MethodsThe Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators and 32,345 of their spouses in Iowa and North Carolina, USA. At enrollment in 1993-1997, participants provided information on mixing, loading and applying individual pesticide active ingredients over their lifetimes. At subsequent interviews, they provided information on chemical products used on specific crops and animals. This self-reported use has been shown to be generally reliable. In addition, farm characteristics and practices allow for the assessment of potential non-occupational exposures for spouses not working on the farm. Incident cancers are identified through regular linkage to the cancer registries in each state.ResultsResults from this study have indicated associations between specific pesticides and several cancer sites, including cancers of the prostate, lung and lymphohematopoietic malignancies. Ongoing analyses are focused on the re-evaluation of previously observed associations, as well as initial investigations of newer and less commonly used chemicals, as well as rarer tumours. Preliminary results of these evaluations have suggested increased risk with specific pesticides and tumours such as liver and ovary. In addition, the evaluation of risks related to non-occupational pesticide exposures is a new area of emphasis.ConclusionsThis study provides a unique opportunity to investigate both occupational and non-occupational exposures to specific pesticides and cancer risk in a prospective setting. JF - Occupational and Environmental Medicine AU - Freeman, Laura Beane AD - Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A115 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Health & Safety Science Abstracts KW - Risk assessment KW - Chemicals KW - ANW, USA, North Carolina KW - Farms KW - Tumors KW - Crops KW - Insects KW - Cancer KW - Weed control KW - Health risks KW - Epidemiology KW - USA, Iowa KW - Lung KW - Pesticides KW - Liver KW - Pests KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827891642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=S13-1Pesticides+and+cancer+epidemiology+in+the+agricultural+health+study&rft.au=Freeman%2C+Laura+Beane&rft.aulast=Freeman&rft.aufirst=Laura&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A115&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.312 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Chemicals; Risk assessment; Farms; Tumors; Weed control; Cancer; Insects; Crops; Health risks; Epidemiology; Lung; Pesticides; Liver; Pests; ANW, USA, North Carolina; USA, Iowa DO - http://dx.doi.org/10.1136/oemed-2016-103951.312 ER - TY - JOUR T1 - O18-5Occupational exposure to diesel exhaust and alterations in immune/inflammatory markers AN - 1827891589; PQ0003697268 AB - IntroductionDiesel engine exhaust (DEE) is a known lung carcinogen in humans (IARC Group 1). However, the biological mechanism underlying this association is unclear. Given the suspected relationship between inflammation and lung carcinogenesis, we evaluated associations between DEE exposure and a multiplex panel of immune markers in workers exposed to DEE and unexposed workers in China.MethodsA cross-sectional molecular epidemiology study was conducted among 54 workers exposed to DEE in a diesel engine testing facility, and 55 unexposed workers who were employed in separate factories. Repeated personal exposure measurements of elemental carbon (EC) were taken from workers before blood collection. Serum levels of immune markers were analysed using a Luminex bead-based assay. Linear regression was used to evaluate differences in marker concentrations between DEE exposed vs. unexposed workers, and to explore exposure-response trends with EC.ResultsFour markers were significantly associated with DEE exposure in analyses of exposed vs. unexposed workers (P-value < 0.05). Significant monotonic trends in relation to increasing EC levels were observed for CXCL-11/I-TAC (19% reduction in exposed workers overall) and CCL15/MIP-1D (21% increase in exposed workers overall). Analyses of DEE exposed vs. unexposed workers stratified by smoking status found that an additional marker (CCL2/MCP-1) was significantly increased in workers exposed to DEE among never and former smokers, but not current smokers (Pinteraction = 0.01).ConclusionsRecent evidence suggests that higher levels of CCL15/MIP-1D and CCL2/MCP-1, two markers in the CC chemokine subfamily that attract white blood cells to sites of inflammation, are associated with increased risk of lung cancer in Asian never-smoking women. Alterations in these markers in the same direction among workers exposed to DEE in our study may provide mechanistic insight into the relationship between DEE and lung carcinogenesis. JF - Occupational and Environmental Medicine AU - Lan, Qing AU - Bassig, Bryan A AU - Vermeulen, Roel AU - Dai, Yufei AU - Ren, Dianzhi AU - Hu, Wei AU - Duan, Huawei AU - Niu, Yong AU - Xu, Jun AU - Shiels, Meredith AU - Kemp, Troy J AU - Fu, Wei AU - Meliefste, Kees AU - Zhou, Baosen AU - Yang, Jufang AU - Ye, Meng AU - Jia, Xiaowei AU - Meng, Tao AU - Bin, Ping AU - Kim, Christopher AU - Hosgood, Dean H AU - Hildesheim, Allan AU - Silverman, Debra T AU - Zheng, Yuxin AU - Rothman, Nathaniel AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A34 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Immunology Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Carcinogens KW - Factories KW - Workers KW - Smoking KW - Carbon KW - Risk factors KW - Dose-response effects KW - Occupational exposure KW - Lung cancer KW - Bioindicators KW - Monocyte chemoattractant protein 1 KW - diesel exhaust* KW - Leukocytes KW - Cancer KW - Exhausts KW - Inflammation KW - Serum levels KW - Health risks KW - Blood KW - Epidemiology KW - CC chemokines KW - Carcinogenesis KW - Diesel KW - Diesel engines KW - X 24380:Social Poisons & Drug Abuse KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827891589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O18-5Occupational+exposure+to+diesel+exhaust+and+alterations+in+immune%2Finflammatory+markers&rft.au=Lan%2C+Qing%3BBassig%2C+Bryan+A%3BVermeulen%2C+Roel%3BDai%2C+Yufei%3BRen%2C+Dianzhi%3BHu%2C+Wei%3BDuan%2C+Huawei%3BNiu%2C+Yong%3BXu%2C+Jun%3BShiels%2C+Meredith%3BKemp%2C+Troy+J%3BFu%2C+Wei%3BMeliefste%2C+Kees%3BZhou%2C+Baosen%3BYang%2C+Jufang%3BYe%2C+Meng%3BJia%2C+Xiaowei%3BMeng%2C+Tao%3BBin%2C+Ping%3BKim%2C+Christopher%3BHosgood%2C+Dean+H%3BHildesheim%2C+Allan%3BSilverman%2C+Debra+T%3BZheng%2C+Yuxin%3BRothman%2C+Nathaniel&rft.aulast=Lan&rft.aufirst=Qing&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A34&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.92 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Monocyte chemoattractant protein 1; Leukocytes; Carcinogens; Inflammation; Exhausts; Serum levels; Smoking; Workers; Carbon; CC chemokines; Epidemiology; Dose-response effects; Carcinogenesis; Diesel; Occupational exposure; Lung cancer; Bioindicators; diesel exhaust*; Cancer; Blood; Factories; Health risks; Risk factors; Diesel engines DO - http://dx.doi.org/10.1136/oemed-2016-103951.92 ER - TY - JOUR T1 - O41-4Altered circulating immune and inflammation markers among hog farmers in the study of biomarkers of exposure and effect in agriculture AN - 1827891387; PQ0003696743 AB - A reduced risk of lung cancer has been observed among farmers with increasing numbers of livestock (mainly hogs) in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. This association may be attributable to exposure to endotoxin, a component of the cell wall of gram-negative bacteria that is consistently associated with decreased lung cancer risk in both agricultural and non-agricultural settings. Levels of endotoxin and other bioaerosols are particularly high in hog farming. Therefore, to characterise potential biologic mechanisms underlying the inverse association with lung cancer and explore other immunologic changes associated with these exposures, we measured serum immune marker levels using a multiplexed bead-based assay in 61 active hog farmers and 61 matched controls. Both groups were selected from non-smoking male Iowans in the study of Biomarkers of Exposure and Effect in Agriculture, a molecular epidemiologic study within the AHS. We compared natural log-transformed analyte levels between hog farmers and controls using multivariate linear regression models adjusted for age, season, body mass index, recent infections, recent use of anti-inflammatory medications, and exposure to other animals. Relative to controls, hog farmers had a 17% decrease (95% confidence interval [CI]: -4% to -28%) in circulating levels of macrophage-derived chemokine (MDC/CCL22), a chemokine of particular interest a priori because high levels have been prospectively linked to an increased risk of lung cancer. Levels of other markers were elevated among hog farmers, including macrophage inflammatory protein-3 alpha (MIP-3 alpha ; 111% increase, 95% CI: 19% to 273%), basic fibroblast growth factor (FGF-2; 95% increase, 11% to 242%), and soluble interleukin-4 receptor (sIL-4R; 12% increase, 1% to 25%). These results provide insights into potential immunomodulatory mechanisms through which endotoxin or other bioaerosol exposures associated with hog farming may influence lung cancer risk, and warrant further investigation with more detailed bioaerosol exposure assessment. JF - Occupational and Environmental Medicine AU - Hofmann, Jonathan N AU - Shiels, Meredith S AU - Friesen, Melissa C AU - Kemp, Troy J AU - Chaturvedi, Anil K AU - Lynch, Charles F AU - Pinto, Ligia A AU - Hildesheim, Allan AU - Alavanja, Michael C AU - Freeman, Laura E Beane AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A80 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Immunology Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Agriculture KW - Endotoxins KW - Interleukin 4 KW - Airborne microorganisms KW - Risk reduction KW - Infection KW - Immunomodulation KW - Risk factors KW - Gram-negative bacteria KW - Regression analysis KW - Growth factors KW - Fibroblast growth factor 2 KW - CCL22 protein KW - CCL20 protein KW - Lung cancer KW - Bioindicators KW - ANW, USA, North Carolina KW - Macrophage-derived chemokine KW - Aerosols KW - biomarkers KW - Cancer KW - Inflammation KW - Livestock KW - Health risks KW - USA, Iowa KW - Body mass index KW - Cell walls KW - X 24370:Natural Toxins KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827891387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O41-4Altered+circulating+immune+and+inflammation+markers+among+hog+farmers+in+the+study+of+biomarkers+of+exposure+and+effect+in+agriculture&rft.au=Hofmann%2C+Jonathan+N%3BShiels%2C+Meredith+S%3BFriesen%2C+Melissa+C%3BKemp%2C+Troy+J%3BChaturvedi%2C+Anil+K%3BLynch%2C+Charles+F%3BPinto%2C+Ligia+A%3BHildesheim%2C+Allan%3BAlavanja%2C+Michael+C%3BFreeman%2C+Laura+E+Beane&rft.aulast=Hofmann&rft.aufirst=Jonathan&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A80&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.215 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Endotoxins; Agriculture; Macrophage-derived chemokine; Interleukin 4; Infection; biomarkers; Immunomodulation; Livestock; Inflammation; Gram-negative bacteria; Regression analysis; CCL22 protein; Fibroblast growth factor 2; Body mass index; CCL20 protein; Lung cancer; Cell walls; Bioindicators; Risk assessment; Aerosols; Airborne microorganisms; Risk reduction; Cancer; Health risks; Risk factors; Growth factors; ANW, USA, North Carolina; USA, Iowa DO - http://dx.doi.org/10.1136/oemed-2016-103951.215 ER - TY - JOUR T1 - O44-3Using meta-regression models to systematically evaluate data in the published literature: relative contributions of agricultural drift, para-occupational, and residential use exposure pathways to house dust pesticide concentrations AN - 1827891300; PQ0003696755 AB - BackgroundData reported in the published literature have frequently been used qualitatively to aid exposure assessment activities in epidemiologic studies. Analysing these data in statistical models presents statistical challenges because these data are usually reported as summary statistics. Most previous analyses using published data have weighted the summary statistics by the number of measurements, but this does not account for the measurements' variability. We describe the application of mixed-effects meta-regression models to evaluate the relative contributions of three exposure pathways (agricultural drift, para-occupational, residential use) on published pesticide concentrations in the house dust of homes in agricultural areas.MethodsWe abstracted pesticide house dust concentrations reported as summary statistics (e.g., geometric means (GM)) from studies in North American agricultural areas published from 1995-2015. We analysed these data using mixed-effects meta-regression models that weighted each summary statistic by its variance. The dependent variable was either the log-transformed GM (drift) or the log-transformed ratio of GMs from two groups (para-occupational, residential use).ResultsFor the drift pathway, the predicted GM decreased 35% (95% Confidence Interval [CI]: 19-48; based on 52 statistics from 7 studies) for each natural log(ft) between homes and fields. For the para-occupational pathway, GMs were 2.3 times higher (95% CI: 1.5-3.3; 15 statistics, 5 studies) in homes of farmers who applied pesticides more versus less recently or frequently. For the residential use pathway, GMs were 1.0 (95% CI: 0.8-1.2), 1.3 (95% CI: 1.1-1.4), and 1.5 (95% CI: 1.2-1.9) times higher in treated versus untreated homes, when the probability that a pesticide was used for the pest treatment was 0%, 1-19%, and greater than or equal to 20%, respectively (88 statistics, 5 studies).ConclusionThese findings quantify relative contributions of three pathways in agricultural populations that may be useful for developing pesticide exposure metrics for epidemiologic studies. The meta-regression models can be updated when additional data become available. JF - Occupational and Environmental Medicine AU - Deziel, Nicole C AU - Freeman, Laura E Beane AU - Graubard, Barry I AU - Jones, Rena R AU - Hoppin, Jane A AU - Thomas, Kent AU - Hines, Cynthia J AU - Blair, Aaron AU - Sandler, Dale P AU - Chen, Honglei AU - Lubin, Jay H AU - Andreotti, Gabriella AU - Alavanja, Michael CR AU - Friesen, Melissa C AD - National Cancer Institute, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A84 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - North America KW - Statistics KW - Data processing KW - Mathematical models KW - Statistical models KW - Statistical analysis KW - Models KW - House dust KW - Drift KW - Pesticides KW - Pests KW - H 1000:Occupational Safety and Health KW - X 24330:Agrochemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827891300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O44-3Using+meta-regression+models+to+systematically+evaluate+data+in+the+published+literature%3A+relative+contributions+of+agricultural+drift%2C+para-occupational%2C+and+residential+use+exposure+pathways+to+house+dust+pesticide+concentrations&rft.au=Deziel%2C+Nicole+C%3BFreeman%2C+Laura+E+Beane%3BGraubard%2C+Barry+I%3BJones%2C+Rena+R%3BHoppin%2C+Jane+A%3BThomas%2C+Kent%3BHines%2C+Cynthia+J%3BBlair%2C+Aaron%3BSandler%2C+Dale+P%3BChen%2C+Honglei%3BLubin%2C+Jay+H%3BAndreotti%2C+Gabriella%3BAlavanja%2C+Michael+CR%3BFriesen%2C+Melissa+C&rft.aulast=Deziel&rft.aufirst=Nicole&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A84&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.226 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Mathematical models; House dust; Data processing; Statistics; Drift; Pesticides; Statistical analysis; Pests; Models; Statistical models; North America DO - http://dx.doi.org/10.1136/oemed-2016-103951.226 ER - TY - JOUR T1 - O47-3Using published data from us workplaces to predict historical air and blood lead concentrations for activities related to lead-based paints and cutting and joining metals AN - 1827891232; PQ0003696771 AB - ObjectivesHistorical exposure data reported in the literature are increasingly being used to estimate intensity in population-based studies. To develop lead intensity estimates for a U.S. case-control study, we used meta-regression models to identify predictors of personal air and blood lead concentrations for US workers performing activities related to lead-based paint and cutting or joining metal with heat using published data.MethodsFrom 69 published papers covering the study years 1962-2005, we extracted personal air and blood lead geometric means (GM), geometric standard deviations (GSD), number of measurements per statistic, and other ancillary exposure variables. Mixed-effects meta-regression models were developed separately for 221 air and 113 blood statistics, with the respective log-transformed GM as the dependent variable. Random intercept was incorporated that weighted each statistic by the inverse of its variance. Variables examined included year, industry, job, sampling duration, lead-based paint removal activities, worst case scenarios, and respirator use. Industry interactions with job and year were also tested.ResultsJob, industry, and year were the main predictors of exposure. Temporal trends declined more in the model based on blood versus air concentrations (6.2 vs. 4.6% per year); however, confidence intervals overlapped. Exposure contrasts in the predicted GMs across the 9 jobs and 5 industries were higher in personal air (238- and 8-fold, respectively) vs. blood lead models (3- and 4-fold, respectively). Welders' blood lead GMs were 1.7 time higher in worst-case vs. non-worst case scenarios. Exposure differences from other ancillary variables were too sparse to incorporate, were insufficiently variable, or were not statistically significant.ConclusionsTime, job, and industry differences in lead exposure were quantified across many studies. The blood lead model's attenuated job exposure contrast likely reflected its integration of exposure over weeks. The steeper temporal trends for blood likely reflected the protective effect of personal protective equipment. JF - Occupational and Environmental Medicine AU - Locke, Sarah AU - Deziel, Nicole AU - Koh, Dong-Hee AU - Graubard, Barry AU - Purdue, Mark AU - Friesen, Melissa AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A89 EP - A90 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Historical account KW - Heavy metals KW - Statistical analysis KW - Lead KW - Models KW - Integration KW - Welding KW - Sampling KW - Occupational exposure KW - Metals KW - Data processing KW - Population studies KW - Protective equipment KW - Blood levels KW - Blood KW - Standard deviation KW - Heat KW - Respirators KW - Paints KW - X 24360:Metals KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827891232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O47-3Using+published+data+from+us+workplaces+to+predict+historical+air+and+blood+lead+concentrations+for+activities+related+to+lead-based+paints+and+cutting+and+joining+metals&rft.au=Locke%2C+Sarah%3BDeziel%2C+Nicole%3BKoh%2C+Dong-Hee%3BGraubard%2C+Barry%3BPurdue%2C+Mark%3BFriesen%2C+Melissa&rft.aulast=Locke&rft.aufirst=Sarah&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A89&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.240 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Data processing; Heavy metals; Statistical analysis; Population studies; Lead; Models; Integration; Blood; Standard deviation; Heat; Welding; Sampling; Respirators; Occupational exposure; Paints; Historical account; Metals; Protective equipment; Blood levels DO - http://dx.doi.org/10.1136/oemed-2016-103951.240 ER - TY - JOUR T1 - O11-1Ergonomic and safety risks among small scale minners in the philippines AN - 1827891138; PQ0003697147 AB - Worldwide, small-scale mining (SSM) provides employment to about 13 million people and affects the livelihood of 80-100 million. This study investigated the ergonomic and safety hazards of small scale miners in one of the largest small scale mining area in the Philippines which is the area of Itogon, Benguet. There were 93 small scale miners who were included in the study as they complied with the inclusion criteria. The methods consisted of survey questionnaires, health physical examination guide, individual interviews, and work process observation tool. The results showed that the small-scale miners worked for an average of 10.7 years, and a maximum work year of 40. The most widely employed mining technique was the dog-hole mining consisting of several sub-processes -tunnelling, ball milling and gravity concentration, cyanide leaching, and smelting. The ergonomic and safety hazards identified were noise exposure from the dynamite blast, temperature extremes, and exposure to dust from dynamite blasting. The miners experienced prolonged crouching and bending, prolonged handling of tools, and carrying heavy sacks filled with mineral ores. There were no standard work protection and safety measures followed by the miners. In the ball milling and gravity concentration process, machine-related accidents were noted such as experiencing cuts from the crusher. In the cyanide leaching which uses massive amounts of cyanide, the most prevalent hazards were heat, dust, and chemicals such as cyanide fumes. Burn injuries were reported among miners. A third (31.2%) of miners have experienced accidents. The most common injury was laceration at 47.8%, followed by methane inhalation, fracture of hand digits, and contusion at 17.4%. It is suggested that intervention programs for ergonomics and safety measures be implemented by the local government for the small scale miners. JF - Occupational and Environmental Medicine AU - Lu, Jinky Leilanie AD - Institute of Health Policy and Development Studies, National Institutes of Health, University of the Philippines Manila, Affiliate Faculty-College of Arts and Sciences, UP, Manila, Philippines Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A22 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Health & Safety Science Abstracts KW - Burns KW - Methane KW - Leaching KW - Injuries KW - Occupational safety KW - Safety KW - Temperature KW - Intervention KW - Dust KW - Working conditions KW - Cyanide KW - ISEW, Philippines KW - Blasting KW - Mining KW - Ergonomics KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827891138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O11-1Ergonomic+and+safety+risks+among+small+scale+minners+in+the+philippines&rft.au=Lu%2C+Jinky+Leilanie&rft.aulast=Lu&rft.aufirst=Jinky&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A22&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.58 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Burns; Methane; Leaching; Injuries; Safety; Occupational safety; Temperature; Intervention; Working conditions; Dust; Cyanide; Blasting; Mining; Ergonomics; ISEW, Philippines DO - http://dx.doi.org/10.1136/oemed-2016-103951.58 ER - TY - JOUR T1 - O47-6Impact of calibrating a benzene job-exposure matrix with measurements on exposure-response associations for non-hodgkin lymphoma AN - 1827889942; PQ0003696774 AB - ObjectivesTo provide insight into the contributions of exposure measurements to job exposure matrices (JEMs), we examined the sensitivity of exposure-response associations between occupational benzene exposure and non-Hodgkin lymphoma (NHL) using benzene JEM-based estimates with and without measurement calibration. Methods NHL risk was examined in a prospective population-based cohort of 73,087 Shanghai women with no prevalent cancer at baseline and a valid occupational history. An 'uncalibrated' benzene JEM was developed using expert judgment to assign ordinal (0 to 3) probability and intensity ratings to each occupation and industry group. JEM intensity estimates were combined with >60,000 short-term, area benzene inspection measurements using a mixed-effects model framework that incorporated fixed effects for year and intensity rating and random effects for occupation, industry, and measurement occurrence. The model was used to derive 'calibrated JEM' estimates from the fixed effect model parameters and 'job/industry-specific' estimates from both the fixed effect model parameters and the best unbiased linear prediction estimates from the occupation and industry random effect terms. Cumulative exposure for each subject was calculated for each approach using varying exposure definition criteria based on the JEM's probability ratings. We examined the agreement between the cumulative metrics and evaluated changes in the benzene-NHL associations.Results For our primary exposure definition, the job/industry-specific estimates were moderately to highly correlated with the calibrated and uncalibrated JEM estimates (Spearman correlation amongst exposed subjects: 0.64-0.87). The uncalibrated, calibrated, and job/industry-specific metrics all resulted in statistically significant exposure-response associations for NHL, with similar model fit. This similarity occurred because the measurement- and ordinal-based weights across the occupation intensity ratings were nearly identical in this study.Conclusions The measurement-based JEM estimates had similar model fit to the uncalibrated JEM estimates in this study; however, the measurement-based estimates allowed us to evaluate quantitative exposure-response curves. JF - Occupational and Environmental Medicine AU - Friesen, Melissa C AU - Bassig, Bryan A AU - Vermeulen, Roel AU - Shu, Xiao-Ou AU - Purdue, Mark P AU - Stewart, Patricia A AU - Xiang, Yong-Bing AU - Chow, Wong-Ho AU - Ji, Bu-Tian AU - Yang, Gong AU - Linet, Martha S AU - Hu, Wei AU - Gao, Yu-Tang AU - Zheng, Wei AU - Rothman, Nathaniel AU - Lan, Qing AD - National Cancer Institute, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A90 EP - A91 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Prediction KW - Sensitivity KW - Historical account KW - Statistical analysis KW - Benzene KW - Cancer KW - Models KW - Non-Hodgkin's lymphoma KW - Health risks KW - Dose-response effects KW - China, People's Rep., Shanghai KW - Inspection KW - Lymphoma KW - Occupational exposure KW - H 1000:Occupational Safety and Health KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827889942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O47-6Impact+of+calibrating+a+benzene+job-exposure+matrix+with+measurements+on+exposure-response+associations+for+non-hodgkin+lymphoma&rft.au=Friesen%2C+Melissa+C%3BBassig%2C+Bryan+A%3BVermeulen%2C+Roel%3BShu%2C+Xiao-Ou%3BPurdue%2C+Mark+P%3BStewart%2C+Patricia+A%3BXiang%2C+Yong-Bing%3BChow%2C+Wong-Ho%3BJi%2C+Bu-Tian%3BYang%2C+Gong%3BLinet%2C+Martha+S%3BHu%2C+Wei%3BGao%2C+Yu-Tang%3BZheng%2C+Wei%3BRothman%2C+Nathaniel%3BLan%2C+Qing&rft.aulast=Friesen&rft.aufirst=Melissa&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A90&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.243 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Dose-response effects; Statistical analysis; Lymphoma; Cancer; Occupational exposure; Benzene; Models; Prediction; Historical account; Sensitivity; Health risks; Non-Hodgkin's lymphoma; Inspection; China, People's Rep., Shanghai DO - http://dx.doi.org/10.1136/oemed-2016-103951.243 ER - TY - JOUR T1 - Adenosine Selectively Depletes Alloreactive T Cells to Prevent GVHD While Conserving Immunity to Viruses and Leukemia AN - 1827888459; PQ0003714215 AB - Selective depletion (SD) of alloreactive T cells from allogeneic hematopoeitic stem cell transplants to prevent graft-versus-host disease (GVHD) without compromising immune reconstitution and antitumor responses remains a challenge. Here, we demonstrate a novel SD strategy whereby alloreacting T cells are efficiently deleted ex vivo with adenosine. SD was achieved in human leukocyte antigen (HLA) mismatched cocultures by multiple exposures to 2 mmol/l adenosine over 7 days. Adenosine depleted greater than to 90% of alloproliferating T cells in mismatched, haploidentical, and matched sibling pairs while conserving response to third-party antigens. Alloreactive CD4 and CD8 T cells were targeted for depletion while NK and B cells were preserved. Our novel approach also preserved nonalloreactive naive, central, and effector memory T-cell subsets, Tregs, and notably preserved T-cell responses against DNA viruses that contribute to transplant related mortality after allogeneic hematopoeitic stem cell transplants. Additionally, T cells recognizing leukemia-associated antigens were efficiently generated in vitro from the cell product post-SD. This study is the first to demonstrate that adenosine depletion of alloactivated T cells maintains a complete immune cell profile and recall viral responses. Expansion of tumor antigen-specific subsets postdepletion opens the possibility of generating T-cell products capable of graft-versus-tumor responses without causing GVHD. JF - Molecular Therapy AU - Whitehill, Greg D AU - Amarnath, Shoba AU - Muranski, Pawel AU - Keyvanfar, Keyvan AU - Battiwalla, Minoo AU - Barrett, Austin J AU - Chinnassamy, Dhanalakshmi AD - Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1655 EP - 1664 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 24 IS - 9 SN - 1525-0016, 1525-0016 KW - Immunology Abstracts; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Histocompatibility antigen HLA KW - Mortality KW - Lymphocytes B KW - Immunological memory KW - Graft-versus-host reaction KW - CD8 antigen KW - Tumors KW - DNA viruses KW - Immune reconstitution KW - Leukemia KW - CD4 antigen KW - Lymphocytes T KW - Antigen (leukemia-associated) KW - Siblings KW - Adenosine KW - Antitumor activity KW - V 22350:Immunology KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827888459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Therapy&rft.atitle=Adenosine+Selectively+Depletes+Alloreactive+T+Cells+to+Prevent+GVHD+While+Conserving+Immunity+to+Viruses+and+Leukemia&rft.au=Whitehill%2C+Greg+D%3BAmarnath%2C+Shoba%3BMuranski%2C+Pawel%3BKeyvanfar%2C+Keyvan%3BBattiwalla%2C+Minoo%3BBarrett%2C+Austin+J%3BChinnassamy%2C+Dhanalakshmi&rft.aulast=Whitehill&rft.aufirst=Greg&rft.date=2016-09-01&rft.volume=24&rft.issue=9&rft.spage=1655&rft.isbn=&rft.btitle=&rft.title=Molecular+Therapy&rft.issn=15250016&rft_id=info:doi/10.1038%2Fmt.2016.147 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Histocompatibility antigen HLA; Mortality; Lymphocytes B; Immunological memory; Graft-versus-host reaction; Tumors; CD8 antigen; DNA viruses; Immune reconstitution; Leukemia; CD4 antigen; Lymphocytes T; Siblings; Antigen (leukemia-associated); Adenosine; Antitumor activity DO - http://dx.doi.org/10.1038/mt.2016.147 ER - TY - JOUR T1 - Vaginal progesterone decreases preterm birth less than or equal to 34weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study AN - 1827887866; PQ0003650973 AB - Objective To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) less than or equal to 25mm. Methods This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL less than or equal to 25mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth less than or equal to 34weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. Results Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth less than or equal to 34weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95%CI, 0.52-0.83); P =0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at <28 to<36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95%CI, 0.27-0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95%CI, 0.38-0.91)), birth weight<1500g (RR, 0.52 (95%CI, 0.34-0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95%CI, 0.50-0.91)). There were no significant differences in neurodevelopmental outcomes at 2years of age between the vaginal progesterone and placebo groups. Conclusion This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL less than or equal to 25mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18-24weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL less than or equal to 25mm. This article has been selected for Journal Club. Click here to view slides and discussion points. JF - Ultrasound in Obstetrics and Gynecology AU - Romero, R AU - Nicolaides, KH AU - Conde-Agudelo, A AU - O'Brien, J M AU - Cetingoz, E AU - Da Fonseca, E AU - Creasy, G W AU - Hassan, S S AD - Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 308 EP - 317 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 48 IS - 3 SN - 0960-7692, 0960-7692 KW - Biotechnology and Bioengineering Abstracts KW - Risk assessment KW - Mortality KW - Age KW - Data processing KW - Gynecology KW - Progesterone KW - Statistical analysis KW - Fetuses KW - Morbidity KW - Pregnancy KW - Intensive care units KW - Bibliographies KW - Reviews KW - Vagina KW - Gestation KW - Neonates KW - Cervix KW - Obstetrics KW - Ultrasound KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827887866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ultrasound+in+Obstetrics+and+Gynecology&rft.atitle=Vaginal+progesterone+decreases+preterm+birth+less+than+or+equal+to+34weeks+of+gestation+in+women+with+a+singleton+pregnancy+and+a+short+cervix%3A+an+updated+meta-analysis+including+data+from+the+OPPTIMUM+study&rft.au=Romero%2C+R%3BNicolaides%2C+KH%3BConde-Agudelo%2C+A%3BO%27Brien%2C+J+M%3BCetingoz%2C+E%3BDa+Fonseca%2C+E%3BCreasy%2C+G+W%3BHassan%2C+S+S&rft.aulast=Romero&rft.aufirst=R&rft.date=2016-09-01&rft.volume=48&rft.issue=3&rft.spage=308&rft.isbn=&rft.btitle=&rft.title=Ultrasound+in+Obstetrics+and+Gynecology&rft.issn=09607692&rft_id=info:doi/10.1002%2Fuog.15953 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Risk assessment; Mortality; Age; Data processing; Progesterone; Gynecology; Statistical analysis; Morbidity; Fetuses; Pregnancy; Intensive care units; Bibliographies; Reviews; Gestation; Vagina; Neonates; Cervix; Ultrasound; Obstetrics DO - http://dx.doi.org/10.1002/uog.15953 ER - TY - JOUR T1 - P223Effects of agricultural work practices and pesticide use on occupational health of farmers AN - 1827886536; PQ0003697102 AB - AimsThe target site is Benguet, Philippines which is the largest vegetable producer in the Philippines. There are about 27.5 thousand farms covering 30 thousand hectares of agricultural land in Benguet. The province is known as the 'salad bowl' of the Philippines as its major crops are tubers, roots and bulbs, and leafy vegetables, stems and flowers.This is a study conducted among 534 farmers in six municipalities in an agricultural area engaged in vegetable industry. It assessed the pesticide exposure and work practices of farmers, and identified physical and neurological health status of the farmers.MethodsSurvey questionnaires look into pesticide exposures and work practices of the farmers. Physical health assessment was conducted by medical doctors from Baguio. Laboratory examination of blood was also done.ResultsMajority were males (53.4%), married (80.5%) with a mean age of 47 years old. 40.9% who underwent the physical examination were diagnosed to have abnormal assessment results. Analyses indicated that pesticide use and risk factors were found to have association at p = 0.05 with easy fatigability, weight loss, loss of appetite, cerebellar function, creatinine levels, haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin count, and platelet count. Conclusion. These results underscore the need to improve protection measures so as to reduce the exposure of the population and environment to pesticides. JF - Occupational and Environmental Medicine AU - Lu, Jinky Leilanie AD - Institute of Health Policy and Development Studies. National Institutes of Health.University of the Philippines Manila. Affiliate Faculty- College of Arts and Sciences, UP, Manila, Philippines Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A196 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - pesticides KW - agriculture KW - neurological assessment KW - health problems KW - farmers KW - RBC cholinesterase KW - Vegetables KW - Age KW - Farms KW - Cerebellum KW - Roots KW - Appetite KW - Medical personnel KW - Crops KW - Hemoglobin KW - Agricultural land KW - ISEW, Philippines KW - Risk factors KW - Tubers KW - Inventories KW - Stems KW - Physical training KW - Blood KW - Creatinine KW - Pesticides KW - Platelets KW - Occupational health KW - Bulbs KW - H 1000:Occupational Safety and Health KW - X 24330:Agrochemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827886536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=P223Effects+of+agricultural+work+practices+and+pesticide+use+on+occupational+health+of+farmers&rft.au=Lu%2C+Jinky+Leilanie&rft.aulast=Lu&rft.aufirst=Jinky&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A196&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.539 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Inventories; Age; Vegetables; Farms; Cerebellum; Roots; Appetite; Stems; Crops; Physical training; Hemoglobin; Blood; Agricultural land; Creatinine; Risk factors; Pesticides; Platelets; Tubers; Bulbs; Medical personnel; Occupational health; ISEW, Philippines DO - http://dx.doi.org/10.1136/oemed-2016-103951.539 ER - TY - JOUR T1 - O08-2Occupational exposure to benzene and alterations in immune/inflammatory markers AN - 1827885871; PQ0003696970 AB - IntroductionBenzene is an occupational solvent that is used in multiple industries, and is a known human carcinogen (IARC Group 1) that is hematotoxic and causes acute myeloid leukaemia. Further, there is some evidence that occupational benzene exposure is associated with certain lymphoid neoplasms. To follow up these observations, we evaluated the relationship between occupational benzene exposure and levels of immune markers that were measured using a multiplex panel. MethodsA Luminex bead-based assay was conducted among 52 factory workers exposed to benzene and 31 unexposed workers that were enrolled in a cross-sectional molecular epidemiology study in China. Personal benzene exposure was repeatedly monitored in workers using a 3 M organic vapour passive monitoring badge before phlebotomy. Linear regression was used to evaluate differences in marker concentrations between benzene exposed vs. unexposed workers, and to explore exposure-response trends (unexposed, less than or equal to 5 ppm, >5 ppm). ResultsMultiple markers were significantly altered in benzene exposed workers compared to unexposed workers (P-value < 0.05), including TNF- alpha (27% increase in exposed workers). Further, eight markers showed evidence of an exposure-response relationship. Among these, BCA-1 (45% reduction overall) and IL-17A (38% reduction overall) were significantly reduced in both lower and higher exposed workers compared to unexposed workers.ConclusionsOccupational exposure to benzene was associated with a range of immune perturbations including alterations in markers that regulate B-cell chemotaxis and regulation of cytotoxic T-cell activity. Notably, two of these markers (TNF- alpha and BCA-1) have previously been associated with risk of non-Hodgkin lymphoma in prospective studies. These observations provide additional biologic insight into the effects of benzene on the immune system. JF - Occupational and Environmental Medicine AU - Rothman, Nathaniel AU - Bassig, Bryan A AU - Zhang, Luoping AU - Vermeulen, Roel AU - Li, Guilan AU - Kemp, Troy J AU - Hu, Wei AU - Purdue, Mark P AU - Yin, Songnian AU - Rappaport, Stephen M AU - Shen, Min AU - Linet, Martha AU - Hayes, Richard B AU - Hildesheim, Allan AU - Smith, Martyn T AU - Lan, Qing AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Nih, Dhhs, Rockville, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A16 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Immunology Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Immune system KW - Carcinogens KW - Chemotaxis KW - Benzene KW - Leukemia KW - Factories KW - Non-Hodgkin's lymphoma KW - Workers KW - Risk factors KW - Dose-response effects KW - Lymphocytes T KW - Lymphoma KW - Occupational exposure KW - Bioindicators KW - Lymphocytes B KW - Solvents KW - Inflammation KW - Cytotoxicity KW - Epidemiology KW - China, People's Rep. KW - Tumor necrosis factor- alpha KW - H 1000:Occupational Safety and Health KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827885871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=O08-2Occupational+exposure+to+benzene+and+alterations+in+immune%2Finflammatory+markers&rft.au=Rothman%2C+Nathaniel%3BBassig%2C+Bryan+A%3BZhang%2C+Luoping%3BVermeulen%2C+Roel%3BLi%2C+Guilan%3BKemp%2C+Troy+J%3BHu%2C+Wei%3BPurdue%2C+Mark+P%3BYin%2C+Songnian%3BRappaport%2C+Stephen+M%3BShen%2C+Min%3BLinet%2C+Martha%3BHayes%2C+Richard+B%3BHildesheim%2C+Allan%3BSmith%2C+Martyn+T%3BLan%2C+Qing&rft.aulast=Rothman&rft.aufirst=Nathaniel&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A16&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.42 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Lymphocytes B; Immune system; Solvents; Carcinogens; Chemotaxis; Benzene; Inflammation; Workers; Cytotoxicity; Epidemiology; Dose-response effects; Lymphocytes T; Tumor necrosis factor- alpha; Lymphoma; Occupational exposure; Bioindicators; Non-Hodgkin's lymphoma; Factories; Leukemia; Risk factors; China, People's Rep. DO - http://dx.doi.org/10.1136/oemed-2016-103951.42 ER - TY - JOUR T1 - P194Recommendations for prioritising expert review of free-text job descriptions that underwent computer-based coding using the soccer algorithm AN - 1827885767; PQ0003697072 AB - ObjectivesPrevious evaluations of algorithms to code job descriptions to standardised occupation classification (SOC) codes suggest that some jobs will need expert coding to reduce misclassification. For jobs coded using the SOCcer algorithm (http://soccer.nci.nih.gov), we evaluated the utility of several metrics for identifying discordances between expert and automated SOC assignments to develop recommendations to prioritise expert review.MethodsThe SOCcer algorithm was applied to expert-coded job descriptions from three studies to obtain each job's top ten scoring U.S. SOC-2010 codes and their 'score' (measure of fit; continuous 0-1). The SOCcer and expert SOC codes were linked to the CANJEM job-exposure matrix comprising exposure estimates for 258 agents (probability, intensity, exposure status: probability > 0 vs. 0). We evaluated the agreement between the expert and the top scoring SOC code (proportion of agreement), and in their agent-specific CANJEM estimates (kappa for exposure status; intra-class correlation coefficient, ICC, for probability and intensity) in subsets of jobs stratified by metrics derived from the SOCcer score and CANJEM. We describe the overall patterns.ResultsModerate agreement was usually achieved for jobs with a maximum score greater than or equal to 0.3. Higher agreement was observed for jobs with SOCcer score distance between the top two scoring SOC codes of greater than or equal to 0.1 versus <0.1. Combining these two characteristics, kappa's and ICC's were 0.7-0.8 for jobs with greater than or equal to 0.3 maximum score and greater than or equal to 0.1 score distance (36-53% of all jobs) compared to 0.3-0.5 for jobs that did not meet both thresholds. We also found higher agreement for jobs with the same versus different exposure status for the top two scoring SOC codes.ConclusionsWhen applying SOCcer to un-coded jobs, we found that expert review would be most informative (reduce misclassification) for jobs with maximum scores < 0.3 and for jobs where the top two ranked SOC codes had score distances < 0.1 or differing exposure estimates. JF - Occupational and Environmental Medicine AU - Russ, Daniel AU - Remen, Thomas AU - Ho, Kwan-Yuet AU - Chow, Wong-Hi AU - Davis, Faith AU - Hofmann, Jonathan AU - Huang, Huang AU - Purdue, Mark AU - Schwartz, Kendra AU - Siemiatycki, Jack AU - Zhang, Yawei AU - Silverman, Debra AU - Johnson, Calvin AU - Lavoue, Jerome AU - Friesen, Melissa AD - Center for Information Technology, National Institutes of Health, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A186 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Health & Safety Science Abstracts KW - Classification KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827885767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=P194Recommendations+for+prioritising+expert+review+of+free-text+job+descriptions+that+underwent+computer-based+coding+using+the+soccer+algorithm&rft.au=Russ%2C+Daniel%3BRemen%2C+Thomas%3BHo%2C+Kwan-Yuet%3BChow%2C+Wong-Hi%3BDavis%2C+Faith%3BHofmann%2C+Jonathan%3BHuang%2C+Huang%3BPurdue%2C+Mark%3BSchwartz%2C+Kendra%3BSiemiatycki%2C+Jack%3BZhang%2C+Yawei%3BSilverman%2C+Debra%3BJohnson%2C+Calvin%3BLavoue%2C+Jerome%3BFriesen%2C+Melissa&rft.aulast=Russ&rft.aufirst=Daniel&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A186&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.511 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Classification DO - http://dx.doi.org/10.1136/oemed-2016-103951.511 ER - TY - JOUR T1 - Molecular Diagnostics for Soil-Transmitted Helminths AN - 1827883968; PQ0003706330 AB - Historically, the diagnosis of soil-transmitted helminths (STHs) (e.g., Strongyloides stercoralis, Trichuris trichiura, Ancylostoma duodenale, Necator americanus, and Ascaris lumbricoides) has relied on often-insensitive microscopy techniques. Over the past several years, there has been an effort to use molecular diagnostics, particularly quantitative polymerase chain reaction (qPCR), to detect intestinal pathogens. While some platforms have been approved by regulatory bodies (e.g., Food and Drug Administration) to detect intestinal bacteria, viruses, and protozoa, there are no approved tests currently available for STH. Although studies comparing qPCR to microscopy methods for STH are imperfect, due in large part to a lack of a sufficient gold standard, they do show a significant increase in sensitivity and specificity of qPCR compared with microscopic techniques. These studies, as well as the advantages and disadvantages of using qPCR for STH diagnosis, are discussed. Guidelines for those designing future studies utilizing qPCR are proposed for optimizing results, as is the proposition for using standardized molecular diagnostics routinely for STH in clinical laboratories and for field-based studies when possible. JF - American Journal of Tropical Medicine and Hygiene AU - O'Connell, Elise M AU - Nutman, Thomas B AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, oconnellem@niaid.nih.gov Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 508 EP - 513 PB - American Society of Tropical Medicine and Hygiene, 60 Revere Drive, Suite 500 Northbrook IL 60062 United States VL - 95 IS - 3 SN - 0002-9637, 0002-9637 KW - Health & Safety Science Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Sensitivity KW - Historical account KW - Bacteria KW - Necator americanus KW - Guidelines KW - Viruses KW - Pathogens KW - Trichuris trichiura KW - Ascaris KW - Strongyloides stercoralis KW - Protozoa KW - Microscopy KW - Intestine KW - Polymerase chain reaction KW - Standards KW - Drugs KW - H 0500:General KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827883968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Molecular+Diagnostics+for+Soil-Transmitted+Helminths&rft.au=O%27Connell%2C+Elise+M%3BNutman%2C+Thomas+B&rft.aulast=O%27Connell&rft.aufirst=Elise&rft.date=2016-09-01&rft.volume=95&rft.issue=3&rft.spage=508&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/10.4269%2Fajtmh.16-0266 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-11-23 N1 - SubjectsTermNotLitGenreText - Protozoa; Microscopy; Intestine; Polymerase chain reaction; Pathogens; Bacteria; Historical account; Sensitivity; Viruses; Guidelines; Standards; Drugs; Ascaris; Necator americanus; Strongyloides stercoralis; Trichuris trichiura DO - http://dx.doi.org/10.4269/ajtmh.16-0266 ER - TY - JOUR T1 - Visceral Leishmaniasis Control and Elimination: Is There a Role for Vaccines in Achieving Regional and Global Goals? AN - 1827883620; PQ0003706331 AB - In September 2015, the National Institute of Allergy and Infectious Diseases organized a workshop to address the roles of vaccines in achieving regional and global goals for visceral leishmaniasis (VL) control and elimination, a critical step in determining desired product characteristics as well as research and development needs and opportunities. Although current regional programs and strategies are making progress to control and perhaps eliminate the disease in some endemic areas, such as India, Bangladesh, and Nepal, workshop participants concluded that vaccines would still be necessary to sustain elimination efforts and ultimately block and reduce transmission. In addition, vaccines would be valuable and even critical tools for other areas of the world, such as east Africa, where treatment options are more limited and control programs for VL are less effective. Because different disease foci present different epidemiological features, product characteristics should be carefully designed to reflect vaccines that either target common antigens for all forms of VL or are tailored to fit regional needs. JF - American Journal of Tropical Medicine and Hygiene AU - Mo, Annie X AU - Pesce, John AU - Hall, B Fenton AD - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, annie.mo@nih.gov Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 514 EP - 521 PB - American Society of Tropical Medicine and Hygiene, 60 Revere Drive, Suite 500 Northbrook IL 60062 United States VL - 95 IS - 3 SN - 0002-9637, 0002-9637 KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Health & Safety Science Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - ISW, Bangladesh KW - Disease control KW - Allergies KW - Nepal KW - India KW - Disease transmission KW - Public health KW - Allergic reactions KW - Hypersensitivity KW - Endemic species KW - Antigens KW - Infectious diseases KW - Conferences KW - Visceral leishmaniasis KW - Control programs KW - Africa KW - Vaccines KW - Hygiene KW - Research programs KW - K 03400:Human Diseases KW - Q1 08485:Species interactions: pests and control KW - Q5 08524:Public health, medicines, dangerous organisms KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827883620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Visceral+Leishmaniasis+Control+and+Elimination%3A+Is+There+a+Role+for+Vaccines+in+Achieving+Regional+and+Global+Goals%3F&rft.au=Mo%2C+Annie+X%3BPesce%2C+John%3BHall%2C+B+Fenton&rft.aulast=Mo&rft.aufirst=Annie&rft.date=2016-09-01&rft.volume=95&rft.issue=3&rft.spage=514&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/10.4269%2Fajtmh.16-0184 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Allergic reactions; Endemic species; Antigens; Infectious diseases; Disease control; Vaccines; Hygiene; Public health; Disease transmission; Hypersensitivity; Conferences; Control programs; Visceral leishmaniasis; Allergies; Research programs; ISW, Bangladesh; Africa; Nepal; India DO - http://dx.doi.org/10.4269/ajtmh.16-0184 ER - TY - JOUR T1 - P034Smoking status, primary adult occupation and risk of recurrent urothelial bladder carcinoma: data from the cancer genome atlas (TCGA) project AN - 1827881259; PQ0003696902 AB - Tobacco smoking and occupational exposures are the leading risk factors for urothelial bladder carcinoma (UBC) incidence, yet little is known about the contribution of these two major risk factors for UBC recurrence. We evaluated whether smoking status and primary adult occupation are associated with time to UBC recurrence for patients with muscle-invasive bladder cancer submitted to The Cancer Genome Atlas (TCGA) project. Of 406 cases, 358 patients had data on recurrence and time to recurrence, of which 133 (37.2%) experienced a recurrence. Kaplan-Meier and Cox proportional hazard methods were used to assess the association between smoking status, employment in a high-risk occupation for bladder cancer, occupational diesel exhaust exposure, and 2010 Standard Occupational Classification (SOC) group and time to UBC recurrence. Current smokers who smoked for more than 40 pack-years had an increased risk of recurrence compared to never smokers (HR 2.1, 95% CI: 1.1, 4.1). Additionally, employment in a high-risk occupation was associated with a shorter time to recurrence (log-rank P = 0.005). We found an increased risk of recurrence for those employed in occupations with probable diesel exhaust exposure (HR: 1.7, 95% CI: 1.0, 2.8) and for those employed in production occupations (HR: 2.0, 95% CI: 1.1, 3.6). This study suggests smoking status impacts risk of UBC recurrence, although several previous studies provided mixed evidence of this association. In addition, while there is a known causal relationship between occupation and bladder cancer risk, our study suggests that occupation may also be related to increased risk of recurrence. JF - Occupational and Environmental Medicine AU - Wilcox, Amber AU - Silverman, Debra AU - Friesen, Melissa AU - Locke, Sarah AU - Russ, Daniel AU - Hyun, Noorie AU - Colt, Joanne AU - Figueroa, Jonine AU - Rothman, Nat AU - Moore, Lee AU - Koutros, Stella AD - US National Cancer Institute, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - A131 EP - A132 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - Suppl 1 SN - 1351-0711, 1351-0711 KW - Genetics Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Genomes KW - Tobacco smoking KW - Data processing KW - Urinary bladder KW - diesel exhaust* KW - Employment KW - urothelial carcinoma KW - Cancer KW - Exhausts KW - Smoking KW - Health risks KW - Atlases KW - Classification KW - Risk factors KW - Tobacco KW - Risk groups KW - Diesel KW - Occupational exposure KW - G 07880:Human Genetics KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827881259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=P034Smoking+status%2C+primary+adult+occupation+and+risk+of+recurrent+urothelial+bladder+carcinoma%3A+data+from+the+cancer+genome+atlas+%28TCGA%29+project&rft.au=Wilcox%2C+Amber%3BSilverman%2C+Debra%3BFriesen%2C+Melissa%3BLocke%2C+Sarah%3BRuss%2C+Daniel%3BHyun%2C+Noorie%3BColt%2C+Joanne%3BFigueroa%2C+Jonine%3BRothman%2C+Nat%3BMoore%2C+Lee%3BKoutros%2C+Stella&rft.aulast=Wilcox&rft.aufirst=Amber&rft.date=2016-09-01&rft.volume=73&rft.issue=Suppl+1&rft.spage=A131&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103951.359 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Genomes; Tobacco smoking; Data processing; Classification; Atlases; Urinary bladder; Risk factors; Risk groups; Diesel; urothelial carcinoma; Occupational exposure; Exhausts; Risk assessment; Health risks; Smoking; diesel exhaust*; Tobacco; Employment; Cancer DO - http://dx.doi.org/10.1136/oemed-2016-103951.359 ER - TY - JOUR T1 - ProteinProcessor: A probabilistic analysis using mass accuracy and the MS spectrum AN - 1827880425; PQ0003656497 AB - Current approaches to protein identification rely heavily on database matching of fragmentation spectra or precursor peptide ions. We have developed a method for MALDI TOF-TOF instrumentation that uses peptide masses and their measurement errors to confirm protein identifications from a first pass MS/MS database search. The method uses MS1-level spectral data that have heretofore been ignored by most search engines. This approach uses the distribution of mass errors of peptide matches in the MS1 spectrum to develop a probability model that is independent of the MS/MS database search identifications. Peptide mass matches can come from both precursor ions that have been fragmented as well as those that are tentatively identified by accurate mass alone. This additional corroboration enables us to confirm protein identifications to MS/MS-based scores that are otherwise considered to be only of moderate quality. Straightforward and easily applicable to current proteomic analyses, this tool termed "ProteinProcessor" provides a robust and invaluable addition to current protein identification tools. JF - Proteomics AU - Epstein, Jonathan A AU - Blank, Paul S AU - Searle, Brian C AU - Catlin, Aaron D AU - Cologna, Stephanie M AU - Olson, Matthew T AU - Backlund, Peter S AU - Coorssen, Jens R AU - Yergey, Alfred L AD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 2480 EP - 2490 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 16 IS - 18 SN - 1615-9853, 1615-9853 KW - Biotechnology and Bioengineering Abstracts KW - Databases KW - Ions KW - Data processing KW - proteomics KW - Models KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827880425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=ProteinProcessor%3A+A+probabilistic+analysis+using+mass+accuracy+and+the+MS+spectrum&rft.au=Epstein%2C+Jonathan+A%3BBlank%2C+Paul+S%3BSearle%2C+Brian+C%3BCatlin%2C+Aaron+D%3BCologna%2C+Stephanie+M%3BOlson%2C+Matthew+T%3BBacklund%2C+Peter+S%3BCoorssen%2C+Jens+R%3BYergey%2C+Alfred+L&rft.aulast=Epstein&rft.aufirst=Jonathan&rft.date=2016-09-01&rft.volume=16&rft.issue=18&rft.spage=2480&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.201600137 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Ions; Databases; Data processing; proteomics; Models DO - http://dx.doi.org/10.1002/pmic.201600137 ER - TY - JOUR T1 - Getting the most out of PubChem for virtual screening. AN - 1825220259; 27454129 AB - With the emergence of the 'big data' era, the biomedical research community has great interest in exploiting publicly available chemical information for drug discovery. PubChem is an example of public databases that provide a large amount of chemical information free of charge. This article provides an overview of how PubChem's data, tools, and services can be used for virtual screening and reviews recent publications that discuss important aspects of exploiting PubChem for drug discovery. PubChem offers comprehensive chemical information useful for drug discovery. It also provides multiple programmatic access routes, which are essential to build automated virtual screening pipelines that exploit PubChem data. In addition, PubChemRDF allows users to download PubChem data and load them into a local computing facility, facilitating data integration between PubChem and other resources. PubChem resources have been used in many studies for developing bioactivity and toxicity prediction models, discovering polypharmacologic (multi-target) ligands, and identifying new macromolecule targets of compounds (for drug-repurposing or off-target side effect prediction). These studies demonstrate the usefulness of PubChem as a key resource for computer-aided drug discovery and related area. JF - Expert opinion on drug discovery AU - Kim, Sunghwan AD - a National Center for Biotechnology Information, National Library of Medicine , National Institutes of Health , Department of Health and Human Services, Bethesda , MD , USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 843 EP - 855 VL - 11 IS - 9 KW - Index Medicus KW - data mining KW - biological assay KW - cheminformatics KW - polypharmacology KW - computer-aided drug discovery KW - computational toxicology KW - PubChem KW - quantitative structure-activity relationship (QSAR) KW - database KW - virtual screening UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1825220259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+drug+discovery&rft.atitle=Getting+the+most+out+of+PubChem+for+virtual+screening.&rft.au=Kim%2C+Sunghwan&rft.aulast=Kim&rft.aufirst=Sunghwan&rft.date=2016-09-01&rft.volume=11&rft.issue=9&rft.spage=843&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+drug+discovery&rft.issn=1746-045X&rft_id=info:doi/10.1080%2F17460441.2016.1216967 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/17460441.2016.1216967 ER - TY - JOUR T1 - Physical abuse, psychological abuse and neglect: Evidence of alcohol-related harm to children in five states of India AN - 1821624522 AB - Introduction and Aims In India, alcohol consumption per capita has increased in recent years, and child maltreatment is highly prevalent. We assess alcohol-related harms to children, including physical abuse, psychological abuse and neglect, and correlates for men reporting these harms. Design and Methods We analysed data from household interviews collected in a cross-sectional, case-control study in five Indian states (n=5026). Data were collected from October 2011 to May 2012. Using multilevel mixed-effects logistic regression, we examined male adult's reports of five types of alcohol-related harm to children (respondents were not necessarily the perpetrators of the harms) and respondents' drinking patterns and socio-demographic characteristics associated with the reporting of these harms. Results In this sample, 43.2% of the men reported at least one alcohol-related harm to children in the past year; among them, 61.6% reported multiple. Among all men, 15.7% reported that a child experienced physical abuse from adults' drinking. Adjusting for respondents' drinking pattern and socio-demographics, multilevel mixed-effects logistic regression showed that living in a rural area was associated with greater odds of reporting alcohol-related physical abuse, psychological harm and neglect to children. Compared with past-year abstainers, both non-heavy episodic and heavy episodic drinkers had significantly greater odds of reporting these harms. We found significant differences in the reporting of harms by location. Discussion and Conclusions This study suggests that adults' drinking is associated with physical and psychological abuse and neglect to children. Greater use of evidence-based alcohol policy interventions may help reduce alcohol-related harms to children in India. [Esser MB, Rao GN, Gururaj G, Murthy P, Jayarajan D, Sethu L, Jernigan DH, Benegal V, Collaborators Group on Epidemiological Study of Patterns and Consequences of Alcohol Misuse in India. Physical abuse, psychological abuse and neglect: Evidence of alcohol-related harm to children in five states of India. Drug Alcohol Rev 2016;35:530-538] JF - Drug and Alcohol Review AU - Esser, Marissa B AU - Rao, Girish N AU - Gururaj, Gopalkrishna AU - Murthy, Pratima AU - Jayarajan, Deepak AU - Sethu, Lakshmanan AU - Jernigan, David H AU - Benegal, Vivek AD - Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA ; Department of Epidemiology, WHO Collaborating Centre for Injury Prevention and Safety Promotion, Centre for Public Health, National Institute of Mental Health and Neuro Sciences, Bangalore, India ; Department of Psychiatry, Centre for Addiction Medicine, National Institute of Mental Health and Neuro Sciences, Bangalore, India ; Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 530 EP - 538 CY - Surry Hills PB - Wiley Subscription Services, Inc. VL - 35 IS - 5 SN - 0959-5236 KW - Education KW - Consumption KW - Sociodemographic aspects KW - Alcohol abuse KW - Alcohol related KW - Demographic aspects KW - Rural communities KW - Maltreatment KW - Perpetrators KW - Child abuse KW - Child neglect KW - Men KW - Psychological abuse KW - Adults KW - Drinking patterns KW - Heavy drinking KW - Maltreated children KW - Child maltreatment KW - Evidence based UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1821624522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Review&rft.atitle=Physical+abuse%2C+psychological+abuse+and+neglect%3A+Evidence+of+alcohol-related+harm+to+children+in+five+states+of+India&rft.au=Esser%2C+Marissa+B%3BRao%2C+Girish+N%3BGururaj%2C+Gopalkrishna%3BMurthy%2C+Pratima%3BJayarajan%2C+Deepak%3BSethu%2C+Lakshmanan%3BJernigan%2C+David+H%3BBenegal%2C+Vivek&rft.aulast=Esser&rft.aufirst=Marissa&rft.date=2016-09-01&rft.volume=35&rft.issue=5&rft.spage=530&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Review&rft.issn=09595236&rft_id=info:doi/10.1111%2Fdar.12377 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 Australasian Professional Society on Alcohol and other Drugs N1 - Last updated - 2016-09-21 DO - http://dx.doi.org/10.1111/dar.12377 ER - TY - JOUR T1 - Prevalence and correlates of alcohol use among adolescents attending school in Kerala, India AN - 1821624121 AB - Introduction and Aims Concern around potentially increasing alcohol use among young people has been growing in public discourse in India. However, there are few published studies on this issue. We studied the prevalence, patterns and correlates of alcohol use among adolescents in Ernakulam, Kerala State, India. Design and Methods A total of 7560 students in the age group 12-19years from 73 schools completed a self-administered questionnaire incorporating standardised instruments to assess alcohol use. Results The overall prevalence of lifetime alcohol among adolescents use was 15% (23.2% among boys and 6.5% among girls) with prevalence increasing with age, and 25.3% of drinkers reported hazardous alcohol use. The mean age at onset of alcohol use was 13.6years. Initiation of alcohol use typically preceded use of tobacco and illicit drugs. Most students reported initiation into alcohol use by family members in the context of family celebrations. The prevalence of alcohol use was higher among students from urban areas and those with a part-time job. Lower use was seen among Muslims. Lifetime alcohol use was associated with significantly higher tobacco and illicit drug use, suicidal thoughts, attention deficit hyperactivity disorder symptom-scores, history of non-contact sexual abuse and with poor academic performance. Discussion and Conclusions Alcohol use among adolescents in India deserves greater attention than it has previously received, marked as it is by an early onset and associated with a range of negative mental health problems. [ Jaisoorya T S, Beena K V, Beena M, Ellangovan K, Jose D C, Thennarasu K, Benegal V. Prevalence and correlates of alcohol use among adolescents attending school in Kerala, India. Drug Alcohol Rev 2016;35:523-529] JF - Drug and Alcohol Review AU - Jaisoorya, TS AU - Beena, KV AU - Beena, M AU - Ellangovan, K AU - Jose, Dalia C AU - Thennarasu, K AU - Benegal, Vivek AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India ; National Rural Health Mission (Kerala), India ; Department of Health and Family Welfare (Kerala), India ; Department of Biostatistics, National Institute of Mental Health and Neurosciences, Bangalore, India ; Centre for Addiction Medicine, National Institute of Mental Health and Neurosciences, Bangalore, India ; Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 523 EP - 529 CY - Surry Hills PB - Wiley Subscription Services, Inc. VL - 35 IS - 5 SN - 0959-5236 KW - Education KW - Muslims KW - Academic achievement KW - Drug abuse KW - Prevalence KW - Urban areas KW - Attention deficit hyperactivity disorder KW - Health problems KW - Mental health KW - Abused adolescent boys KW - Early onset KW - Suicidal ideation KW - Alcohol consumption KW - Young people KW - Tobacco KW - Age of onset KW - Questionnaires KW - Relatives KW - Sexual abuse KW - Adolescents KW - Suicidal behaviour KW - Initiation KW - Mental illness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1821624121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Review&rft.atitle=Prevalence+and+correlates+of+alcohol+use+among+adolescents+attending+school+in+Kerala%2C+India&rft.au=Jaisoorya%2C+TS%3BBeena%2C+KV%3BBeena%2C+M%3BEllangovan%2C+K%3BJose%2C+Dalia+C%3BThennarasu%2C+K%3BBenegal%2C+Vivek&rft.aulast=Jaisoorya&rft.aufirst=TS&rft.date=2016-09-01&rft.volume=35&rft.issue=5&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Review&rft.issn=09595236&rft_id=info:doi/10.1111%2Fdar.12358 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 Australasian Professional Society on Alcohol and other Drugs N1 - Last updated - 2016-09-21 DO - http://dx.doi.org/10.1111/dar.12358 ER - TY - JOUR T1 - SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer. AN - 1820595875; 27259717 AB - The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types but has not been investigated in human endometrial cancer. In a model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen genistein (GEN) or the synthetic estrogen diethylstilbestrol (DES) develop endometrial cancer as adults. Previously, we demonstrated that SIX1 becomes aberrantly expressed in the uteri of these mice. Here, we used this mouse model to investigate the role of SIX1 expression in endometrial carcinoma development and used human tissue microarrays to explore the utility of SIX1 as a biomarker in human endometrial cancer. In mice neonatally exposed to GEN or DES, the Six1 transcript level increased dramatically over time in uteri at 6, 12, and 18 months of age and was associated with development of endometrial carcinoma. SIX1 protein localized within abnormal basal cells and all atypical hyperplastic and neoplastic lesions. These findings indicate that developmental estrogenic chemical exposure induces persistent endometrial SIX1 expression that is strongly associated with abnormal cell differentiation and cancer development. In human endometrial tissue specimens, SIX1 was not present in normal endometrium but was expressed in a subset of endometrial cancers in patients who were also more likely to have late-stage disease. These findings identify SIX1 as a disease biomarker in a model of hormonal carcinogenesis and suggest that SIX1 plays a role in endometrial cancer development in both mice and women. The SIX1 oncoprotein is aberrantly expressed in the endometrium following developmental exposure to estrogenic chemicals, correlates with uterine cancer, and is a biomarker in human endometrial cancers. Mol Cancer Res; 14(9); 849-58. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Molecular cancer research : MCR AU - Suen, Alisa A AU - Jefferson, Wendy N AU - Wood, Charles E AU - Padilla-Banks, Elizabeth AU - Bae-Jump, Victoria L AU - Williams, Carmen J AD - Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. ; Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. ; Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina. ; Division of Gynecologic Oncology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. ; Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. williamsc5@niehs.nih.gov Victoria.Bae-Jump@unchealth.unc.edu. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 849 EP - 858 VL - 14 IS - 9 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1820595875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+research+%3A+MCR&rft.atitle=SIX1+Oncoprotein+as+a+Biomarker+in+a+Model+of+Hormonal+Carcinogenesis+and+in+Human+Endometrial+Cancer.&rft.au=Suen%2C+Alisa+A%3BJefferson%2C+Wendy+N%3BWood%2C+Charles+E%3BPadilla-Banks%2C+Elizabeth%3BBae-Jump%2C+Victoria+L%3BWilliams%2C+Carmen+J&rft.aulast=Suen&rft.aufirst=Alisa&rft.date=2016-09-01&rft.volume=14&rft.issue=9&rft.spage=849&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+research+%3A+MCR&rft.issn=1557-3125&rft_id=info:doi/10.1158%2F1541-7786.MCR-16-0084 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-16 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1158/1541-7786.MCR-16-0084 ER - TY - JOUR T1 - [beta]-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia AN - 1819143065; PQ0003621089 AB - [beta]-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study, we examined whether [beta]-1,3-glucans are masked by surface proteins in Pneumocystis and what role [beta]-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, [beta]-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of [beta]-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon [gamma], tumor necrosis factor [alpha], interleukin 1[beta], interleukin 6, and multiple chemokines/chemokine ligands. Thus, [beta]-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses. JF - Journal of Infectious Diseases AU - Kutty, Geetha AU - Davis, A Sally AU - Ferreyra, Gabriela A AU - Qiu, Ju AU - Huang, Da Wei AU - Sassi, Monica AU - Bishop, Lisa AU - Handley, Grace AU - Sherman, Brad AU - Lempicki, Richard AU - Kovacs, Joseph A AD - Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, jkovacs@nih.gov Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 782 EP - 791 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 214 IS - 5 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts; Health & Safety Science Abstracts KW - Pneumocystis KW - glucan KW - cell wall KW - Msg KW - Bioindicators KW - Interleukin 6 KW - Mortality KW - gamma -Interferon KW - Chemokines KW - Pneumocystis carinii KW - Trypsin KW - Caspofungin KW - Animal models KW - Tumors KW - Cysts KW - Inflammation KW - Infectious diseases KW - Lung KW - Proteins KW - Polymerase chain reaction KW - Tumor necrosis factor- alpha KW - Immune response KW - Pneumonia KW - glucans KW - Cell walls KW - K 03410:Animal Diseases KW - H 6000:Natural Disasters/Civil Defense/Emergency Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819143065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=%5Bbeta%5D-Glucans+Are+Masked+but+Contribute+to+Pulmonary+Inflammation+During+Pneumocystis+Pneumonia&rft.au=Kutty%2C+Geetha%3BDavis%2C+A+Sally%3BFerreyra%2C+Gabriela+A%3BQiu%2C+Ju%3BHuang%2C+Da+Wei%3BSassi%2C+Monica%3BBishop%2C+Lisa%3BHandley%2C+Grace%3BSherman%2C+Brad%3BLempicki%2C+Richard%3BKovacs%2C+Joseph+A&rft.aulast=Kutty&rft.aufirst=Geetha&rft.date=2016-09-01&rft.volume=214&rft.issue=5&rft.spage=782&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw249 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-09-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Interleukin 6; gamma -Interferon; Chemokines; Trypsin; Caspofungin; Animal models; Cysts; Inflammation; Lung; Polymerase chain reaction; Immune response; Tumor necrosis factor- alpha; glucans; Pneumonia; Cell walls; Bioindicators; Mortality; Infectious diseases; Proteins; Tumors; Pneumocystis carinii DO - http://dx.doi.org/10.1093/infdis/jiw249 ER - TY - JOUR T1 - Cervical Infection With Vaccine-Associated Human Papillomavirus (HPV) Genotypes as a Predictor of Acquisition and Clearance of Other HPV Infections AN - 1819140009; PQ0003621076 AB - Background. Recent birth cohorts vaccinated against human papillomavirus (HPV) may be protected against up to 4 genotypes (HPV-6, -11, -16, and -18). If natural competition exists between these and other HPV types, then the prevalence of other types may increase after vaccination. Methods. Cohort information from 3 studies was used to compare acquisition and clearance of 30 different HPV types (individually and grouped by species), according to infection status with vaccine-targeted types at baseline and the time of the index infection, respectively. Hazard ratios (HRs) were adjusted for predictors of multiple-type infection. Results. Among 3200 females across all studies, 857 were infected with HPV at baseline, and 994 acquired new infections during follow-up. Females infected with HPV-16 were at higher risk of acquiring other [alpha]-9 HPV types (HR, 1.9; 95% confidence interval [CI], 1.2-3.0) but at similar risk of clearing existing [alpha]-9 HPV infections (HR, 0.9; 95% CI, .7-1.3). Females infected with vaccine-targeted types were generally at higher risk of acquiring additional types (HRs, > 1.0) and at equal risk of clearing existing infections. Accounting for multiple comparisons, none of the HRs of 1.0 were statistically significant in our analyses of acquisition or clearance. Conclusions. Vaccine-targeted HPV types do not appear to compete with other types, suggesting that HPV type replacement is unlikely to occur. JF - Journal of Infectious Diseases AU - Tota, Joseph E AU - Ramanakumar, Agnihotram V AU - Villa, Luisa L AU - Richardson, Harriet AU - Burchell, Ann N AU - Coutlee, Francois AU - Franco, Eduardo L AD - Division of Cancer Epidemiology, Department of Oncology, joseph.tota@nih.gov Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 676 EP - 684 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 214 IS - 5 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Immunology Abstracts; Health & Safety Science Abstracts KW - human papillomavirus KW - vaccination KW - type replacement KW - type competition KW - females KW - Statistical analysis KW - Papillomaviridae KW - Genotypes KW - Infection KW - Vaccination KW - Infectious diseases KW - Risk factors KW - Vaccines KW - Competition KW - Human papillomavirus KW - V 22310:Genetics, Taxonomy & Structure KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1819140009?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Cervical+Infection+With+Vaccine-Associated+Human+Papillomavirus+%28HPV%29+Genotypes+as+a+Predictor+of+Acquisition+and+Clearance+of+Other+HPV+Infections&rft.au=Tota%2C+Joseph+E%3BRamanakumar%2C+Agnihotram+V%3BVilla%2C+Luisa+L%3BRichardson%2C+Harriet%3BBurchell%2C+Ann+N%3BCoutlee%2C+Francois%3BFranco%2C+Eduardo+L&rft.aulast=Tota&rft.aufirst=Joseph&rft.date=2016-09-01&rft.volume=214&rft.issue=5&rft.spage=676&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw215 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-09-01 N1 - Last updated - 2016-11-09 N1 - SubjectsTermNotLitGenreText - Risk factors; Statistical analysis; Genotypes; Infection; Competition; Vaccination; Infectious diseases; Vaccines; Papillomaviridae; Human papillomavirus DO - http://dx.doi.org/10.1093/infdis/jiw215 ER - TY - JOUR T1 - Established and Emerging Roles of Biomarkers in Heart Failure Clinical Trials. AN - 1816636637; 27582282 AB - The role of circulating biomarkers in heart failure clinical trials has evolved in recent decades. Increasing evidence behind the use of natriuretic peptides, emergence of novel biomarkers, and increased emphasis on targeting therapies toward physiological basis of disease (so-called precision medicine) have all contributed to the continued expansion of biomarker use in heart failure clinical trials. We will explore the advantages and pitfalls encountered through the use of biomarkers in clinical trials as an inclusion criterion, toxicity marker, and end point. We will also review their role in providing insights into the mechanism of action of therapeutics and guiding therapy in the management of patients with heart failure. © 2016 American Heart Association, Inc. JF - Circulation. Heart failure AU - Ibrahim, Nasrien E AU - Gaggin, Hanna K AU - Konstam, Marvin A AU - Januzzi, James L AD - From the Cardiology Division, Massachusetts General Hospital, Boston (N.E.I., H.K.G., J.L.J.); Harvard Clinical Research Institute, Boston, MA (H.K.G., J.L.J.); and The Cardiovascular Center, Tufts Medical Center, Boston, MA (M.A.K.). ; From the Cardiology Division, Massachusetts General Hospital, Boston (N.E.I., H.K.G., J.L.J.); Harvard Clinical Research Institute, Boston, MA (H.K.G., J.L.J.); and The Cardiovascular Center, Tufts Medical Center, Boston, MA (M.A.K.). jjanuzzi@partners.org. Y1 - 2016/09// PY - 2016 DA - September 2016 VL - 9 IS - 9 KW - Index Medicus KW - precision medicine KW - natriuretic peptides KW - retrospective study KW - heart failure KW - biomarkers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1816636637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation.+Heart+failure&rft.atitle=Established+and+Emerging+Roles+of+Biomarkers+in+Heart+Failure+Clinical+Trials.&rft.au=Ibrahim%2C+Nasrien+E%3BGaggin%2C+Hanna+K%3BKonstam%2C+Marvin+A%3BJanuzzi%2C+James+L&rft.aulast=Ibrahim&rft.aufirst=Nasrien&rft.date=2016-09-01&rft.volume=9&rft.issue=9&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Circulation.+Heart+failure&rft.issn=1941-3297&rft_id=info:doi/10.1161%2FCIRCHEARTFAILURE.115.002528 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002528 ER - TY - JOUR T1 - Cooking Coal Use and All-Cause and Cause-Specific Mortality in a Prospective Cohort Study of Women in Shanghai, China. AN - 1816630804; 27091488 AB - Nearly 4.3 million deaths worldwide were attributable to exposure to household air pollution in 2012. However, household coal use remains widespread. We investigated the association of cooking coal and all-cause and cause-specific mortality in a prospective cohort of primarily never-smoking women in Shanghai, China. A cohort of 74,941 women were followed from 1996 through 2009 with annual linkage to the Shanghai vital statistics database. Cause-specific mortality was identified through 2009. Use of household coal for cooking was assessed through a residential history questionnaire. Cox proportional hazards models estimated the risk of mortality associated with household coal use. In this cohort, 63% of the women ever used coal (n = 46,287). Compared with never coal use, ever use of coal was associated with mortality from all causes [hazard ratio (HR) = 1.12; 95% confidence interval (CI): 1.05, 1.21], cancer (HR = 1.14; 95% CI: 1.03, 1.27), and ischemic heart disease (overall HR = 1.61; 95% CI: 1.14, 2.27; HR for myocardial infarction specifically = 1.80; 95% CI: 1.16, 2.79). The risk of cardiovascular mortality increased with increasing duration of coal use, compared with the risk in never users. The association between coal use and ischemic heart disease mortality diminished with increasing years since cessation of coal use. Evidence from this study suggests that past use of coal among women in Shanghai is associated with excess all-cause mortality, and from cardiovascular diseases in particular. The decreasing association with cardiovascular mortality as the time since last use of coal increased emphasizes the importance of reducing use of household coal where use is still widespread. Kim C, Seow WJ, Shu XO, Bassig BA, Rothman N, Chen BE, Xiang YB, Hosgood HD III, Ji BT, Hu W, Wen C, Chow WH, Cai Q, Yang G, Gao YT, Zheng W, Lan Q. 2016. Cooking coal use and all-cause and cause-specific mortality in a prospective cohort study of women in Shanghai, China. Environ Health Perspect 124:1384-1389; http://dx.doi.org/10.1289/EHP236. JF - Environmental health perspectives AU - Kim, Christopher AU - Seow, Wei Jie AU - Shu, Xiao-Ou AU - Bassig, Bryan A AU - Rothman, Nathaniel AU - Chen, Bingshu E AU - Xiang, Yong-Bing AU - Hosgood, H Dean AU - Ji, Bu-Tian AU - Hu, Wei AU - Wen, Cuiju AU - Chow, Wong-Ho AU - Cai, Qiuyin AU - Yang, Gong AU - Gao, Yu-Tang AU - Zheng, Wei AU - Lan, Qing AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1384 EP - 1389 VL - 124 IS - 9 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1816630804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Cooking+Coal+Use+and+All-Cause+and+Cause-Specific+Mortality+in+a+Prospective+Cohort+Study+of+Women+in+Shanghai%2C+China.&rft.au=Kim%2C+Christopher%3BSeow%2C+Wei+Jie%3BShu%2C+Xiao-Ou%3BBassig%2C+Bryan+A%3BRothman%2C+Nathaniel%3BChen%2C+Bingshu+E%3BXiang%2C+Yong-Bing%3BHosgood%2C+H+Dean%3BJi%2C+Bu-Tian%3BHu%2C+Wei%3BWen%2C+Cuiju%3BChow%2C+Wong-Ho%3BCai%2C+Qiuyin%3BYang%2C+Gong%3BGao%2C+Yu-Tang%3BZheng%2C+Wei%3BLan%2C+Qing&rft.aulast=Kim&rft.aufirst=Christopher&rft.date=2016-09-01&rft.volume=124&rft.issue=9&rft.spage=1384&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP236 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/EHP236 ER - TY - JOUR T1 - Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine. AN - 1816630758; 27561454 AB - Great research effort has been focused on elucidating the contribution of host genetic variability on pharmacological outcomes in cancer. Nuclear receptors have emerged as mediators between environmental stimuli and drug pharmacokinetics and pharmacodynamics. The pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors have been reported to regulate transcription of genes that encode drug metabolizing enzymes and transporters. Altered nuclear receptor expression has been shown to affect the metabolism and pharmacological profile of traditional chemotherapeutics and targeted agents. Accordingly, polymorphic variants in these genes have been studied as pharmacogenetic markers of outcome variability. This review summarizes the state of knowledge about the roles played by pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factor expression and genetics as predictive markers of anticancer drug toxicity and efficacy, which can improve cancer precision medicine. JF - Pharmacogenomics AU - De Mattia, Elena AU - Cecchin, Erika AU - Roncato, Rossana AU - Toffoli, Giuseppe AD - Experimental & Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1547 EP - 1571 VL - 17 IS - 14 KW - Index Medicus KW - inflammation KW - PXR KW - transporters KW - polymorphisms KW - metabolic enzymes KW - CAR KW - pharmacogenetics KW - HNFs KW - chemotherapy KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1816630758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Pregnane+X+receptor%2C+constitutive+androstane+receptor+and+hepatocyte+nuclear+factors+as+emerging+players+in+cancer+precision+medicine.&rft.au=De+Mattia%2C+Elena%3BCecchin%2C+Erika%3BRoncato%2C+Rossana%3BToffoli%2C+Giuseppe&rft.aulast=De+Mattia&rft.aufirst=Elena&rft.date=2016-09-01&rft.volume=17&rft.issue=14&rft.spage=1547&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=1744-8042&rft_id=info:doi/10.2217%2Fpgs-2016-0095 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.2217/pgs-2016-0095 ER - TY - JOUR T1 - Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women's Health Study AN - 1815711911; PQ0003596865 AB - BackgroundFew studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate levels in public water supplies (PWS). However, elevated nitrate levels may reflect the presence of other agricultural chemicals, such as atrazine, one of the most commonly detected pesticides in Iowa PWS.MethodsWe evaluated the association between atrazine in drinking water and incident ovarian cancer (N=145, 1986-2010) among 13041 postmenopausal women in the Iowa Women's Health Study who used their PWS for greater than or equal to 11years as reported in 1989. Average levels of atrazine (1986-1987), nitrate-nitrogen (NO3-N, 1955-1988) and estimated levels of total trihalomethanes (TTHM, 1955-1988) from PWS monitoring data were linked to the participants' cities of residence. We computed HRs and 95% CIs by categories of the average atrazine level (not detected, less than or equal to or >0.37 parts per billion=median) using Cox proportional hazards regression adjusting for ovarian cancer risk factors.ResultsAtrazine was detected in water samples from 69 cities where 4155 women (32%) lived and levels were moderately correlated with NO3-N ( rho =0.35) and TTHM ( rho =0.24). Atrazine levels were not associated with ovarian cancer risk with or without adjusting for NO3-N and TTHM levels (p-trend=0.50 and 0.81, respectively). Further, there was no evidence for effect modification of the atrazine association by NO3-N or TTHM levels.ConclusionsIn our study with low atrazine detection rates, we found no association between atrazine in PWS and postmenopausal ovarian cancer risk. JF - Occupational and Environmental Medicine AU - Inoue-Choi, Maki AU - Weyer, Peter J AU - Jones, Rena R AU - Booth, Benjamin J AU - Cantor, Kenneth P AU - Robien, Kim AU - Ward, Mary H AD - National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 582 EP - 587 PB - B M J Publishing Group, B.M.A. House London WC1H 9JR United Kingdom VL - 73 IS - 9 SN - 1351-0711, 1351-0711 KW - Health & Safety Science Abstracts KW - atrazine KW - public water supplies KW - ovarian cancer KW - Water sampling KW - Nitrates KW - Byproducts KW - Herbicides KW - Agrochemicals KW - Cities KW - USA, Iowa KW - Trihalomethanes KW - Risk factors KW - Pesticides KW - Atrazine KW - Chlorination KW - Ovarian carcinoma KW - Females KW - Drinking water KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815711911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Atrazine+in+public+water+supplies+and+risk+of+ovarian+cancer+among+postmenopausal+women+in+the+Iowa+Women%27s+Health+Study&rft.au=Inoue-Choi%2C+Maki%3BWeyer%2C+Peter+J%3BJones%2C+Rena+R%3BBooth%2C+Benjamin+J%3BCantor%2C+Kenneth+P%3BRobien%2C+Kim%3BWard%2C+Mary+H&rft.aulast=Inoue-Choi&rft.aufirst=Maki&rft.date=2016-09-01&rft.volume=73&rft.issue=9&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/10.1136%2Foemed-2016-103575 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Nitrates; Water sampling; Byproducts; Herbicides; Agrochemicals; Cities; Risk factors; Trihalomethanes; Atrazine; Pesticides; Ovarian carcinoma; Chlorination; Females; Drinking water; USA, Iowa DO - http://dx.doi.org/10.1136/oemed-2016-103575 ER - TY - JOUR T1 - Mechanical Properties of the Tumor Stromal Microenvironment Probed In Vitro and Ex Vivo by In Situ-Calibrated Optical Trap-Based Active Microrheology AN - 1815703666; PQ0003589055 AB - One of the hallmarks of the malignant transformation of epithelial tissue is the modulation of stromal components of the microenvironment. In particular, aberrant extracellular matrix (ECM) remodeling and stiffening enhances tumor growth and survival and promotes metastasis. Type I collagen is one of the major ECM components. It serves as a scaffold protein in the stroma contributing to the tissue's mechanical properties, imparting tensile strength and rigidity to tissues such as those of the skin, tendons, and lungs. Here we investigate the effects of intrinsic spatial heterogeneities due to fibrillar architecture, pore size and ligand density on the microscale and bulk mechanical properties of the ECM. Type I collagen hydrogels with topologies tuned by polymerization temperature and concentration to mimic physico-chemical properties of a normal tissue and tumor microenvironment were measured by in situ-calibrated Active Microrheology by Optical Trapping revealing significantly different microscale complex shear moduli at Hz-kHz frequencies and two orders of magnitude of strain amplitude that we compared to data from bulk rheology measurements. Access to higher frequencies enabled observation of transitions from elastic to viscous behavior that occur at ~200-2750 Hz, which largely was dependent on tissue architecture well outside the dynamic range of instrument acquisition possible with SAOS bulk rheology. We determined that mouse melanoma tumors and human breast tumors displayed complex moduli ~5-1000 Pa, increasing with frequency and displaying a nonlinear stress-strain response. Thus, we show the feasibility of a mechanical biopsy in efforts to provide a diagnostic tool to aid in the design of therapeutics complementary to those based on standard histopathology. JF - Cellular and Molecular Bioengineering AU - Staunton, Jack R AU - Vieira, Wilfred AU - Fung, King Leung AU - Lake, Ross AU - Devine, Alexus AU - Tanner, Kandice AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute (NIH), Bethesda, MD, 20892, USA, kandice.tanner@nih.gov Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 398 EP - 417 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 9 IS - 3 SN - 1865-5025, 1865-5025 KW - Biotechnology and Bioengineering Abstracts KW - Temperature effects KW - Stroma KW - Polymerization KW - Data processing KW - Physicochemical properties KW - Biopsy KW - Tumors KW - Trapping KW - Melanoma KW - Rheology KW - hydrogels KW - Lung KW - Extracellular matrix KW - Spatial heterogeneity KW - Microenvironments KW - Tensile strength KW - Collagen (type I) KW - Tendons KW - Mechanical properties KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815703666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+Molecular+Bioengineering&rft.atitle=Mechanical+Properties+of+the+Tumor+Stromal+Microenvironment+Probed+In+Vitro+and+Ex+Vivo+by+In+Situ-Calibrated+Optical+Trap-Based+Active+Microrheology&rft.au=Staunton%2C+Jack+R%3BVieira%2C+Wilfred%3BFung%2C+King+Leung%3BLake%2C+Ross%3BDevine%2C+Alexus%3BTanner%2C+Kandice&rft.aulast=Staunton&rft.aufirst=Jack&rft.date=2016-09-01&rft.volume=9&rft.issue=3&rft.spage=398&rft.isbn=&rft.btitle=&rft.title=Cellular+and+Molecular+Bioengineering&rft.issn=18655025&rft_id=info:doi/10.1007%2Fs12195-016-0460-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 107 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Stroma; Temperature effects; Data processing; Polymerization; Physicochemical properties; Biopsy; Tumors; Trapping; Melanoma; Rheology; hydrogels; Lung; Extracellular matrix; Spatial heterogeneity; Microenvironments; Tensile strength; Collagen (type I); Tendons; Mechanical properties DO - http://dx.doi.org/10.1007/s12195-016-0460-9 ER - TY - JOUR T1 - Anomalous T sub(2) relaxation in normal and degraded cartilage AN - 1815702395; PQ0003584464 AB - Purpose To compare the ordinary monoexponential model with three anomalous relaxation models-the stretched Mittag-Leffler, stretched exponential, and biexponential functions-using both simulated and experimental cartilage relaxation data. Methods Monte Carlo simulations were used to examine both the ability of identifying a given model under high signal-to-noise ratio (SNR) conditions and the accuracy and precision of parameter estimates under more modest SNR as would be encountered clinically. Experimental transverse relaxation data were analyzed from normal and enzymatically degraded cartilage samples under high SNR and rapid echo sampling to compare each model. Results Both simulation and experimental results showed improvement in signal representation with the anomalous relaxation models. The stretched exponential model consistently showed the lowest mean squared error in experimental data and closely represents the signal decay over multiple decades of the decay time (e.g., 1-10 ms, 10-100 ms, and >100 ms). The stretched exponential parameter alpha sub(se) showed an inverse correlation with biochemically derived cartilage proteoglycan content. Conclusion Experimental results obtained at high field suggest potential application of alpha sub(se) as a measure of matrix integrity. Simulation reflecting more clinical imaging conditions, indicate the ability to robustly estimate alpha sub(se) and distinguish between normal and degraded tissue, highlighting its potential as a biomarker for human studies. Magn Reson Med 76:953-962, 2016. JF - Magnetic Resonance in Medicine AU - Reiter, David A AU - Magin, Richard L AU - Li, Weiguo AU - Trujillo, Juan J AU - Pilar Velasco, M AU - Spencer, Richard G AD - Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 953 EP - 962 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 76 IS - 3 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Proteoglycans KW - Monte Carlo simulation KW - Data processing KW - Cartilage KW - N.M.R. KW - Sampling KW - imaging KW - biomarkers KW - Models KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815702395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Anomalous+T+sub%282%29+relaxation+in+normal+and+degraded+cartilage&rft.au=Reiter%2C+David+A%3BMagin%2C+Richard+L%3BLi%2C+Weiguo%3BTrujillo%2C+Juan+J%3BPilar+Velasco%2C+M%3BSpencer%2C+Richard+G&rft.aulast=Reiter&rft.aufirst=David&rft.date=2016-09-01&rft.volume=76&rft.issue=3&rft.spage=953&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25913 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Monte Carlo simulation; Proteoglycans; Data processing; Cartilage; N.M.R.; Sampling; biomarkers; imaging; Models DO - http://dx.doi.org/10.1002/mrm.25913 ER - TY - JOUR T1 - Simultaneous quantification of glutamate and glutamine by J-modulated spectroscopy at 3 Tesla AN - 1815699268; PQ0003584452 AB - Purpose The echo time (TE) averaged spectrum is the one-dimensional (1D) cross-section of the J-resolved spectrum at J=0. In multiecho TE-averaged spectroscopy, glutamate (Glu) is differentiated from glutamine (Gln) at 3 Tesla (T). This method, however, almost entirely suppresses Gln resonance lines around 2.35 ppm, leaving Gln undetermined. This study presents a novel method for quantifying both Glu and Gln using multi-echo spectral data. Methods A 1D cross-section of J-resolved spectroscopy at J=7.5 Hz-referred to as J-modulated spectroscopy-was developed to simultaneously quantify Glu and Gln levels in the human brain. The transverse relaxation times (T sub(2)s) of metabolites were first determined using conventional TE-averaged spectroscopy with different starting echo time and then incorporated into the spectral model for fitting J-modulated data. Results Simulation and in vivo data showed that the resonance signals of Glu and Gln were clearly separated around 2.35 ppm in J-modulated spectroscopy. In the anterior cingulate cortex, both Glu and Gln levels were found to be significantly higher in gray matter than in white matter in healthy subjects (P<10 super(-10) and<10 super(-5), respectively). Conclusion Gln resonances can be clearly separated from Glu and N-acetyl-aspartate around 2.35 ppm using J-modulated spectroscopy. This method can be used to quantitatively measure Glu and Gln simultaneously at 3T. Magn Reson Med 76:725-732, 2016. JF - Magnetic Resonance in Medicine AU - Zhang, Yan AU - Shen, Jun AD - MR Spectroscopy Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 725 EP - 732 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 76 IS - 3 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Glutamine KW - Data processing KW - Brain KW - Substantia alba KW - N.M.R. KW - Metabolites KW - Glutamic acid KW - Spectroscopy KW - Cortex (cingulate) KW - Substantia grisea KW - Models KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815699268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Simultaneous+quantification+of+glutamate+and+glutamine+by+J-modulated+spectroscopy+at+3+Tesla&rft.au=Zhang%2C+Yan%3BShen%2C+Jun&rft.aulast=Zhang&rft.aufirst=Yan&rft.date=2016-09-01&rft.volume=76&rft.issue=3&rft.spage=725&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25922 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Glutamine; Data processing; Brain; Substantia alba; Metabolites; N.M.R.; Glutamic acid; Spectroscopy; Cortex (cingulate); Models; Substantia grisea DO - http://dx.doi.org/10.1002/mrm.25922 ER - TY - JOUR T1 - Cannabis Abusers Show Hypofrontality and Blunted Brain Responses to a Stimulant Challenge in Females but not in Males AN - 1815693618; PQ0003564547 AB - The extent to which cannabis is deleterious to the human brain is not well understood. Here, we test whether cannabis abusers (CA) have impaired frontal function and reactivity to dopaminergic signaling, which are fundamental to relapse in addiction. We measured brain glucose metabolism using PET and [ super(18)F]FDG both at baseline (placebo) and after challenge with methylphenidate (MP), a dopamine-enhancing drug, in 24 active CA (50% female) and 24 controls (HC; 50% female). Results show that (i) CA had lower baseline glucose metabolism than HC in frontal cortex including anterior cingulate, which was associated with negative emotionality. (ii) MP increased whole-brain glucose metabolism in HC but not in CA; and group by challenge effects were most profound in putamen, caudate, midbrain, thalamus, and cerebellum. In CA, MP-induced metabolic increases in putamen correlated negatively with addiction severity. (iii) There were significant gender effects, such that both the group differences at baseline in frontal metabolism and the attenuated regional brain metabolic responses to MP were observed in female CA but not in male CA. As for other drug addictions, reduced baseline frontal metabolism is likely to contribute to relapse in CA. The attenuated responses to MP in midbrain and striatum are consistent with decreased brain reactivity to dopamine stimulation and might contribute to addictive behaviors in CA. The gender differences suggest that females are more sensitive than males to the adverse effects of cannabis in brain. JF - Neuropsychopharmacology AU - Wiers, Corinde E AU - Shokri-Kojori, Ehsan AU - Wong, Christopher T AU - Abi-Dargham, Anissa AU - Demiral, Suekrue B AU - Tomasi, Dardo AU - Wang, Gene-Jack AU - Volkow, Nora D AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 2596 EP - 2605 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 10 SN - 0893-133X, 0893-133X KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Emotions KW - Cerebellum KW - Brain KW - Methylphenidate KW - Cortex (frontal) KW - Stimulants KW - Glucose metabolism KW - Sex differences KW - Drug abuse KW - Thalamus KW - Putamen KW - Cortex (cingulate) KW - Mesencephalon KW - Dopamine KW - Neostriatum KW - Cannabis KW - Positron emission tomography KW - Drug addiction KW - Side effects KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815693618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology&rft.atitle=Cannabis+Abusers+Show+Hypofrontality+and+Blunted+Brain+Responses+to+a+Stimulant+Challenge+in+Females+but+not+in+Males&rft.au=Wiers%2C+Corinde+E%3BShokri-Kojori%2C+Ehsan%3BWong%2C+Christopher+T%3BAbi-Dargham%2C+Anissa%3BDemiral%2C+Suekrue+B%3BTomasi%2C+Dardo%3BWang%2C+Gene-Jack%3BVolkow%2C+Nora+D&rft.aulast=Wiers&rft.aufirst=Corinde&rft.date=2016-09-01&rft.volume=41&rft.issue=10&rft.spage=2596&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/10.1038%2Fnpp.2016.67 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Emotions; Brain; Cerebellum; Cortex (frontal); Methylphenidate; Stimulants; Glucose metabolism; Drug abuse; Sex differences; Cortex (cingulate); Putamen; Thalamus; Mesencephalon; Dopamine; Neostriatum; Positron emission tomography; Cannabis; Drug addiction; Side effects DO - http://dx.doi.org/10.1038/npp.2016.67 ER - TY - JOUR T1 - Cytochrome P450 2E1 is responsible for the initiation of 1,2-dichloropropane-induced liver damage. AN - 1814684332; 25681370 AB - 1,2-Dichloropropane (1,2-DCP), a solvent, which is the main component of the cleaner used in the offset printing companies in Japan, is suspected to be the causative agent of bile duct cancer, which has been recently reported at high incidence in those offset printing workplaces. While there are some reports about the acute toxicity of 1,2-DCP, no information about its metabolism related to toxicity in animals is available. As part of our efforts toward clarifying the role of 1,2-DCP in the development of cancer, we studied the metabolic pathways and the hepatotoxic effect of 1,2-DCP in mice with or without cytochrome P450 2E1 (CYP2E1) activity. In an in vitro reaction system containing liver homogenate, 1,2-DCP was only metabolized by liver tissue of wild-type mice but not by that of cyp2e1-null mice. Furthermore, the kinetics of the solvent in mice revealed a great difference between the two genotypes; 1,2-DCP administration resulted in dose-dependent hepatic damage, as shown biochemically and pathologically, but this effect was only observed in wild-type mice. The nuclear factor κB p52 pathway was involved in the liver response to 1,2-DCP. Our results clearly indicate that the oxidative metabolism of 1,2-DCP in mice is exclusively catalyzed by CYP2E1, and this step is indispensable for the manifestation of the hepatotoxic effect of the solvent. © The Author(s) 2015. JF - Toxicology and industrial health AU - Yanagiba, Yukie AU - Suzuki, Tetsuya AU - Suda, Megumi AU - Hojo, Rieko AU - Gonzalez, Frank J AU - Nakajima, Tamie AU - Wang, Rui-Sheng AD - Division of Health Effects Research, National Institute of Occupational Safety and Health, Kawasaki, Japan. ; Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; College of Life and Health Sciences, Chubu University, Kasugai, Japan. ; Division of Health Effects Research, National Institute of Occupational Safety and Health, Kawasaki, Japan wang@h.jniosh.go.jp. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1589 EP - 1597 VL - 32 IS - 9 KW - Index Medicus KW - DNA damage KW - metabolism KW - 1,2-Dichloropropane KW - CYP2E1 KW - hepatotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814684332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+industrial+health&rft.atitle=Cytochrome+P450+2E1+is+responsible+for+the+initiation+of+1%2C2-dichloropropane-induced+liver+damage.&rft.au=Yanagiba%2C+Yukie%3BSuzuki%2C+Tetsuya%3BSuda%2C+Megumi%3BHojo%2C+Rieko%3BGonzalez%2C+Frank+J%3BNakajima%2C+Tamie%3BWang%2C+Rui-Sheng&rft.aulast=Yanagiba&rft.aufirst=Yukie&rft.date=2016-09-01&rft.volume=32&rft.issue=9&rft.spage=1589&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=1477-0393&rft_id=info:doi/10.1177%2F0748233714568801 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0748233714568801 ER - TY - JOUR T1 - Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models. AN - 1814682235; 27558906 AB - To demonstrate that exosomes (exo) could increase the therapeutic index of doxorubicin (DOX). Exosomes were characterized by nanoparticle tracking analysis and western blot. Tissue toxicity was evaluated by histopathological analysis and drug efficacy by measuring tumor volume. DOX biodistribution was analyzed by MS. Exosomal doxorubicin (exoDOX) avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells. For this reason, mice can be treated with higher concentration of exoDOX thus increasing the efficacy of DOX as demonstrated in breast and ovarian mouse tumors. ExoDOX is safer and more effective than free DOX. Importantly, the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer was utilized for providing a new therapeutic opportunity. JF - Nanomedicine (London, England) AU - Hadla, Mohamad AU - Palazzolo, Stefano AU - Corona, Giuseppe AU - Caligiuri, Isabella AU - Canzonieri, Vincenzo AU - Toffoli, Giuseppe AU - Rizzolio, Flavio AD - Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 2431 EP - 2441 VL - 11 IS - 18 KW - Index Medicus KW - doxorubicin KW - exosomes KW - drug delivery KW - therapeutic index KW - breast and ovarian cancers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814682235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nanomedicine+%28London%2C+England%29&rft.atitle=Exosomes+increase+the+therapeutic+index+of+doxorubicin+in+breast+and+ovarian+cancer+mouse+models.&rft.au=Hadla%2C+Mohamad%3BPalazzolo%2C+Stefano%3BCorona%2C+Giuseppe%3BCaligiuri%2C+Isabella%3BCanzonieri%2C+Vincenzo%3BToffoli%2C+Giuseppe%3BRizzolio%2C+Flavio&rft.aulast=Hadla&rft.aufirst=Mohamad&rft.date=2016-09-01&rft.volume=11&rft.issue=18&rft.spage=2431&rft.isbn=&rft.btitle=&rft.title=Nanomedicine+%28London%2C+England%29&rft.issn=1748-6963&rft_id=info:doi/10.2217%2Fnnm-2016-0154 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.2217/nnm-2016-0154 ER - TY - JOUR T1 - AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma. AN - 1814682153; 26951379 AB - Few prospective studies have assessed the role of bevacizumab and included a control arm with standard treatments for recurrent glioblastoma. We conducted a noncomparative phase II trial (AVAREG) to examine the efficacy of bevacizumab or fotemustine in this setting. Eligible patients were randomized 2:1 to receive bevacizumab (10 mg/kg every 2 weeks) or fotemustine (75 mg/m(2) on days 1, 8, and 15, then 100 mg/m(2) every 3 weeks after a 35-day interval). The primary endpoint was 6-month overall survival (OS) rate (OS-6). No formal efficacy comparison was made between the treatment arms. Ninety-one patients were enrolled (bevacizumab n = 59; fotemustine n = 32). Median age was 57 years (range, 28-78 y), and patients had Eastern Cooperative Oncology Group performance status of 0 (n = 42), 1 (n = 35), or 2 (n = 14). OS-6 rate was 62.1% (95% confidence interval [CI], 48.4-74.5) with bevacizumab and 73.3% (95% CI, 54.1-87.7) with fotemustine. OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors (50% and 85%, respectively), but higher in fotemustine-treated patients (87.5% and 50%, respectively). OS rates at 9 months were 37.9% (95% CI, 25.5-51.6) and 46.7% (95% CI, 28.3-65.7) with bevacizumab and fotemustine, respectively, and median OS was 7.3 months (95% CI, 5.8-9.2) and 8.7 months (95% CI, 6.3-15.4), respectively. Toxicity was as expected with the 2 agents. Single-agent bevacizumab may have a role in patients with recurrent glioblastoma. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. JF - Neuro-oncology AU - Brandes, Alba A AU - Finocchiaro, Gaetano AU - Zagonel, Vittorina AU - Reni, Michele AU - Caserta, Claudia AU - Fabi, Alessandra AU - Clavarezza, Matteo AU - Maiello, Evaristo AU - Eoli, Marica AU - Lombardi, Giuseppe AU - Monteforte, Marta AU - Proietti, Emanuela AU - Agati, Raffaele AU - Eusebi, Vincenzo AU - Franceschi, Enrico AD - Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Bologna, Italy (A.A.B., E.F.); Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy (G.F., M.E.); Department of Clinical and Experimental Oncology, Medical Oncology, Veneto Institute of Oncology- IRCCS Padua, Italy (V.Z., G.L.); Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy (M.R.); Oncology Department, Santa Maria Hospital, Terni, Italy (C.C.); Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy (A.F.); E.O. Ospedale Galliera, Genova, Italy (M.C.); Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (E.M.); OPIS, Palazzo Aliprandi, Desio MB, Italy (M.M.); Roche S.p.A. Medical Affairs and CO, Monza, Italy (E.P.); Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Ospedale Bellaria, Bologna, Italy (R.A.); Department of Biomedical and Neuromotor Science, University of Bologna, Section of Anatomic Pathology M. Malpighi-Bellaria Hospital, Bologna, Italy (V.E.) alba.brandes@yahoo.it. ; Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Bologna, Italy (A.A.B., E.F.); Molecular Neuro-Oncology Unit, IRCCS Foundation Carlo Besta, Milan, Italy (G.F., M.E.); Department of Clinical and Experimental Oncology, Medical Oncology, Veneto Institute of Oncology- IRCCS Padua, Italy (V.Z., G.L.); Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy (M.R.); Oncology Department, Santa Maria Hospital, Terni, Italy (C.C.); Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy (A.F.); E.O. Ospedale Galliera, Genova, Italy (M.C.); Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (E.M.); OPIS, Palazzo Aliprandi, Desio MB, Italy (M.M.); Roche S.p.A. Medical Affairs and CO, Monza, Italy (E.P.); Neuroradiology Department, Bellaria-Maggiore Hospital, Azienda USL-IRCCS Institute of Neurological Sciences, Ospedale Bellaria, Bologna, Italy (R.A.); Department of Biomedical and Neuromotor Science, University of Bologna, Section of Anatomic Pathology M. Malpighi-Bellaria Hospital, Bologna, Italy (V.E.). Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1304 EP - 1312 VL - 18 IS - 9 KW - Index Medicus KW - fotemustine KW - AVAREG KW - bevacizumab KW - overall survival KW - glioblastoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814682153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuro-oncology&rft.atitle=AVAREG%3A+a+phase+II%2C+randomized%2C+noncomparative+study+of+fotemustine+or+bevacizumab+for+patients+with+recurrent+glioblastoma.&rft.au=Brandes%2C+Alba+A%3BFinocchiaro%2C+Gaetano%3BZagonel%2C+Vittorina%3BReni%2C+Michele%3BCaserta%2C+Claudia%3BFabi%2C+Alessandra%3BClavarezza%2C+Matteo%3BMaiello%2C+Evaristo%3BEoli%2C+Marica%3BLombardi%2C+Giuseppe%3BMonteforte%2C+Marta%3BProietti%2C+Emanuela%3BAgati%2C+Raffaele%3BEusebi%2C+Vincenzo%3BFranceschi%2C+Enrico&rft.aulast=Brandes&rft.aufirst=Alba&rft.date=2016-09-01&rft.volume=18&rft.issue=9&rft.spage=1304&rft.isbn=&rft.btitle=&rft.title=Neuro-oncology&rft.issn=1523-5866&rft_id=info:doi/10.1093%2Fneuonc%2Fnow035 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/neuonc/now035 ER - TY - JOUR T1 - Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma. AN - 1814675551; 27501506 AB - Radiotherapy is a good option for inoperable and frail patients diagnosed with endometrial cancer. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of this specific approach. We performed a bibliographic search for articles in English or French which were published in PubMed from the start of this database in January 1969 to identify publications on radiation therapy (RT) as single treatment for localised non-operable carcinoma of the endometrium. The review was completed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Twenty-five reports containing 2694 patients treated with RT as single treatment were identified that fulfilled the selection criteria. Disease-specific survival (DSS) at 5 years was reported for a cohort of 1322 (49.1%) patients. The combined DSS for this group of patients was 78.5% (range: 68.4-92%; 95% confidence interval: 74.5-82.5). External beam radiation therapy (EBRT) combined with brachytherapy (BT) was used in 1278 patients (47.4%), BT alone in 1383 patients (51.3%), and EBRT alone in 33 patients (1.2%). The average occurrence of grade III or worse late toxicity was 3.7% for EBRT + BT, 2.8% for BT alone, and 1.2% for EBRT alone. RT is in terms of disease control and toxicity, an acceptable option for non-surgical candidate patients. Prospective multicentre randomised or observational trials are needed to validate these results. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - European journal of cancer (Oxford, England : 1990) AU - van der Steen-Banasik, E AU - Christiaens, M AU - Shash, E AU - Coens, C AU - Casado, A AU - Herrera, F G AU - Ottevanger, P B AU - European Organisation for Research and Treatment of Cancer, Gynaecological Cancer Group (EORTC-GCG) AD - Radiation Oncology Department, Radiotherapiegroep, Wagnerlaan 47, 6815 AD Arnhem, The Netherlands. Electronic address: E.vanderSteen-Banasik@radiotherapiegroep.nl. ; EORTC HQ, Avenue Emmanuel Mounier 83/11, 1200 Brussels, Belgium; Clinic for Particle Therapy, West German Proton Therapy Center Essen, West German Cancer Center, University Hospital Essen, Am Mühlenbach 1, 45147 Essen, Germany. Electronic address: Melissa.Christiaens@uk-essen.de. ; EORTC HQ, Avenue Emmanuel Mounier 83/11, 1200 Brussels, Belgium; Medical Oncology Department, National Cancer Institute Cairo University, Kasr Al Eini Street, Fom el Khalig, Cairo, Egypt. Electronic address: emad.shash@nci.cu.edu.eg. ; EORTC HQ, Avenue Emmanuel Mounier 83/11, 1200 Brussels, Belgium. Electronic address: Corneel.Coens@eortc.be. ; Medical Oncology Department, University Hospital Clínico San Carlos, Madrid 28040, Spain. Electronic address: AntonioCasado@telefonica.net. ; Radiation Oncology Department, University Hospital of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Fernanda.Herrara@chuv.ch. ; Medical Oncology Department, Radboudumc, Comeniuslaan 4, 6525 HP Nijmegen, The Netherlands. Electronic address: Nelleke.Ottevanger@radboudumc.nl. ; European Organisation for Research and Treatment of Cancer, Gynaecological Cancer Group (EORTC-GCG) Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 172 EP - 181 VL - 65 KW - Index Medicus KW - Genital neoplasms, female KW - Carcinoma, endometrioid KW - Brachytherapy KW - Uterine neoplasms KW - Intracavity radiotherapy KW - Endometrial carcinoma KW - Radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814675551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Systemic+review%3A+Radiation+therapy+alone+in+medical+non-operable+endometrial+carcinoma.&rft.au=van+der+Steen-Banasik%2C+E%3BChristiaens%2C+M%3BShash%2C+E%3BCoens%2C+C%3BCasado%2C+A%3BHerrera%2C+F+G%3BOttevanger%2C+P+B%3BEuropean+Organisation+for+Research+and+Treatment+of+Cancer%2C+Gynaecological+Cancer+Group+%28EORTC-GCG%29&rft.aulast=van+der+Steen-Banasik&rft.aufirst=E&rft.date=2016-09-01&rft.volume=65&rft.issue=&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=1879-0852&rft_id=info:doi/10.1016%2Fj.ejca.2016.07.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ejca.2016.07.005 ER - TY - JOUR T1 - A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer: A suitable tool for preclinical studies. AN - 1814662839; 26704357 AB - Transgenic mouse models designed to recapitulate genetic and pathologic aspects of cancer are useful to study early stages of disease as well as its progression. Among several, two of the most sophisticated models for pancreatic ductal adenocarcinoma (PDAC) are the LSL-Kras(G12D/+);Pdx-1-Cre (KC) and LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre (KPC) mice, in which the Cre-recombinase regulated by a pancreas-specific promoter activates the expression of oncogenic Kras alone or in combination with a mutant p53, respectively. Non-invasive in vivo imaging offers a novel approach to preclinical studies introducing the possibility to investigate biological events in the spatio/temporal dimension. We recently developed a mouse model, MITO-Luc, engineered to express the luciferase reporter gene in cells undergoing active proliferation. In this model, proliferation events can be visualized non-invasively by bioluminescence imaging (BLI) in every body district in vivo. Here, we describe the development and characterization of MITO-Luc-KC- and -KPC mice. In these mice we have now the opportunity to follow PDAC evolution in the living animal in a time frame process. Moreover, by relating in vivo and ex vivo BLI and histopathological data we provide evidence that these mice could represents a suitable tool for pancreatic cancer preclinical studies. Our data also suggest that aberrant proliferation events take place early in pancreatic carcinogenesis, before tumour appearance. Copyright © 2015 Elsevier GmbH. All rights reserved. JF - Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft AU - de Latouliere, Luisa AU - Manni, Isabella AU - Iacobini, Carla AU - Pugliese, Giuseppe AU - Grazi, Gian Luca AU - Perri, Pasquale AU - Cappello, Paola AU - Novelli, Franco AU - Menini, Stefano AU - Piaggio, Giulia AD - Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy. ; Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy. Electronic address: manni@ifo.it. ; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035-1039, Rome 00189, Italy. ; Department of Experimental Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy. ; Department of Molecular Biotechnologies and Health Sciences, University of Turin, Via Nizza 52, Torino 10126, Italy; Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino, Via Santena 5, Torino 10126, Italy. ; Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome 00144, Italy. Electronic address: piaggio@ifo.it. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 2 EP - 8 VL - 207 KW - Index Medicus KW - Disease animal models KW - Comparative pathology KW - Proliferation KW - Pancreatic cancer KW - Molecular imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814662839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+anatomy+%3D+Anatomischer+Anzeiger+%3A+official+organ+of+the+Anatomische+Gesellschaft&rft.atitle=A+bioluminescent+mouse+model+of+proliferation+to+highlight+early+stages+of+pancreatic+cancer%3A+A+suitable+tool+for+preclinical+studies.&rft.au=de+Latouliere%2C+Luisa%3BManni%2C+Isabella%3BIacobini%2C+Carla%3BPugliese%2C+Giuseppe%3BGrazi%2C+Gian+Luca%3BPerri%2C+Pasquale%3BCappello%2C+Paola%3BNovelli%2C+Franco%3BMenini%2C+Stefano%3BPiaggio%2C+Giulia&rft.aulast=de+Latouliere&rft.aufirst=Luisa&rft.date=2016-09-01&rft.volume=207&rft.issue=&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Annals+of+anatomy+%3D+Anatomischer+Anzeiger+%3A+official+organ+of+the+Anatomische+Gesellschaft&rft.issn=1618-0402&rft_id=info:doi/10.1016%2Fj.aanat.2015.11.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.aanat.2015.11.010 ER - TY - JOUR T1 - Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials. AN - 1814656041; 27325863 AB - Neuropathy is a debilitating toxicity associated with various chemotherapy agents. We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in patients treated with taxane-based chemotherapy. We examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy. A total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P < .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patients with no diabetes. In contrast, patients with autoimmune disease were half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy. We found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of neuropathy. Patients with diabetic complications may choose to avoid paclitaxel or taxane plus platinum combination therapies if other efficacious options exist. © 2016 by American Society of Clinical Oncology. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Hershman, Dawn L AU - Till, Cathee AU - Wright, Jason D AU - Awad, Danielle AU - Ramsey, Scott D AU - Barlow, William E AU - Minasian, Lori M AU - Unger, Joseph AD - Dawn L. Hershman, Jason D. Wright, and Danielle Awad, Columbia University Medical Center, New York, NY; Cathee Till, Scott D. Ramsey, and Joseph Unger, Fred Hutchinson Cancer Research Center; William E. Barlow, University of Washington, Seattle, WA; and Lori M. Minasian, National Cancer Institute, Bethesda, MD. dlh23@columbia.edu. ; Dawn L. Hershman, Jason D. Wright, and Danielle Awad, Columbia University Medical Center, New York, NY; Cathee Till, Scott D. Ramsey, and Joseph Unger, Fred Hutchinson Cancer Research Center; William E. Barlow, University of Washington, Seattle, WA; and Lori M. Minasian, National Cancer Institute, Bethesda, MD. Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 3014 EP - 3022 VL - 34 IS - 25 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814656041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Comorbidities+and+Risk+of+Chemotherapy-Induced+Peripheral+Neuropathy+Among+Participants+65+Years+or+Older+in+Southwest+Oncology+Group+Clinical+Trials.&rft.au=Hershman%2C+Dawn+L%3BTill%2C+Cathee%3BWright%2C+Jason+D%3BAwad%2C+Danielle%3BRamsey%2C+Scott+D%3BBarlow%2C+William+E%3BMinasian%2C+Lori+M%3BUnger%2C+Joseph&rft.aulast=Hershman&rft.aufirst=Dawn&rft.date=2016-09-01&rft.volume=34&rft.issue=25&rft.spage=3014&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/10.1200%2FJCO.2015.66.2346 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1200/JCO.2015.66.2346 ER - TY - JOUR T1 - Anxiously elaborating the social percept: Anxiety and age differences in functional connectivity of the fusiform face area in a peer evaluation paradigm AN - 1814175921 AB - Objectives Social anxiety disorder involves biased cognition and altered neural responses to social stimuli. This study further assesses the precise ways in which neural activation associated with perceptual processing of faces differs in socially anxious and non-anxious individuals. Method Functional magnetic resonance imaging data were acquired as 90 anxious or healthy juveniles and adults performed a peer feedback task. Psychophysiological functional connectivity analysis was performed on all participants using a seed placed in the right fusiform face area (rFFA). Results Social anxiety was associated with enhanced rFFA coupling in several areas of ventral visual stream when viewing feedback from peers previously rejected by participants; healthy participants demonstrated the opposite pattern. Moreover, anxious juveniles had greater positive rFFA coupling with right inferior temporal gyrus during feedback from rejected peers; other groups showed the opposite pattern. Finally, anxious juveniles had greater positive rFFA coupling with pregenual anterior cingulate cortex during negative peer feedback; other groups displayed the opposite pattern. Conclusions Anxious individuals, and juveniles in particular, may dedicate more neural resources to stimuli associated with potentially negative, relative to positive, social outcomes; non-anxious individuals may do the opposite. JF - Australian Journal of Psychology AU - Beer, Joanne C AU - Smith, Ashley R AU - Jarcho, Johanna M AU - Chen, Gang AU - Reynolds, Richard C AU - Pine, Daniel S AU - Nelson, Eric E AD - Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA ; Scientific and Statistical Computing Core, National Institute of Mental Health, Bethesda, MD, USA ; Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 154 EP - 165 CY - Melbourne PB - Wiley Subscription Services, Inc. VL - 68 IS - 3 SN - 0004-9530 KW - Psychology KW - Age differences KW - Anxiety disorders KW - Bias KW - Cognition KW - Cortex KW - Feedback KW - Functional connectivity KW - Functional magnetic resonance imaging KW - Magnetic resonance imaging KW - Negative feedback KW - Peer reviews KW - Psychophysiological aspects KW - Social anxiety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814175921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Australian+Journal+of+Psychology&rft.atitle=Anxiously+elaborating+the+social+percept%3A+Anxiety+and+age+differences+in+functional+connectivity+of+the+fusiform+face+area+in+a+peer+evaluation+paradigm&rft.au=Beer%2C+Joanne+C%3BSmith%2C+Ashley+R%3BJarcho%2C+Johanna+M%3BChen%2C+Gang%3BReynolds%2C+Richard+C%3BPine%2C+Daniel+S%3BNelson%2C+Eric+E&rft.aulast=Beer&rft.aufirst=Joanne&rft.date=2016-09-01&rft.volume=68&rft.issue=3&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=Australian+Journal+of+Psychology&rft.issn=00049530&rft_id=info:doi/10.1111%2Fajpy.12130 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © 2016 The Australian Psychological Society N1 - Last updated - 2016-08-26 DO - http://dx.doi.org/10.1111/ajpy.12130 ER - TY - JOUR T1 - Results of treatment of lymphoblastic lymphoma at the children cancer hospital Egypt - A single center experience. AN - 1814142485; 27339800 AB - Introduction Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are neoplasms of immature B or T-cell precursors. They are considered as a unique biological entity in the 2008 World Health Organization Classification of Hematologic Neoplasm. Both entities are arbitrarily separated by a cut-off point of 20-25% of blast cells in the bone marrow. Treatment of LBL has evolved over time from conventional high-grade NHL schedules to ALL-derived protocols. The aim of this work is to report the clinical characteristics, overall survival (OS), event free survival (EFS), and common chemotherapy toxicities of lymphoblastic lymphoma (LBL) patients during a 5.5year period. Patients and methods A Retrospective review of patient's charts diagnosed and treated as LBL during the period between July 2007 and end of December 2012 was done. Patients were treated according to St. Jude Children Research Hospital ALL Total Therapy XV protocol, standard risk arm. Results This study included 77 patients. T-cell LBL patients were 67, while 10 were of B-cell origin. The median age at diagnosis was 9years (95% CI: 7-10). The majority were males 54/77. Stage III patients were 51, stage IV 13, stage II 11 and stage I 2 patients. Two patients were excluded from analysis as they died before receiving chemotherapy. Complete remission post induction chemotherapy was seen in 22 patients considered early responders, and partial remission in 55 considered late responders. With a median follow up duration of 47months (95% CI: 38-56), the 4year overall survival and event free survival were 86.45% (95% CI: 73.78-94.09) and 82.18% (95% CI: 69.25-90.61) respectively. Twelve patients died during the study period; 2 early deaths before starting chemotherapy from disease progression, 2 in CR due to chemotherapy related toxicity and 8 from disease progression. All the relapsed patients were T-cell, had advanced disease at presentation (6 with stage III; 2 with stage IV). Two patients (2.6%) had isolated local, BM, and CNS relapse each, while 1 (1.3%) had both local and CNS relapse. Disease recurrence was local in 3 patients (3.9%), and systemic in 5 (6.4%), while it was early in 6 (7.8%), and late in 2 (2.6%) patients. Median time to disease progression was 20months (range 5-39months). All relapsed patients did not survive salvage chemotherapy. The most common chemotherapy toxicities were cerebral venous thrombosis (20%), followed by bone infarcts (10.6%), and avascular necrosis (AVN) of head of femur (9.3%). One patient developed secondary acute myeloid leukemia after 3years of FU with unfavorable cytogenetic abnormalities. Conclusion Results of treatment of LBL on the St Jude's total therapy XV study are comparable to most of the similar reported studies. Outcome of relapsing patients is extremely poor, hence there is a need to identify biologic or clinical prognostic factors including minimal residual tumor to better evaluate chemotherapy response. Steroid induced AVN, and cerebral vascular thrombosis were the main chemotherapeutic adverse events. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved. JF - Journal of the Egyptian National Cancer Institute AU - Rahman Sayed, Hany Abdel AU - Sedky, Mohamed AU - Hamoda, Asmaa AU - Kinaaie, Naglaa El AU - Wakeel, Madeha El AU - Hesham, Dina AD - Department of Pediatric Oncology, National Cancer Institute, Cairo University and Children Cancer Hospital, Egypt. Electronic address: hanyrahman@hotmail.com. ; Department of Pediatrics, National Research Center and Children Cancer Hospital, Egypt. ; Department of Pediatric Oncology, National Cancer Institute, Cairo University and Children Cancer Hospital, Egypt. ; Department of Pathology, National Cancer Institute, Cairo University and Children Cancer Hospital, Egypt. ; Department of Radiodiagnosis, National Cancer Institute, Cairo University and Children Cancer Hospital, Egypt. ; Department of Clinical Research, Children Cancer Hospital, Egypt. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 175 EP - 181 VL - 28 IS - 3 SN - 1110-0362, 1110-0362 KW - Index Medicus KW - Pediatric KW - Children cancer hospital Egypt KW - Lymphoblastic lymphoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814142485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+Egyptian+National+Cancer+Institute&rft.atitle=Results+of+treatment+of+lymphoblastic+lymphoma+at+the+children+cancer+hospital+Egypt+-+A+single+center+experience.&rft.au=Rahman+Sayed%2C+Hany+Abdel%3BSedky%2C+Mohamed%3BHamoda%2C+Asmaa%3BKinaaie%2C+Naglaa+El%3BWakeel%2C+Madeha+El%3BHesham%2C+Dina&rft.aulast=Rahman+Sayed&rft.aufirst=Hany&rft.date=2016-09-01&rft.volume=28&rft.issue=3&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Egyptian+National+Cancer+Institute&rft.issn=11100362&rft_id=info:doi/10.1016%2Fj.jnci.2016.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jnci.2016.05.001 ER - TY - JOUR T1 - Examining the Efficacy of HIV Risk-Reduction Counseling on the Sexual Risk Behaviors of a National Sample of Drug Abuse Treatment Clients: Analysis of Subgroups AN - 1813588742 AB - HIV counseling with testing has been part of HIV prevention in the U.S. since the 1980s. Despite the long-standing history of HIV testing with prevention counseling, the CDC released HIV testing recommendations for health care settings contesting benefits of prevention counseling with testing in reducing sexual risk behaviors among HIV-negatives in 2006. Efficacy of brief HIV risk-reduction counseling (RRC) in decreasing sexual risk among subgroups of substance use treatment clients was examined using multi-site RCT data. Interaction tests between RRC and subgroups were performed; multivariable regression evaluated the relationship between RRC (with rapid testing) and sex risk. Subgroups were defined by demographics, risk type and level, attitudes/perceptions, and behavioral history. There was an effect (p < .0028) of counseling on number of sex partners among some subgroups. Certain subgroups may benefit from HIV RRC; this should be examined in studies with larger sample sizes, designed to assess the specific subgroup(s). JF - AIDS and Behavior AU - Gooden, Lauren AU - Metsch, Lisa R AU - Pereyra, Margaret R AU - Malotte, C Kevin AU - Haynes, Louise F AU - Douaihy, Antoine AU - Chally, Jack AU - Mandler, Raul N AU - Feaster, Daniel J AD - Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Sociomedical Sciences, Mailman School of Public Health, Miami Research Center, Columbia University, Miami, FL, USA ; Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA ; Department of Health Science, California State University, Long Beach, CA, USA ; Department of Psychiatry and Behavioral Science, Medical University of South Carolina, Charleston, SC, USA ; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA ; Johns Hopkins University, Baltimore, MD, USA; EMMES Corporation, Inc., Rockville, MD, USA ; National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA ; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA ; Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Sociomedical Sciences, Mailman School of Public Health, Miami Research Center, Columbia University, Miami, FL, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 1893 EP - 1906 CY - New York PB - Springer Science & Business Media VL - 20 IS - 9 SN - 1090-7165 KW - Psychology KW - HIV KW - Prevention KW - Counseling KW - Substance use KW - Drug treatment KW - Acquired Immune Deficiency Syndrome KW - Drug Abuse KW - Health Care Services KW - Sexual Behavior KW - Risk KW - Substance Abuse KW - United States--US KW - 6129:addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813588742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=Examining+the+Efficacy+of+HIV+Risk-Reduction+Counseling+on+the+Sexual+Risk+Behaviors+of+a+National+Sample+of+Drug+Abuse+Treatment+Clients%3A+Analysis+of+Subgroups&rft.au=Gooden%2C+Lauren%3BMetsch%2C+Lisa+R%3BPereyra%2C+Margaret+R%3BMalotte%2C+C+Kevin%3BHaynes%2C+Louise+F%3BDouaihy%2C+Antoine%3BChally%2C+Jack%3BMandler%2C+Raul+N%3BFeaster%2C+Daniel+J&rft.aulast=Gooden&rft.aufirst=Lauren&rft.date=2016-09-01&rft.volume=20&rft.issue=9&rft.spage=1893&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1300-6 LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-12-07 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10461-016-1300-6 ER - TY - JOUR T1 - Social and Structural Determinants of Cervical Health among Women Engaged in HIV Care AN - 1813588544 AB - Cervical cancer prevention/control efforts among women living with HIV/AIDS (WLH) are socially and structurally challenging. Healthcare access and perceived HIV stigma and discrimination are factors that may challenge risk reduction efforts. This study examined socio-structural determinants of cervical cancer screening among women engaged in HIV care. One hundred forty-five WLH seeking health/social services from AIDS Service Organizations in the southeastern US completed a questionnaire assessing factors related to cervical cancer prevention/control. Ninety percent were African American, mean age 46.15 ± 10.65 years. Eighty-one percent had a Pap test <1 year ago. Low healthcare access was positively associated with having a Pap test <1 year ago, (Odds ratio [OR] 3.80; 95 % Confidence interval [CI] 1.34-10.78). About 36 % reported [greater than or equal to]2 Pap tests during the first year after HIV diagnosis. Lower educational attainment was positively associated with having [greater than or equal to]2 Pap tests, OR 3.22; CI 1.08-9.62. Thirty-five percent reported more frequent Pap tests after diagnosis. Lower income was moderately associated with more frequent Pap tests post-diagnosis, OR 2.47; CI .98-6.23. Findings highlight the successes of HIV initiatives targeting socio-economically disadvantaged women and provide evidence that health policy aimed at providing and expanding healthcare access for vulnerable WLH has beneficial health implications. JF - AIDS and Behavior AU - Bynum, Shalanda A AU - Wigfall, Lisa T AU - Brandt, Heather M AU - Julious, Carmen Hampton AU - Glover, Saundra H AU - Hébert, James R AD - Division of AIDS, Behavioral, and Population Sciences, Center for Scientific Review, National Institutes of Health, Bethesda, MD, USA ; Institute for Partnerships to Eliminate Health Disparities, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; South Carolina Statewide Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA ; South Carolina Statewide Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Department of Health Promotion, Education and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA ; Palmetto AIDS Life Support Services, Inc., Columbia, SC, USA ; Institute for Partnerships to Eliminate Health Disparities, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA ; South Carolina Statewide Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA ; Division of AIDS, Behavioral, and Population Sciences, Center for Scientific Review, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 2101 EP - 2109 CY - New York PB - Springer Science & Business Media VL - 20 IS - 9 SN - 1090-7165 KW - Psychology KW - Cervical cancer KW - Papanicolaou test KW - HIV/AIDS KW - Health status disparities KW - Women KW - Black Americans KW - Educational Attainment KW - Disadvantaged KW - Health Care Utilization KW - Income KW - Social Services KW - Access KW - Health Care Services Policy KW - Vulnerability KW - Tests KW - Acquired Immune Deficiency Syndrome KW - Prevention KW - Discrimination KW - Females KW - Low Income Groups KW - Cancer KW - United States--US KW - 6129:addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813588544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=Social+and+Structural+Determinants+of+Cervical+Health+among+Women+Engaged+in+HIV+Care&rft.au=Bynum%2C+Shalanda+A%3BWigfall%2C+Lisa+T%3BBrandt%2C+Heather+M%3BJulious%2C+Carmen+Hampton%3BGlover%2C+Saundra+H%3BH%C3%A9bert%2C+James+R&rft.aulast=Bynum&rft.aufirst=Shalanda&rft.date=2016-09-01&rft.volume=20&rft.issue=9&rft.spage=2101&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1345-6 LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-12-07 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10461-016-1345-6 ER - TY - JOUR T1 - HPTN 068: A Randomized Control Trial of a Conditional Cash Transfer to Reduce HIV Infection in Young Women in South Africa--Study Design and Baseline Results AN - 1813587855 AB - Young women in South Africa are at high risk for HIV infection. Cash transfers offer promise to reduce HIV risk. We present the design and baseline results from HPTN 068, a phase III, individually randomized trial to assess the effect of a conditional cash transfer on HIV acquisition among South African young women. A total of 2533 young women were randomized to receive a monthly cash transfer conditional on school attendance or to a control group. A number of individual-, partner-, household- and school-level factors were associated with HIV and HSV-2 infection. After adjusting for age, all levels were associated with an increased odds of HIV infection with partner-level factors conveying the strongest association (aOR 3.05 95 % CI 1.84-5.06). Interventions like cash transfers that address structural factors such as schooling and poverty have the potential to reduce HIV risk in young women in South Africa. JF - AIDS and Behavior AU - Pettifor, Audrey AU - Macphail, Catherine AU - Selin, Amanda AU - Gómez-olivé, F Xavier AU - Rosenberg, Molly AU - Wagner, Ryan G AU - Mabuza, Wonderful AU - Hughes, James P AU - Suchindran, Chirayath AU - Piwowar-manning, Estelle AU - Wang, Jing AU - Twine, Rhian AU - Daniel, Tamu AU - Andrew, Philip AU - Laeyendecker, Oliver AU - Agyei, Yaw AU - Tollman, Stephen AU - Kahn, Kathleen AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA; MRC/Wits Rural Public Health and Health Transitions Unit, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA ; MRC/Wits Rural Public Health and Health Transitions Unit, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa; School of Health, University of New England, Armidale, Australia ; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA ; MRC/Wits Rural Public Health and Health Transitions Unit, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa ; Center for Population and Development Studies, Harvard University, Cambridge, MA, USA ; SCHARP, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA ; HPTN Laboratory Center, Johns Hopkins University, Baltimore, MD, USA ; SCHARP, Seattle, WA, USA ; FHI360, Durham, NC, USA ; Laboratory of Immunoregulation, NIAID, NIH, Baltimore, MD, USA; Departments of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD, USA ; MRC/Wits Rural Public Health and Health Transitions Unit, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Umeå Centre for Global Health Research, Umeå, Sweden; INDEPTH Network, Accra, Ghana ; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA; MRC/Wits Rural Public Health and Health Transitions Unit, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 1863 EP - 1882 CY - New York PB - Springer Science & Business Media VL - 20 IS - 9 SN - 1090-7165 KW - Psychology KW - HIV KW - Adolescents KW - South Africa KW - Young women KW - HIV prevention KW - Cash transfers KW - Education KW - Acquired Immune Deficiency Syndrome KW - Poverty KW - Risk KW - Females KW - School Attendance KW - 6129:addiction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813587855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=HPTN+068%3A+A+Randomized+Control+Trial+of+a+Conditional+Cash+Transfer+to+Reduce+HIV+Infection+in+Young+Women+in+South+Africa--Study+Design+and+Baseline+Results&rft.au=Pettifor%2C+Audrey%3BMacphail%2C+Catherine%3BSelin%2C+Amanda%3BG%C3%B3mez-oliv%C3%A9%2C+F+Xavier%3BRosenberg%2C+Molly%3BWagner%2C+Ryan+G%3BMabuza%2C+Wonderful%3BHughes%2C+James+P%3BSuchindran%2C+Chirayath%3BPiwowar-manning%2C+Estelle%3BWang%2C+Jing%3BTwine%2C+Rhian%3BDaniel%2C+Tamu%3BAndrew%2C+Philip%3BLaeyendecker%2C+Oliver%3BAgyei%2C+Yaw%3BTollman%2C+Stephen%3BKahn%2C+Kathleen&rft.aulast=Pettifor&rft.aufirst=Audrey&rft.date=2016-09-01&rft.volume=20&rft.issue=9&rft.spage=1863&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-015-1270-0 LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-12-07 N1 - SubjectsTermNotLitGenreText - South Africa DO - http://dx.doi.org/10.1007/s10461-015-1270-0 ER - TY - JOUR T1 - Nutritional supplementation to reduce child aggression: a randomized, stratified, single-blind, factorial trial AN - 1813218887 AB - Background While some studies suggest that nutritional supplementation may reduce aggressive behavior in children, they have not examined whether its efficacy may be enhanced in conjunction with other treatment approaches. This study tests the hypothesis that a nutritional supplementation of omega-3, multivitamins, and minerals over 3 months, combined with cognitive behavior therapy, will reduce childhood aggression. Methods In this randomized, single-blind, stratified, factorial trial, a high-risk community sample of 290 children aged 11-12 years were randomized into Nutrition only, cognitive behavioral therapy (CBT) only, Nutrition + CBT, and Control groups. The primary outcome measures of child- and parent-reported aggressive and antisocial behavior were collected at 0 months (baseline), 3 months (end of treatment), 6 months (3 months posttreatment), and 12 months (9 months posttreatment). The trial ('Healthy Brains & Behavior: Understanding and Treating Youth Aggression (HBB)' was registered at ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT00842439 Results For child self-reports, children in the Nutrition only group showed reduced externalizing behavior compared to Controls at 3 months. At 6 months, the Nutrition + CBT group scored lower on externalizing behavior compared to both CBT only and Control groups. Findings were more in evidence for an Aggressive-Reactive form of antisocial behavior than for a Callous-Proactive form. Effect sizes were in the small-to-medium range (d = -.33 to -.37). Group differences were not sustained 9 months posttreatment, and no other effects were significant. Conclusions Findings provide some limited support for the efficacy of omega-3, vitamin, and mineral supplementation in reducing aggressive behavior in children, and represent the first evaluation of nutritional supplements in conjunction with CBT. JF - Journal of Child Psychology and Psychiatry AU - Raine, Adrian AU - Cheney, Rose A AU - Ho, Ringo AU - Portnoy, Jill AU - Liu, Jianghong AU - Soyfer, Liana AU - Hibbeln, Joseph AU - Richmond, Therese S AD - Departments of Criminology, Psychiatry, and Psychology, University of Pennsylvania, Philadelphia, PA, USA ; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA ; Division of Psychology, Nanyang Technological University, Singapore City, Singapore ; Department of Criminology, University of Pennsylvania, Philadelphia, PA, USA ; School of Nursing, University of Pennsylvania, Philadelphia, PA, USA ; Section on Nutritional Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA ; Departments of Criminology, Psychiatry, and Psychology, University of Pennsylvania, Philadelphia, PA, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 1038 EP - 1046 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 9 KW - Psychology KW - High risk KW - Nutrition KW - Aggression KW - Efficacy KW - Externalizing behaviour KW - Minerals KW - Vitamin supplements KW - Antisocial behaviour KW - Young people KW - Aggressive children KW - Cognitive behaviour therapy KW - Childhood KW - Treatment methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813218887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Nutritional+supplementation+to+reduce+child+aggression%3A+a+randomized%2C+stratified%2C+single-blind%2C+factorial+trial&rft.au=Raine%2C+Adrian%3BCheney%2C+Rose+A%3BHo%2C+Ringo%3BPortnoy%2C+Jill%3BLiu%2C+Jianghong%3BSoyfer%2C+Liana%3BHibbeln%2C+Joseph%3BRichmond%2C+Therese+S&rft.aulast=Raine&rft.aufirst=Adrian&rft.date=2016-09-01&rft.volume=57&rft.issue=9&rft.spage=1038&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12565 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/jcpp.12565 ER - TY - JOUR T1 - Attention bias in the developmental unfolding of post-traumatic stress symptoms in young children at risk AN - 1813218882 AB - Background Threat-related attention bias relates to anxiety and posttraumatic stress symptoms in adults and adolescents, but few longitudinal studies examine such associations in young children. This study examines prospective relations among attention bias, trauma exposure, and anxiety and trauma symptoms in a sample previously reported to manifest cross-sectional associations between attention bias and observed anxiety at preschool age. Methods Young children [mean (MN) = 5.0, ±0.7 years, n = 208] from a community-based sample completed the dot-probe task to assess their attention biases in response to angry faces. At baseline (T1) and at follow-up approximately 9 months later (T2), anxiety and trauma exposure (i.e. violent and noninterpersonal events) and symptoms were assessed by maternal report. Results Neither attention bias nor baseline or recent trauma exposure predicted later anxiety. In contrast, attention bias toward threat and recent trauma exposure significantly predicted later trauma symptoms. There was evidence of symptom specificity such that attention bias toward threat significantly predicted hyperarousal and dissociation, but not avoidance or re-experiencing symptoms. Finally, moderation analyses indicated that the relationship between attention bias and trauma symptoms may differ according to children's experiences of probable abuse. Conclusions Attention profiles and trauma exposure may increase the risk that young children will develop trauma symptoms. Individual differences in these attentional patterns and children's exposure history may impact outcomes among high-risk children with potential implications for intervention. JF - Journal of Child Psychology and Psychiatry AU - Briggs-Gowan, Margaret J AU - Grasso, Damion AU - Bar-Haim, Yair AU - Voss, Joel AU - McCarthy, Kimberly J AU - Pine, Daniel S AU - Wakschlag, Lauren S AD - Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA ; School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel ; Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA ; Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD, USA ; Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 1083 EP - 1091 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 9 KW - Psychology KW - High risk KW - Psychological trauma KW - Young children KW - At risk KW - Moderation KW - Response bias KW - Posttraumatic stress disorder KW - Attentional bias KW - Child abuse KW - Preschool children KW - Hyperarousal KW - Individual differences KW - Anxiety KW - Dissociation KW - Avoidance KW - Traumatic stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813218882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Attention+bias+in+the+developmental+unfolding+of+post-traumatic+stress+symptoms+in+young+children+at+risk&rft.au=Briggs-Gowan%2C+Margaret+J%3BGrasso%2C+Damion%3BBar-Haim%2C+Yair%3BVoss%2C+Joel%3BMcCarthy%2C+Kimberly+J%3BPine%2C+Daniel+S%3BWakschlag%2C+Lauren+S&rft.aulast=Briggs-Gowan&rft.aufirst=Margaret&rft.date=2016-09-01&rft.volume=57&rft.issue=9&rft.spage=1083&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12577 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1111/jcpp.12577 ER - TY - JOUR T1 - Future HIV Mentoring Programs to Enhance Diversity AN - 1813138756 AB - Issue Title: Securing the Future: Mentoring to Diversify the Biomedical HIV Research Workforce This paper proposes a general template to guide future mentoring program development addressing: (i) considerations to ensure an adequate research workforce; (ii) key guidelines and principles of mentoring; and (iii) use of a logic model to develop program milestones, outcomes and evaluation. We focus on these areas to guide and inform the most effective mentoring program components, which we find to be more helpful than identifying specific features and ingredients. Although the focus is on the development of a new generation of investigators from diverse backgrounds, this template may also apply to mentoring programs for other investigators and for disciplines beyond HIV. JF - AIDS and Behavior AU - Stoff, David M AU - Cargill, Victoria A AD - Division of AIDS Research, National Institute of Mental Health, Bethesda, USA ; Office of AIDS Research, National Institutes of Health, Bethesda, USA ; Division of AIDS Research, National Institute of Mental Health, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 318 EP - 325 CY - New York PB - Springer Science & Business Media VL - 20 SN - 1090-7165 KW - Psychology KW - Research mentoring program development KW - Diversity KW - HIV research workforce KW - Acquired Immune Deficiency Syndrome KW - Biomedicine KW - Cultural Pluralism KW - Program Evaluation KW - Logic KW - Mentoring UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813138756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=AIDS+and+Behavior&rft.atitle=Future+HIV+Mentoring+Programs+to+Enhance+Diversity&rft.au=Stoff%2C+David+M%3BCargill%2C+Victoria+A&rft.aulast=Stoff&rft.aufirst=David&rft.date=2016-09-01&rft.volume=20&rft.issue=&rft.spage=318&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1502-y LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-23 DO - http://dx.doi.org/10.1007/s10461-016-1502-y ER - TY - JOUR T1 - Advancing the Progress of Mentoring for Diversity in AIDS Research: Warming the Mentoring Climate AN - 1813138739 AB - Issue Title: Securing the Future: Mentoring to Diversify the Biomedical HIV Research Workforce JF - AIDS and Behavior AU - Valantine, Hannah A AD - National Institutes of Health, Bethesda, MD, USA ; National Institutes of Health, Bethesda, MD, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 219 EP - 221 CY - New York PB - Springer Science & Business Media VL - 20 SN - 1090-7165 KW - Psychology KW - Acquired Immune Deficiency Syndrome KW - Biomedicine KW - Cultural Pluralism KW - Mentoring KW - 6126:acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813138739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=Advancing+the+Progress+of+Mentoring+for+Diversity+in+AIDS+Research%3A+Warming+the+Mentoring+Climate&rft.au=Valantine%2C+Hannah+A&rft.aulast=Valantine&rft.aufirst=Hannah&rft.date=2016-09-01&rft.volume=20&rft.issue=&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1490-y LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-09-07 DO - http://dx.doi.org/10.1007/s10461-016-1490-y ER - TY - JOUR T1 - Building a More Diverse Workforce in HIV/AIDS Research: The Time has Come AN - 1813138738 AB - Issue Title: Securing the Future: Mentoring to Diversify the Biomedical HIV Research Workforce Investigators from diverse racial and ethnic backgrounds are grossly underrepresented in the nation's biomedical research enterprise. Projections of current demographic trends suggest that population growth rates of minority populations will outpace that of the Caucasian population by 2060. Thus, this workforce will remain a poor reflection of the U.S. population. As a result of this underrepresentation of all sectors of the U.S. populace, the majority of the HIV research involving minority populations--those disproportionately impacted by HIV infection--will be conducted by investigators who do not resemble them. Although this does not necessarily preclude scientifically valid and important research, it produces research without the important cultural and contextual issues that can enhance the utility and generalizability of specific findings or interventions. The goal of this review is to not only raise awareness of the small numbers of minority investigators engaged in biomedical research, but also to identify the challenges to recruiting and retaining these investigators. In this article, while we discuss issues of diversity in general, the focus will be upon the mental health aspects of the HIV epidemic for illustrative purposes: to demonstrate the issues associated with enhancing investigator diversity as a strategy for remediating the chronic shortage of historically underrepresented investigators in scientific research. After presenting the magnitude of the problem and a rationale for enhancing diversity of the biomedical research workforce, we identify a number of potential reasons and challenges for the shortage of minority investigators. Aspects of the mentoring process, together with ten key suggestions, are discussed as the backdrop for the supplement papers that follow (dealing with mentoring principles, challenges, and mentoring-related issues on mentee, mentor, mentee-mentor relationship, and programs). By identifying these realities we hope to: (1) promote greater discussions of these challenges in academic institutions and settings; (2) suggest meaningful strategies to address these challenges; and (3) foster a national discussion about the long-term investment necessary for permanent change, as there are no easy 'fixes' for these challenges. JF - AIDS and Behavior AU - Stoff, David M AU - Cargill, Victoria A AD - Division of AIDS Research, National Institute of Mental Health, Bethesda, USA ; Office of AIDS Research, National Institutes of Health, Bethesda, USA ; Division of AIDS Research, National Institute of Mental Health, Bethesda, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 222 EP - 230 CY - New York PB - Springer Science & Business Media VL - 20 SN - 1090-7165 KW - Psychology KW - Diversity KW - Mentoring KW - Research workforce KW - HIV/AIDS KW - Health Problems KW - Cultural Pluralism KW - Consciousness KW - Population Growth KW - Mental Health KW - Scientific Research KW - Medical Research KW - Acquired Immune Deficiency Syndrome KW - Ethnicity KW - Biomedicine KW - Will KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813138738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=AIDS+and+Behavior&rft.atitle=Building+a+More+Diverse+Workforce+in+HIV%2FAIDS+Research%3A+The+Time+has+Come&rft.au=Stoff%2C+David+M%3BCargill%2C+Victoria+A&rft.aulast=Stoff&rft.aufirst=David&rft.date=2016-09-01&rft.volume=20&rft.issue=&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-016-1501-z LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-23 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10461-016-1501-z ER - TY - JOUR T1 - Rilpivirine Pharmacokinetics Without and With Darunavir/Ritonavir Once Daily in Adolescents and Young Adults. AN - 1812889226; 27187753 AB - Rilpivirine (RPV), a recently developed, once daily human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor, is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the PK interactions between RPV and DRV/r once daily in adolescents and young adults. Human immunodeficiency virus-infected subjects 12 to <24 years old receiving a stable background therapy including RPV 25 mg once daily without or combined with DRV/r 800/100 mg once daily were enrolled. Intensive 24-hour blood sampling was performed, and PK indices were determined using noncompartmental analysis. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen. Fifteen subjects receiving RPV without and 14 subjects with DRV/r were enrolled. When dosed without DRV/r, the RPV geometric mean (90% confidence interval) for RPV AUC0-24, Cmax and C24 h were 2.38 μg h/mL (1.92-2.94), 0.14 μg/mL (0.12-0.18) and 0.07 μg/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC24, Cmax and C24 h were 6.74 μg h/mL (4.89-9.28), 0.39 μg/mL (0.27-0.57) and 0.23 μg/mL (0.17-0.32), respectively, well above the target ranges based on adult data. DRV/r PK was not affected by coadministration of RPV. RPV PK in this adolescent population was similar to adults when dosed without DRV/r. DRV/r coadministration increased RPV exposure 2- to 3-fold, indicating that drug-related side effects should be closely monitored. JF - The Pediatric infectious disease journal AU - Foca, Marc AU - Yogev, Ram AU - Wiznia, Andrew AU - Hazra, Rohan AU - Jean-Philippe, Patrick AU - Graham, Bobbie AU - Britto, Paula AU - Carey, Vincent J AU - King, Jennifer AU - Acosta, Edward P AU - Cressey, Tim R AU - IMPAACT P1058A Team AD - From the *Columbia University Medical Center, New York, NY; †Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; ‡Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY; §National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Pediatric Infectious Disease Branch, Bethesda, MD; ¶HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to NIAID, NIH, DHHS, Bethesda, MD; ‖Frontier Science & Technology, Amherst, NY; **Harvard School of Public Health, Boston, MA; ††Abbvie, Chicago, IL; ‡‡The University of Alabama at Birmingham, Birmingham, AL; and §§Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. ; IMPAACT P1058A Team Y1 - 2016/09// PY - 2016 DA - September 2016 SP - e271 EP - e274 VL - 35 IS - 9 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812889226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Rilpivirine+Pharmacokinetics+Without+and+With+Darunavir%2FRitonavir+Once+Daily+in+Adolescents+and+Young+Adults.&rft.au=Foca%2C+Marc%3BYogev%2C+Ram%3BWiznia%2C+Andrew%3BHazra%2C+Rohan%3BJean-Philippe%2C+Patrick%3BGraham%2C+Bobbie%3BBritto%2C+Paula%3BCarey%2C+Vincent+J%3BKing%2C+Jennifer%3BAcosta%2C+Edward+P%3BCressey%2C+Tim+R%3BIMPAACT+P1058A+Team&rft.aulast=Foca&rft.aufirst=Marc&rft.date=2016-09-01&rft.volume=35&rft.issue=9&rft.spage=e271&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=1532-0987&rft_id=info:doi/10.1097%2FINF.0000000000001214 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-16 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1097/INF.0000000000001214 ER - TY - JOUR T1 - Dysregulated axonal RNA translation in amyotrophic lateral sclerosis. AN - 1812888799; 27038103 AB - Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease that has been associated with a diverse array of genetic changes. Prominent among these are mutations in RNA-binding proteins (RBPs) or repeat expansions that give rise to toxic RNA species. RBPs are additionally central components of pathologic aggregates that constitute a disease hallmark, suggesting that dysregulation of RNA metabolism underlies disease progression. In the context of neuronal physiology, transport of RNAs and localized RNA translation in axons are fundamental to neuronal survival and function. Several lines of evidence suggest that axonal RNA translation is a central process perturbed by various pathogenic events associated with ALS. Dysregulated translation of specific RNA groups could underlie feedback effects that connect and reinforce disease manifestations. Among such candidates are RNAs encoding proteins involved in the regulation of microtubule dynamics. Further understanding of axonally dysregulated RNA targets and of the feedback mechanisms they induce could provide useful therapeutic insights. WIREs RNA 2016, 7:589-603. doi: 10.1002/wrna.1352 For further resources related to this article, please visit the WIREs website. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Wiley interdisciplinary reviews. RNA AU - Yasuda, Kyota AU - Mili, Stavroula AD - Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 589 EP - 603 VL - 7 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812888799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Wiley+interdisciplinary+reviews.+RNA&rft.atitle=Dysregulated+axonal+RNA+translation+in+amyotrophic+lateral+sclerosis.&rft.au=Yasuda%2C+Kyota%3BMili%2C+Stavroula&rft.aulast=Yasuda&rft.aufirst=Kyota&rft.date=2016-09-01&rft.volume=7&rft.issue=5&rft.spage=589&rft.isbn=&rft.btitle=&rft.title=Wiley+interdisciplinary+reviews.+RNA&rft.issn=1757-7012&rft_id=info:doi/10.1002%2Fwrna.1352 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/wrna.1352 ER - TY - JOUR T1 - Chromosome 8p tumor suppressor genes SH2D4A and SORBS3 cooperate to inhibit interleukin-6 signaling in hepatocellular carcinoma. AN - 1812884119; 27311882 AB - Several chronic inflammatory liver diseases, e.g., chronic hepatitis B or C viral infection and steatohepatitis, have been shown to predispose to the development of hepatocellular carcinoma (HCC). In patients with chronic liver disease, interleukin-6 (IL-6) serum levels are elevated and increase even more when HCC develops. However, the impact and regulatory mechanisms of IL-6 signaling during hepatocarcinogenesis are still poorly defined. Here, we show that gene expression profiles of patients with chromosome 8p loss correlate with increased IL-6 signaling. In addition, the chromosome 8p tumor suppressor genes Src homology 2 domain containing 4A (SH2D4A) and Sorbin and Src homology 3 domain containing 3 (SORBS3) together exerted greater inhibition of cell growth and clonogenicity compared to a single gene. Overexpression of SH2D4A and SORBS3 in HCC cells led to decreased IL-6 target gene expression and reduced signal transducer and activator of transcription 3 (STAT3) signaling. In situ and in vitro coimmunoprecipitation assays revealed that SH2D4A directly interacts with STAT3, thereby retaining STAT3 in the cytoplasm and inhibiting STAT3 transcriptional activity. On the other hand, SORBS3 coactivated estrogen receptor α signaling, leading indirectly to repression of STAT3 signaling. In human HCC tissues, SH2D4A was positively associated with infiltrating regulatory and cytotoxic T-cell populations, suggesting distinct immunophenotypes in HCC subgroups with chromosome 8p loss. Thus, the genetically linked tumor suppressors SH2D4A and SORBS3 functionally cooperate to inhibit STAT3 signaling in HCC. The chromosome 8p tumor suppressor genes SORBS3 and SH2D4A are physically and functionally linked and provide a molecular mechanism of inhibiting STAT3-mediated IL-6 signaling in HCC cells. (Hepatology 2016;64:828-842). © 2016 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Ploeger, Carolin AU - Waldburger, Nina AU - Fraas, Angelika AU - Goeppert, Benjamin AU - Pusch, Stefan AU - Breuhahn, Kai AU - Wang, Xin Wei AU - Schirmacher, Peter AU - Roessler, Stephanie AD - Department of General Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. ; Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. ; Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 828 EP - 842 VL - 64 IS - 3 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812884119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Chromosome+8p+tumor+suppressor+genes+SH2D4A+and+SORBS3+cooperate+to+inhibit+interleukin-6+signaling+in+hepatocellular+carcinoma.&rft.au=Ploeger%2C+Carolin%3BWaldburger%2C+Nina%3BFraas%2C+Angelika%3BGoeppert%2C+Benjamin%3BPusch%2C+Stefan%3BBreuhahn%2C+Kai%3BWang%2C+Xin+Wei%3BSchirmacher%2C+Peter%3BRoessler%2C+Stephanie&rft.aulast=Ploeger&rft.aufirst=Carolin&rft.date=2016-09-01&rft.volume=64&rft.issue=3&rft.spage=828&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28684 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28684 ER - TY - JOUR T1 - Pro-toxic 1,2-Dehydropyrrolizidine Alkaloid Esters, Including Unprecedented 10-Membered Macrocyclic Diesters, in the Medicinally-used Alafia cf. caudata and Amphineurion marginatum (Apocynaceae: Apocynoideae: Nerieae and Apocyneae). AN - 1812227753; 27432636 AB - Within the Apocynoideae (Apocynaceae) pro-toxic dehydropyrrolizidine alkaloids have been reported only in Echiteae. However, attraction of pyrrolizidine alkaloid-pharmacophagous insects suggested their presence in Alafia cf. caudata Stapf (Nerieae: Alafiinae) and Amphineurion marginatum (Roxb.) D.J. Middleton (Apocyneae: Amphineuriinae), both used as medicinal plants. To confirm the presence of dehydropyrrolizidine alkaloids in Alafia cf. caudata and Amphineurion marginatum and identify their structures. Methanol extracts of air-dried roots, stems and leaves of non-flowering plants were analysed using HPLC-ESI(+)MS and MS/MS or collision-induced dissociation MS in low and/or high resolution modes. Pyrrolizidine alkaloids were tentatively identified based on the mass spectrometry data. Solid phase extraction combined with semi-preparative HPLC were used to isolate major alkaloids. Structures were elucidated using NMR spectroscopy. Monoesters of retronecine with senecioic, hydroxysenecioic or syringic acids were identified in roots of Alafia cf. caudata. Two unprecedented 10-membered macrocyclic dehydropyrrolizidine alkaloid diesters were isolated from roots of Amphineurion marginatum. Pyrrolizidine alkaloids were detected in root and leaf material of Alafia cf. caudata at 0.34 and 0.01% dry weight (DW), and 0.13, 0.02 and 0.09% DW in root, leaf and stem material of Amphineurion marginatum. The presence of pro-toxic dehydropyrrolizidine alkaloids suggests that medical preparations of these plants pose potential health risks to consumers. Dehydropyrrolizidine alkaloids are evidently more widespread in Apocynoideae than previously assumed, and it would seem rewarding to study other members of this family for the presence of pyrrolizidines, dehydropyrrolizidines and dihydropyrrolizines. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd. JF - Phytochemical analysis : PCA AU - Colegate, Steven M AU - Gardner, Dale R AU - Betz, Joseph M AU - Fischer, Ottmar W AU - Liede-Schumann, Sigrid AU - Boppré, Michael AD - USDA, ARS, Poisonous Plant Research Laboratory, Logan, UT, 84341, USA. ; Office of Dietary Supplements, National Institutes of Health, 6100 Executive Blvd., Room 3B01, Bethesda, MD, 20892, USA. ; Forstzoologie und Entomologie, Albert-Ludwigs-Universität, D-79085, Freiburg, Germany. ; LS Pflanzensystematik, Universität Bayreuth, D-95440, Bayreuth, Germany. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 257 EP - 276 VL - 27 IS - 5 KW - Index Medicus KW - shimbaine KW - health risk KW - Amphineurine KW - hydroxysenecioylretronecine KW - pyrrolizidine alkaloid-pharmacophagous insects KW - isoshimbaine KW - marginatine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812227753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Phytochemical+analysis+%3A+PCA&rft.atitle=Pro-toxic+1%2C2-Dehydropyrrolizidine+Alkaloid+Esters%2C+Including+Unprecedented+10-Membered+Macrocyclic+Diesters%2C+in+the+Medicinally-used+Alafia+cf.+caudata+and+Amphineurion+marginatum+%28Apocynaceae%3A+Apocynoideae%3A+Nerieae+and+Apocyneae%29.&rft.au=Colegate%2C+Steven+M%3BGardner%2C+Dale+R%3BBetz%2C+Joseph+M%3BFischer%2C+Ottmar+W%3BLiede-Schumann%2C+Sigrid%3BBoppr%C3%A9%2C+Michael&rft.aulast=Colegate&rft.aufirst=Steven&rft.date=2016-09-01&rft.volume=27&rft.issue=5&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Phytochemical+analysis+%3A+PCA&rft.issn=1099-1565&rft_id=info:doi/10.1002%2Fpca.2624 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/pca.2624 ER - TY - JOUR T1 - PET/CT comparing super(68)Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma AN - 1811876584; PQ0003553410 AB - Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). super(68)Ga-DOTA(0)-Tyr(3)-octreotate ( super(68)Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of super(68)Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 plus or minus 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent super(68)Ga-DOTATATE, super(18)F-fluoro-2-deoxy-D-glucose ( super(18)F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional super(18)F-fluorodihydroxyphenylalanine ( super(18)F-FDOPA) PET/CT scan and only 11 patients underwent an additional super(18)F-fluorodopamine ( super(18)F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. super(68)Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). super(18)F-FDG PET/CT, super(18)F-FDOPA PET/CT, super(18)F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p<0.01), 74.8 % (CI 69.0 - 79.9 %); p<0.01), 77.7 % (CI 71.5 - 82.8 %; p<0.01), and 81.6 % (CI 77.8 - 84.8 %; p<0.01), respectively. The results of this study demonstrate the superiority of super(68)Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. JF - European Journal of Nuclear Medicine and Molecular Imaging AU - Janssen, Ingo AU - Chen, Clara C AU - Millo, Corina M AU - Ling, Alexander AU - Taieb, David AU - Lin, Frank I AU - Adams, Karen T AU - Wolf, Katherine I AU - Herscovitch, Peter AU - Fojo, Antonio T AU - Buchmann, Inga AU - Kebebew, Electron AU - Pacak, Karel AD - Program in Adult and Reproductive Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Building 10, CRC, Room 1E-3140, 10 Center Drive MSC-1109, Bethesda, MD, 20892, USA, karel@mail.nih.gov Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1784 EP - 1791 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 43 IS - 10 SN - 1619-7070, 1619-7070 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Somatostatin receptors KW - Magnetic resonance imaging KW - Tumors KW - Pheochromocytoma KW - Metastases KW - Paraganglioma KW - Computed tomography KW - Positron emission tomography KW - Radioisotopes KW - Pharmaceuticals KW - Nuclear medicine KW - Genetic screening KW - W 30910:Imaging KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811876584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Nuclear+Medicine+and+Molecular+Imaging&rft.atitle=PET%2FCT+comparing+super%2868%29Ga-DOTATATE+and+other+radiopharmaceuticals+and+in+comparison+with+CT%2FMRI+for+the+localization+of+sporadic+metastatic+pheochromocytoma+and+paraganglioma&rft.au=Janssen%2C+Ingo%3BChen%2C+Clara+C%3BMillo%2C+Corina+M%3BLing%2C+Alexander%3BTaieb%2C+David%3BLin%2C+Frank+I%3BAdams%2C+Karen+T%3BWolf%2C+Katherine+I%3BHerscovitch%2C+Peter%3BFojo%2C+Antonio+T%3BBuchmann%2C+Inga%3BKebebew%2C+Electron%3BPacak%2C+Karel&rft.aulast=Janssen&rft.aufirst=Ingo&rft.date=2016-09-01&rft.volume=43&rft.issue=10&rft.spage=1784&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Nuclear+Medicine+and+Molecular+Imaging&rft.issn=16197070&rft_id=info:doi/10.1007%2Fs00259-016-3357-x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 37 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Metastases; Paraganglioma; Somatostatin receptors; Magnetic resonance imaging; Computed tomography; Radioisotopes; Positron emission tomography; Genetic screening; Nuclear medicine; Pharmaceuticals; Tumors; Pheochromocytoma DO - http://dx.doi.org/10.1007/s00259-016-3357-x ER - TY - JOUR T1 - Ethical Reflections on Genetic Enhancement with the Aim of Enlarging Altruism AN - 1811757492 AB - Issue Title: Translational Bodies - Ethical Aspects of Uses of Human Biomaterials When it comes to caring about and helping those in need, our imaginations tend to be weak and our motivation tends to be parochial. This is a major moral problem in view of how much unmet need there is in the world and how much material capacity there is to address that need. With this problem in mind, the present paper will focus on genetic means to the enhancement of a moral capacity--a disposition to altruism--and of a cognitive capacity that facilitates use of the moral capacity: the ability to grasp vividly the needs of individuals who are unknown and not present. I will address two questions, with more extensive attention to the first question. First, assuming we had excellent reason to believe that the enhancements were safe, effective, and available to all who desired them, would seeking these enhancements be inherently morally acceptable--that is, free of inherent wrongness? Second, would it be wise for a society to pursue these enhancements? I will defend an affirmative answer to the first question while leaving the second question open. JF - Health Care Analysis : HCA AU - Degrazia, David AD - Department of Bioethics, National Institutes of Health, Bethesda, MD, USA; Department of Philosophy, George Washington University, Washington, DC, USA ; Department of Bioethics, National Institutes of Health, Bethesda, MD, USA; Department of Philosophy, George Washington University, Washington, DC, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 180 EP - 195 CY - Chichester PB - Springer Science & Business Media VL - 24 IS - 3 SN - 1065-3058 KW - Medical Sciences KW - Altruism KW - Enhancement KW - Genetic enhancement KW - Moral enhancement KW - Embryo selection KW - Addressing human need KW - Moral dilemmas KW - Motivation KW - Capacity KW - Moral aspects KW - Ethical aspects KW - Caring UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811757492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Care+Analysis+%3A+HCA&rft.atitle=Ethical+Reflections+on+Genetic+Enhancement+with+the+Aim+of+Enlarging+Altruism&rft.au=Degrazia%2C+David&rft.aulast=Degrazia&rft.aufirst=David&rft.date=2016-09-01&rft.volume=24&rft.issue=3&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=Health+Care+Analysis+%3A+HCA&rft.issn=10653058&rft_id=info:doi/10.1007%2Fs10728-015-0303-1 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-23 DO - http://dx.doi.org/10.1007/s10728-015-0303-1 ER - TY - JOUR T1 - Severe Acute Hepatocellular Injury Attributed to OxyELITE Pro: A Case Series. AN - 1811291902; 27142670 AB - Herbal and dietary supplement (HDS) hepatotoxicity is increasingly being reported in the USA. This case series describes the presenting clinical features and outcomes of seven patients with liver injury attributed to OxyELITE Pro enrolled in the Drug-Induced Liver Injury Network (DILIN) study. The 6-month outcomes of patients with hepatotoxicity attributed to OxyELITE Pro enrolled in the DILIN prospective registry between 2004 and 2015 are presented. Six of the seven patients (86 %) presented in 2013 with symptoms of hepatitis and acute hepatocellular injury. The median duration of OxyELITE Pro use was 18 weeks (range 5-102 weeks). Median age was 36 years (range 28-62), 86 % were female, and 43 % were Asian. One patient had rash, none had eosinophilia, and three had antinuclear antibody reactivity. The median peak ALT was 2242 U/L, alkaline phosphatase 284 U/L and bilirubin 15.0 mg/dL. Six patients (86 %) were hospitalized, three developed acute liver failure and two underwent liver transplantation. DILIN causality scores for OxyELITE Pro were definite in 1, highly likely in 3, probable in 2, and possible in 1. Four of the five patients without liver transplant recovered completely within 6 months, while one patient had mild residual ALT elevations. Seven cases of severe acute hepatocellular injury attributed to OxyELITE Pro are reported. These results reinforce the need to assess for HDS supplement use in patients presenting with unexplained acute hepatitis and point to the need for additional regulatory oversight of HDS products. JF - Digestive diseases and sciences AU - Heidemann, Lauren A AU - Navarro, Victor J AU - Ahmad, Jawad AU - Hayashi, Paul H AU - Stolz, Andrew AU - Kleiner, David E AU - Fontana, Robert J AD - Department of Internal Medicine, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI, 48109-0362, USA. ; Department of Medicine, Einstein Healthcare Network, Philadelphia, PA, USA. ; Department of Medicine, Icahn School of Medicine at Mount Sinai Medical Center, New York, NY, USA. ; University of North Carolina, Chapel Hill, NC, USA. ; University of Southern California, Los Angeles, CA, USA. ; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Department of Internal Medicine, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI, 48109-0362, USA. rfontana@med.umich.edu. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 2741 EP - 2748 VL - 61 IS - 9 KW - Abridged Index Medicus KW - Index Medicus KW - Herbal and dietary supplement KW - Hepatotoxicity KW - Drug-induced liver injury UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811291902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Digestive+diseases+and+sciences&rft.atitle=Severe+Acute+Hepatocellular+Injury+Attributed+to+OxyELITE+Pro%3A+A+Case+Series.&rft.au=Heidemann%2C+Lauren+A%3BNavarro%2C+Victor+J%3BAhmad%2C+Jawad%3BHayashi%2C+Paul+H%3BStolz%2C+Andrew%3BKleiner%2C+David+E%3BFontana%2C+Robert+J&rft.aulast=Heidemann&rft.aufirst=Lauren&rft.date=2016-09-01&rft.volume=61&rft.issue=9&rft.spage=2741&rft.isbn=&rft.btitle=&rft.title=Digestive+diseases+and+sciences&rft.issn=1573-2568&rft_id=info:doi/10.1007%2Fs10620-016-4181-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-11 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Erratum In: Dig Dis Sci. 2016 Oct 6;: [27714508] Dig Dis Sci. 2016 Dec;61(12 ):3638 [27714508] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10620-016-4181-7 ER - TY - JOUR T1 - Institutional Context of Family Eldercare in Mexico and the United States AN - 1810714593 JF - Journal of Cross-Cultural Gerontology AU - Angel, Jacqueline L AU - Angel, Ronald J AU - López-ortega, Mariana AU - Robledo, Luis Miguel; Gutiérrez AU - Wallace, Robert B AD - LBJ School of Public Affairs and Population Research Center, The University of Texas at Austin, Austin, TX, USA ; Department of Sociology, 3.530 CLA A1700, The University of Texas, Austin, TX, USA ; National Institute of Geriatrics, National Institutes of Health, Mexico City, Mexico ; Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA ; LBJ School of Public Affairs and Population Research Center, The University of Texas at Austin, Austin, TX, USA Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 327 EP - 336 CY - Dordrecht PB - Springer Science & Business Media VL - 31 IS - 3 SN - 0169-3816 KW - Gerontology And Geriatrics KW - Mexico KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1810714593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cross-Cultural+Gerontology&rft.atitle=Institutional+Context+of+Family+Eldercare+in+Mexico+and+the+United+States&rft.au=Angel%2C+Jacqueline+L%3BAngel%2C+Ronald+J%3BL%C3%B3pez-ortega%2C+Mariana%3BRobledo%2C+Luis+Miguel%3B+Guti%C3%A9rrez%3BWallace%2C+Robert+B&rft.aulast=Angel&rft.aufirst=Jacqueline&rft.date=2016-09-01&rft.volume=31&rft.issue=3&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cross-Cultural+Gerontology&rft.issn=01693816&rft_id=info:doi/10.1007%2Fs10823-016-9291-3 LA - English DB - Social Services Abstracts; Sociological Abstracts N1 - Name - Family Eldercare N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - United States--US; Mexico DO - http://dx.doi.org/10.1007/s10823-016-9291-3 ER - TY - JOUR T1 - How International Research on Parenting Advances Understanding of Child Development AN - 1810577268 AB - International research on parenting and child development can advance our understanding of similarities and differences in how parenting is related to children's development across countries. Challenges to conducting international research include operationalizing culture, disentangling effects within and between countries, and balancing emic and etic perspectives. Benefits of international research include testing whether findings regarding parenting and child development replicate across diverse samples, incorporating cultural and contextual diversity to foster more inclusive and representative research samples and investigators than has typically occurred, and understanding how children develop in proximal parenting and family and distal international contexts. JF - Child Development Perspectives AU - Lansford, Jennifer E AU - Bornstein, Marc H AU - Deater-Deckard, Kirby AU - Dodge, Kenneth A AU - Al-Hassan, Suha M AU - Bacchini, Dario AU - Bombi, Anna Silvia AU - Chang, Lei AU - Chen, Bin-Bin AU - Di Giunta, Laura AU - Malone, Patrick S AU - Oburu, Paul AU - Pastorelli, Concetta AU - Skinner, Ann T AU - Sorbring, Emma AU - Steinberg, Laurence AU - Tapanya, Sombat AU - Alampay, Liane P AU - Uribe Tirado, Liliana M AU - Zelli, Arnaldo AD - Duke University ; Eunice Kennedy Shriver National Institute of Child Health and Human Development ; University of Massachusetts, Amherst ; Hashemite University; Emirates College for Advanced Education ; Second University of Naples ; Università di Roma La Sapienza ; University of Macau ; Fudan University ; Maseno University ; University West ; Temple University; King Abdulaziz University ; Chiang Mai University ; Ateneo de Manila University ; Universidad San Buenaventura ; University of Rome Foro Italico ; Duke University Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 202 EP - 207 CY - Ann Arbor PB - Wiley Subscription Services, Inc. VL - 10 IS - 3 SN - 1750-8592 KW - Psychology KW - Alliances KW - Child development KW - Parenting KW - Diversity KW - Understanding UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1810577268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development+Perspectives&rft.atitle=How+International+Research+on+Parenting+Advances+Understanding+of+Child+Development&rft.au=Lansford%2C+Jennifer+E%3BBornstein%2C+Marc+H%3BDeater-Deckard%2C+Kirby%3BDodge%2C+Kenneth+A%3BAl-Hassan%2C+Suha+M%3BBacchini%2C+Dario%3BBombi%2C+Anna+Silvia%3BChang%2C+Lei%3BChen%2C+Bin-Bin%3BDi+Giunta%2C+Laura%3BMalone%2C+Patrick+S%3BOburu%2C+Paul%3BPastorelli%2C+Concetta%3BSkinner%2C+Ann+T%3BSorbring%2C+Emma%3BSteinberg%2C+Laurence%3BTapanya%2C+Sombat%3BAlampay%2C+Liane+P%3BUribe+Tirado%2C+Liliana+M%3BZelli%2C+Arnaldo&rft.aulast=Lansford&rft.aufirst=Jennifer&rft.date=2016-09-01&rft.volume=10&rft.issue=3&rft.spage=202&rft.isbn=&rft.btitle=&rft.title=Child+Development+Perspectives&rft.issn=17508592&rft_id=info:doi/10.1111%2Fcdep.12186 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Child Development Perspectives © 2016 The Society for Research in Child Development, Inc. N1 - Last updated - 2016-08-17 DO - http://dx.doi.org/10.1111/cdep.12186 ER - TY - JOUR T1 - Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature. AN - 1810555529; 26974995 AB - Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas. JF - International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists AU - Moulla, Alexandra A AU - Magdy, Nesreen AU - Francis, Nicholas AU - Taube, Janis AU - Ronnett, Brigitte M AU - El-Bahrawy, Mona AD - Department of Histopathology (A.AM., N.M., N.F., M.E.-B.), Imperial College, London, UK Department of Pathology (N.M.), National Cancer Institute, Cairo, Egypt Department of Pathology (M.E.-B.), Faculty of Medicine, Alexandria University, Alexandria, Egypt Departments of Dermatology (J.T.) Pathology (B.M.R.), Johns Hopkins Medical Institutions, Baltimore, Maryland. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 448 EP - 455 VL - 35 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1810555529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+gynecological+pathology+%3A+official+journal+of+the+International+Society+of+Gynecological+Pathologists&rft.atitle=Rare+Skin+Adnexal+and+Melanocytic+Tumors+Arising+in+Ovarian+Mature+Cystic+Teratomas%3A+A+Report+of+3+Cases+and+Review+of+the+Literature.&rft.au=Moulla%2C+Alexandra+A%3BMagdy%2C+Nesreen%3BFrancis%2C+Nicholas%3BTaube%2C+Janis%3BRonnett%2C+Brigitte+M%3BEl-Bahrawy%2C+Mona&rft.aulast=Moulla&rft.aufirst=Alexandra&rft.date=2016-09-01&rft.volume=35&rft.issue=5&rft.spage=448&rft.isbn=&rft.btitle=&rft.title=International+journal+of+gynecological+pathology+%3A+official+journal+of+the+International+Society+of+Gynecological+Pathologists&rft.issn=1538-7151&rft_id=info:doi/10.1097%2FPGP.0000000000000278 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1097/PGP.0000000000000278 ER - TY - JOUR T1 - p53 isoforms regulate astrocyte-mediated neuroprotection and neurodegeneration. AN - 1810355860; 27104929 AB - Bidirectional interactions between astrocytes and neurons have physiological roles in the central nervous system and an altered state or dysfunction of such interactions may be associated with neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Astrocytes exert structural, metabolic and functional effects on neurons, which can be either neurotoxic or neuroprotective. Their neurotoxic effect is mediated via the senescence-associated secretory phenotype (SASP) involving pro-inflammatory cytokines (e.g., IL-6), while their neuroprotective effect is attributed to neurotrophic growth factors (e.g., NGF). We here demonstrate that the p53 isoforms Δ133p53 and p53β are expressed in astrocytes and regulate their toxic and protective effects on neurons. Primary human astrocytes undergoing cellular senescence upon serial passaging in vitro showed diminished expression of Δ133p53 and increased p53β, which were attributed to the autophagic degradation and the SRSF3-mediated alternative RNA splicing, respectively. Early-passage astrocytes with Δ133p53 knockdown or p53β overexpression were induced to show SASP and to exert neurotoxicity in co-culture with neurons. Restored expression of Δ133p53 in near-senescent, otherwise neurotoxic astrocytes conferred them with neuroprotective activity through repression of SASP and induction of neurotrophic growth factors. Brain tissues from AD and ALS patients possessed increased numbers of senescent astrocytes and, like senescent astrocytes in vitro, showed decreased Δ133p53 and increased p53β expression, supporting that our in vitro findings recapitulate in vivo pathology of these neurodegenerative diseases. Our finding that Δ133p53 enhances the neuroprotective function of aged and senescent astrocytes suggests that the p53 isoforms and their regulatory mechanisms are potential targets for therapeutic intervention in neurodegenerative diseases. JF - Cell death and differentiation AU - Turnquist, C AU - Horikawa, I AU - Foran, E AU - Major, E O AU - Vojtesek, B AU - Lane, D P AU - Lu, X AU - Harris, B T AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. ; Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. ; Regional Centre for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic. ; p53 Laboratory, Biomedical Sciences Institutes (A*STAR), Singapore 138648, Singapore. ; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK. ; Department of Neurology, Georgetown University Medical Center, Washington DC 20007, USA. Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 1515 EP - 1528 VL - 23 IS - 9 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1810355860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+death+and+differentiation&rft.atitle=p53+isoforms+regulate+astrocyte-mediated+neuroprotection+and+neurodegeneration.&rft.au=Turnquist%2C+C%3BHorikawa%2C+I%3BForan%2C+E%3BMajor%2C+E+O%3BVojtesek%2C+B%3BLane%2C+D+P%3BLu%2C+X%3BHarris%2C+B+T%3BHarris%2C+C+C&rft.aulast=Turnquist&rft.aufirst=C&rft.date=2016-09-01&rft.volume=23&rft.issue=9&rft.spage=1515&rft.isbn=&rft.btitle=&rft.title=Cell+death+and+differentiation&rft.issn=1476-5403&rft_id=info:doi/10.1038%2Fcdd.2016.37 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/cdd.2016.37 ER - TY - JOUR T1 - Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor. AN - 1810353612; 27346274 AB - Bombesin-receptor-subtype-3 (BB3 receptor) is a G-protein-coupled-orphan-receptor classified in the mammalian Bombesin-family because of high homology to gastrin-releasing peptide (BB2 receptor)/neuromedin-B receptors (BB1 receptor). There is increased interest in BB3 receptor because studies primarily from knockout-mice suggest it plays roles in energy/glucose metabolism, insulin-secretion, as well as motility and tumor-growth. Investigations into its roles in physiological/pathophysiological processes are limited because of lack of selective ligands. Recently, a selective, peptide-antagonist, Bantag-1, was described. However, because BB3 receptor has low-affinity for all natural, Bn-related peptides, little is known of the molecular basis of its high-affinity/selectivity. This was systematically investigated in this study for Bantag-1 using a chimeric-approach making both Bantag-1 loss-/gain-of-affinity-chimeras, by exchanging extracellular (EC) domains of BB3/BB2 receptor, and using site-directed-mutagenesis. Receptors were transiently expressed and affinities determined by binding studies. Bantag-1 had >5000-fold selectivity for BB3 receptor over BB2/BB1 receptors and substitution of the first EC-domain (EC1) in loss-/gain-of affinity-chimeras greatly affected affinity. Mutagenesis of each amino acid difference in EC1 between BB3 receptor/BB2 receptor showed replacement of His(107) in BB3 receptor by Lys(107) (H107K-BB3 receptor-mutant) from BB2 receptor, decreased affinity 60-fold, and three replacements [H107K, E11D, G112R] decreased affinity 500-fold. Mutagenesis in EC1's surrounding transmembrane-regions (TMs) demonstrated TM2 differences were not important, but R127Q in TM3 alone decreased affinity 400-fold. Additional mutants in EC1/TM3 explored the molecular basis for these changes demonstrated in EC1, particularly important is the presence of aromatic-interactions by His(107), rather than hydrogen-bonding or charge-charge interactions, for determining Bantag-1 high affinity/selectivity. In regard to Arg(127) in TM3, both hydrogen-bonding and charge-charge interactions contribute to the high-affinity/selectivity for Bantag-1. Published by Elsevier Inc. JF - Biochemical pharmacology AU - Nakamura, Taichi AU - Ramos-Álvarez, Irene AU - Iordanskaia, Tatiana AU - Moreno, Paola AU - Mantey, Samuel A AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1804, USA. ; Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1804, USA. Electronic address: robertj@bdg10.niddk.nih.gov. Y1 - 2016/09/01/ PY - 2016 DA - 2016 Sep 01 SP - 64 EP - 76 VL - 115 KW - Index Medicus KW - Gastrin-releasing peptide KW - Obesity KW - Satiety KW - Bombesin KW - Neuromedin B UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1810353612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Molecular+basis+for+high+affinity+and+selectivity+of+peptide+antagonist%2C+Bantag-1%2C+for+the+orphan+BB3+receptor.&rft.au=Nakamura%2C+Taichi%3BRamos-%C3%81lvarez%2C+Irene%3BIordanskaia%2C+Tatiana%3BMoreno%2C+Paola%3BMantey%2C+Samuel+A%3BJensen%2C+R+T&rft.aulast=Nakamura&rft.aufirst=Taichi&rft.date=2016-09-01&rft.volume=115&rft.issue=&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=1873-2968&rft_id=info:doi/10.1016%2Fj.bcp.2016.06.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bcp.2016.06.013 ER - TY - JOUR T1 - Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water. AN - 1809048636; 27223060 AB - Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0-2000 mg STD/L in their drinking water for 28 d, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3(+) T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely affect cell-mediated immunity. JF - Journal of immunotoxicology AU - Frawley, Rachel P AU - Smith, Matthew J AU - White, Kimber L AU - Elmore, Susan A AU - Herbert, Ron AU - Moore, Rebecca AU - Staska, Lauren M AU - Behl, Mamta AU - Hooth, Michelle J AU - Kissling, Grace E AU - Germolec, Dori R AD - a Division of the National Toxicology Program , National Institute of Environmental Health Sciences (NIEHS) Research Triangle Park , NC , USA ; ; b Department of Pharmacology and Toxicology , Virginia Commonwealth University , Richmond , VA ; ; c Experimental Pathology Laboratories Inc., Research Triangle Park , NC , USA ; ; d WIL Research , Hillsborough , NC , USA ; ; e Division of Intramural Research , NIEHS, Research Triangle Park , NC , USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 666 EP - 675 VL - 13 IS - 5 KW - Index Medicus KW - Cell-mediated immunity KW - sodium tungstate dihydrate KW - cytotoxic T-lymphocyte UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1809048636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotoxicology&rft.atitle=Immunotoxic+effects+of+sodium+tungstate+dihydrate+on+female+B6C3F1%2FN+mice+when+administered+in+drinking+water.&rft.au=Frawley%2C+Rachel+P%3BSmith%2C+Matthew+J%3BWhite%2C+Kimber+L%3BElmore%2C+Susan+A%3BHerbert%2C+Ron%3BMoore%2C+Rebecca%3BStaska%2C+Lauren+M%3BBehl%2C+Mamta%3BHooth%2C+Michelle+J%3BKissling%2C+Grace+E%3BGermolec%2C+Dori+R&rft.aulast=Frawley&rft.aufirst=Rachel&rft.date=2016-09-01&rft.volume=13&rft.issue=5&rft.spage=666&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotoxicology&rft.issn=1547-6901&rft_id=info:doi/10.3109%2F1547691X.2016.1154118 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.3109/1547691X.2016.1154118 ER - TY - JOUR T1 - Association of MHC region SNPs with irritant susceptibility in healthcare workers. AN - 1809046673; 27258892 AB - Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in "wet-work" occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC). Genotyping was performed using Illumina Goldengate MHC panels. A number of SNPs within the MHC Class I (OR2B3, TRIM31, TRIM10, TRIM40 and IER3), Class II (HLA-DPA1, HLA-DPB1) and Class III (C2) genes were associated (p < 0.001) with skin response to tested irritants in different genetic models. Linkage disequilibrium patterns and functional annotations identified two SNPs in the TRIM40 (rs1573298) and HLA-DPB1 (rs9277554) genes, with a potential impact on gene regulation. In addition, SNPs in PSMB9 (rs10046277 and ITPR3 (rs499384) were associated with hand dermatitis. The results are of interest as they demonstrate that genetic variations in inflammation-related genes within the MHC can influence chemical-induced skin irritation and may explain the connection between inflamed skin and propensity to subsequent allergic contact sensitization. JF - Journal of immunotoxicology AU - Yucesoy, Berran AU - Talzhanov, Yerkebulan AU - Michael Barmada, M AU - Johnson, Victor J AU - Kashon, Michael L AU - Baron, Elma AU - Wilson, Nevin W AU - Frye, Bonnie AU - Wang, Wei AU - Fluharty, Kara AU - Gharib, Rola AU - Meade, Jean AU - Germolec, Dori AU - Luster, Michael I AU - Nedorost, Susan AD - a Health Effects Laboratory Division , CDC/NIOSH , Morgantown , WV , USA ; ; b Department of Human Genetics, Graduate School of Public Health , University of Pittsburgh , Pittsburgh , PA , USA ; ; c BRT-Burleson Research Technologies , Morrisville , NC , USA ; ; d University Hospitals Case Medical Center, Case Western Reserve University , Cleveland , OH , USA ; ; e Department of Pediatrics, School of Medicine , University of Nevada , Reno , NV , USA ; ; f Department of Dermatology, School of Medicine , West Virginia University , Morgantown , WV , USA ; ; g Office of Director, CDC/NIOSH , Morgantown , WV , USA ; ; h Toxicology Branch, DNTP/NIEHS, Research Triangle Park , NC , USA ; ; i School of Public Health, West Virginia University , Morgantown , WV , USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 738 EP - 744 VL - 13 IS - 5 KW - Index Medicus KW - Genetics KW - healthcare workers KW - irritant contact dermatitis KW - MHC UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1809046673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotoxicology&rft.atitle=Association+of+MHC+region+SNPs+with+irritant+susceptibility+in+healthcare+workers.&rft.au=Yucesoy%2C+Berran%3BTalzhanov%2C+Yerkebulan%3BMichael+Barmada%2C+M%3BJohnson%2C+Victor+J%3BKashon%2C+Michael+L%3BBaron%2C+Elma%3BWilson%2C+Nevin+W%3BFrye%2C+Bonnie%3BWang%2C+Wei%3BFluharty%2C+Kara%3BGharib%2C+Rola%3BMeade%2C+Jean%3BGermolec%2C+Dori%3BLuster%2C+Michael+I%3BNedorost%2C+Susan&rft.aulast=Yucesoy&rft.aufirst=Berran&rft.date=2016-09-01&rft.volume=13&rft.issue=5&rft.spage=738&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotoxicology&rft.issn=1547-6901&rft_id=info:doi/10.3109%2F1547691X.2016.1173135 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.3109/1547691X.2016.1173135 ER - TY - JOUR T1 - Contextualizing Hepatocyte Functionality of Cryopreserved HepaRG Cell Cultures. AN - 1809046216; 27338863 AB - Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (∼28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format of HepaRG cells (termed here "cryo-HepaRG") has emerged as a new model that improves global availability and experimental flexibility; however, it is largely unknown whether HepaRG cells in this format fully retain their hepatic characteristics. Therefore, we systematically investigated the hepatocyte functionality of cryo-HepaRG cultures in context with the range of interindividual variation observed with PHH in both sandwich-culture and suspension formats. These evaluations uncovered a novel adaptation period for the cryo-HepaRG format and demonstrated the impact of extracellular matrix on cryo-HepaRG functionality. Pharmacologically important drug-metabolizing alleles were genotyped in HepaRG cells and poor metabolizer alleles for CYP2D6, CYP2C9, and CYP3A5 were identified and consistent with higher frequency alleles found in individuals of Caucasian decent. We observed liver enzyme inducibility with aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor activators comparable to that of sandwich-cultured PHH. Finally, we show for the first time that cryo-HepaRG supports proper CAR cytosolic sequestration and translocation to hepatocyte nuclei in response to phenobarbital treatment. Taken together, these data reveal important considerations for the use of this cell model and demonstrate that cryo-HepaRG are suitable for metabolism and toxicology screening. U.S. Government work not protected by U.S. copyright. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Jackson, Jonathan P AU - Li, Linhou AU - Chamberlain, Erica D AU - Wang, Hongbing AU - Ferguson, Stephen S AD - Life Technologies, Cell System Division, ADME/Tox, Durham, North Carolina (J.P.J., E.D., S.S.F.); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.W.). ; Life Technologies, Cell System Division, ADME/Tox, Durham, North Carolina (J.P.J., E.D., S.S.F.); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland (L.L., H.W.) stephen.ferguson@nih.gov. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1463 EP - 1479 VL - 44 IS - 9 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1809046216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Contextualizing+Hepatocyte+Functionality+of+Cryopreserved+HepaRG+Cell+Cultures.&rft.au=Jackson%2C+Jonathan+P%3BLi%2C+Linhou%3BChamberlain%2C+Erica+D%3BWang%2C+Hongbing%3BFerguson%2C+Stephen+S&rft.aulast=Jackson&rft.aufirst=Jonathan&rft.date=2016-09-01&rft.volume=44&rft.issue=9&rft.spage=1463&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=1521-009X&rft_id=info:doi/10.1124%2Fdmd.116.069831 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/dmd.116.069831 ER - TY - JOUR T1 - Noble metal nanoparticle-induced oxidative stress modulates tumor associated macrophages (TAMs) from an M2 to M1 phenotype: An in vitro approach. AN - 1807894183; 27344639 AB - Diagnosis of cancer and photothermal therapy using optoelectronic properties of noble metal nanoparticles (NPs) has established a new therapeutic approach for treating cancer. Here we address the intrinsic properties of noble metal NPs (gold and silver) as well as the mechanism of their potential antitumor activity. For this, the study addresses the functional characterization of tumor associated macrophages (TAMs) isolated from murine fibrosarcoma induced by a chemical carcinogen, 3-methylcholanthrene (MCA). We have previously shown antitumor activity of both gold nanoparticles (AuNPs) and silver nanoparticle (AgNPs) in vivo in a murine fibrosarcoma model. In the present study, it has been seen that AuNPs and AgNPs modulate the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, suppressing the antioxidant system of cells (TAMs). Moreover, the antioxidant-mimetic action of these NPs maintain the ROS and RNS levels in TAMs which act as second messengers to activate the proinflammatory signaling cascades. Thus, while there is a downregulation of tumor necrosis factor-α (TNF-α) and Interleukin-10 (IL-10) in the TAMs, the proinflammatory cytokine Interleukin-12 (IL-12) is upregulated resulting in a polarization of TAMs from M2 (anti-inflammatory) to M1 (pro-inflammatory) nature. Copyright © 2016. Published by Elsevier B.V. JF - International immunopharmacology AU - Pal, Ramkrishna AU - Chakraborty, Biswajit AU - Nath, Anupam AU - Singh, Leichombam Mohindro AU - Ali, Mohammed AU - Rahman, Dewan Shahidur AU - Ghosh, Sujit Kumar AU - Basu, Abhishek AU - Bhattacharya, Sudin AU - Baral, Rathindranath AU - Sengupta, Mahuya AD - Department of Biotechnology, Assam University, Silchar, Assam, India, 788011. ; Department of Chemistry, Assam University, Silchar, Assam, India, 788011. ; Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India, 700026. ; Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata, India, 700026. ; Department of Biotechnology, Assam University, Silchar, Assam, India, 788011. Electronic address: senguptamahuya35@gmail.com. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 332 EP - 341 VL - 38 KW - Index Medicus KW - Noble metal nanoparticles KW - ROS KW - Chemical carcinogen KW - TAMs KW - Silver nanoparticles KW - RNS KW - Gold nanoparticles UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807894183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+immunopharmacology&rft.atitle=Noble+metal+nanoparticle-induced+oxidative+stress+modulates+tumor+associated+macrophages+%28TAMs%29+from+an+M2+to+M1+phenotype%3A+An+in+vitro+approach.&rft.au=Pal%2C+Ramkrishna%3BChakraborty%2C+Biswajit%3BNath%2C+Anupam%3BSingh%2C+Leichombam+Mohindro%3BAli%2C+Mohammed%3BRahman%2C+Dewan+Shahidur%3BGhosh%2C+Sujit+Kumar%3BBasu%2C+Abhishek%3BBhattacharya%2C+Sudin%3BBaral%2C+Rathindranath%3BSengupta%2C+Mahuya&rft.aulast=Pal&rft.aufirst=Ramkrishna&rft.date=2016-09-01&rft.volume=38&rft.issue=&rft.spage=332&rft.isbn=&rft.btitle=&rft.title=International+immunopharmacology&rft.issn=1878-1705&rft_id=info:doi/10.1016%2Fj.intimp.2016.06.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.intimp.2016.06.006 ER - TY - JOUR T1 - Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6-Mercaptopurine in Children With Acute Lymphoblastic Leukemia. AN - 1806076511; 27163515 AB - The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases. The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens. © 2016 Wiley Periodicals, Inc. JF - Pediatric blood & cancer AU - Abdelaziz, Doaa H AU - Elhosseiny, Noha M AU - Khaleel, Sahar A AU - Sabry, Nirmeen A AU - Attia, Ahmed S AU - El-Sayed, Manal H AD - Department of Clinical Pharmacy, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt. ; Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. ; Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt. ; Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt. ; Department of Pediatrics, Hematology-Oncology Division, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1539 EP - 1545 VL - 63 IS - 9 KW - Index Medicus KW - toxicities KW - genetic polymorphism KW - acute lymphoblastic leukemia KW - children KW - HCV KW - chemotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806076511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+blood+%26+cancer&rft.atitle=Association+Between+Combined+Presence+of+Hepatitis+C+Virus+and+Polymorphisms+in+Different+Genes+With+Toxicities+of+Methotrexate+and+6-Mercaptopurine+in+Children+With+Acute+Lymphoblastic+Leukemia.&rft.au=Abdelaziz%2C+Doaa+H%3BElhosseiny%2C+Noha+M%3BKhaleel%2C+Sahar+A%3BSabry%2C+Nirmeen+A%3BAttia%2C+Ahmed+S%3BEl-Sayed%2C+Manal+H&rft.aulast=Abdelaziz&rft.aufirst=Doaa&rft.date=2016-09-01&rft.volume=63&rft.issue=9&rft.spage=1539&rft.isbn=&rft.btitle=&rft.title=Pediatric+blood+%26+cancer&rft.issn=1545-5017&rft_id=info:doi/10.1002%2Fpbc.26045 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/pbc.26045 ER - TY - JOUR T1 - Cool-temperature-mediated activation of phospholipase C-γ2 in the human hereditary disease PLAID. AN - 1804866854; 27196803 AB - Deletions in the gene encoding signal-transducing inositol phospholipid-specific phospholipase C-γ2 (PLCγ2) are associated with the novel human hereditary disease PLAID (PLCγ2-associated antibody deficiency and immune dysregulation). PLAID is characterized by a rather puzzling concurrence of augmented and diminished functions of the immune system, such as cold urticaria triggered by only minimal decreases in temperature, autoimmunity, and immunodeficiency. Understanding of the functional effects of the genomic alterations at the level of the affected enzyme, PLCγ2, is currently lacking. PLCγ2 is critically involved in coupling various cell surface receptors to regulation of important functions of immune cells such as mast cells, B cells, monocytes/macrophages, and neutrophils. PLCγ2 is unique by carrying three Src (SH) and one split pleckstrin homology domain (spPH) between the two catalytic subdomains (spPHn-SH2n-SH2c-SH3-spPHc). Prevailing evidence suggests that activation of PLCγ2 is primarily due to loss of SH-region-mediated autoinhibition and/or enhanced plasma membrane translocation. Here, we show that the two PLAID PLCγ2 mutants lacking portions of the SH region are strongly (>100-fold), rapidly, and reversibly activated by cooling by only a few degrees. We found that the mechanism(s) underlying PLCγ2 PLAID mutant activation by cool temperatures is distinct from a mere loss of SH-region-mediated autoinhibition and dependent on both the integrity and the pliability of the spPH domain. The results suggest a new mechanism of PLCγ activation with unique thermodynamic features and assign a novel regulatory role to its spPH domain. Involvement of this mechanism in other human disease states associated with cooling such as exertional asthma and certain acute coronary events appears an intriguing possibility. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Cellular signalling AU - Schade, Anja AU - Walliser, Claudia AU - Wist, Martin AU - Haas, Jennifer AU - Vatter, Petra AU - Kraus, Johann M AU - Filingeri, Davide AU - Havenith, George AU - Kestler, Hans A AU - Milner, Joshua D AU - Gierschik, Peter AD - Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89070 Ulm, Germany. ; Institute of Medical Systems Biology, Ulm University, 89081 Ulm, Germany. ; Environmental Ergonomics Research Centre, Loughborough University, Leicestershire LE11 3TU, United Kingdom. ; Allergic Inflammation Unit, Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD 20892, USA. ; Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89070 Ulm, Germany. Electronic address: peter.gierschik@uni-ulm.de. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1237 EP - 1251 VL - 28 IS - 9 KW - Index Medicus KW - Inositol phospholipid KW - Split PH domain KW - Rac2 GTPase KW - Phospholipase C-γ(2) KW - Cold temperature sensitivity KW - Autoinhibition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804866854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+signalling&rft.atitle=Cool-temperature-mediated+activation+of+phospholipase+C-%CE%B32+in+the+human+hereditary+disease+PLAID.&rft.au=Schade%2C+Anja%3BWalliser%2C+Claudia%3BWist%2C+Martin%3BHaas%2C+Jennifer%3BVatter%2C+Petra%3BKraus%2C+Johann+M%3BFilingeri%2C+Davide%3BHavenith%2C+George%3BKestler%2C+Hans+A%3BMilner%2C+Joshua+D%3BGierschik%2C+Peter&rft.aulast=Schade&rft.aufirst=Anja&rft.date=2016-09-01&rft.volume=28&rft.issue=9&rft.spage=1237&rft.isbn=&rft.btitle=&rft.title=Cellular+signalling&rft.issn=1873-3913&rft_id=info:doi/10.1016%2Fj.cellsig.2016.05.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.cellsig.2016.05.010 ER - TY - JOUR T1 - Integrated decision strategies for skin sensitization hazard. AN - 1804855247; 26851134 AB - One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by the Organisation for Economic Co-operation and Development (OECD). Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens assay. Data for six physicochemical properties, which may affect skin penetration, were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89-96% for the test set and 96-99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA. JF - Journal of applied toxicology : JAT AU - Strickland, Judy AU - Zang, Qingda AU - Kleinstreuer, Nicole AU - Paris, Michael AU - Lehmann, David M AU - Choksi, Neepa AU - Matheson, Joanna AU - Jacobs, Abigail AU - Lowit, Anna AU - Allen, David AU - Casey, Warren AD - ILS, Research Triangle Park, North Carolina, 27709, USA. ; EPA/NHEERL/EPHD/CIB, Research Triangle Park, North Carolina, 27709, USA. ; U.S. Consumer Product Safety Commission, Bethesda, Maryland, 20814, USA. ; FDA/CDER, Silver Spring, Maryland, 20993, USA. ; EPA/OCSPP/OPP/HED, Washington, District of Columbia, 20460, USA. ; NIH/NIEHS/DNTP/NICEATM, Research Triangle Park, North Carolina, 27709, USA. Y1 - 2016/09// PY - 2016 DA - September 2016 SP - 1150 EP - 1162 VL - 36 IS - 9 KW - Index Medicus KW - support vector machine KW - skin sensitization KW - machine learning KW - LLNA KW - DPRA KW - h-CLAT KW - KeratinoSens KW - integrated decision strategy KW - allergic contact dermatitis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804855247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+toxicology+%3A+JAT&rft.atitle=Integrated+decision+strategies+for+skin+sensitization+hazard.&rft.au=Strickland%2C+Judy%3BZang%2C+Qingda%3BKleinstreuer%2C+Nicole%3BParis%2C+Michael%3BLehmann%2C+David+M%3BChoksi%2C+Neepa%3BMatheson%2C+Joanna%3BJacobs%2C+Abigail%3BLowit%2C+Anna%3BAllen%2C+David%3BCasey%2C+Warren&rft.aulast=Strickland&rft.aufirst=Judy&rft.date=2016-09-01&rft.volume=36&rft.issue=9&rft.spage=1150&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=1099-1263&rft_id=info:doi/10.1002%2Fjat.3281 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-14 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/jat.3281 ER - TY - JOUR T1 - Homophobic Prejudice in Czech Youth: a Sociodemographic Analysis of Young People's Opinions on Homosexuality AN - 1802451340 AB - The aims of this study are to provide momentum to research on homophobic prejudice in Czechia and to identify the significant factors influencing or mediating homophobic attitudes in Czech youth. The paper first contextualizes homophobia within the context of the Central and Eastern European countries and then refers to the role of schools and education tools in the prevention of homophobia. Results of a quantitative analysis based on original data collected during a research survey from 9th graders (N=1082) in 35 selected Czech elementary schools are presented in the empirical part of the paper. We identify demographic, socioeconomic, psychological, and environmental factors that are significantly linked with homophobic attitudes in youth. Gender differences as well as relationship satisfaction with parents or peers, psychological status, and perception of quality of the environment one lives in were found to be among the most significant factors influencing prejudicial opinions in youth. Metropolitan youth were found to be significantly less prejudiced against nonheterosexuals. By taking lessons from abroad, we propose a number of possible policy interventions mainly in the realm of curricular documents and teacher training. JF - Sexuality Research & Social Policy AU - Pitoák, Michal AU - Spilková, Jana AD - Department of Social Geography and Regional Development, Faculty of Science, Charles University in Prague, Prague 2, Czech Republic; Centre of Epidemiological and Clinical Research of Drug Abuse and Dependence, National Institute of Mental Health, Klecany, Czech Republic Y1 - 2016/09// PY - 2016 DA - Sep 2016 SP - 215 EP - 229 CY - Berkeley PB - Springer Science & Business Media VL - 13 IS - 3 SN - 1868-9884 KW - Sociology KW - Sexual prejudice KW - Homophobia in youths KW - Nonheterosexuals KW - Heteronormativity KW - Schools KW - Sex education KW - Homosexuality KW - Environmental Factors KW - Sex Differences KW - Quantitative Methods KW - Parents KW - Peers KW - Satisfaction KW - Sex KW - Attitudes KW - Psychological Factors KW - Youth KW - Prejudice KW - Socioeconomic Factors KW - Prevention KW - Training KW - Elementary Schools KW - Homophobia KW - Interpersonal Relationship Satisfaction KW - Sociodemographic Factors KW - Sociodemographic aspects KW - Young people KW - Environmental aspects KW - Gender differences KW - Psychological status KW - Elementary schools KW - Quantitative analysis KW - 1940:the family and socialization; sociology of sexual behavior KW - 1939:the family and socialization; adolescence & youth UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802451340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Sexuality+Research+%26+Social+Policy&rft.atitle=Homophobic+Prejudice+in+Czech+Youth%3A+a+Sociodemographic+Analysis+of+Young+People%27s+Opinions+on+Homosexuality&rft.au=Pito%C3%A1k%2C+Michal%3BSpilkov%C3%A1%2C+Jana&rft.aulast=Pito%C3%A1k&rft.aufirst=Michal&rft.date=2016-09-01&rft.volume=13&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Sexuality+Research+%26+Social+Policy&rft.issn=18689884&rft_id=info:doi/10.1007%2Fs13178-015-0215-8 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA); Sociological Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-10-24 DO - http://dx.doi.org/10.1007/s13178-015-0215-8 ER - TY - JOUR T1 - HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women. AN - 1786517679; 27130930 AB - HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects (90th percentile) or cold (<10th percentile) using site-specific and window-specific temperature distributions were defined for three-months preconception, seven-week periods during the first two trimesters, one week preceding delivery, and whole pregnancy. Poisson regression with generalized estimating equations calculated the relative risk (RR) and 95% confidence interval for early deliveries associated with hot/cold exposures adjusting for conception month, humidity, site, sex, maternal demographics, parity, insurance, pre-pregnancy BMI, pregnancy complications, and smoking or drinking during pregnancy. Acute temperature associations were estimated separately for warm (May-September) and cold season (October-April) in a case-crossover analysis using conditional logistic regression. Compared with mild temperature (10-90th percentile), exposure to hot or cold during weeks 1-7 increased risk for early preterm (<34 weeks) [RRhot: 1.11(1.01-1.21); RRcold: 1.20(1.11-1.30)], late preterm (34-36 weeks) [RRcold: 1.09(1.04-1.15)], and early term (37-38 weeks) [RRhot: 1.04(1.02-1.07); RRcold: 1.03(1.00-1.05)] delivery. Findings were similar for hot exposures during weeks 15-21. Examining deliveries at each week from 23-38, whole-pregnancy hot exposures increased delivery risk by 6%-21% at weeks 34 and 36-38. In the case-crossover analysis, a 5 ˚F increase during the week preceding delivery was associated with 12-16% higher and 4-5% lower early delivery risk during warm and cold season, respectively. Both acute and chronic ambient temperature extremes may impact early delivery risk. JF - Environmental health perspectives AU - Ha, Sandie AU - Liu, Danping AU - Zhu, Yeyi AU - Kim, Sung Soo AU - Sherman, Seth AU - Mendola, Pauline AD - Epidemiology Branch, Division of Intramural Population Health Research, NICHD, Rockville, MD, USA. ; Biostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, NICHD, Rockville, MD, USA. ; The Emmes Corporation, Rockville, MD, USA. Y1 - 2016/08/31/ PY - 2016 DA - 2016 Aug 31 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859740069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Ambient+Temperature+and+Early+Delivery+of+Singleton+Pregnancies.&rft.au=Ha%2C+Sandie%3BLiu%2C+Danping%3BZhu%2C+Yeyi%3BKim%2C+Sung+Soo%3BSherman%2C+Seth%3BMendola%2C+Pauline&rft.aulast=Ha&rft.aufirst=Sandie&rft.date=2016-08-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain. AN - 1815974553; 27578558 AB - C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date. JF - Nature communications AU - Wang, Yu-Chuan AU - Chin, Ko-Hsin AU - Tu, Zhi-Le AU - He, Jin AU - Jones, Christopher J AU - Sanchez, David Zamorano AU - Yildiz, Fitnat H AU - Galperin, Michael Y AU - Chou, Shan-Ho AD - Institute of Biochemistry, National Chung Hsing University, Taichung 40227, Taiwan, Republic of China. ; Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan, Republic of China. ; State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China. ; Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California 95064, USA. ; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 2016/08/31/ PY - 2016 DA - 2016 Aug 31 SP - 12481 VL - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815974553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Nucleotide+binding+by+the+widespread+high-affinity+cyclic+di-GMP+receptor+MshEN+domain.&rft.au=Wang%2C+Yu-Chuan%3BChin%2C+Ko-Hsin%3BTu%2C+Zhi-Le%3BHe%2C+Jin%3BJones%2C+Christopher+J%3BSanchez%2C+David+Zamorano%3BYildiz%2C+Fitnat+H%3BGalperin%2C+Michael+Y%3BChou%2C+Shan-Ho&rft.aulast=Wang&rft.aufirst=Yu-Chuan&rft.date=2016-08-31&rft.volume=7&rft.issue=&rft.spage=12481&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms12481 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms12481 ER - TY - JOUR T1 - Significant interactions between maternal PAH exposure and single nucleotide polymorphisms in candidate genes on B[a]P-DNA adducts in a cohort of non-smoking Polish mothers and newborns. AN - 1856590867; 27565807 AB - Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking women (n = 368) with available data on maternal PAH exposure, paired cord adducts, and genetic data who resided in Krakow, Poland. We selected eight common variants in maternal and newborn candidate genes related to B[a]P metabolism, detoxification, and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM1, GSTT2, NQO1, and XRCC1 We observed significant interactions between maternal PAH exposure and SNPs on cord B[a]P-DNA adducts in the following genes: maternal CYP1A1 and GSTT2, and newborn CYP1A1 and CYP1B1 These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. JF - Carcinogenesis AU - Iyer, Shoba AU - Wang, Ya AU - Xiong, Wei AU - Tang, Deliang AU - Jedrychowski, Wieslaw AU - Chanock, Stephen AU - Wang, Shuang AU - Stigter, Laura AU - Mróz, Elzbieta AU - Perera, Frederica AD - Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. ; Former Chair of Epidemiology and Preventive Medicine, Jagiellonian University Medical College, Krakow 31-007, Poland. ; National Cancer Institute, Gaithersburg, MD 20877, USA and. ; Chair of Epidemiology and Preventive Medicine, Jagiellonian University Medical College, Krakow 31-007, Poland. Y1 - 2016/08/26/ PY - 2016 DA - 2016 Aug 26 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1856590867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Significant+interactions+between+maternal+PAH+exposure+and+single+nucleotide+polymorphisms+in+candidate+genes+on+B%5Ba%5DP-DNA+adducts+in+a+cohort+of+non-smoking+Polish+mothers+and+newborns.&rft.au=Iyer%2C+Shoba%3BWang%2C+Ya%3BXiong%2C+Wei%3BTang%2C+Deliang%3BJedrychowski%2C+Wieslaw%3BChanock%2C+Stephen%3BWang%2C+Shuang%3BStigter%2C+Laura%3BMr%C3%B3z%2C+Elzbieta%3BPerera%2C+Frederica&rft.aulast=Iyer&rft.aufirst=Shoba&rft.date=2016-08-26&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=1460-2180&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-09-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells. AN - 1811294643; 27320055 AB - Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5mM, with similar effects observed after MDPV exposures starting at 1mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced disruption of the endothelial monolayer from 1mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥0.5mM without vacuole formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic. Published by Elsevier Ireland Ltd. JF - Neuroscience letters AU - Rosas-Hernandez, Hector AU - Cuevas, Elvis AU - Lantz, Susan M AU - Rice, Kenner C AU - Gannon, Brenda M AU - Fantegrossi, William E AU - Gonzalez, Carmen AU - Paule, Merle G AU - Ali, Syed F AD - Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, USA. ; Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA/NIAAA, Bethesda, MD, USA. ; Department of Pharmacology & Toxicology, UAMS, Little Rock, AR, USA. ; Facultad de Ciencias Quimicas, UASLP, SLP, Mexico. ; Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, USA. Electronic address: Syed.Ali@fda.hhs.gov. Y1 - 2016/08/26/ PY - 2016 DA - 2016 Aug 26 SP - 125 EP - 130 VL - 629 KW - Index Medicus KW - MDPV KW - Methamphetamine KW - Cytotoxicity KW - Blood-brain barrier KW - MDMA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811294643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=Methamphetamine%2C+3%2C4-methylenedioxymethamphetamine+%28MDMA%29+and+3%2C4-methylenedioxypyrovalerone+%28MDPV%29+induce+differential+cytotoxic+effects+in+bovine+brain+microvessel+endothelial+cells.&rft.au=Rosas-Hernandez%2C+Hector%3BCuevas%2C+Elvis%3BLantz%2C+Susan+M%3BRice%2C+Kenner+C%3BGannon%2C+Brenda+M%3BFantegrossi%2C+William+E%3BGonzalez%2C+Carmen%3BPaule%2C+Merle+G%3BAli%2C+Syed+F&rft.aulast=Rosas-Hernandez&rft.aufirst=Hector&rft.date=2016-08-26&rft.volume=629&rft.issue=&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=1872-7972&rft_id=info:doi/10.1016%2Fj.neulet.2016.06.029 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neulet.2016.06.029 ER - TY - JOUR T1 - Highly Selective Dopamine D3 Receptor (D3R) Antagonists and Partial Agonists Based on Eticlopride and the D3R Crystal Structure: New Leads for Opioid Dependence Treatment. AN - 1814655461; 27508895 AB - The recent and precipitous increase in opioid analgesic abuse and overdose has inspired investigation of the dopamine D3 receptor (D3R) as a target for therapeutic intervention. Metabolic instability or predicted toxicity has precluded successful translation of previously reported D3R-selective antagonists to clinical use for cocaine abuse. Herein, we report a series of novel and D3R crystal structure-guided 4-phenylpiperazines with exceptionally high D3R affinities and/or selectivities with varying efficacies. Lead compound 19 was selected based on its in vitro profile: D3R Ki = 6.84 nM, 1700-fold D3R versus D2R binding selectivity, and its metabolic stability in mouse microsomes. Compound 19 inhibited oxycodone-induced hyperlocomotion in mice and reduced oxycodone-induced locomotor sensitization. In addition, pretreatment with 19 also dose-dependently inhibited the acquisition of oxycodone-induced conditioned place preference (CPP) in rats. These findings support the D3R as a target for opioid dependence treatment and compound 19 as a new lead molecule for development. JF - Journal of medicinal chemistry AU - Kumar, Vivek AU - Bonifazi, Alessandro AU - Ellenberger, Michael P AU - Keck, Thomas M AU - Pommier, Elie AU - Rais, Rana AU - Slusher, Barbara S AU - Gardner, Eliot AU - You, Zhi-Bing AU - Xi, Zheng-Xiong AU - Newman, Amy Hauck AD - Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health , 333 Cassell Drive, Baltimore, Maryland 21224, United States. ; Department of Neurology, Johns Hopkins Drug Discovery, The Johns Hopkins University School of Medicine , 855 North Wolfe Street, Baltimore, Maryland 21205, United States. Y1 - 2016/08/25/ PY - 2016 DA - 2016 Aug 25 SP - 7634 EP - 7650 VL - 59 IS - 16 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814655461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Highly+Selective+Dopamine+D3+Receptor+%28D3R%29+Antagonists+and+Partial+Agonists+Based+on+Eticlopride+and+the+D3R+Crystal+Structure%3A+New+Leads+for+Opioid+Dependence+Treatment.&rft.au=Kumar%2C+Vivek%3BBonifazi%2C+Alessandro%3BEllenberger%2C+Michael+P%3BKeck%2C+Thomas+M%3BPommier%2C+Elie%3BRais%2C+Rana%3BSlusher%2C+Barbara+S%3BGardner%2C+Eliot%3BYou%2C+Zhi-Bing%3BXi%2C+Zheng-Xiong%3BNewman%2C+Amy+Hauck&rft.aulast=Kumar&rft.aufirst=Vivek&rft.date=2016-08-25&rft.volume=59&rft.issue=16&rft.spage=7634&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=1520-4804&rft_id=info:doi/10.1021%2Facs.jmedchem.6b00860 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jmedchem.6b00860 ER - TY - JOUR T1 - Multiwalled Carbon Nanotube Functionalization with High Molecular Weight Hyaluronan Significantly Reduces Pulmonary Injury. AN - 1813900754; 27459049 AB - Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs. Using in vivo and in vitro approaches, we investigated the effectiveness of MWCNT functionalization with HA in increasing nanotube biocompatibility and reducing lung inflammatory and fibrotic effects. We utilized three-dimensional cultures of differentiated primary human bronchial epithelia to translate findings from rodent assays to humans. We found that HA functionalization increased stability and dispersion of MWCNTs and reduced postexposure lung inflammation, fibrosis, and mucus cell metaplasia compared with nonfunctionalized MWCNTs. Cocultures of fully differentiated bronchial epithelial cells (cultivated at air-liquid interface) and human lung fibroblasts (submerged) displayed significant reduction in injury, oxidative stress, as well as pro-inflammatory gene and protein expression after exposure to HA-functionalized MWCNTs compared with MWCNTs alone. In contrast, neither type of nanotubes stimulated cytokine production in primary human alveolar macrophages. In aggregate, our results demonstrate the effectiveness of HA functionalization as a safer design approach to eliminate MWCNT-induced lung injury and suggest that HA functionalization works by reducing MWCNT-induced epithelial injury. JF - ACS nano AU - Hussain, Salik AU - Ji, Zhaoxia AU - Taylor, Alexia J AU - DeGraff, Laura M AU - George, Margaret AU - Tucker, Charles J AU - Chang, Chong Hyun AU - Li, Ruibin AU - Bonner, James C AU - Garantziotis, Stavros AD - Clinical Research Unit, National Institute of Environmental Health Sciences (NIEHS)/National Institute of Health (NIH) , Research Triangle Park, North Carolina 27709, United States. ; UC Center for Environmental Implications of Nanotechnology, University of California , Los Angeles, California 90095, United States. ; Toxicology Program, Department of Biological Sciences, North Carolina State University , Raleigh, North Carolina 27695, United States. Y1 - 2016/08/23/ PY - 2016 DA - 2016 Aug 23 SP - 7675 EP - 7688 VL - 10 IS - 8 KW - Index Medicus KW - multiwalled carbon nanotubes KW - lung KW - inflammation KW - mucous metaplasia KW - hyaluronan KW - differentiated human bronchial epithelia KW - fibrosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1813900754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+nano&rft.atitle=Multiwalled+Carbon+Nanotube+Functionalization+with+High+Molecular+Weight+Hyaluronan+Significantly+Reduces+Pulmonary+Injury.&rft.au=Hussain%2C+Salik%3BJi%2C+Zhaoxia%3BTaylor%2C+Alexia+J%3BDeGraff%2C+Laura+M%3BGeorge%2C+Margaret%3BTucker%2C+Charles+J%3BChang%2C+Chong+Hyun%3BLi%2C+Ruibin%3BBonner%2C+James+C%3BGarantziotis%2C+Stavros&rft.aulast=Hussain&rft.aufirst=Salik&rft.date=2016-08-23&rft.volume=10&rft.issue=8&rft.spage=7675&rft.isbn=&rft.btitle=&rft.title=ACS+nano&rft.issn=1936-086X&rft_id=info:doi/10.1021%2Facsnano.6b03013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acsnano.6b03013 ER - TY - JOUR T1 - Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study. AN - 1859718753; 27539829 AB - Early life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula and result in high serum concentrations. To determine if soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls. Using the Illumina HumanMethylation450 BeadChip we evaluated epigenome-wide DNA methylation in vaginal cells from four soy-formula-fed and six cow-formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and nine months of age from 50 girls (28 soy-formula-fed and 22 cow-formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue. The epigenome-wide scan suggested differences in methylation between soy-formula-fed and cow-formula-fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p<104). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls. Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene. JF - Environmental health perspectives AU - Harlid, Sophia AU - Adgent, Margaret AU - Jefferson, Wendy N AU - Panduri, Vijayalakshmi AU - Umbach, David M AU - Xu, Zongli AU - Stallings, Virginia A AU - Williams, Carmen J AU - Rogan, Walter J AU - Taylor, Jack A AD - Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. ; Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. ; Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. ; Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. ; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Y1 - 2016/08/19/ PY - 2016 DA - 2016 Aug 19 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859718753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Soy+Formula+and+Epigenetic+Modifications%3A+Analysis+of+Vaginal+Epithelial+Cells+from+Infant+Girls+in+the+IFED+Study.&rft.au=Harlid%2C+Sophia%3BAdgent%2C+Margaret%3BJefferson%2C+Wendy+N%3BPanduri%2C+Vijayalakshmi%3BUmbach%2C+David+M%3BXu%2C+Zongli%3BStallings%2C+Virginia+A%3BWilliams%2C+Carmen+J%3BRogan%2C+Walter+J%3BTaylor%2C+Jack+A&rft.aulast=Harlid&rft.aufirst=Sophia&rft.date=2016-08-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription. AN - 1812891129; 27253715 AB - Potent and selective recognition and modulation of disease-relevant RNAs remain a daunting challenge. We previously examined the utility of the U1A N-terminal RNA recognition motif as a scaffold for tailoring new RNA hairpin recognition and showed that as few as one or two mutations can result in moderate affinity (low μM dissociation constant) for the human immunodeficiency virus (HIV) trans-activation response element (TAR) RNA, an RNA hairpin controlling transcription of the human immunodeficiency virus (HIV) genome. Here, we use yeast display and saturation mutagenesis of established RNA-binding regions in U1A to identify new synthetic proteins that potently and selectively bind TAR RNA. Our best candidate has truly altered, not simply broadened, RNA-binding selectivity; it binds TAR with subnanomolar affinity (apparent dissociation constant of ∼0.5 nM) but does not appreciably bind the original U1A RNA target (U1hpII). It specifically recognizes the TAR RNA hairpin in the context of the HIV-1 5'-untranslated region, inhibits the interaction between TAR RNA and an HIV trans-activator of transcription (Tat)-derived peptide, and suppresses Tat/TAR-dependent transcription. Proteins described in this work are among the tightest TAR RNA-binding reagents-small molecule, nucleic acid, or protein-reported to date and thus have potential utility as therapeutics and basic research tools. Moreover, our findings demonstrate how a naturally occurring RNA recognition motif can be dramatically resurfaced through mutation, leading to potent and selective recognition-and modulation-of disease-relevant RNA. JF - ACS chemical biology AU - Crawford, David W AU - Blakeley, Brett D AU - Chen, Po-Han AU - Sherpa, Chringma AU - Le Grice, Stuart F J AU - Laird-Offringa, Ite A AU - McNaughton, Brian R AD - Department of Surgery and Department of Biochemistry & Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine , Los Angeles, California 90033, United States. ; Basic Research Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States. Y1 - 2016/08/19/ PY - 2016 DA - 2016 Aug 19 SP - 2206 EP - 2215 VL - 11 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812891129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+chemical+biology&rft.atitle=An+Evolved+RNA+Recognition+Motif+That+Suppresses+HIV-1+Tat%2FTAR-Dependent+Transcription.&rft.au=Crawford%2C+David+W%3BBlakeley%2C+Brett+D%3BChen%2C+Po-Han%3BSherpa%2C+Chringma%3BLe+Grice%2C+Stuart+F+J%3BLaird-Offringa%2C+Ite+A%3BMcNaughton%2C+Brian+R&rft.aulast=Crawford&rft.aufirst=David&rft.date=2016-08-19&rft.volume=11&rft.issue=8&rft.spage=2206&rft.isbn=&rft.btitle=&rft.title=ACS+chemical+biology&rft.issn=1554-8937&rft_id=info:doi/10.1021%2Facschembio.6b00145 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acschembio.6b00145 ER - TY - JOUR T1 - Viruses and mobile elements as drivers of evolutionary transitions AN - 1808737237; PQ0003490882 AB - The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of 'public goods'. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host-parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.This article is part of the themed issue 'The major synthetic evolutionary transitions'. JF - Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences AU - Koonin, Eugene V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, , Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2016/08/19/ PY - 2016 DA - 2016 Aug 19 SP - 20150442 PB - Royal Society of London, 6 Carlton House Terrace London SW1Y 5AG United Kingdom VL - 371 IS - 1701 SN - 0962-8436, 0962-8436 KW - Virology & AIDS Abstracts; Ecology Abstracts KW - evolutionary transitions KW - mobile genetic elements KW - parasites KW - viruses KW - antivirus defence KW - host-parasite coevolution KW - Transposons KW - Parasites KW - Mathematical models KW - Coevolution KW - Genomic analysis KW - Genetic diversity KW - Autonomy KW - Plasmids KW - Pressure KW - Evolution KW - D 04040:Ecosystem and Ecology Studies KW - V 22310:Genetics, Taxonomy & Structure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808737237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Philosophical+Transactions+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.atitle=Viruses+and+mobile+elements+as+drivers+of+evolutionary+transitions&rft.au=Koonin%2C+Eugene+V&rft.aulast=Koonin&rft.aufirst=Eugene&rft.date=2016-08-19&rft.volume=371&rft.issue=1701&rft.spage=20150442&rft.isbn=&rft.btitle=&rft.title=Philosophical+Transactions+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.issn=09628436&rft_id=info:doi/10.1098%2Frstb.2015.0442 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Transposons; Parasites; Mathematical models; Coevolution; Genomic analysis; Genetic diversity; Autonomy; Pressure; Plasmids; Evolution DO - http://dx.doi.org/10.1098/rstb.2015.0442 ER - TY - JOUR T1 - Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy AN - 1850786456; PQ0003837597 AB - Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting antitumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4 super(+) CD25 super(+) Foxp3 super(+) regulatory T cells (T sub(regs)) are well-known immunosuppressor cells that play a key role in tumor immunoevasion and have been the target of systemic immunotherapies. We used CD25-targeted near-infrared photoimmunotherapy (NIR-PIT) to selectively deplete T sub(regs), thus activating CD8 T and natural killer cells and restoring local antitumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of T sub(regs), thereby providing an alternative approach to cancer immunotherapy. JF - Science Translational Medicine AU - Sato, Kazuhide AU - Sato, Noriko AU - Xu, Biying AU - Nakamura, Yuko AU - Nagaya, Tadanobu AU - Choyke, Peter L AU - Hasegawa, Yoshinori AU - Kobayashi, Hisataka AD - Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA, kobayash@mail.nih.gov Y1 - 2016/08/17/ PY - 2016 DA - 2016 Aug 17 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 United States VL - 8 IS - 352 SN - 1946-6234, 1946-6234 KW - Biotechnology and Bioengineering Abstracts KW - Translation KW - Immunoregulation KW - I.R. radiation KW - Immunotherapy KW - Natural killer cells KW - Homeostasis KW - CD8 antigen KW - Tumors KW - CD25 antigen KW - Cancer KW - Effector cells KW - CD4 antigen KW - Foxp3 protein KW - Lymphocytes T KW - Side effects KW - Antitumor activity KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1850786456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+Translational+Medicine&rft.atitle=Spatially+selective+depletion+of+tumor-associated+regulatory+T+cells+with+near-infrared+photoimmunotherapy&rft.au=Sato%2C+Kazuhide%3BSato%2C+Noriko%3BXu%2C+Biying%3BNakamura%2C+Yuko%3BNagaya%2C+Tadanobu%3BChoyke%2C+Peter+L%3BHasegawa%2C+Yoshinori%3BKobayashi%2C+Hisataka&rft.aulast=Sato&rft.aufirst=Kazuhide&rft.date=2016-08-17&rft.volume=8&rft.issue=352&rft.spage=352ra110&rft.isbn=&rft.btitle=&rft.title=Science+Translational+Medicine&rft.issn=19466234&rft_id=info:doi/10.1126%2Fscitranslmed.aaf6843 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Immunoregulation; Translation; I.R. radiation; Immunotherapy; Natural killer cells; Tumors; CD8 antigen; Homeostasis; CD25 antigen; Cancer; Effector cells; CD4 antigen; Foxp3 protein; Lymphocytes T; Side effects; Antitumor activity DO - http://dx.doi.org/10.1126/scitranslmed.aaf6843 ER - TY - JOUR T1 - Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of Non-MMSET Myeloma Patients AN - 1815701839; PQ0003584893 AB - Purpose: The poor prognosis of multiple myeloma with t(4; 14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined.Experimental Design: We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients.Results: Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways.Conclusions: MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. Clin Cancer Res; 22(16); 4039-44. [copy2016 AACR. JF - Clinical Cancer Research AU - Wu, SPeter AU - Pfeiffer, Ruth M AU - Ahn, Inhye E AU - Mailankody, Sham AU - Sonneveld, Pieter AU - van Duin, Mark AU - Munshi, Nikhil C AU - Walker, Brian A AU - Morgan, Gareth AU - Landgren, Ola AD - Multiple Myeloma Section, NCI, NIH, Bethesda, Maryland, landgrec@mskcc.org Y1 - 2016/08/15/ PY - 2016 DA - 2016 Aug 15 SP - 4039 EP - 4044 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 16 SN - 1078-0432, 1078-0432 KW - Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Probes KW - Prognosis KW - Survival KW - Clinical trials KW - Cancer KW - p53 protein KW - Gene expression KW - Myc protein KW - Multiple myeloma KW - Risk factors KW - Risk groups KW - Immunoglobulins KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815701839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Impact+of+Genes+Highly+Correlated+with+MMSET+Myeloma+on+the+Survival+of+Non-MMSET+Myeloma+Patients&rft.au=Wu%2C+SPeter%3BPfeiffer%2C+Ruth+M%3BAhn%2C+Inhye+E%3BMailankody%2C+Sham%3BSonneveld%2C+Pieter%3Bvan+Duin%2C+Mark%3BMunshi%2C+Nikhil+C%3BWalker%2C+Brian+A%3BMorgan%2C+Gareth%3BLandgren%2C+Ola&rft.aulast=Wu&rft.aufirst=SPeter&rft.date=2016-08-15&rft.volume=22&rft.issue=16&rft.spage=4039&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2366 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Myc protein; Gene expression; Multiple myeloma; Risk factors; Prognosis; Probes; Risk groups; Survival; Clinical trials; Cancer; Immunoglobulins; p53 protein DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2366 ER - TY - JOUR T1 - Probing extracellular Sonic hedgehog in neurons AN - 1815700252; PQ0003584781 AB - The bioactivity of Sonic hedgehog (Shh) depends on specific lipid modifications; a palmitate at its N-terminus and a cholesterol at its C-terminus. This dual-lipid modification makes Shh molecules lipophilic, which prevents them from diffusing freely in extracellular space. Multiple lines of evidence indicate that Shh proteins are carried by various forms of extracellular vesicles (EVs). It also has been shown, for instance, that in some tissues Shh proteins are transported to neighboring cells directly via filopodia. We have previously reported that Shh proteins are expressed in hippocampal neurons. In this study we show that, in the hippocampus and cerebellum of postnatal day (P)2 rats, Shh is mostly found near or on the membrane surface of small neurites or filopodia. We also examined cultured hippocampal neurons where we observed noticeable and widespread Shh-immunolabeled vesicles located outside neurons. Through immunoelectron microscopy and biochemical analysis, we find Shh-containing EVs with a wide range of sizes. Unlike robust Shh activity in EVs isolated from cells overexpressing an N-terminal Shh fragment construct, we did not detect measurable Shh activity in EVs purified from the medium of cultured hippocampal neurons. These results suggest the complexity of the transcellular Shh signaling mechanisms in neurons. Summary: In the developing brain, Sonic hedgehog molecules localize in neuronal filopodia and preferentially position at cell-to-cell contacts. In cultured neurons, Sonic hedgehog is also found in extracellular vesicles. JF - Biology Open AU - Eitan, Erez AU - Petralia, Ronald S AU - Wang, Ya-Xian AU - Indig, Fred E AU - Mattson, Mark P AU - Yao, Pamela J AD - Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA, yaopa@grc.nia.nih.gov Y1 - 2016/08/15/ PY - 2016 DA - 2016 Aug 15 SP - 1086 EP - 1092 PB - The Company of Biologists Ltd., 140 Cowley Rd Cambridge, CB4 0DL United Kingdom VL - 5 IS - 8 SN - 2046-6390, 2046-6390 KW - Biotechnology and Bioengineering Abstracts KW - Sonic hedgehog KW - Hippocampal neurons KW - Extracellular vesicle KW - Filopodia KW - Hippocampus KW - Lipids KW - C-Terminus KW - Brain KW - Cerebellum KW - Biochemical analysis KW - Immunoelectron microscopy KW - Cholesterol KW - Lipophilic KW - N-Terminus KW - Pseudopodia KW - Hedgehog protein KW - Palmitic acid KW - Neurons KW - Vesicles KW - Axons KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815700252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+Open&rft.atitle=Probing+extracellular+Sonic+hedgehog+in+neurons&rft.au=Eitan%2C+Erez%3BPetralia%2C+Ronald+S%3BWang%2C+Ya-Xian%3BIndig%2C+Fred+E%3BMattson%2C+Mark+P%3BYao%2C+Pamela+J&rft.aulast=Eitan&rft.aufirst=Erez&rft.date=2016-08-15&rft.volume=5&rft.issue=8&rft.spage=1086&rft.isbn=&rft.btitle=&rft.title=Biology+Open&rft.issn=20466390&rft_id=info:doi/10.1242%2Fbio.019422 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Hippocampus; Lipids; C-Terminus; Cerebellum; Brain; Biochemical analysis; Cholesterol; Immunoelectron microscopy; Lipophilic; N-Terminus; Hedgehog protein; Pseudopodia; Neurons; Palmitic acid; Axons; Vesicles DO - http://dx.doi.org/10.1242/bio.019422 ER - TY - JOUR T1 - VAR2CSA Domain-Specific Analysis of Naturally Acquired Functional Antibodies to Plasmodium falciparum Placental Malaria AN - 1811887179; PQ0003534623 AB - Background. Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) that surface-express VAR2CSA and bind chondroitin sulfate A. The inflammatory response to placenta-sequestered parasites is associated with poor pregnancy outcomes, and protection may be mediated in part by VAR2CSA antibodies that block placental IE adhesion. Methods. In this study, we used a new approach to assess VAR2CSA domains for functional epitopes recognized by naturally acquired antibodies. Antigen-specific immunoglobulin (Ig) G targeting Duffy binding-like (DBL) domains from different alleles were sequentially purified from plasma pooled from multigravid women and then characterized using enzyme-linked immunosorbent assay, flow cytometry, and antiadhesion assays. Results. Different DBL domain-specific IgGs could react to homologous as well as heterologous antigens and parasites, suggesting that conserved epitopes are shared between allelic variants. Homologous blocking of IE binding was observed with ID1-DBL2-ID2a-, DBL4-, and DBL5-specific IgG (range, 42%-75%), whereas partial cross-inhibition activity was observed with purified IgG specific to ID1-DBL2-ID2a and DBL4 antigens. Plasma retained broadly neutralizing activity after complete depletion of these VAR2CSA specificities. Conclusions. Broadly neutralizing antibodies of multigravidae are not depleted on VAR2CSA recombinant antigens, and hence development of VAR2CSA vaccines based on a single construct and variant might induce antibodies with limited broadly neutralizing activity. JF - Journal of Infectious Diseases AU - Doritchamou, Justin Yai Alamou AU - Herrera, Raul AU - Aebig, Joan A AU - Morrison, Robert AU - Nguyen, Vu AU - Reiter, Karine AU - Shimp, Richard L AU - Macdonald, Nicholas J AU - Narum, David L AU - Fried, Michal AU - Duffy, Patrick E AD - Laboratory of Malaria Immunology & Vaccinology, National Institute of Allergy and Infectious Disease, National Institute of Health, Rockville, Maryland, patrick.duffy@nih.gov Y1 - 2016/08/15/ PY - 2016 DA - 2016 Aug 15 SP - 577 EP - 586 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 214 IS - 4 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts; Health & Safety Science Abstracts KW - malaria KW - pregnancy KW - multigravidae KW - VAR2CSA KW - DBL domains KW - functional antibody KW - vaccine KW - Sulfates KW - Parasites KW - Enzyme-linked immunosorbent assay KW - Chondroitin sulfate KW - Erythrocytes KW - Malaria KW - Plasmodium falciparum KW - Adhesion KW - Inflammation KW - Pregnancy KW - Flow cytometry KW - Infectious diseases KW - Placenta KW - Immunoglobulin G KW - Vaccines KW - Immunoassays KW - Epitopes KW - K 03300:Methods KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811887179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=VAR2CSA+Domain-Specific+Analysis+of+Naturally+Acquired+Functional+Antibodies+to+Plasmodium+falciparum+Placental+Malaria&rft.au=Doritchamou%2C+Justin+Yai+Alamou%3BHerrera%2C+Raul%3BAebig%2C+Joan+A%3BMorrison%2C+Robert%3BNguyen%2C+Vu%3BReiter%2C+Karine%3BShimp%2C+Richard+L%3BMacdonald%2C+Nicholas+J%3BNarum%2C+David+L%3BFried%2C+Michal%3BDuffy%2C+Patrick+E&rft.aulast=Doritchamou&rft.aufirst=Justin+Yai&rft.date=2016-08-15&rft.volume=214&rft.issue=4&rft.spage=577&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw197 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Flow cytometry; Parasites; Enzyme-linked immunosorbent assay; Chondroitin sulfate; Placenta; Erythrocytes; Immunoglobulin G; Malaria; Vaccines; Epitopes; Pregnancy; Inflammation; Sulfates; Infectious diseases; Immunoassays; Adhesion; Plasmodium falciparum DO - http://dx.doi.org/10.1093/infdis/jiw197 ER - TY - JOUR T1 - Polychlorinated Biphenyls Induce Oxidative DNA Adducts in Female Sprague-Dawley Rats. AN - 1811843125; 27436759 AB - Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague-Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N(6)-ethenodeoxyadenosine (1,N(6)-εdA), N(2),3-ethenoguanine (N(2),3-εG), 1,N(2)-ethenodeoxyguanosine (1,N(2)-εdG), as well as malondialdehyde (M1dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-hydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG and 1,N(6)-εdA concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 μg/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 μg/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, and M1dG. Exposure to PCB 153 (1000 μg/kg/day) for 53 wks increased 8-oxo-dG, and 1,N(6)-εdA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, 1,N(2)-εdG, and N(2),3-εG significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153, or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and carcinogenesis in female Sprague-Dawley rats. JF - Chemical research in toxicology AU - Mutlu, Esra AU - Gao, Lina AU - Collins, Leonard B AU - Walker, Nigel J AU - Hartwell, Hadley J AU - Olson, James R AU - Sun, Wei AU - Gold, Avram AU - Ball, Louise M AU - Swenberg, James A AD - National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, North Carolina 27709, United States. ; Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States. ; Department of Pharmacology and Toxicology, State University of New York at Buffalo , Buffalo, New York 14214, United States. ; Department of Biostatistics, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States. Y1 - 2016/08/15/ PY - 2016 DA - 2016 Aug 15 SP - 1335 EP - 1344 VL - 29 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811843125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Polychlorinated+Biphenyls+Induce+Oxidative+DNA+Adducts+in+Female+Sprague-Dawley+Rats.&rft.au=Mutlu%2C+Esra%3BGao%2C+Lina%3BCollins%2C+Leonard+B%3BWalker%2C+Nigel+J%3BHartwell%2C+Hadley+J%3BOlson%2C+James+R%3BSun%2C+Wei%3BGold%2C+Avram%3BBall%2C+Louise+M%3BSwenberg%2C+James+A&rft.aulast=Mutlu&rft.aufirst=Esra&rft.date=2016-08-15&rft.volume=29&rft.issue=8&rft.spage=1335&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=1520-5010&rft_id=info:doi/10.1021%2Facs.chemrestox.6b00146 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.chemrestox.6b00146 ER - TY - JOUR T1 - Laser ablation-inductively coupled plasma-mass spectrometry imaging of white and gray matter iron distribution in Alzheimer's disease frontal cortex. AN - 1798721321; 27233149 AB - Iron deposition in the brain is a feature of normal aging, though in several neurodegenerative disorders, including Alzheimer's disease, the rate of iron accumulation is more advanced than in age-matched controls. Using laser ablation-inductively coupled plasma-mass spectrometry imaging we present here a pilot study that quantitatively assessed the iron content of white and gray matter in paraffin-embedded sections from the frontal cortex of Alzheimer's and control subjects. Using the phosphorus image as a confirmed proxy for the white/gray matter boundary, we found that increased intrusion of iron into gray matter occurs in the Alzheimer's brain compared to controls, which may be indicative of either a loss of iron homeostasis in this vulnerable brain region, or provide evidence of increased inflammatory processes as a response to chronic neurodegeneration. We also observed a trend of increasing iron within the white matter of the frontal cortex, potentially indicative of disrupted iron metabolism preceding loss of myelin integrity. Considering the known potential toxicity of excessive iron in the brain, our results provide supporting evidence for the continuous development of novel magnetic resonance imaging approaches for assessing white and gray matter iron accumulation in Alzheimer's disease. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved. JF - NeuroImage AU - Hare, Dominic J AU - Raven, Erika P AU - Roberts, Blaine R AU - Bogeski, Mirjana AU - Portbury, Stuart D AU - McLean, Catriona A AU - Masters, Colin L AU - Connor, James R AU - Bush, Ashley I AU - Crouch, Peter J AU - Doble, Philip A AD - Elemental Bio-imaging Facility, University of Technology Sydney, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia. Electronic address: dominic.hare@uts.edu.au. ; Center for Functional and Molecular Imaging, Georgetown University Medical Center, United States; Advanced Magnetic Resonance Imaging Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States. ; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia. ; Department of Anatomical Pathology, Alfred Hospital, Australia; Department of Medicine, Central Clinical School, Monash University, Australia. ; Department of Neural and Behavioral Sciences, Penn State Hershey Medical Center, United States; Department of Neurosurgery, Penn State Hershey Medical Center, United States. ; Department of Pathology, School of Biomedical Sciences, University of Melbourne, Australia. ; Elemental Bio-imaging Facility, University of Technology Sydney, Australia. Electronic address: philip.doble@uts.edu.au. Y1 - 2016/08/15/ PY - 2016 DA - 2016 Aug 15 SP - 124 EP - 131 VL - 137 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1798721321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Laser+ablation-inductively+coupled+plasma-mass+spectrometry+imaging+of+white+and+gray+matter+iron+distribution+in+Alzheimer%27s+disease+frontal+cortex.&rft.au=Hare%2C+Dominic+J%3BRaven%2C+Erika+P%3BRoberts%2C+Blaine+R%3BBogeski%2C+Mirjana%3BPortbury%2C+Stuart+D%3BMcLean%2C+Catriona+A%3BMasters%2C+Colin+L%3BConnor%2C+James+R%3BBush%2C+Ashley+I%3BCrouch%2C+Peter+J%3BDoble%2C+Philip+A&rft.aulast=Hare&rft.aufirst=Dominic&rft.date=2016-08-15&rft.volume=137&rft.issue=&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=1095-9572&rft_id=info:doi/10.1016%2Fj.neuroimage.2016.05.057 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuroimage.2016.05.057 ER - TY - JOUR T1 - Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. AN - 1859713039; 27446476 AB - Human hepatocellular carcinoma (HCC) is one of the most common types of cancer and has a very poor prognosis; thus, the development of effective therapies for the treatment of advanced HCC is of high clinical priority. In the present study, the anti-oncogenic effect of combined knockdown of c-Myc expression and ectopic restoration of deleted in liver cancer 1 (DLC1) expression was investigated in human liver cancer cells. Expression of c-Myc in human HCC cells was knocked down by stable transfection with a Myc-specific short hairpin (sh) RNA vector. DLC1 expression in Huh7 cells was restored by adenovirus transduction, and the effects of DLC1 expression and c-Myc knockdown on Ras homolog gene family, member A (RhoA) levels, cell proliferation, soft agar colony formation and cell invasion were measured. Downregulation of c-Myc or re-expression of DLC1 led to a marked reduction in RhoA levels, which was associated with decreases in cell proliferation, soft agar colony formation and invasiveness; this inhibitory effect was augmented with a combination of DLC1 transduction and c-Myc suppression. To determine whether liver cell-specific delivery of DLC1 was able to enhance the inhibitory effect of c-Myc knockdown on tumor growth in vivo, DLC1 vector DNA complexed with galactosylated polyethylene glycol-linear polyethyleneimine was administered by tail vein injection to mice bearing subcutaneous xenografts of Huh7 cells transfected with shMyc or control shRNA. A cooperative inhibitory effect of DLC1 expression and c-Myc knockdown on the growth of Huh7-derived tumors was observed, suggesting that targeted liver cell delivery of DLC1 and c-Myc shRNA may serve as a possible gene therapy modality for the treatment of human HCC. JF - Oncology letters AU - Yang, Xuyu AU - Zhou, Xiaoling AU - Tone, Paul AU - Durkin, Marian E AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 2089-4262, USA; Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Development, Bethesda, MD 2089-4262, USA. ; Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 2089-4262, USA; Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 2089-4262, USA. ; Department of Medicine, Richmond University Medical Center, Staten Island, NY 10310, USA. ; Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 2089-4262, USA; Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4262, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1591 EP - 1596 VL - 12 IS - 2 SN - 1792-1074, 1792-1074 KW - Ras homolog gene family guanosine triphosphatase KW - tumorigenesis KW - deleted in liver cancer 1 KW - hepatocellular carcinoma KW - c-Myc UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859713039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+letters&rft.atitle=Cooperative+antiproliferative+effect+of+coordinated+ectopic+expression+of+DLC1+tumor+suppressor+protein+and+silencing+of+MYC+oncogene+expression+in+liver+cancer+cells%3A+Therapeutic+implications.&rft.au=Yang%2C+Xuyu%3BZhou%2C+Xiaoling%3BTone%2C+Paul%3BDurkin%2C+Marian+E%3BPopescu%2C+Nicholas+C&rft.aulast=Yang&rft.aufirst=Xuyu&rft.date=2016-08-01&rft.volume=12&rft.issue=2&rft.spage=1591&rft.isbn=&rft.btitle=&rft.title=Oncology+letters&rft.issn=17921074&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations AN - 1859496987; PQ0003988363 AB - Background: Accurate methods for cross-sectional incidence estimation are needed for HIV surveillance and prevention research. We developed an avidity assay based on the fourth-generation Genetic Systems HIV Combo Ag/Ab EIA (Bio-Rad Combo assay) and evaluated its performance. Materials and Methods: The Bio-Rad Combo assay was modified incubating samples with and without 0.025M diethylamine (DEA). The avidity index (AI) was calculated as the ratio of the DEA-treated to untreated result for a specific sample. We analyzed 2,140 samples from 808 individuals from the United States with known duration of HIV infection. The mean duration of recent infection (MDRI) and the false-recent rate (FRR, fraction of samples from individuals known to be infected >2 years misclassified as recent) were calculated for AI cutoffs of 20%-90% for the avidity assay alone and in combination with a viral load assay (VL, limit of detection 400 copies/ml). Factors associated with misclassification of samples collected greater than or equal to 2 years after infections were also evaluated. Results: The MDRI for the Bio-Rad Combo Avidity assay ranged from 50 days using an AI cutoff of 20% to 276 days using an AI cutoff of 90%; the FRR ranged from 0% to 9%. When samples with a VL 80%. In adjusted analysis, viral suppression and low CD4 cell count were significantly associated with misclassification among individuals infected >2 years. Conclusions: This modified Bio-Rad Combo Avidity assay may be a useful tool for cross-sectional HIV incidence estimation. Further research is needed to evaluate use of this assay in combination with other assays to accurately estimate population-level HIV incidence. JF - AIDS Research and Human Retroviruses AU - Kirkpatrick, Allison R AU - Patel, Eshan U AU - Celum, Connie L AU - Moore, Richard D AU - Blankson, Joel N AU - Mehta, Shruti H AU - Kirk, Gregory D AU - Margolick, Joseph B AU - Quinn, Thomas C AU - Eshleman, Susan H AU - Laeyendecker, Oliver AD - Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 756 EP - 762 PB - Mary Ann Liebert, Inc., 140 Huguenot Street New Rochelle NY 10801 United States VL - 32 IS - 8 SN - 0889-2229, 0889-2229 KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859496987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Research+and+Human+Retroviruses&rft.atitle=Development+and+Evaluation+of+a+Modified+Fourth-Generation+Human+Immunodeficiency+Virus+Enzyme+Immunoassay+for+Cross-Sectional+Incidence+Estimation+in+Clade+B+Populations&rft.au=Kirkpatrick%2C+Allison+R%3BPatel%2C+Eshan+U%3BCelum%2C+Connie+L%3BMoore%2C+Richard+D%3BBlankson%2C+Joel+N%3BMehta%2C+Shruti+H%3BKirk%2C+Gregory+D%3BMargolick%2C+Joseph+B%3BQuinn%2C+Thomas+C%3BEshleman%2C+Susan+H%3BLaeyendecker%2C+Oliver&rft.aulast=Kirkpatrick&rft.aufirst=Allison&rft.date=2016-08-01&rft.volume=32&rft.issue=8&rft.spage=756&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&rft_id=info:doi/10.1089%2Faid.2015.0198 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2017-01-01 N1 - Number of references - 32 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1089/aid.2015.0198 ER - TY - JOUR T1 - Multiple approaches to understanding and preventing elder abuse: Introduction to the cross-disciplinary National Institutes of Health workshop AN - 1844383103 AB - On October 30, 2015, the National Institutes of Health (NIH) convened a workshop, "Multiple Approaches to Understanding and Preventing Elder Abuse," in Bethesda, Maryland. The workshop brought together experts from across disciplines to discuss research challenges, opportunities, and lessons learned from other fields. Participants included experts in elder abuse, child abuse, intimate partner violence (IPV), emergency medicine, and neuroscience. In this special issue of the Journal of Elder Abuse and Neglect, participants address topics explored before, during, and after the day-long workshop. JF - Journal of Elder Abuse & Neglect AU - Saylor, Katherine Witte AD - Office of Science Policy, National Institutes of Health, Bethesda, Maryland, USA ; Office of Science Policy, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2016///Aug/Dec PY - 2016 DA - Aug/Dec 2016 SP - 179 EP - 184 CY - London PB - Taylor & Francis Group VL - 28 IS - 4-5 SN - 0894-6566 KW - Gerontology And Geriatrics KW - Child abuse KW - cross-disciplinary KW - elder abuse research KW - intimate partner violence KW - National Institutes of Health KW - workshop KW - Adult abuse & neglect KW - Child abuse & neglect KW - Domestic violence KW - Interdisciplinary aspects KW - Medicine KW - Elder Abuse KW - Children KW - Partner Abuse KW - Child Abuse KW - 2190:social problems and social welfare; victimology (rape, family violence, & child abuse) KW - 6143:child & family welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844383103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Elder+Abuse+%26+Neglect&rft.atitle=Multiple+approaches+to+understanding+and+preventing+elder+abuse%3A+Introduction+to+the+cross-disciplinary+National+Institutes+of+Health+workshop&rft.au=Saylor%2C+Katherine+Witte&rft.aulast=Saylor&rft.aufirst=Katherine&rft.date=2016-08-01&rft.volume=28&rft.issue=4-5&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Journal+of+Elder+Abuse+%26+Neglect&rft.issn=08946566&rft_id=info:doi/10.1080%2F08946566.2016.1235998 LA - English DB - Social Services Abstracts; Sociological Abstracts N1 - Copyright - This article not subject to US copyright law. N1 - Last updated - 2017-01-27 DO - http://dx.doi.org/10.1080/08946566.2016.1235998 ER - TY - JOUR T1 - Elder mistreatment in underserved populations: Opportunities and challenges to developing a contemporary program of research AN - 1844382998 AB - This article provides an overview of the status of research on elder mistreatment among underserved populations in the United States, including gaps in our current knowledge base and scientific and structural barriers to growing research on the exploitation, neglect, and abuse of older people from diverse and disadvantaged ethnic/racial, geographic, sexual identity, and socioeconomic groups. High-priority areas in need of new elder mistreatment research with underserved populations are identified, and suggestions are given for how this research can be facilitated by researchers, university institutional review boards, and funding agencies. JF - Journal of Elder Abuse & Neglect AU - Jervis, Lori L AU - Hamby, Sherry AU - Beach, Scott R AU - Williams, Mary L AU - Maholmes, Valerie AU - Castille, Dorothy M AD - Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA; Center for Applied Social Research, University of Oklahoma, Norman, Oklahoma, USA ; Life Paths Appalachian Research Center, Monteagle, Tennessee, USA; Department of Psychology, University of the South, Sewanee, Tennessee, USA ; University Center for Social and Urban Research (UCSUR), University of Pittsburgh, Pittsburgh, Pennsylvania, USA ; Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA ; Pediatric Trauma and Critical Illness Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA ; National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, Maryland, USA ; Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA; Center for Applied Social Research, University of Oklahoma, Norman, Oklahoma, USA Y1 - 2016///Aug/Dec PY - 2016 DA - Aug/Dec 2016 SP - 301 EP - 319 CY - London PB - Taylor & Francis Group VL - 28 IS - 4-5 SN - 0894-6566 KW - Gerontology And Geriatrics KW - Elder mistreatment KW - ethnic/racial minorities KW - poverty KW - rural KW - underserved KW - Research KW - Review boards KW - Ethnicity KW - Disadvantaged KW - Elder Abuse KW - Sexuality KW - Ethnic Identity KW - Socioeconomic Status KW - Scientific Knowledge KW - Elderly KW - Exploitation KW - 2190:social problems and social welfare; victimology (rape, family violence, & child abuse) KW - 6143:child & family welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1844382998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Elder+Abuse+%26+Neglect&rft.atitle=Elder+mistreatment+in+underserved+populations%3A+Opportunities+and+challenges+to+developing+a+contemporary+program+of+research&rft.au=Jervis%2C+Lori+L%3BHamby%2C+Sherry%3BBeach%2C+Scott+R%3BWilliams%2C+Mary+L%3BMaholmes%2C+Valerie%3BCastille%2C+Dorothy+M&rft.aulast=Jervis&rft.aufirst=Lori&rft.date=2016-08-01&rft.volume=28&rft.issue=4-5&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Journal+of+Elder+Abuse+%26+Neglect&rft.issn=08946566&rft_id=info:doi/10.1080%2F08946566.2016.1245644 LA - English DB - Social Services Abstracts; Sociological Abstracts N1 - Copyright - © 2016 Taylor & Francis N1 - Last updated - 2017-01-27 DO - http://dx.doi.org/10.1080/08946566.2016.1245644 ER - TY - JOUR T1 - Novel cell-based assay for detection of thyroid receptor beta-interacting environmental contaminants AN - 1837324520; PQ0003764237 AB - Even though the presence of endocrine disrupting chemicals (EDCs) with thyroid hormone (TH)-like activities in the environment is a major health concern, the methods for their efficient detection and monitoring are still limited. Here we describe a novel cell assay, based on the translocation of a green fluorescent protein (GFP)-tagged chimeric molecule of glucocorticoid receptor (GR) and the thyroid receptor beta (TR beta ) from the cytoplasm to the nucleus in the presence of TR ligands. Unlike the constitutively nuclear TR beta , this GFP-GR-TR beta chimera is cytoplasmic in the absence of hormone while translocating to the nucleus in a time- and concentration-dependent manner upon stimulation with triiodothyronine (T3) and thyroid hormone analogue, TRIAC, while the reverse triiodothyronine (3,3',5'-triiodothyronine, or rT3) was inactive. Moreover, GFP-GR-TR beta chimera does not show any cross-reactivity with the GR-activating hormones, thus providing a clean system for the screening of TR beta-interacting EDCs. Using this assay, we demonstrated that Bisphenol A (BPA) and 3,3',5,5'-Tetrabromobisphenol (TBBPA) induced GFP-GR-TR beta translocation at micro molar concentrations. We screened over 100 concentrated water samples from different geographic locations in the United States and detected a low, but reproducible contamination in 53% of the samples. This system provides a novel high-throughput approach for screening for endocrine disrupting chemicals (EDCs) interacting with TR beta. JF - Toxicology AU - Stavreva, Diana A AU - Varticovski, Lyuba AU - Levkova, Ludmila AU - George, Anuja A AU - Davis, Luke AU - Pegoraro, Gianluca AU - Blazer, Vicki AU - Iwanowicz, Luke AU - Hager, Gordon L AD - Laboratory of Receptor Biology and Gene Expression, Building 41, B602, 41 Library Dr., National Cancer Institute, NIH, Bethesda, MD 20892-5055, United States Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 69 EP - 79 PB - Elsevier B.V., P.O. Box 85 Limerick Ireland VL - 368 SN - 0300-483X, 0300-483X KW - Pollution Abstracts; Environment Abstracts; Toxicology Abstracts KW - EDCs endocrine disrupting chemicals KW - TH thyroid hormone KW - GR glucocorticoid receptor KW - TR thyroid receptor KW - T3 3,3',5-triiodothyronine KW - TRIAC Tiratricol or triiodothyroacetic acid KW - rT3 reverse triiodothyronine or 3,3',5'-triiodothyronine KW - T4 thyroxine KW - BPA Bisphenol A KW - TBBPA 3,3',5,5'-tetrabromobisphenol A KW - TREs TH-response elements KW - RXR retinoid X receptor KW - NCoR nuclear corepressor KW - SMRT silencing mediator of retinoid and thyroid hormone receptor KW - HDAC histone deacetylase KW - HAT histone acetyl transferase KW - POCIS polar organic chemical integrative samplers KW - DBD DNA binding domain KW - LBD ligand binding domain KW - hPCK1 phosphoenolpyruvate carboxykinase 1 KW - COQ10A coenzyme Q10 homolog A KW - GAPDH glyceraldehyde-3-phosphate dehydrogenase KW - T3-EQ T3-equivalent KW - EDCs KW - TR beta KW - High-throughput cell assay KW - BPA KW - TBBPA KW - Chemicals KW - Pollution monitoring KW - Cross-reactivity KW - Water sampling KW - Contamination KW - Endocrine disruptors KW - Green fluorescent protein KW - Hormones KW - Bisphenol A KW - Nuclear transport KW - Thyroid hormones KW - Cytoplasm KW - Nuclei KW - Translocation KW - Protein transport KW - Thyroid KW - Assays KW - Triiodothyronine KW - Chimeras KW - USA KW - Glucocorticoid receptors KW - Proteins KW - Contaminants KW - P 2000:FRESHWATER POLLUTION KW - X 24350:Industrial Chemicals KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1837324520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Novel+cell-based+assay+for+detection+of+thyroid+receptor+beta-interacting+environmental+contaminants&rft.au=Stavreva%2C+Diana+A%3BVarticovski%2C+Lyuba%3BLevkova%2C+Ludmila%3BGeorge%2C+Anuja+A%3BDavis%2C+Luke%3BPegoraro%2C+Gianluca%3BBlazer%2C+Vicki%3BIwanowicz%2C+Luke%3BHager%2C+Gordon+L&rft.aulast=Stavreva&rft.aufirst=Diana&rft.date=2016-08-01&rft.volume=368&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2016.08.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-11-01 N1 - Number of references - 46 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Protein transport; Cross-reactivity; Contamination; Endocrine disruptors; Green fluorescent protein; Triiodothyronine; Bisphenol A; Thyroid hormones; Chimeras; Nuclear transport; Glucocorticoid receptors; Cytoplasm; Contaminants; Nuclei; Translocation; Chemicals; Pollution monitoring; Water sampling; Thyroid; Assays; Proteins; Hormones; USA DO - http://dx.doi.org/10.1016/j.tox.2016.08.012 ER - TY - JOUR T1 - Linking DNA adduct formation and human cancer risk in chemical carcinogenesis AN - 1815705939; PQ0003581844 AB - Over two centuries ago, Sir Percival Pott, a London surgeon, published a pioneering treatise showing that soot exposure was the cause of high incidences of scrotal cancers occurring in young men who worked as chimney sweeps. Practicing at a time when cellular pathology was not yet recognized, Sir Percival nonetheless observed that the high incidence and short latency of the chimney sweep cancers, was fundamentally different from the rare scrotal cancers typically found in elderly men. Furthermore, his diagnosis that the etiology of these cancers was related to chimney soot exposure, was absolutely accurate, conceptually novel, and initiated the field of "occupational cancer epidemiology." After many intervening years of research focused on mechanisms of chemical carcinogenesis, briefly described here, it is clear that DNA damage, or DNA adduct formation, is "necessary but not sufficient" for tumor induction, and that many additional factors contribute to carcinogenesis. This review includes a synopsis of carcinogen-induced DNA adduct formation in experimental models and in the human population, with particular attention paid to molecular dosimetry and molecular cancer epidemiology. Environ. Mol. Mutagen. 57:499-507, 2016. JF - Environmental and Molecular Mutagenesis AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bldg 37, Rm 4032, NIH. 37 Convent Drive, MSC-4255, Bethesda, Maryland. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 499 EP - 507 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 57 IS - 7 SN - 0893-6692, 0893-6692 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Environment Abstracts KW - Mutagens KW - Molecular modelling KW - Pathology KW - British Isles, England, Greater London, London KW - Elderly KW - Medical personnel KW - Mutagenesis KW - Geriatrics KW - Occupational exposure KW - DNA adducts KW - Etiology KW - Human populations KW - Dosimetry KW - Tumors KW - Cancer KW - Health risks KW - DNA damage KW - Soot KW - Epidemiology KW - Reviews KW - Carcinogenesis KW - DNA KW - N 14820:DNA Metabolism & Structure KW - X 24300:Methods KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815705939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+Molecular+Mutagenesis&rft.atitle=Linking+DNA+adduct+formation+and+human+cancer+risk+in+chemical+carcinogenesis&rft.au=Poirier%2C+Miriam+C&rft.aulast=Poirier&rft.aufirst=Miriam&rft.date=2016-08-01&rft.volume=57&rft.issue=7&rft.spage=499&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/10.1002%2Fem.22030 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - DNA adducts; Molecular modelling; Mutagens; Etiology; Dosimetry; Tumors; Cancer; Mutagenesis; DNA damage; Epidemiology; Carcinogenesis; Geriatrics; Occupational exposure; Pathology; Human populations; Elderly; Medical personnel; Health risks; Soot; Reviews; DNA; British Isles, England, Greater London, London DO - http://dx.doi.org/10.1002/em.22030 ER - TY - JOUR T1 - Signaling via pattern recognition receptors NOD2 and TLR2 contributes to immunomodulatory control of lethal pneumovirus infection AN - 1815697804; PQ0003565038 AB - Pattern recognition receptors (PRRs) engage microbial components in the lung, although their role in providing primary host defense against respiratory virus infection is not fully understood. We have previously shown that Gram-positive Lactobacillus plantarum (Lp) administered to the respiratory tract promotes full and sustained protection in response to an otherwise lethal mouse pneumovirus (PVM) infection, a robust example of heterologous immunity. While Lp engages PRRs TLR2 and NOD2 in ex vivo signaling assays, we found that Lp-mediated protection was unimpaired in single gene-deleted TLR2-/- and NOD2-/- mice. Here we demonstrate substantial loss of Lp-mediated protection in a double gene-deleted NOD2-/-TLR2-/- strain. Furthermore, we demonstrate protection against PVM infection by administration of the bi-functional NOD2-TLR2 agonist, CL-429. The bi-functional NOD2-TLR2 ligand CL-429 not only suppresses virus-induced inflammation, it is significantly more effective at preventing lethal infection than equivalent amounts of mono-molecular TLR2 and NOD2 agonists. Interestingly, and in contrast to biochemical NOD2 and/or TLR2 agonists, Lp remained capable of eliciting primary proinflammatory responses from NOD2-/-TLR2-/- mice in vivo and from alveolar macrophages challenged ex vivo. Taken together, we conclude that coordinate engagement of NOD2 and TLR2 constitutes a key step in the genesis of Lp-mediated protection from a lethal respiratory virus infection, and represents a critical target for modulation of virus-induced inflammatory pathology. JF - Antiviral Research AU - Rice, Tyler A AU - Brenner, Todd A AU - Percopo, Caroline M AU - Ma, Michelle AU - Keicher, Jesse D AU - Domachowske, Joseph B AU - Rosenberg, Helene F AD - Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 131 EP - 140 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 132 SN - 0166-3542, 0166-3542 KW - Immunology Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Inflammation KW - Cytokines KW - Pattern recognition receptors KW - Pneumovirus KW - Probiotic KW - PVM pneumonia virus of mice KW - Lp Lactobacillus plantarum KW - RSV respiratory syncytial virus KW - PRR pattern recognition receptor KW - Macrophages KW - NOD2 protein KW - Plant protection KW - Lactobacillus plantarum KW - TLR2 protein KW - Immunity KW - Infection KW - Immunomodulation KW - Alveoli KW - Pattern recognition KW - Lung KW - Toll-like receptors KW - Respiratory tract KW - A 01340:Antibiotics & Antimicrobials KW - V 22410:Animal Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815697804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+Research&rft.atitle=Signaling+via+pattern+recognition+receptors+NOD2+and+TLR2+contributes+to+immunomodulatory+control+of+lethal+pneumovirus+infection&rft.au=Rice%2C+Tyler+A%3BBrenner%2C+Todd+A%3BPercopo%2C+Caroline+M%3BMa%2C+Michelle%3BKeicher%2C+Jesse+D%3BDomachowske%2C+Joseph+B%3BRosenberg%2C+Helene+F&rft.aulast=Rice&rft.aufirst=Tyler&rft.date=2016-08-01&rft.volume=132&rft.issue=&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2Fj.antiviral.2016.06.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Macrophages; NOD2 protein; Plant protection; TLR2 protein; Immunity; Infection; Immunomodulation; Alveoli; Inflammation; Pattern recognition; Lung; Toll-like receptors; Respiratory tract; Pneumovirus; Lactobacillus plantarum DO - http://dx.doi.org/10.1016/j.antiviral.2016.06.002 ER - TY - JOUR T1 - Mitochondrial compromise in 3-year old patas monkeys exposed in utero to human-equivalent antiretroviral therapies AN - 1815690862; PQ0003581847 AB - Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother-to-child transmission of human immunodeficiency virus 1 (HIV-1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15-year old human) after exposure of the dams to human-equivalent in utero ARV exposure protocols. Pregnant patas dams (3-5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P < 0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3-year-old patas offspring was 50% reduced in AZT/3TC/ABC-exposed patas (P < 0.01), but not in AZT/3TC/NVP-exposed patas. Overall the data show that 3-year-old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526-534, 2016. JF - Environmental and Molecular Mutagenesis AU - Liu, Yongmin AU - Shim Park, Eunwoo AU - Gibbons, Alexander T AU - Shide, Eric D AU - Divi, Rao L AU - Woodward, Ruth A AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, Laboratory of Cancer Biology and Genetics, CCR, National Cancer Institute, NIH, Bethesda, Madison. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 526 EP - 534 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 57 IS - 7 SN - 0893-6692, 0893-6692 KW - Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Environment Abstracts KW - Mutagens KW - Age KW - Viruses KW - Bone marrow KW - Zidovudine KW - Mitochondria KW - Offspring KW - Mutagenesis KW - Fibroblasts KW - Disease transmission KW - Lentivirus KW - Antiviral agents KW - Perinatal exposure KW - Dams KW - Hybrids KW - Human immunodeficiency virus 1 KW - Gestation KW - Chemiluminescence KW - Mesenchyme KW - Abacavir KW - Drugs KW - Electron microscopy KW - Oxygen consumption KW - Heart KW - Data processing KW - Intrauterine exposure KW - Children KW - Antiretroviral agents KW - Fetuses KW - Pregnancy KW - Birth KW - Nevirapine KW - Mitochondrial DNA KW - Morphology KW - Microscopy KW - Progeny KW - Erythrocebus patas KW - Infants KW - V 22360:AIDS and HIV KW - N 14840:Antisense, Nucleotide Analogs KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815690862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+and+Molecular+Mutagenesis&rft.atitle=Mitochondrial+compromise+in+3-year+old+patas+monkeys+exposed+in+utero+to+human-equivalent+antiretroviral+therapies&rft.au=Liu%2C+Yongmin%3BShim+Park%2C+Eunwoo%3BGibbons%2C+Alexander+T%3BShide%2C+Eric+D%3BDivi%2C+Rao+L%3BWoodward%2C+Ruth+A%3BPoirier%2C+Miriam+C&rft.aulast=Liu&rft.aufirst=Yongmin&rft.date=2016-08-01&rft.volume=57&rft.issue=7&rft.spage=526&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/10.1002%2Fem.22033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Mutagens; Age; Bone marrow; Mitochondria; Zidovudine; Disease transmission; Fibroblasts; Mutagenesis; Perinatal exposure; Antiviral agents; Dams; Hybrids; Gestation; Abacavir; Mesenchyme; Chemiluminescence; Drugs; Electron microscopy; Heart; Oxygen consumption; Data processing; Intrauterine exposure; Children; Fetuses; Pregnancy; Birth; Mitochondrial DNA; Nevirapine; Progeny; Infants; Viruses; Offspring; Antiretroviral agents; Microscopy; Morphology; Lentivirus; Human immunodeficiency virus 1; Erythrocebus patas DO - http://dx.doi.org/10.1002/em.22033 ER - TY - JOUR T1 - Linear combination methods to improve diagnostic/prognostic accuracy on future observations AN - 1814271964 AB - Multiple diagnostic tests or biomarkers can be combined to improve diagnostic accuracy. The problem of finding the optimal linear combinations of biomarkers to maximise the area under the receiver operating characteristic curve has been extensively addressed in the literature. The purpose of this article is threefold: (1) to provide an extensive review of the existing methods for biomarker combination; (2) to propose a new combination method, namely, the nonparametric stepwise approach; (3) to use leave-one-pair-out cross-validation method, instead of re-substitution method, which is overoptimistic and hence might lead to wrong conclusion, to empirically evaluate and compare the performance of different linear combination methods in yielding the largest area under receiver operating characteristic curve. A data set of Duchenne muscular dystrophy was analysed to illustrate the applications of the discussed combination methods. JF - Statistical Methods in Medical Research AU - Kang, Le AU - Liu, Aiyi AU - Tian, Lili AD - Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA ; Biostatistics and Bioinformatics Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA ; Department of Biostatistics, State University of New York at Buffalo, Buffalo, NY, USA ; Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA Y1 - 2016/08// PY - 2016 DA - Aug 2016 SP - 1359 EP - 1380 CY - London PB - Sage Publications Ltd. VL - 25 IS - 4 SN - 0962-2802 KW - Medical Sciences KW - Multiple biomarkers KW - receiver operating characteristic curve KW - area under the receiver operating characteristic curve KW - linear combination KW - diagnostic/prognostic accuracy KW - Accuracy KW - Biological markers KW - Duchenne muscular dystrophy KW - Prognosis KW - Validation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814271964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistical+Methods+in+Medical+Research&rft.atitle=Linear+combination+methods+to+improve+diagnostic%2Fprognostic+accuracy+on+future+observations&rft.au=Kang%2C+Le%3BLiu%2C+Aiyi%3BTian%2C+Lili&rft.aulast=Kang&rft.aufirst=Le&rft.date=2016-08-01&rft.volume=25&rft.issue=4&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=Statistical+Methods+in+Medical+Research&rft.issn=09622802&rft_id=info:doi/10.1177%2F0962280213481053 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2013 N1 - Last updated - 2016-08-27 DO - http://dx.doi.org/10.1177/0962280213481053 ER - TY - JOUR T1 - Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. AN - 1812887410; 27074126 AB - Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial. JF - Pediatric research AU - Phelps, Dale L AU - Ward, Robert M AU - Williams, Rick L AU - Nolen, Tracy L AU - Watterberg, Kristi L AU - Oh, William AU - Goedecke, Michael AU - Ehrenkranz, Richard A AU - Fennell, Timothy AU - Poindexter, Brenda B AU - Cotten, C Michael AU - Hallman, Mikko AU - Frantz, Ivan D AU - Faix, Roger G AU - Zaterka-Baxter, Kristin M AU - Das, Abhik AU - Ball, M Bethany AU - Lacy, Conra Backstrom AU - Walsh, Michele C AU - Carlo, Waldemar A AU - Sánchez, Pablo J AU - Bell, Edward F AU - Shankaran, Seetha AU - Carlton, David P AU - Chess, Patricia R AU - Higgins, Rosemary D AD - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York. ; Department of Pediatrics, and Pediatric Pharmacology, University of Utah School of Medicine, Salt Lake City, Utah. ; Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina. ; Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico. ; Department of Pediatrics, Women & Infants' Hospital Brown University, Providence, Rhode Island. ; Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut. ; Pharmacology and Toxicology Division, RTI International, Research Triangle Park, North Carolina. ; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana. ; Department of Pediatrics, Duke University, Durham, North Carolina. ; PEDEGO Research Center, and MRC Oulu, and Oulu University Hospital, Oulu, Finland. ; Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts. ; Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland. ; Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California. ; Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio. ; Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham, Birmingham, Alabama. ; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. ; Department of Pediatrics, University of Iowa, Iowa City, Iowa. ; Department of Pediatrics, Wayne State University, Detroit, Michigan. ; Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 209 EP - 217 VL - 80 IS - 2 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1812887410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+research&rft.atitle=Safety+and+pharmacokinetics+of+multiple+dose+myo-inositol+in+preterm+infants.&rft.au=Phelps%2C+Dale+L%3BWard%2C+Robert+M%3BWilliams%2C+Rick+L%3BNolen%2C+Tracy+L%3BWatterberg%2C+Kristi+L%3BOh%2C+William%3BGoedecke%2C+Michael%3BEhrenkranz%2C+Richard+A%3BFennell%2C+Timothy%3BPoindexter%2C+Brenda+B%3BCotten%2C+C+Michael%3BHallman%2C+Mikko%3BFrantz%2C+Ivan+D%3BFaix%2C+Roger+G%3BZaterka-Baxter%2C+Kristin+M%3BDas%2C+Abhik%3BBall%2C+M+Bethany%3BLacy%2C+Conra+Backstrom%3BWalsh%2C+Michele+C%3BCarlo%2C+Waldemar+A%3BS%C3%A1nchez%2C+Pablo+J%3BBell%2C+Edward+F%3BShankaran%2C+Seetha%3BCarlton%2C+David+P%3BChess%2C+Patricia+R%3BHiggins%2C+Rosemary+D&rft.aulast=Phelps&rft.aufirst=Dale&rft.date=2016-08-01&rft.volume=80&rft.issue=2&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Pediatric+research&rft.issn=1530-0447&rft_id=info:doi/10.1038%2Fpr.2016.97 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-19 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1038/pr.2016.97 ER - TY - JOUR T1 - Cortical hyperexcitability in patients with C9ORF72 mutations: Relationship to phenotype AN - 1811906774; PQ0003466745 AB - Introduction Patients with mutations in C9orf72 can have amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or ALS-FTD. The goals were to establish whether cortical hyperexcitability occurs in C9orf72 patients with different clinical presentations. Methods: Cortical thresholds and silent periods were measured in thenar muscles in 19 participants with C9orf72 expansions and 21 healthy controls using transcranial magnetic stimulation (TMS). El Escorial and Rascovsky criteria were used to diagnose ALS and FTD. Fourteen participants with C9orf72 expansions were re-tested 6 months later. Correlations with finger-tapping speed, timed peg test, the ALS functional rating scale, and Dementia Rating Scale were examined. Results: Most participants with C9orf72 expansions had normal or low cortical thresholds. Among them, ALS patients had the lowest thresholds and significantly shorter silent periods. Thresholds correlated with timed peg-test scores. TMS did not correlate with the Dementia Rating Scale. Conclusions: TMS measures of cortical excitability may serve as noninvasive biomarkers of ALS disease activity. Muscle Nerve, 2016 Muscle Nerve 54: 264-269, 2016 JF - Muscle & Nerve AU - Schanz, Olivia AU - Bageac, Devin AU - Braun, Laura AU - Traynor, Bryan J AU - Lehky, Tanya J AU - Floeter, MARY Kay AD - Motor Neuron Disorders Unit, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 264 EP - 269 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 54 IS - 2 SN - 0148-639X, 0148-639X KW - Toxicology Abstracts KW - Nerves KW - Transcranial magnetic stimulation KW - Amyotrophic lateral sclerosis KW - Cortex KW - Frontotemporal dementia KW - Dementia disorders KW - Muscles KW - Excitability KW - Mutation KW - biomarkers KW - X 24390:Radioactive Materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811906774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Muscle+%26+Nerve&rft.atitle=Cortical+hyperexcitability+in+patients+with+C9ORF72+mutations%3A+Relationship+to+phenotype&rft.au=Schanz%2C+Olivia%3BBageac%2C+Devin%3BBraun%2C+Laura%3BTraynor%2C+Bryan+J%3BLehky%2C+Tanya+J%3BFloeter%2C+MARY+Kay&rft.aulast=Schanz&rft.aufirst=Olivia&rft.date=2016-08-01&rft.volume=54&rft.issue=2&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Muscle+%26+Nerve&rft.issn=0148639X&rft_id=info:doi/10.1002%2Fmus.25047 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Nerves; Transcranial magnetic stimulation; Frontotemporal dementia; Cortex; Amyotrophic lateral sclerosis; Dementia disorders; Muscles; Excitability; biomarkers; Mutation DO - http://dx.doi.org/10.1002/mus.25047 ER - TY - JOUR T1 - A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial AN - 1811901154; PQ0003515073 AB - Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993-2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9-12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER-/PR-. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR. Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33-2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63-3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19-2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors. There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1. JF - Cancer Causes & Control AU - Falk, Roni T AU - Staff, Annetine Cathrine AU - Bradwin, Gary AU - Karumanchi, SAnanth AU - Troisi, Rebecca AD - Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, 9609 Medical Center Drive, Bethesda, MD, 20852, USA, falkr@mail.nih.gov Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1009 EP - 1017 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 27 IS - 8 SN - 0957-5243, 0957-5243 KW - Toxicology Abstracts KW - Vascular endothelial growth factor KW - Ovarian cancer KW - Invasiveness KW - Etiology KW - Prognosis KW - Angiogenesis KW - Tumors KW - Models KW - Serum levels KW - Progesterone receptors KW - Blood KW - Post-menopause KW - Placenta KW - Risk factors KW - Protein-tyrosine kinase KW - Regression analysis KW - Breast cancer KW - Estrogen receptors KW - Prostate KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811901154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=A+prospective+study+of+angiogenic+markers+and+postmenopausal+breast+cancer+risk+in+the+prostate%2C+lung%2C+colorectal%2C+and+ovarian+cancer+screening+trial&rft.au=Falk%2C+Roni+T%3BStaff%2C+Annetine+Cathrine%3BBradwin%2C+Gary%3BKarumanchi%2C+SAnanth%3BTroisi%2C+Rebecca&rft.aulast=Falk&rft.aufirst=Roni&rft.date=2016-08-01&rft.volume=27&rft.issue=8&rft.spage=1009&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1007%2Fs10552-016-0779-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 43 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Vascular endothelial growth factor; Ovarian cancer; Etiology; Invasiveness; Angiogenesis; Prognosis; Tumors; Models; Serum levels; Blood; Progesterone receptors; Post-menopause; Risk factors; Placenta; Protein-tyrosine kinase; Regression analysis; Breast cancer; Prostate; Estrogen receptors DO - http://dx.doi.org/10.1007/s10552-016-0779-5 ER - TY - JOUR T1 - Receipt of mammography recommendations among White and non-White women before and after the 2009 United States Preventive Services Task Force recommendation change AN - 1811897468; PQ0003515070 AB - Receipt of a mammography recommendation from a physician is a strong predictor of obtaining a mammogram. In 2009, the United States Preventive Services Task Force (USPSTF) recommended routine biennial mammography for women aged 50-74 but not for women aged 40-49. We examined changes in reports of clinician recommendations for mammography among White and non-White women after these age-specific recommendations were issued. Data from women aged 40-49 and 50-74 were drawn from the 2008 and 2013 National Health Interview Surveys. We used linear probability models to determine whether the proportions of women reporting a mammography recommendation changed after the USPSTF recommendation was issued and whether any changes observed differed across White and non-White women. All analyses were stratified by age groups and mammography history. Among women without a recent mammogram, reported clinician recommendations did not change for White women, but they decreased by 13-percentage points (95 % CI -0.22, -0.03) among non-White women aged 40-49 (p = 0.01) and increased by 9-percentage points (95 % CI 0.01, 0.17) among non-White women aged 50-74 (p = 0.04). Among women with a mammogram in the past 2 years, reported mammography recommendation from a clinician did not change for White or non-White women. Recommendations to reduce screening may be differentially implemented across racial/ethnic groups. Changes in reports of mammography recommendation from a clinician after the USPSTF breast cancer screening recommendation change were observed only among non-White women without a recent history of mammography. It is unclear whether these differences are due to the clinician, the women, or both. JF - Cancer Causes & Control AU - Gonzales, Felisa A AU - Taplin, Stephen H AU - Yu, Mandi AU - Breen, Nancy AU - Cronin, Kathy A AD - Division of Cancer Control and Population Sciences, National Cancer Institute, BG 9609 RM 3E502 MSC 9712, 9609 Medical Center Drive, Rockville, MD, 20850-9712, USA, Felisa.gonzales@nih.gov Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 977 EP - 987 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 27 IS - 8 SN - 0957-5243, 0957-5243 KW - Toxicology Abstracts KW - Age KW - Mammography KW - Data processing KW - Breast cancer KW - Ethnic groups KW - Models KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811897468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Receipt+of+mammography+recommendations+among+White+and+non-White+women+before+and+after+the+2009+United+States+Preventive+Services+Task+Force+recommendation+change&rft.au=Gonzales%2C+Felisa+A%3BTaplin%2C+Stephen+H%3BYu%2C+Mandi%3BBreen%2C+Nancy%3BCronin%2C+Kathy+A&rft.aulast=Gonzales&rft.aufirst=Felisa&rft.date=2016-08-01&rft.volume=27&rft.issue=8&rft.spage=977&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1007%2Fs10552-016-0775-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 65 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Age; Data processing; Mammography; Breast cancer; Ethnic groups; Models DO - http://dx.doi.org/10.1007/s10552-016-0775-9 ER - TY - JOUR T1 - Preterm birth and air pollution: Critical windows of exposure for women with asthma AN - 1811893441; PQ0003556946 AB - Background Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied. Objective We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk. Methods Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated. Results On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma. Conclusions Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy. JF - Journal of Allergy and Clinical Immunology AU - Mendola, Pauline AU - Wallace, Maeve AU - Hwang, Beom Seuk AU - Liu, Danping AU - Robledo, Candace AU - Maennisto, Tuija AU - Sundaram, Rajeshwari AU - Sherman, Seth AU - Ying, Qi AU - Grantz, Katherine L AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 432 EP - 440.e5 PB - Elsevier Science Ltd., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 138 IS - 2 SN - 0091-6749, 0091-6749 KW - Pollution Abstracts; Immunology Abstracts KW - Asthma KW - pregnancy KW - preterm birth KW - air pollution KW - CO Carbon monoxide KW - NOx Nitrogen oxides KW - O3 Ozone KW - PM10 Particulate matter with aerodynamic diameter of less than 10 microns KW - PM2.5 Particulate matter with aerodynamic diameter of less than 2.5 microns KW - SO2 Sulfur dioxide KW - Risk assessment KW - Air quality KW - Particulates KW - Respiratory diseases KW - Nitrogen oxides KW - Allergies KW - Pregnancy KW - Carbon monoxide KW - Air pollution KW - Photochemicals KW - Sulfur dioxide KW - Aerodynamics KW - Females KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811893441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Allergy+and+Clinical+Immunology&rft.atitle=Preterm+birth+and+air+pollution%3A+Critical+windows+of+exposure+for+women+with+asthma&rft.au=Mendola%2C+Pauline%3BWallace%2C+Maeve%3BHwang%2C+Beom+Seuk%3BLiu%2C+Danping%3BRobledo%2C+Candace%3BMaennisto%2C+Tuija%3BSundaram%2C+Rajeshwari%3BSherman%2C+Seth%3BYing%2C+Qi%3BGrantz%2C+Katherine+L&rft.aulast=Mendola&rft.aufirst=Pauline&rft.date=2016-08-01&rft.volume=138&rft.issue=2&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=Journal+of+Allergy+and+Clinical+Immunology&rft.issn=00916749&rft_id=info:doi/10.1016%2Fj.jaci.2015.12.1309 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 41 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Risk assessment; Asthma; Air quality; Respiratory diseases; Particulates; Nitrogen oxides; Allergies; Pregnancy; Air pollution; Carbon monoxide; Sulfur dioxide; Photochemicals; Aerodynamics; Females DO - http://dx.doi.org/10.1016/j.jaci.2015.12.1309 ER - TY - JOUR T1 - MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research AN - 1811891351; PQ0003550939 AB - Purpose: We undertook a multidimensional clinical genomics study of children and adolescent young adults with relapsed and refractory cancers to determine the feasibility of genome-guided precision therapy.Experimental Design: Patients with non-central nervous system solid tumors underwent a combination of whole exome sequencing (WES), whole transcriptome sequencing (WTS), and high-density single-nucleotide polymorphism array analysis of the tumor, with WES of matched germline DNA. Clinically actionable alterations were identified as a reportable germline mutation, a diagnosis change, or a somatic event (including a single nucleotide variant, an indel, an amplification, a deletion, or a fusion gene), which could be targeted with drugs in existing clinical trials or with FDA-approved drugs.Results: Fifty-nine patients in 20 diagnostic categories were enrolled from 2010 to 2014. Ages ranged from 7 months to 25 years old. Seventy-three percent of the patients had prior chemotherapy, and the tumors from these patients with relapsed or refractory cancers had a higher mutational burden than that reported in the literature. Thirty patients (51% of total) had clinically actionable mutations, of which 24 (41%) had a mutation that was currently targetable in a clinical trial setting, 4 patients (7%) had a change in diagnosis, and 7 patients (12%) had a reportable germline mutation.Conclusions: We found a remarkably high number of clinically actionable mutations in 51% of the patients, and 12% with significant germline mutations. We demonstrated the clinical feasibility of next-generation sequencing in a diverse population of relapsed and refractory pediatric solid tumors. Clin Cancer Res; 22(15); 3810-20. copyright 2016 AACR. JF - Clinical Cancer Research AU - Chang, Wendy AU - Brohl, Andrew S AU - Patidar, Rajesh AU - Sindiri, Sivasish AU - Shern, Jack F AU - Wei, Jun S AU - Song, Young K AU - Yohe, Marielle E AU - Gryder, Berkley AU - Zhang, Shile AU - Calzone, Kathleen A AU - Shivaprasad, Nityashree AU - Wen, Xinyu AU - Badgett, Thomas C AU - Miettinen, Markku AU - Hartman, Kip R AU - League-Pascual, James C AU - Trahair, Toby N AU - Widemann, Brigitte C AU - Merchant, Melinda S AU - Kaplan, Rosandra N AU - Lin, Jimmy C AU - Khan, Javed AD - Department of Pediatrics, Molecular Genetics, Columbia University Medical Center, New York, New York, khanjav@mail.nih.gov Y1 - 2016/08/01/ PY - 2016 DA - 2016 Aug 01 SP - 3810 EP - 3820 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 15 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Age KW - Solid tumors KW - Pediatrics KW - Chemotherapy KW - Adolescence KW - Tumors KW - Children KW - Clinical trials KW - Cancer KW - Gene expression KW - Gene deletion KW - Nervous system KW - DNA sequencing KW - Single-nucleotide polymorphism KW - DNA KW - genomics KW - Fusion protein KW - Drugs KW - Mutation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811891351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=MultiDimensional+ClinOmics+for+Precision+Therapy+of+Children+and+Adolescent+Young+Adults+with+Relapsed+and+Refractory+Cancer%3A+A+Report+from+the+Center+for+Cancer+Research&rft.au=Chang%2C+Wendy%3BBrohl%2C+Andrew+S%3BPatidar%2C+Rajesh%3BSindiri%2C+Sivasish%3BShern%2C+Jack+F%3BWei%2C+Jun+S%3BSong%2C+Young+K%3BYohe%2C+Marielle+E%3BGryder%2C+Berkley%3BZhang%2C+Shile%3BCalzone%2C+Kathleen+A%3BShivaprasad%2C+Nityashree%3BWen%2C+Xinyu%3BBadgett%2C+Thomas+C%3BMiettinen%2C+Markku%3BHartman%2C+Kip+R%3BLeague-Pascual%2C+James+C%3BTrahair%2C+Toby+N%3BWidemann%2C+Brigitte+C%3BMerchant%2C+Melinda+S%3BKaplan%2C+Rosandra+N%3BLin%2C+Jimmy+C%3BKhan%2C+Javed&rft.aulast=Chang&rft.aufirst=Wendy&rft.date=2016-08-01&rft.volume=22&rft.issue=15&rft.spage=3810&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2717 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Age; Pediatrics; Solid tumors; Adolescence; Chemotherapy; Tumors; Children; Clinical trials; Cancer; Gene expression; DNA sequencing; Nervous system; Gene deletion; Single-nucleotide polymorphism; DNA; Fusion protein; genomics; Mutation; Drugs DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2717 ER - TY - JOUR T1 - Associations of NSAID and paracetamol use with risk of primary liver cancer in the Clinical Practice Research Datalink AN - 1811889202; PQ0003498433 AB - Liver cancer incidence has been rising rapidly in Western countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are widely-used analgesics that may modulate the risk of liver cancer, but population-based evidence is limited. We conducted a case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink to examine the association between the use of prescription NSAIDs and paracetamol and development of liver cancer. Multivariable-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Overall, ever-use of NSAIDs was not associated with risk of liver cancer (aOR=1.05, 95% CI=0.88-1.24), regardless of recency and intensity of use. Use of paracetamol was associated with a slightly increased risk of liver cancer (aOR=1.18, 95% CI=1.00-1.39), particularly among individuals with body mass index<25kg/m2 (aOR=1.56, 95% CI=1.17-2.09). Our results suggest that NSAID use was not associated with liver cancer risk in this population. Ever-use of paracetamol may be associated with slightly higher liver cancer risk, but results should be interpreted cautiously due to methodological limitations. Given that paracetamol is a widely-used analgesic, further examination of its relationship with liver cancer is warranted. JF - Cancer Epidemiology AU - Yang, Baiyu AU - Petrick, Jessica L AU - Chen, Jie AU - Hagberg, Katrina Wilcox AU - Sahasrabuddhe, Vikrant V AU - Graubard, Barry I AU - Jick, Susan AU - McGlynn, Katherine A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892-9774, USA Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 105 EP - 111 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 43 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - BMI body mass index KW - CI confidence interval KW - COX cyclooxygenase KW - CPRD Clinical Practice Research Datalink KW - GP general practitioner KW - HBV hepatitis B virus KW - HCC hepatocellular carcinoma KW - HCV hepatitis C virus KW - NSAID Nonsteroidal anti-inflammatory drug KW - OR odds ratio KW - OTC over-the-counter KW - Analgesics KW - Liver cancer KW - Case-control study KW - Medical records database KW - paracetamol KW - Body mass KW - Risk factors KW - Nonsteroidal antiinflammatory drugs KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811889202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Associations+of+NSAID+and+paracetamol+use+with+risk+of+primary+liver+cancer+in+the+Clinical+Practice+Research+Datalink&rft.au=Yang%2C+Baiyu%3BPetrick%2C+Jessica+L%3BChen%2C+Jie%3BHagberg%2C+Katrina+Wilcox%3BSahasrabuddhe%2C+Vikrant+V%3BGraubard%2C+Barry+I%3BJick%2C+Susan%3BMcGlynn%2C+Katherine+A&rft.aulast=Yang&rft.aufirst=Baiyu&rft.date=2016-08-01&rft.volume=43&rft.issue=&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.06.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 27 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - paracetamol; Risk factors; Body mass; Liver cancer; Analgesics; Nonsteroidal antiinflammatory drugs DO - http://dx.doi.org/10.1016/j.canep.2016.06.009 ER - TY - JOUR T1 - Molecular Changes in the Nasal Cavity after N, N-dimethyl-p-toluidine Exposure AN - 1811887042; PQ0003545187 AB - N, N -dimethyl-p-toluidine (DMPT; Cas No. 99-97-8), an accelerant for methyl methacrylate monomers in medical devices, is a nasal cavity carcinogen according to a 2-yr cancer study of male and female F344/N rats, with the nasal tumors arising from the transitional cell epithelium. In this study, we exposed male F344/N rats for 5 days to DMPT (0, 1, 6, 20, 60, or 120 mg/kg [oralgavage]) to explore the early changes in the nasal cavity after short-term exposure. Lesions occurred in the nasal cavity including hyperplasia of transitional cell epithelium (60 and 120 mg/kg). Nasal tissue was rapidly removed and preserved for subsequent laser capture microdissection and isolation of the transitional cell epithelium (0 and 120 mg/kg) for transcriptomic studies. DMPT transitional cell epithelium gene transcript patterns were characteristic of an antioxidative damage response (e.g., Akr7a3 , Maff , and Mgst3 ), cell proliferation, and decrease in signals for apoptosis. The transcripts of amino acid transporters were upregulated (e.g., Slc7a11 ). The DMPT nasal transcript expression pattern was similar to that found in the rat nasal cavity after formaldehyde exposure, with over 1,000 transcripts in common. Molecular changes in the nasal cavity after DMPT exposure suggest that oxidative damage is a mechanism of the DMPT toxic and/or carcinogenic effects. JF - Toxicologic Pathology AU - Dunnick, June K AU - Merrick, BAlex AU - Brix, Amy AU - Morgan, Daniel L AU - Gerrish, Kevin AU - Wang, Yu AU - Flake, Gordon AU - Foley, Julie AU - Shockley, Keith R AD - 1 .Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA, dunnickj@niehs.nih.gov Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 835 EP - 847 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 6 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - N KW - N-dimethyl-p-toluidine KW - nasal cavity toxicity KW - molecular markers KW - Apoptosis KW - Amino acids KW - Formaldehyde KW - Transcription KW - Carcinogens KW - Tumors KW - Cancer KW - Monomers KW - Hyperplasia KW - Lasers KW - Epithelium KW - Nose KW - Cell proliferation KW - X 24390:Radioactive Materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811887042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Molecular+Changes+in+the+Nasal+Cavity+after+N%2C+N-dimethyl-p-toluidine+Exposure&rft.au=Dunnick%2C+June+K%3BMerrick%2C+BAlex%3BBrix%2C+Amy%3BMorgan%2C+Daniel+L%3BGerrish%2C+Kevin%3BWang%2C+Yu%3BFlake%2C+Gordon%3BFoley%2C+Julie%3BShockley%2C+Keith+R&rft.aulast=Dunnick&rft.aufirst=June&rft.date=2016-08-01&rft.volume=44&rft.issue=6&rft.spage=835&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316637708 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 75 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Amino acids; Apoptosis; Transcription; Formaldehyde; Tumors; Carcinogens; Cancer; Monomers; Hyperplasia; Nose; Epithelium; Lasers; Cell proliferation DO - http://dx.doi.org/10.1177/0192623316637708 ER - TY - JOUR T1 - Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays AN - 1811884130; PQ0003545193 AB - Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light-induced retinal degeneration has a central/hemispherical localization whereas chemical-induced retinal degeneration has a diffuse localization. This study was conducted to identify and characterize treatment-related retinal degeneration in National Toxicology Program rodent bioassays. A total of 3 chronic bioassays in F344/N rats (but not in B6C3F1/N mice) were identified that had treatment-related increases in retinal degeneration (kava kava extract, acrylamide, and leucomalachite green). A retrospective light microscopic evaluation of the retinas from rats in these 3 studies showed a dose-related increase in the frequencies of retinal degeneration, beginning with the loss of photoreceptor cells, followed by the inner nuclear layer cells. These dose-related increased frequencies of degenerative retinal lesions localized within the central/hemispherical region are suggestive of exacerbation of light-induced retinal degeneration. JF - Toxicologic Pathology AU - Yamashita, Haruhiro AU - Hoenerhoff, Mark J AU - Peddada, Shyamal D AU - Sills, Robert C AU - Pandiri, Arun R AD - 1 .Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA, pandiriak@niehs.nih.gov Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 892 EP - 903 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 6 SN - 0192-6233, 0192-6233 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - F344/N rat KW - ocular phototoxicity KW - retinal degeneration KW - light-induced exacerbation KW - carcinogenicity bioassay KW - NTP database survey KW - retinal atrophy KW - Age KW - Acrylamide KW - Retina KW - Drugs KW - Photoreceptors KW - Light effects KW - N3 11028:Neuropharmacology & toxicology KW - X 24320:Food Additives & Contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811884130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Chemical+Exacerbation+of+Light-induced+Retinal+Degeneration+in+F344%2FN+Rats+in+National+Toxicology+Program+Rodent+Bioassays&rft.au=Yamashita%2C+Haruhiro%3BHoenerhoff%2C+Mark+J%3BPeddada%2C+Shyamal+D%3BSills%2C+Robert+C%3BPandiri%2C+Arun+R&rft.aulast=Yamashita&rft.aufirst=Haruhiro&rft.date=2016-08-01&rft.volume=44&rft.issue=6&rft.spage=892&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316650050 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 67 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Age; Acrylamide; Retina; retinal degeneration; Drugs; Photoreceptors; Light effects DO - http://dx.doi.org/10.1177/0192623316650050 ER - TY - JOUR T1 - The impact of genetic variants on BMI increase during childhood versus adulthood AN - 1811881174; PQ0003547659 AB - Background: Genetic variants that predispose individuals to obesity may have differing influences during childhood versus adulthood, and additive effects of such variants are likely to occur. Our ongoing studies to identify genetic determinants of obesity in American Indians have identified 67 single-nucleotide polymorphisms (SNPs) that reproducibly associate with maximum lifetime non-diabetic body mass index (BMI). This study aimed to identify when, during the lifetime, these variants have their greatest impact on BMI increase.Subjects/ Methods: A total of 5906 Native Americans of predominantly Pima Indian heritage with repeated measures of BMI between the ages of 5 and 45 years were included in this study. The association between each SNP with the rates of BMI increase during childhood (5-19 years) and adulthood (20-45 years) were assessed separately. The significant SNPs were used to calculate a cumulative allelic risk score (ARS) for childhood and adulthood, respectively, to assess the additive effect of these variants within each period of life. Results: The majority of these SNPs (36 of 67) were associated with rate of BMI increase during childhood (P-value range: 0.00004-0.05), whereas only nine SNPs were associated with rate of BMI change during adulthood (P-value range: 0.002-0.02). These 36 SNPs associated with childhood BMI gain likely had a cumulative effect as a higher childhood-ARS associated with rate of BMI change ( beta =0.032 kg m super(-2) per year per risk allele, 95% confidence interval: 0.027-0.036, P<0.0001), such that at age 19 years, individuals with the highest number of risk alleles had a BMI of 10.2 kg m super(-2) greater than subjects with the lowest number of risk alleles. Conclusions: Overall, our data indicates that genetic polymorphisms associated with lifetime BMI may influence the rate of BMI increase during different periods in the life course. The majority of these polymorphisms have a larger impact on BMI during childhood, providing further evidence that prevention of obesity will need to begin early in life. JF - International Journal of Obesity AU - Hohenadel, M G AU - Baier, L J AU - Piaggi, P AU - Muller, Y L AU - Hanson, R L AU - Krakoff, J AU - Thearle, M S AD - Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1301 EP - 1309 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 40 IS - 8 SN - 0307-0565, 0307-0565 KW - Genetics Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Obesity KW - Age KW - Data processing KW - Body mass KW - Gene polymorphism KW - Children KW - Prevention KW - Single-nucleotide polymorphism KW - Risk factors KW - Body mass index KW - Ethnic groups KW - G 07880:Human Genetics KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811881174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=The+impact+of+genetic+variants+on+BMI+increase+during+childhood+versus+adulthood&rft.au=Hohenadel%2C+M+G%3BBaier%2C+L+J%3BPiaggi%2C+P%3BMuller%2C+Y+L%3BHanson%2C+R+L%3BKrakoff%2C+J%3BThearle%2C+M+S&rft.aulast=Hohenadel&rft.aufirst=M&rft.date=2016-08-01&rft.volume=40&rft.issue=8&rft.spage=1301&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2016.53 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Obesity; Age; Data processing; Single-nucleotide polymorphism; Gene polymorphism; Risk factors; Body mass index; Children; Ethnic groups; Risk assessment; Prevention; Body mass DO - http://dx.doi.org/10.1038/ijo.2016.53 ER - TY - JOUR T1 - Horizontal Transfer of Carbapenemase-Encoding Plasmids and Comparison with Hospital Epidemiology Data AN - 1811875975; PQ0003555315 AB - Carbapenemase-producing organisms have spread worldwide, and infections with these bacteria cause significant morbidity. Horizontal transfer of plasmids carrying genes that encode carbapenemases plays an important role in the spread of multidrug-resistant Gram-negative bacteria. Here we investigate parameters regulating conjugation using an Escherichia coli laboratory strain that lacks plasmids or restriction enzyme modification systems as a recipient and also using patient isolates as donors and recipients. Because conjugation is tightly regulated, we performed a systematic analysis of the transfer of Klebsiella pneumoniae carbapenemase (blaKPC)-encoding plasmids into multiple strains under different environmental conditions to investigate critical variables. We used four blaKPC-carrying plasmids isolated from patient strains obtained from two hospitals: pKpQIL and pKPC-47e from the National Institutes of Health, and pKPC_UVA01 and pKPC_UVA02 from the University of Virginia. Plasmid transfer frequency differed substantially between different donor and recipient pairs, and the frequency was influenced by plasmid content, temperature, and substrate, in addition to donor and recipient strain. pKPC-47e was attenuated in conjugation efficiency across all conditions tested. Despite its presence in multiple clinical species, pKPC_UVA01 had lower conjugation efficiencies than pKpQIL into recipient strains. The conjugation frequency of these plasmids into K. pneumoniae and E. coli patient isolates ranged widely without a clear correlation with clinical epidemiological data. Our results highlight the importance of each variable examined in these controlled experiments. The in vitro models did not reliably predict plasmid mobilization observed in a patient population, indicating that further studies are needed to understand the most important variables affecting horizontal transfer in vivo. JF - Antimicrobial Agents & Chemotherapy AU - Hardiman, C A AU - Weingarten, R A AU - Conlan, S AU - Khil, P AU - Dekker, J P AU - Mathers, A J AU - Sheppard, A E AU - Segre, J A AU - Frank, K M AD - << + $0, karen.frank@nih.gov. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 4910 EP - 4919 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 60 IS - 8 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Temperature effects KW - Conjugation KW - Data processing KW - Drug resistance KW - Enzymes KW - carbapenemase KW - Infection KW - Plasmids KW - Morbidity KW - Horizontal transfer KW - Models KW - Epidemiology KW - Gram-negative bacteria KW - Escherichia coli KW - Environmental conditions KW - Klebsiella pneumoniae KW - Hospitals KW - A 01340:Antibiotics & Antimicrobials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811875975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Horizontal+Transfer+of+Carbapenemase-Encoding+Plasmids+and+Comparison+with+Hospital+Epidemiology+Data&rft.au=Hardiman%2C+C+A%3BWeingarten%2C+R+A%3BConlan%2C+S%3BKhil%2C+P%3BDekker%2C+J+P%3BMathers%2C+A+J%3BSheppard%2C+A+E%3BSegre%2C+J+A%3BFrank%2C+K+M&rft.aulast=Hardiman&rft.aufirst=C&rft.date=2016-08-01&rft.volume=60&rft.issue=8&rft.spage=4910&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/10.1128%2FAAC.00014-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 56 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Temperature effects; Conjugation; Data processing; Drug resistance; Enzymes; carbapenemase; Plasmids; Infection; Horizontal transfer; Morbidity; Models; Epidemiology; Gram-negative bacteria; Environmental conditions; Hospitals; Escherichia coli; Klebsiella pneumoniae DO - http://dx.doi.org/10.1128/AAC.00014-16 ER - TY - JOUR T1 - Combined Effects of High-Dose Bisphenol A and Oxidizing Agent (KBrO3) on Cellular Microenvironment, Gene Expression, and Chromatin Structure of Ku70-deficient Mouse Embryonic Fibroblasts. AN - 1809046512; 27082013 AB - Exposure to bisphenol A (BPA) has been reported to alter global gene expression, induce epigenetic modifications, and interfere with complex regulatory networks of cells. In addition to these reprogramming events, we have demonstrated that BPA exposure generates reactive oxygen species and promotes cellular survival when co-exposed with the oxidizing agent potassium bromate (KBrO3). We determined the cellular microenvironment changes induced by co-exposure of BPA and KBrO3 versus either agent alone. Ku70-deficient cells were exposed to 150 μM BPA, 20 mM KBrO3, or co-exposed to both agents. Four and 24 hr post-damage initiation by KBrO3, with BPA-only samples timed to coincide with these designated time points, we performed whole-genome microarray analysis and evaluated chromatin structure, DNA lesion load, glutathione content, and intracellular pH. We found that 4 hr post-damage initiation, BPA exposure and co-exposure transiently condensed chromatin compared with untreated and KBrO3-only treated cells; the transcription of DNA repair proteins was also reduced. At this time point, BPA exposure and co-exposure also reduced the change in intracellular pH observed after treatment with KBrO3 alone. Twenty-four hours post-damage initiation, BPA-exposed cells showed less condensed chromatin than cells treated with KBrO3 alone; the intracellular pH of the co-exposed cells was significantly reduced compared with untreated and KBrO3-treated cells; and significant up-regulation of DNA repair proteins was observed after co-exposure. These results support the induction of an adaptive response by BPA co-exposure that alters the microcellular environment and modulates DNA repair. Further work is required to determine whether BPA induces similar DNA lesions in vivo at environmentally relevant doses; however, in the Ku70-deficient mouse embryonic fibroblasts, exposure to a high dose of BPA was associated with changes in the cellular microenvironment that may promote survival. Gassman NR, Coskun E, Jaruga P, Dizdaroglu M, Wilson SH. 2016. Combined effects of high-dose bisphenol A and oxidizing agent (KBrO3) on cellular microenvironment, gene expression, and chromatin structure of Ku70-deficient mouse embryonic fibroblasts. Environ Health Perspect 124:1241-1252; http://dx.doi.org/10.1289/EHP237. JF - Environmental health perspectives AU - Gassman, Natalie R AU - Coskun, Erdem AU - Jaruga, Pawel AU - Dizdaroglu, Miral AU - Wilson, Samuel H AD - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1241 EP - 1252 VL - 124 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1809046512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Combined+Effects+of+High-Dose+Bisphenol+A+and+Oxidizing+Agent+%28KBrO3%29+on+Cellular+Microenvironment%2C+Gene+Expression%2C+and+Chromatin+Structure+of+Ku70-deficient+Mouse+Embryonic+Fibroblasts.&rft.au=Gassman%2C+Natalie+R%3BCoskun%2C+Erdem%3BJaruga%2C+Pawel%3BDizdaroglu%2C+Miral%3BWilson%2C+Samuel+H&rft.aulast=Gassman&rft.aufirst=Natalie&rft.date=2016-08-01&rft.volume=124&rft.issue=8&rft.spage=1241&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP237 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/EHP237 ER - TY - JOUR T1 - Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data. AN - 1809046364; 26978842 AB - Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program. Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data. We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and β cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform. More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research: a screening approach using ToxCast™ high-throughput data. Environ Health Perspect 124:1141-1154; http://dx.doi.org/10.1289/ehp.1510456. JF - Environmental health perspectives AU - Auerbach, Scott AU - Filer, Dayne AU - Reif, David AU - Walker, Vickie AU - Holloway, Alison C AU - Schlezinger, Jennifer AU - Srinivasan, Supriya AU - Svoboda, Daniel AU - Judson, Richard AU - Bucher, John R AU - Thayer, Kristina A AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1141 EP - 1154 VL - 124 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1809046364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Prioritizing+Environmental+Chemicals+for+Obesity+and+Diabetes+Outcomes+Research%3A+A+Screening+Approach+Using+ToxCast%E2%84%A2+High-Throughput+Data.&rft.au=Auerbach%2C+Scott%3BFiler%2C+Dayne%3BReif%2C+David%3BWalker%2C+Vickie%3BHolloway%2C+Alison+C%3BSchlezinger%2C+Jennifer%3BSrinivasan%2C+Supriya%3BSvoboda%2C+Daniel%3BJudson%2C+Richard%3BBucher%2C+John+R%3BThayer%2C+Kristina+A&rft.aulast=Auerbach&rft.aufirst=Scott&rft.date=2016-08-01&rft.volume=124&rft.issue=8&rft.spage=1141&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1510456 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-03 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1289/ehp.1510456 ER - TY - JOUR T1 - Exercise adherence in a randomized trial of exercise on aromatase inhibitor arthralgias in breast cancer survivors: the Hormones and Physical Exercise (HOPE) study AN - 1808739802; PQ0003350928 AB - Up to 50 % of postmenopausal breast cancer survivors taking aromatase inhibitors (AIs) experience AI-associated arthralgias, or joint pain, which causes many to stop taking AIs and may inhibit exercise, despite known health benefits. We thus evaluated exercise adherence and factors associated with better exercise adherence in breast cancer survivors experiencing AI-induced arthralgia in the (HOPE) year long randomized controlled trial. We included 61 HOPE women randomized to exercise (150 min/week of moderate-intensity aerobic exercise and twice-weekly supervised strength training). Our main outcomes were aerobic exercise measured with daily activity logs, attendance at supervised exercise sessions, and changes in cardiorespiratory fitness, measured maximal oxygen consumption (VO sub(2)max). We examined means and standard deviations (SDs) for exercise adherence by demographic and medical characteristics and used the t test for mean differences. We also examined predictors of adherence using linear regression. On average, at the end of the year long trial, women reported 119 (SD 78)min/week of moderate-intensity aerobic exercise and participated in 70 % of supervised exercise training sessions. After adjustment for other factors that influence adherence, at 6 months postrandomization, only baseline VO sub(2)max was associated with higher aerobic exercise levels and at 12 months, only older age predicted better supervised exercise training attendance. Breast cancer survivors taking AIs and experiencing arthralgia are able to initiate and maintain a year long exercise program, regardless of other factors that influence activity levels. Breast cancer survivors can exercise at levels that have been shown to improve AI-associated arthralgia. JF - Journal of Cancer Survivorship AU - Arem, Hannah AU - Sorkin, Mia AU - Cartmel, Brenda AU - Fiellin, Martha AU - Capozza, Scott AU - Harrigan, Maura AU - Ercolano, Elizabeth AU - Zhou, Yang AU - Sanft, Tara AU - Gross, Cary AU - Schmitz, Kathryn AU - Neogi, Tuhina AU - Hershman, Dawn AU - Ligibel, Jennifer AU - Irwin, Melinda L AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, melinda.irwin@yale.edu Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 654 EP - 662 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 10 IS - 4 SN - 1932-2259, 1932-2259 KW - Toxicology Abstracts KW - Oxygen consumption KW - Fitness KW - Survival KW - Pain KW - Hormones KW - Joints KW - Physical training KW - Demography KW - Standard deviation KW - Aromatase KW - Post-menopause KW - Geriatrics KW - Breast cancer KW - Arthralgia KW - X 24500:Reviews, Legislation, Book & Conference Notices UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808739802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Cancer+Survivorship&rft.atitle=Exercise+adherence+in+a+randomized+trial+of+exercise+on+aromatase+inhibitor+arthralgias+in+breast+cancer+survivors%3A+the+Hormones+and+Physical+Exercise+%28HOPE%29+study&rft.au=Arem%2C+Hannah%3BSorkin%2C+Mia%3BCartmel%2C+Brenda%3BFiellin%2C+Martha%3BCapozza%2C+Scott%3BHarrigan%2C+Maura%3BErcolano%2C+Elizabeth%3BZhou%2C+Yang%3BSanft%2C+Tara%3BGross%2C+Cary%3BSchmitz%2C+Kathryn%3BNeogi%2C+Tuhina%3BHershman%2C+Dawn%3BLigibel%2C+Jennifer%3BIrwin%2C+Melinda+L&rft.aulast=Arem&rft.aufirst=Hannah&rft.date=2016-08-01&rft.volume=10&rft.issue=4&rft.spage=654&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cancer+Survivorship&rft.issn=19322259&rft_id=info:doi/10.1007%2Fs11764-015-0511-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 23 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Fitness; Oxygen consumption; Survival; Pain; Hormones; Physical training; Joints; Demography; Standard deviation; Aromatase; Post-menopause; Geriatrics; Breast cancer; Arthralgia DO - http://dx.doi.org/10.1007/s11764-015-0511-6 ER - TY - JOUR T1 - Using a lipidomics approach for nutritional phenotyping in response to a test meal containing gamma-linolenic acid AN - 1808712175; PQ0003470271 AB - Plasma fatty acids are derived from preformed sources in the diet and de novo synthesis through the action of desaturase and elongase enzymes. This study was designed to examine the elongation of gamma-linolenic acid (GLA, 18:3n6) into dihomo-gamma-linolenic acid (DGLA, 20:3n6) over an 8-h period using both targeted gas chromatography-flame ionization detection and untargeted liquid chromatography-mass spectrometry-based lipidomics utilizing the sequential window acquisition of all theoretical fragment-ion spectra (SWATH). In a single blind, placebo-controlled, crossover design, seven healthy subjects consumed a test meal that consisted of GLA fat (borage oil) or a control fat (a mixture of corn, safflower, sunflower and extra-virgin light olive oils) on three separate test days for each test meal. Total plasma fatty acid concentrations and 366 unique lipid species were measured at 0, 2, 4, 6 and 8 h in response to the test meals. Mean plasma 18:3n6 was 7-fold higher to the GLA challenge compared with baseline and the control meal. By 8 h, mean plasma 20:3n6 was significantly higher in response to the GLA test meal than baseline and the control group. Five of the seven subjects were "responders" in converting GLA into DGLA, but two subjects did not show this conversion. The conversion was independent of physical activity level. Using polyunsaturated fatty acid metabolism as an example, this study demonstrates inter-individual differences in enzymatic capacities to inform exact nutritional and metabolic phenotyping that could be used for precision medicine. [Figure not available: see fulltext.] JF - Metabolomics AU - Cajka, Tomas AU - Davis, Ryan AU - Austin, Kathryn J AU - Newman, John W AU - German, JBruce AU - Fiehn, Oliver AU - Smilowitz, Jennifer T AD - National Institutes of Health West Coast Metabolomics Center, University of California Davis, Davis, 95616, CA, USA, jensm@ucdavis.edu Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1 EP - 16 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 12 IS - 8 SN - 1573-3882, 1573-3882 KW - Biotechnology and Bioengineering Abstracts KW - Diets KW - Olea KW - Lipids KW - Physical activity KW - Enzymes KW - Olive oil KW - Light effects KW - Elongation KW - Phenotyping KW - Fatty acids KW - Polyunsaturated fatty acids KW - desaturase KW - Ionization KW - metabolomics KW - Metabolism KW - Helianthus KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808712175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Metabolomics&rft.atitle=Using+a+lipidomics+approach+for+nutritional+phenotyping+in+response+to+a+test+meal+containing+gamma-linolenic+acid&rft.au=Cajka%2C+Tomas%3BDavis%2C+Ryan%3BAustin%2C+Kathryn+J%3BNewman%2C+John+W%3BGerman%2C+JBruce%3BFiehn%2C+Oliver%3BSmilowitz%2C+Jennifer+T&rft.aulast=Cajka&rft.aufirst=Tomas&rft.date=2016-08-01&rft.volume=12&rft.issue=8&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Metabolomics&rft.issn=15733882&rft_id=info:doi/10.1007%2Fs11306-016-1075-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 43 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Diets; Physical activity; Lipids; Enzymes; Olive oil; Light effects; Phenotyping; Elongation; Fatty acids; Polyunsaturated fatty acids; desaturase; Ionization; Metabolism; metabolomics; Olea; Helianthus DO - http://dx.doi.org/10.1007/s11306-016-1075-9 ER - TY - JOUR T1 - Surgical ligation of patent ductus arteriosus in premature infants: trends and practice variation AN - 1808698159; PQ0003374757 AB - We sought to analyse the variation in the incidence of patent ductus arteriosus over three recent time points and characterise ductal ligation practices in preterm infants in the United States, adjusting for demographic and morbidity factors. Using the Kids' Inpatient Database from 2003, 2006, and 2009, we identified infants born at 32 weeks of gestation with International Classification of Diseases, Ninth Revision diagnosis of patent ductus arteriosus and ligation code. We examined patient and hospital characteristics and identified patient and hospital variables associated with ligation. Of 182,610 preterm births, 30,714 discharges included a patent ductus arteriosus diagnosis. The rate of patent ductus arteriosus diagnosis increased from 14% in 2003 to 21% in 2009 (p<0.001). A total of 4181 ligations were performed, with an overall ligation rate of 14%. Ligation rate in infants born at 28 weeks of gestation was 20% overall, increasing from 18% in 2003 to 21% in 2009 (p<0.001). The ligation rate varied by state (4-28%), and ligation was associated with earlier gestational age, associated diagnoses, hospital type, teaching hospital status, and region (p<0.001). The rates of patent ductus arteriosus diagnosis and ligation have increased in the recent years. Variation exists in the practice of patent ductus arteriosus ligation and is influenced by patient and non-patient factors. JF - Cardiology in the Young AU - Weinberg, Jacqueline G AU - Evans, Frank J AU - Burns, Kristin M AU - Pearson, Gail D AU - Kaltman, Jonathan R AD - National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America, jacqui.gale@gmail.com Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1107 EP - 1114 PB - Greenwich Medical Media Ltd., 219 The Linen Hall London W1R 5TB United Kingdom VL - 26 IS - 6 SN - 1047-9511, 1047-9511 KW - Biotechnology and Bioengineering Abstracts KW - Demography KW - Birth KW - Databases KW - Gestational age KW - Classification KW - Morbidity KW - Infants KW - Hospitals KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808698159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cardiology+in+the+Young&rft.atitle=Surgical+ligation+of+patent+ductus+arteriosus+in+premature+infants%3A+trends+and+practice+variation&rft.au=Weinberg%2C+Jacqueline+G%3BEvans%2C+Frank+J%3BBurns%2C+Kristin+M%3BPearson%2C+Gail+D%3BKaltman%2C+Jonathan+R&rft.aulast=Weinberg&rft.aufirst=Jacqueline&rft.date=2016-08-01&rft.volume=26&rft.issue=6&rft.spage=1107&rft.isbn=&rft.btitle=&rft.title=Cardiology+in+the+Young&rft.issn=10479511&rft_id=info:doi/10.1017%2FS1047951115001869 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 38 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Birth; Demography; Databases; Gestational age; Classification; Morbidity; Hospitals; Infants DO - http://dx.doi.org/10.1017/S1047951115001869 ER - TY - JOUR T1 - Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats Exposed Prenatally and/or Postnatally to Methamphetamine AN - 1808673076; PQ0003488391 AB - Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to prenatal MA exposure via changes in the reserve pool and those of preadolescent females to postnatal MA exposure via the same mechanism. The combination of prenatal and postnatal MA exposure increases the risk of dopaminergic deficits via alterations in the activity of surface-expressed DATs especially in preadolescent females. MA-mediated changes in DATs of preadolescent females could be still enhanced via nonspecific disordering actions of MA on striatal membranes. JF - Neurochemical Research AU - Sirova, Jana AU - Kristofikova, Zdenka AU - Vrajova, Monika AU - Fujakova-Lipski, Michaela AU - Ripova, Daniela AU - Klaschka, Jan AU - Slamberova, Romana AD - National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic, zdenka.kristofikova@nudz.cz Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1911 EP - 1923 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 41 IS - 8 SN - 0364-3190, 0364-3190 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Sexual dimorphism KW - Milk KW - Fluidity KW - Prenatal experience KW - Brain KW - Drug abuse KW - Sex differences KW - Children KW - Lipophilic KW - Pregnancy KW - Lactation KW - Methamphetamine KW - Dopamine transporter KW - Placenta KW - Neostriatum KW - Genetic crosses KW - Sex KW - X 24380:Social Poisons & Drug Abuse KW - N3 11008:Neurochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808673076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemical+Research&rft.atitle=Sex-Dependent+Changes+in+Striatal+Dopamine+Transport+in+Preadolescent+Rats+Exposed+Prenatally+and%2For+Postnatally+to+Methamphetamine&rft.au=Sirova%2C+Jana%3BKristofikova%2C+Zdenka%3BVrajova%2C+Monika%3BFujakova-Lipski%2C+Michaela%3BRipova%2C+Daniela%3BKlaschka%2C+Jan%3BSlamberova%2C+Romana&rft.aulast=Sirova&rft.aufirst=Jana&rft.date=2016-08-01&rft.volume=41&rft.issue=8&rft.spage=1911&rft.isbn=&rft.btitle=&rft.title=Neurochemical+Research&rft.issn=03643190&rft_id=info:doi/10.1007%2Fs11064-016-1902-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 65 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Sexual dimorphism; Prenatal experience; Fluidity; Milk; Brain; Children; Sex differences; Drug abuse; Lipophilic; Lactation; Pregnancy; Dopamine transporter; Methamphetamine; Placenta; Neostriatum; Genetic crosses; Sex DO - http://dx.doi.org/10.1007/s11064-016-1902-4 ER - TY - JOUR T1 - SARS and MERS: recent insights into emerging coronaviruses AN - 1808673026; PQ0003465663 AB - The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. JF - Nature Reviews: Microbiology AU - de Wit, Emmie AU - van Doremalen, Neeltje AU - Falzarano, Darryl AU - Munster, Vincent J AD - Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 523 EP - 534 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 14 IS - 8 SN - 1740-1526, 1740-1526 KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - pandemics KW - Coronavirus KW - Epidemiology KW - Severe acute respiratory syndrome KW - Drug development KW - SARS coronavirus KW - Disease transmission KW - Hospitals KW - V 22490:Miscellaneous KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808673026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Reviews%3A+Microbiology&rft.atitle=SARS+and+MERS%3A+recent+insights+into+emerging+coronaviruses&rft.au=de+Wit%2C+Emmie%3Bvan+Doremalen%2C+Neeltje%3BFalzarano%2C+Darryl%3BMunster%2C+Vincent+J&rft.aulast=de+Wit&rft.aufirst=Emmie&rft.date=2016-08-01&rft.volume=14&rft.issue=8&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Microbiology&rft.issn=17401526&rft_id=info:doi/10.1038%2Fnrmicro.2016.81 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - pandemics; Epidemiology; Severe acute respiratory syndrome; Drug development; Hospitals; Disease transmission; Coronavirus; SARS coronavirus DO - http://dx.doi.org/10.1038/nrmicro.2016.81 ER - TY - JOUR T1 - Use of Hepatitis C Virus (HCV) Immunoglobulin G Antibody Avidity as a Biomarker to Estimate the Population-Level Incidence of HCV Infection AN - 1808672658; PQ0003478549 AB - Background. Sensitive methods are needed to estimate the population-level incidence of hepatitis C virus (HCV) infection. Methods. We developed an HCV immunoglobulin G (IgG) antibody avidity assay by modifying the Ortho 3.0 HCV enzyme-linked immunoassay and tested 997 serum or plasma samples from 568 people who inject drugs enrolled in prospective cohort studies. Avidity-based testing algorithms were evaluated by their (1) mean duration of recent infection (MDRI), defined as the average time an individual is identified as having been recently infected, according to a given algorithm; (2) false-recent rate, defined as the proportion of samples collected >2 years after HCV seroconversion that were misclassified as recent; (3) sample sizes needed to estimate incidence; and (4) power to detect a reduction in incidence between serial cross-sectional surveys. Results. A multiassay algorithm (defined as an avidity index of 80% power to detect a 50% reduction in incidence. Conclusions. Avidity-based algorithms have the capacity to accurately estimate HCV infection incidence and rapidly assess the impact of public health efforts among high-risk populations. Efforts to optimize this method should be prioritized. JF - Journal of Infectious Diseases AU - Patel, Eshan U AU - Cox, Andrea L AU - Mehta, Shruti H AU - Boon, Denali AU - Mullis, Caroline E AU - Astemborski, Jacquie AU - Osburn, William O AU - Quinn, Jeffrey AU - Redd, Andrew D AU - Kirk, Gregory D AU - Thomas, David L AU - Quinn, Thomas C AU - Laeyendecker, Oliver AD - Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, olaeyen1@jhmi.edu Y1 - 2016/08/01/ PY - 2016 DA - 2016 Aug 01 SP - 344 EP - 352 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 214 IS - 3 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Immunology Abstracts; Health & Safety Science Abstracts KW - HCV KW - HIV KW - surveillance KW - recent infection KW - antibody response KW - incidence testing KW - people who inject drugs KW - Bioindicators KW - Viruses KW - Algorithms KW - Drug abuse KW - Infection KW - biomarkers KW - Public health KW - Hepatitis C virus KW - Infectious diseases KW - Human immunodeficiency virus KW - Avidity KW - Immunoglobulin G KW - Risk groups KW - Seroconversion KW - Viremia KW - Immunoassays KW - Drugs KW - V 22360:AIDS and HIV KW - F 06910:Microorganisms & Parasites KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808672658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Use+of+Hepatitis+C+Virus+%28HCV%29+Immunoglobulin+G+Antibody+Avidity+as+a+Biomarker+to+Estimate+the+Population-Level+Incidence+of+HCV+Infection&rft.au=Patel%2C+Eshan+U%3BCox%2C+Andrea+L%3BMehta%2C+Shruti+H%3BBoon%2C+Denali%3BMullis%2C+Caroline+E%3BAstemborski%2C+Jacquie%3BOsburn%2C+William+O%3BQuinn%2C+Jeffrey%3BRedd%2C+Andrew+D%3BKirk%2C+Gregory+D%3BThomas%2C+David+L%3BQuinn%2C+Thomas+C%3BLaeyendecker%2C+Oliver&rft.aulast=Patel&rft.aufirst=Eshan&rft.date=2016-08-01&rft.volume=214&rft.issue=3&rft.spage=344&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Avidity; Immunoglobulin G; Algorithms; Seroconversion; Risk groups; Viremia; Infection; Drugs; Immunoassays; biomarkers; Public health; Bioindicators; Infectious diseases; Viruses; Drug abuse; Hepatitis C virus; Human immunodeficiency virus DO - http://dx.doi.org/10.1093/infdis/jiw005 ER - TY - JOUR T1 - Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens AN - 1808667730; PQ0003478553 AB - Human immunodeficiency virus (HIV)-specific B-cell responses in infected individuals are maintained by active HIV replication. Suppression of viremia by antiretroviral therapy (ART) leads to quantitative and qualitative changes that remain unclear. Accordingly, B-cell responses were investigated in elite controllers (ECs), who maintain undetectable HIV levels without ART, and in individuals whose viremia was suppressed by ART. Despite a higher HIV burden in the ART group, compared with the EC group, frequencies of HIV-specific B cells were higher in the EC group, compared with those in the ART group. However, the initiation of ART in several ECs was associated with reduced frequencies of HIV-specific B cells, suggesting that responses are at least in part sustained by HIV replication. Furthermore, B-cell responses to tetanus toxin but not influenza hemagglutinin in the ART group were lower than those in the EC group. Thus, the superior HIV-specific humoral response in ECs versus ART-treated individuals is likely due to a more intact humoral immune response in ECs and/or distinct responses to residual HIV replication. JF - Journal of Infectious Diseases AU - Buckner, Clarisa M AU - Kardava, Lela AU - Zhang, Xiaozhen AU - Gittens, Kathleen AU - Justement, J Shawn AU - Kovacs, Colin AU - McDermott, Adrian B AU - Li, Yuxing AU - Sajadi, Mohammad M AU - Chun, Tae-Wook AU - Fauci, Anthony S AU - Moir, Susan AD - Laboratory of Immunoregulation, smoir@niaid.nih.gov Y1 - 2016/08/01/ PY - 2016 DA - 2016 Aug 01 SP - 390 EP - 398 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 214 IS - 3 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Immunology Abstracts; Health & Safety Science Abstracts KW - HIV KW - B cells KW - elite controllers KW - humoral immunity KW - viremia KW - Lymphocytes B KW - ECS KW - Replication KW - Hemagglutinins KW - antiretroviral therapy KW - Immunological memory KW - Antiretroviral agents KW - Maintenance KW - Toxins KW - Influenza KW - Replication initiation KW - Infectious diseases KW - Human immunodeficiency virus KW - Immune response KW - Viremia KW - tetanus toxin KW - Immune response (humoral) KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - V 22360:AIDS and HIV KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808667730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Maintenance+of+HIV-Specific+Memory+B-Cell+Responses+in+Elite+Controllers+Despite+Low+Viral+Burdens&rft.au=Buckner%2C+Clarisa+M%3BKardava%2C+Lela%3BZhang%2C+Xiaozhen%3BGittens%2C+Kathleen%3BJustement%2C+J+Shawn%3BKovacs%2C+Colin%3BMcDermott%2C+Adrian+B%3BLi%2C+Yuxing%3BSajadi%2C+Mohammad+M%3BChun%2C+Tae-Wook%3BFauci%2C+Anthony+S%3BMoir%2C+Susan&rft.aulast=Buckner&rft.aufirst=Clarisa&rft.date=2016-08-01&rft.volume=214&rft.issue=3&rft.spage=390&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw163 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Influenza; Replication initiation; Replication; ECS; Lymphocytes B; Hemagglutinins; antiretroviral therapy; Immunological memory; tetanus toxin; Viremia; Immune response (humoral); Infectious diseases; Immune response; Antiretroviral agents; Toxins; Maintenance; Human immunodeficiency virus DO - http://dx.doi.org/10.1093/infdis/jiw163 ER - TY - JOUR T1 - Blockade of Nicotine and Cannabinoid Reinforcement and Relapse by a Cannabinoid CB1-Receptor Neutral Antagonist AM4113 and Inverse Agonist Rimonabant in Squirrel Monkeys AN - 1808660572; PQ0003465635 AB - Nicotine, the main psychoactive component of tobacco, and (-)- Delta super(9)-tetrahydroca nnabinol (THC), the main psychoactive ingredient in cannabis, play major roles in tobacco and marijuana dependence as reinforcers of drug-seeking and drug-taking behavior. Drugs that act as inverse agonists of cannabinoid CB1 receptors in the brain can attenuate the rewarding and abuse-related effects of nicotine and THC, but their clinical use is hindered by potentially serious side effects. The recently developed CB1-receptor neutral antagonists may provide an alternative therapeutic approach to nicotine and cannabinoid dependence. Here we compare attenuation of nicotine and THC reinforcement and reinstatement in squirrel monkeys by the CB1-receptor inverse agonist rimonabant and by the recently developed CB1-receptor neutral antagonist AM4113. Both rimonabant and AM4113 reduced two effects of nicotine and THC that play major roles in tobacco and marijuana dependence: (1) maintenance of high rates of drug-taking behavior, and (2) priming- or cue-induced reinstatement of drug-seeking behavior in abstinent subjects (models of relapse). In contrast, neither rimonabant nor AM4113 modified cocaine-reinforced or food-reinforced operant behavior under similar experimental conditions. However, both rimonabant and AM4113 reduced cue-induced reinstatement in monkeys trained to self-administer cocaine, suggesting the involvement of a common cannabinoid-mediated mechanism in the cue-induced reinstatement for different drugs of abuse. These findings point to CB1-receptor neutral antagonists as a new class of medications for treatment of both tobacco dependence and cannabis dependence. JF - Neuropsychopharmacology AU - Schindler, Charles W AU - Redhi, Godfrey H AU - Vemuri, Kiran AU - Makriyannis, Alexandros AU - Le Foll, Bernard AU - Bergman, Jack AU - Goldberg, Steven R AU - Justinova, Zuzana AD - Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 2283 EP - 2293 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 41 IS - 9 SN - 0893-133X, 0893-133X KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Inverse agonists KW - Operant conditioning KW - Food KW - Brain KW - Drug abuse KW - Reinstatement KW - Tetrahydrocannabinol KW - Saimiri KW - Drug dependence KW - Nicotine KW - Reinforcement KW - Cannabis KW - Tobacco KW - Drug addiction KW - Cannabinoid CB1 receptors KW - Cocaine KW - Side effects KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808660572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology&rft.atitle=Blockade+of+Nicotine+and+Cannabinoid+Reinforcement+and+Relapse+by+a+Cannabinoid+CB1-Receptor+Neutral+Antagonist+AM4113+and+Inverse+Agonist+Rimonabant+in+Squirrel+Monkeys&rft.au=Schindler%2C+Charles+W%3BRedhi%2C+Godfrey+H%3BVemuri%2C+Kiran%3BMakriyannis%2C+Alexandros%3BLe+Foll%2C+Bernard%3BBergman%2C+Jack%3BGoldberg%2C+Steven+R%3BJustinova%2C+Zuzana&rft.aulast=Schindler&rft.aufirst=Charles&rft.date=2016-08-01&rft.volume=41&rft.issue=9&rft.spage=2283&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/10.1038%2Fnpp.2016.27 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Inverse agonists; Operant conditioning; Food; Brain; Drug abuse; Reinstatement; Tetrahydrocannabinol; Drug dependence; Nicotine; Tobacco; Cannabis; Reinforcement; Cocaine; Cannabinoid CB1 receptors; Drug addiction; Side effects; Saimiri DO - http://dx.doi.org/10.1038/npp.2016.27 ER - TY - JOUR T1 - Investigating the Role of Helicobacter pylori PriA Protein AN - 1808650542; PQ0003413946 AB - Background In bacteria, PriA protein, a conserved DEXH-type DNA helicase, plays a central role in replication restart at stalled replication forks. Its unique DNA binding property allows it to recognize and stabilize stalled forks and the structures derived from them. PriA plays a very critical role in replication fork stabilization and DNA repair in E. coli and N. gonorrhoeae. In our in vivo expression technology screen, priA gene was induced in vivo when Helicobacter pylori infects mouse stomach. Materials and Methods We decided to elucidate the role of H. pylori PriA protein in survival in mouse stomach, survival in gastric epithelial cells and macrophage cells, DNA repair, acid stress, and oxidative stress. Results The priA null mutant strain was unable to colonize mice stomach mucosa after long-term infections. Mouse colonization was observed after 1 week of infection, but the levels were much lower than the wild-type HpSS1 strain. PriA protein was found to be important for intracellular survival of epithelial cell-/macrophage cell-ingested H. pylori. Also, a priA null mutant was more sensitive to DNA-damaging agents and was much more sensitive to acid and oxidative stress as compared to the wild-type strain. Conclusions These data suggest that the PriA protein is needed for survival and persistence of H. pylori in mice stomach mucosa. JF - Helicobacter (Online) AU - Singh, Aparna AU - Blaskovic, Dusan AU - Joo, Jungsoo AU - Yang, Zhen AU - Jackson, Sharon H AU - Coleman, William G AU - Yan, Ming AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 295 EP - 304 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 21 IS - 4 SN - 1083-4389, 1083-4389 KW - Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Cell survival KW - Helicobacter pylori KW - Epithelial cells KW - Data processing KW - Replication KW - Mucosa KW - DNA repair KW - Infection KW - Colonization KW - Replication forks KW - Oxidative stress KW - Escherichia coli KW - DNA helicase KW - Stomach KW - Internet KW - PriA protein KW - J 02410:Animal Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808650542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Helicobacter+%28Online%29&rft.atitle=Investigating+the+Role+of+Helicobacter+pylori+PriA+Protein&rft.au=Singh%2C+Aparna%3BBlaskovic%2C+Dusan%3BJoo%2C+Jungsoo%3BYang%2C+Zhen%3BJackson%2C+Sharon+H%3BColeman%2C+William+G%3BYan%2C+Ming&rft.aulast=Singh&rft.aufirst=Aparna&rft.date=2016-08-01&rft.volume=21&rft.issue=4&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Helicobacter+%28Online%29&rft.issn=10834389&rft_id=info:doi/10.1111%2Fhel.12283 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Cell survival; Macrophages; Epithelial cells; Data processing; Replication; Mucosa; Infection; DNA repair; Colonization; Replication forks; Oxidative stress; DNA helicase; Internet; Stomach; PriA protein; Helicobacter pylori; Escherichia coli DO - http://dx.doi.org/10.1111/hel.12283 ER - TY - JOUR T1 - Effects of a rapid-resisted elliptical training program on motor, cognitive and neurobehavioral functioning in adults with chronic traumatic brain injury AN - 1808636686; PQ0003358702 AB - This small clinical trial utilized a novel rehabilitation strategy, rapid-resisted elliptical training, in an effort to increase motor, and thereby cognitive, processing speed in ambulatory individuals with traumatic brain injury (TBI). As an initial step, multimodal functional abilities were quantified and compared in 12 ambulatory adults with and 12 without TBI. After the baseline assessment, the group with TBI participated in an intensive 8-week daily exercise program using an elliptical trainer and was reassessed after completion and at an 8-week follow-up. The focus of training was on achieving a fast movement speed, and once the target was reached, resistance to motion was increased in small increments to increase intensity of muscle activation. Primary outcomes were: High-Level Mobility Assessment Tool (HiMAT), instrumented balance tests, dual-task (DT) performance and neurobehavioral questionnaires. The group with TBI had poorer movement excursion during balance tests and poorer dual-task (DT) performance. After training, balance reaction times improved and were correlated with gains in the HiMAT and DT. Sleep quality also improved and was correlated with improved depression and learning. This study illustrates how brain injury can affect multiple linked aspects of functioning and provides preliminary evidence that intensive rapid-resisted training has specific positive effects on dynamic balance and more generalized effects on sleep quality in TBI. JF - Experimental Brain Research AU - Damiano, Diane L AU - Zampieri, Cristiane AU - Ge, Jie AU - Acevedo, Ana AU - Dsurney, John AD - Functional and Applied Biomechanics Section, Rehabilitation Medicine Department, 10 Center Drive, Room 1-1468, MSC 1604, Bethesda, MD, 20892-1604, USA, damianod@cc.nih.gov Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 2245 EP - 2252 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 234 IS - 8 SN - 0014-4819, 0014-4819 KW - Physical Education Index; CSA Neurosciences Abstracts KW - Inventories KW - Muscle contraction KW - Learning KW - Brain injury KW - Depression KW - Mobility KW - Rehabilitation KW - Injuries KW - Brain KW - Adults KW - Clinical trials KW - Movement KW - Exercise (programs) KW - Physical training KW - Speed KW - Reaction time task KW - Cognitive ability KW - Information processing KW - Sleep KW - Performance KW - Traumatic brain injury KW - Balance KW - N3 11001:Behavioral and Cognitive Neuroscience KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808636686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+Brain+Research&rft.atitle=Effects+of+a+rapid-resisted+elliptical+training+program+on+motor%2C+cognitive+and+neurobehavioral+functioning+in+adults+with+chronic+traumatic+brain+injury&rft.au=Damiano%2C+Diane+L%3BZampieri%2C+Cristiane%3BGe%2C+Jie%3BAcevedo%2C+Ana%3BDsurney%2C+John&rft.aulast=Damiano&rft.aufirst=Diane&rft.date=2016-08-01&rft.volume=234&rft.issue=8&rft.spage=2245&rft.isbn=&rft.btitle=&rft.title=Experimental+Brain+Research&rft.issn=00144819&rft_id=info:doi/10.1007%2Fs00221-016-4630-8 LA - English DB - Physical Education Index N1 - Date revised - 2016-07-01 N1 - Number of references - 34 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Speed; Injuries; Sleep; Brain; Adults; Performance; Exercise (programs); Movement; Balance; Muscle contraction; Inventories; Learning; Depression; Brain injury; Rehabilitation; Mobility; Clinical trials; Physical training; Cognitive ability; Reaction time task; Information processing; Traumatic brain injury DO - http://dx.doi.org/10.1007/s00221-016-4630-8 ER - TY - JOUR T1 - Changes over 12 months in eye glances during secondary task engagement among novice drivers AN - 1808628415; PQ0003321901 AB - During their first year of driving, crash rates among novice drivers are very high but decline rapidly. However, it is not clear what skills or knowledge they are acquiring in this period. Secondary task engagement while driving is a contributing factor to many traffic collisions and some of the elevated crash risk among novices could be explained by greater prevalence or longer periods of eyes off the road while engaging in these non-driving tasks. The current study looked at the eye glances of novice teen drivers engaging in secondary tasks on a test track at 0 and 12 months of licensure and compared their performance with their parents. Novices improved from 0 to 12 months on their longest single glance off the forward roadway and total percentage of time for eyes off the forward roadway, but parents remained stable. Compared with their parents, the longest single glance off the forward roadway was longer for novices at 0 months, but by 12 months there was no difference between the groups. However, for total percentage of time for eyes off the forward roadway, novices performed the same as their parents at 0 months and actually had shorter times at 12 months. These findings could reflect the combined development of driving skills over 12 months and the relative experience that modern teenagers have with portable electronic devices. The results suggest that novice drivers are particularly poor at engaging with secondary tasks while driving. JF - Accident Analysis & Prevention AU - O'Brien, Fearghal AU - Klauer, Sheila G AU - Ehsani, Johnathon AU - Simons-Morton, Bruce G AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, 6100 Executive Blvd, Bethesda, MD 20892, United States Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 48 EP - 54 PB - Elsevier B.V., P.O. Box 800 Kidlington Oxford OX5 1DX United Kingdom VL - 93 SN - 0001-4575, 0001-4575 KW - Health & Safety Science Abstracts KW - Young novice drivers KW - Eye glances KW - Secondary task engagement KW - Test track KW - Experience KW - Accidents KW - Prevention KW - Driving ability KW - Eye KW - Risk factors KW - Highways KW - Adolescents KW - H 2000:Transportation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808628415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Accident+Analysis+%26+Prevention&rft.atitle=Changes+over+12+months+in+eye+glances+during+secondary+task+engagement+among+novice+drivers&rft.au=O%27Brien%2C+Fearghal%3BKlauer%2C+Sheila+G%3BEhsani%2C+Johnathon%3BSimons-Morton%2C+Bruce+G&rft.aulast=O%27Brien&rft.aufirst=Fearghal&rft.date=2016-08-01&rft.volume=93&rft.issue=&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Accident+Analysis+%26+Prevention&rft.issn=00014575&rft_id=info:doi/10.1016%2Fj.aap.2016.04.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Prevention; Accidents; Driving ability; Eye; Risk factors; Highways; Adolescents DO - http://dx.doi.org/10.1016/j.aap.2016.04.022 ER - TY - JOUR T1 - EHP Highlights of the Past Year. AN - 1808607719; 27479990 JF - Environmental health perspectives AU - Darney, Sally Perreault AD - Environmental Health Perspectives, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/08/01/ PY - 2016 DA - 2016 Aug 01 SP - 1 VL - 124 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808607719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=EHP+Highlights+of+the+Past+Year.&rft.au=Darney%2C+Sally+Perreault&rft.aulast=Darney&rft.aufirst=Sally&rft.date=2016-08-01&rft.volume=124&rft.issue=8&rft.spage=A132&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP777 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/EHP777 ER - TY - JOUR T1 - The Exposome: Embracing the Complexity for Discovery in Environmental Health. AN - 1808606747; 27479988 JF - Environmental health perspectives AU - Cui, Yuxia AU - Balshaw, David M AU - Kwok, Richard K AU - Thompson, Claudia L AU - Collman, Gwen W AU - Birnbaum, Linda S AD - Exposure, Response, and Technology Branch, Division of Extramural Research and Training, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA. Y1 - 2016/08/01/ PY - 2016 DA - 2016 Aug 01 SP - A137 EP - A140 VL - 124 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808606747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+Exposome%3A+Embracing+the+Complexity+for+Discovery+in+Environmental+Health.&rft.au=Cui%2C+Yuxia%3BBalshaw%2C+David+M%3BKwok%2C+Richard+K%3BThompson%2C+Claudia+L%3BCollman%2C+Gwen+W%3BBirnbaum%2C+Linda+S&rft.aulast=Cui&rft.aufirst=Yuxia&rft.date=2016-08-01&rft.volume=124&rft.issue=8&rft.spage=A137&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2FEHP412 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/EHP412 ER - TY - JOUR T1 - Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. AN - 1807881046; 26892991 AB - Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. We included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were -5.4% (95% confidence interval -19,10) and 0.3% (95% confidence interval -69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval -131, 82) and -211% (95% confidence interval -2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval -43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively. We find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies. Published by Elsevier Inc. JF - American journal of obstetrics and gynecology AU - Hildesheim, Allan AU - Gonzalez, Paula AU - Kreimer, Aimee R AU - Wacholder, Sholom AU - Schussler, John AU - Rodriguez, Ana C AU - Porras, Carolina AU - Schiffman, Mark AU - Sidawy, Mary AU - Schiller, John T AU - Lowy, Douglas R AU - Herrero, Rolando AU - Costa Rica HPV Vaccine Trial (CVT) Group AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Electronic address: Hildesha@mail.nih.gov. ; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; Information Management Services, Silver Spring, Maryland. ; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC. ; Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. ; Costa Rica HPV Vaccine Trial (CVT) Group Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 212.e1 EP - 212.e15 VL - 215 IS - 2 KW - Abridged Index Medicus KW - Index Medicus KW - vaccines KW - human papillomaviruses KW - prevention KW - clinical trial KW - cervical cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807881046?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+obstetrics+and+gynecology&rft.atitle=Impact+of+human+papillomavirus+%28HPV%29+16+and+18+vaccination+on+prevalent+infections+and+rates+of+cervical+lesions+after+excisional+treatment.&rft.au=Hildesheim%2C+Allan%3BGonzalez%2C+Paula%3BKreimer%2C+Aimee+R%3BWacholder%2C+Sholom%3BSchussler%2C+John%3BRodriguez%2C+Ana+C%3BPorras%2C+Carolina%3BSchiffman%2C+Mark%3BSidawy%2C+Mary%3BSchiller%2C+John+T%3BLowy%2C+Douglas+R%3BHerrero%2C+Rolando%3BCosta+Rica+HPV+Vaccine+Trial+%28CVT%29+Group&rft.aulast=Hildesheim&rft.aufirst=Allan&rft.date=2016-08-01&rft.volume=215&rft.issue=2&rft.spage=212.e1&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=1097-6868&rft_id=info:doi/10.1016%2Fj.ajog.2016.02.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ajog.2016.02.021 ER - TY - JOUR T1 - Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin. AN - 1807081835; 27167730 AB - Loricrin is a major component of the cornified cell envelope, a highly insoluble structure composed of covalently cross-linked proteins. Although loricrin knockout mice only exhibit a mild transient phenotype at birth, they show a marked delay in the formation of an epidermal barrier in utero. We recently discovered that induction of a compensatory response to repair the defective barrier is initiated by amniotic fluid via activation of NF-E2-related factor 2 and identified Sprr2d and Sprr2h as direct transcriptional targets. Proteomic analysis suggested that other proteins were also incorporated into the loricrin knockout cell envelope, in addition to the small proline rich proteins. Here we present evidence suggesting that the late cornified envelope 1 proteins are also compensatory components as determined by their localization within the loricrin knockout cell envelope via immunoelectron microscopy. We also demonstrate that late cornified envelope 1 genes are upregulated at the transcriptional level in loricrin knockout mouse skin and confirm that late cornified envelope 1 genes are transcriptional targets of NRF2. Our present study further highlights the complexity and importance of a compensatory mechanism that evolved in terrestrial animals to ensure the formation of a functional epidermal barrier. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. JF - The Journal of investigative dermatology AU - Ishitsuka, Yosuke AU - Huebner, Aaron J AU - Rice, Robert H AU - Koch, Peter J AU - Speransky, Vladislav V AU - Steven, Alasdair C AU - Roop, Dennis R AD - Department of Dermatology and Charles C. Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. ; Department of Environmental Toxicology, University of California, Davis, California, USA. ; Ted Pella, Life Sciences, Redding, California, USA. ; Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Dermatology and Charles C. Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. Electronic address: dennis.roop@ucdenver.edu. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1656 EP - 1663 VL - 136 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807081835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Lce1+Family+Members+Are+Nrf2-Target+Genes+that+Are+Induced+to+Compensate+for%C2%A0the+Loss+of+Loricrin.&rft.au=Ishitsuka%2C+Yosuke%3BHuebner%2C+Aaron+J%3BRice%2C+Robert+H%3BKoch%2C+Peter+J%3BSperansky%2C+Vladislav+V%3BSteven%2C+Alasdair+C%3BRoop%2C+Dennis+R&rft.aulast=Ishitsuka&rft.aufirst=Yosuke&rft.date=2016-08-01&rft.volume=136&rft.issue=8&rft.spage=1656&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=1523-1747&rft_id=info:doi/10.1016%2Fj.jid.2016.04.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jid.2016.04.022 ER - TY - JOUR T1 - Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors. AN - 1807081156; 27161622 AB - Filoviruses are highly infectious, and no FDA-approved drug therapy for filovirus infection is available. Most work to find a treatment has involved only a few strains of Ebola virus and testing of relatively small drug libraries or compounds that have shown efficacy against other virus types. Here we report the findings of a high-throughput screening of 319,855 small molecules from the Molecular Libraries Small Molecule Repository library for their activities against Marburg virus and Ebola virus. Nine of the most potent, novel compounds that blocked infection by both viruses were analyzed in detail for their mechanisms of action. The compounds inhibited known key steps in the Ebola virus infection mechanism by blocking either cell surface attachment, macropinocytosis-mediated uptake, or endosomal trafficking. To date, very few specific inhibitors of macropinocytosis have been reported. The 2 novel macropinocytosis inhibitors are more potent inhibitors of Ebola virus infection and less toxic than ethylisopropylamiloride, one commonly accepted macropinocytosis inhibitor. Each compound blocked infection of primary human macrophages, indicating their potential to be developed as new antifiloviral therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Antimicrobial agents and chemotherapy AU - Anantpadma, Manu AU - Kouznetsova, Jennifer AU - Wang, Hang AU - Huang, Ruili AU - Kolokoltsov, Andrey AU - Guha, Rajarshi AU - Lindstrom, Aaron R AU - Shtanko, Olena AU - Simeonov, Anton AU - Maloney, David J AU - Maury, Wendy AU - LaCount, Douglas J AU - Jadhav, Ajit AU - Davey, Robert A AD - Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas, USA. ; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA. ; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA. ; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA. ; Department of Microbiology, University of Iowa, Iowa City, Iowa, USA. ; Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas, USA rdavey@txbiomed.org. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 4471 EP - 4481 VL - 60 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807081156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Large-Scale+Screening+and+Identification+of+Novel+Ebola+Virus+and+Marburg+Virus+Entry+Inhibitors.&rft.au=Anantpadma%2C+Manu%3BKouznetsova%2C+Jennifer%3BWang%2C+Hang%3BHuang%2C+Ruili%3BKolokoltsov%2C+Andrey%3BGuha%2C+Rajarshi%3BLindstrom%2C+Aaron+R%3BShtanko%2C+Olena%3BSimeonov%2C+Anton%3BMaloney%2C+David+J%3BMaury%2C+Wendy%3BLaCount%2C+Douglas+J%3BJadhav%2C+Ajit%3BDavey%2C+Robert+A&rft.aulast=Anantpadma&rft.aufirst=Manu&rft.date=2016-08-01&rft.volume=60&rft.issue=8&rft.spage=4471&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=1098-6596&rft_id=info:doi/10.1128%2FAAC.00543-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-25 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1128/AAC.00543-16 ER - TY - JOUR T1 - N-methyl-N-nitrosourea-induced schwannomas in male Sprague-Dawley rats with a literature review of inducible and spontaneous lesions. AN - 1807080036; 27233116 AB - N-methyl-N-nitrosourea (MNU) possesses peripheral nervous system carcinogenic activity in rats and induces benign and malignant schwannomas in systemic organs. In this retrospective study, we compared the characteristics of various immunohistochemical markers in MNU-induced schwannomas in male Crj:CD(SD)IGS rats including: vimentin (Vim), S100, p75 nerve growth factor receptor (LNGFR), CD57, pancytokeratin (CK), myoglobin, desmin and α smooth muscle actin (SMA). Single intraperitoneal exposures of 50 or 75mg/kg MNU in male rats at the age of 4 weeks induced schwannomas in 43 surviving and terminated rats up to 30-weeks-old. The incidence rate of neoplastic lesions was 37% (16 of 43 rats). Benign schwannomas (mesentery, pancreas, thymus) and malignant schwannomas (subendocardium, cardiac intramural, thoracic cavity, abdominal cavity, prostate), occurred in nine and seven rats, respectively. All neoplastic lesions were moderately or strongly positive for Vim, S100 and LNGFR proteins. Benign tumors were weakly positive and malignant tumors strongly positive for Ki-67, suggesting a high active proliferation rate of Schwann cell precursors. All lesions were negative for CD57, CK, myoglobin, desmin and SMA. This data may provide useful immunohistochemical information for the investigation of schwannomas in rat chemical carcinogenicity studies. Copyright © 2016 Elsevier GmbH. All rights reserved. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Yoshizawa, Katsuhiko AU - Yuki, Michiko AU - Kinoshita, Yuichi AU - Emoto, Yuko AU - Yuri, Takashi AU - Elmore, Susan A AU - Tsubura, Airo AD - Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan. Electronic address: yoshizak@hirakata.kmu.ac.jp. ; Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan. ; Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; Division of Diagnostic Cytopathology and Histopathology, Kansai Medical University Medical Center, Fumizono 10-15, Moriguchi, Osaka 570-8507, Japan. ; Cellular & Molecular Pathology Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 371 EP - 379 VL - 68 IS - 7 KW - Index Medicus KW - Rat KW - Ntp KW - Immunohistochemistry KW - Neurofibromatosis KW - N-methyl-N-nitrosourea KW - Schwannoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807080036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=N-methyl-N-nitrosourea-induced+schwannomas+in+male+Sprague-Dawley+rats+with+a+literature+review+of+inducible+and+spontaneous+lesions.&rft.au=Yoshizawa%2C+Katsuhiko%3BYuki%2C+Michiko%3BKinoshita%2C+Yuichi%3BEmoto%2C+Yuko%3BYuri%2C+Takashi%3BElmore%2C+Susan+A%3BTsubura%2C+Airo&rft.aulast=Yoshizawa&rft.aufirst=Katsuhiko&rft.date=2016-08-01&rft.volume=68&rft.issue=7&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=1618-1433&rft_id=info:doi/10.1016%2Fj.etp.2016.05.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.etp.2016.05.005 ER - TY - JOUR T1 - Biomarker development in the precision medicine era: lung cancer as a case study. AN - 1807078119; 27388699 AB - Precision medicine relies on validated biomarkers with which to better classify patients by their probable disease risk, prognosis and/or response to treatment. Although affordable 'omics'-based technology has enabled faster identification of putative biomarkers, the validation of biomarkers is still stymied by low statistical power and poor reproducibility of results. This Review summarizes the successes and challenges of using different types of molecule as biomarkers, using lung cancer as a key illustrative example. Efforts at the national level of several countries to tie molecular measurement of samples to patient data via electronic medical records are the future of precision medicine research. JF - Nature reviews. Cancer AU - Vargas, Ashley J AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Room 3068A, MSC 425, 837 Convent Drive, Bethesda, Maryland 20892-4258, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 525 EP - 537 VL - 16 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807078119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Cancer&rft.atitle=Biomarker+development+in+the+precision+medicine+era%3A+lung+cancer+as+a+case+study.&rft.au=Vargas%2C+Ashley+J%3BHarris%2C+Curtis+C&rft.aulast=Vargas&rft.aufirst=Ashley&rft.date=2016-08-01&rft.volume=16&rft.issue=8&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Cancer&rft.issn=1474-1768&rft_id=info:doi/10.1038%2Fnrc.2016.56 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nrc.2016.56 ER - TY - JOUR T1 - DNMT1 is a required genomic regulator for murine liver histogenesis and regeneration. AN - 1806445251; 26999257 AB - DNA methyltransferase 1 (DNMT1) is an essential regulator maintaining both epigenetic reprogramming during DNA replication and genome stability. We investigated the role of DNMT1 in the regulation of postnatal liver histogenesis under homeostasis and stress conditions. We generated Dnmt1 conditional knockout mice (Dnmt1(Δalb) ) by crossing Dnmt1(fl/fl) with albumin-cyclization recombination transgenic mice. Serum, liver tissues, and primary hepatocytes were collected from 1-week-old to 20-week old mice. The Dnmt1(Δalb) phenotype was assessed by histology, confocal and electron microscopy, biochemistry, as well as transcriptome and methylation profiling. Regenerative growth was induced by partial hepatectomy and exposure to carbon tetrachloride. The impact of Dnmt1 knockdown was also analyzed in hepatic progenitor cell lines; proliferation, apoptosis, DNA damage, and sphere formation were assessed. Dnmt1 loss in postnatal hepatocytes caused global hypomethylation, enhanced DNA damage response, and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated through activation and repopulation from progenitors due to lineage-dependent differences in albumin-cyclization recombination expression, providing a basis for selection of less mature and therefore less damaged hepatic progenitor cell progeny. Consistently, efficient knockdown of Dnmt1 in cultured hepatic progenitor cells caused severe DNA damage, cell cycle arrest, senescence, and cell death. Mx1-cyclization recombination-driven deletion of Dnmt1 in adult quiescent hepatocytes did not affect liver homeostasis. These results establish the indispensable role of DNMT1-mediated epigenetic regulation in postnatal liver growth and regeneration; Dnmt1(Δalb) mice provide a unique experimental model to study the role of senescence and the contribution of progenitor cells to physiological and regenerative liver growth. (Hepatology 2016;64:582-598). Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Hepatology (Baltimore, Md.) AU - Kaji, Kosuke AU - Factor, Valentina M AU - Andersen, Jesper B AU - Durkin, Marian E AU - Tomokuni, Akira AU - Marquardt, Jens U AU - Matter, Matthias S AU - Hoang, Tanya AU - Conner, Elizabeth A AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 582 EP - 598 VL - 64 IS - 2 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806445251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=DNMT1+is+a+required+genomic+regulator+for+murine+liver+histogenesis+and+regeneration.&rft.au=Kaji%2C+Kosuke%3BFactor%2C+Valentina+M%3BAndersen%2C+Jesper+B%3BDurkin%2C+Marian+E%3BTomokuni%2C+Akira%3BMarquardt%2C+Jens+U%3BMatter%2C+Matthias+S%3BHoang%2C+Tanya%3BConner%2C+Elizabeth+A%3BThorgeirsson%2C+Snorri+S&rft.aulast=Kaji&rft.aufirst=Kosuke&rft.date=2016-08-01&rft.volume=64&rft.issue=2&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28563 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28563 ER - TY - JOUR T1 - Insights into the complex levels of regulation imposed on Escherichia coli DNA polymerase V. AN - 1806442719; 27236212 AB - It is now close to 40 years since the isolation of non-mutable umu/uvm strains of Escherichia coli and the realization that damage induced mutagenesis in E.coli is not a passive process. Early models of mutagenesis envisioned the Umu proteins as accessory factors to the cell's replicase that not only reduced its normally high fidelity, but also allowed the enzyme to traverse otherwise replication-blocking lesions in the genome. However, these models underwent a radical revision approximately 15 years ago, with the discovery that the Umu proteins actually encode for a DNA polymerase, E.coli pol V. The polymerase lacks 3'→5' exonucleolytic proofreading activity and is inherently error-prone when replicating both undamaged and damage DNA. So as to limit any "gratuitous" mutagenesis, the activity of pol V is strictly regulated in the cell at multiple levels. This review will summarize our current understanding of the myriad levels of regulation imposed on pol V including transcriptional control, posttranslational modification, targeted proteolysis, activation of the catalytic activity of pol V through protein-protein interactions and the very recently described intracellular spatial regulation of pol V. Remarkably, despite the multiple levels at which pol V is regulated, the enzyme is nevertheless able to contribute to the genetic diversity and evolutionary fitness of E.coli. Published by Elsevier B.V. JF - DNA repair AU - Goodman, Myron F AU - McDonald, John P AU - Jaszczur, Malgorzata M AU - Woodgate, Roger AD - Departments of Biological Sciences and Chemistry, University of Southern California, University Park, Los Angeles, CA 90089-2910, USA. Electronic address: mgoodman@usc.edu. ; Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA. ; Department of Biological Sciences, University of Southern California, University Park, Los Angeles, CA 90089-2910, USA. ; Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA. Electronic address: woodgate@mail.nih.gov. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 42 EP - 50 VL - 44 KW - Index Medicus KW - Proteolysis KW - Posttranslational regulation KW - Translesion DNA synthesis KW - Y-family DNA polymerase UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806442719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+repair&rft.atitle=Insights+into+the+complex+levels+of+regulation+imposed+on+Escherichia+coli+DNA+polymerase+V.&rft.au=Goodman%2C+Myron+F%3BMcDonald%2C+John+P%3BJaszczur%2C+Malgorzata+M%3BWoodgate%2C+Roger&rft.aulast=Goodman&rft.aufirst=Myron&rft.date=2016-08-01&rft.volume=44&rft.issue=&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=1568-7856&rft_id=info:doi/10.1016%2Fj.dnarep.2016.05.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.dnarep.2016.05.005 ER - TY - JOUR T1 - Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings. AN - 1806077836; 26300477 AB - Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. JF - Neuropathology and applied neurobiology AU - Thom, Maria AU - Michalak, Zuzanna AU - Wright, Gabriella AU - Dawson, Timothy AU - Hilton, David AU - Joshi, Abhijit AU - Diehl, Beate AU - Koepp, Matthias AU - Lhatoo, Samden AU - Sander, Josemir W AU - Sisodiya, Sanjay M AD - Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK. ; Department of Neuropathology, Lancashire Teaching Hospitals, Preston, UK. ; Department of Cellular Pathology, Derriford Hospital, Plymouth, UK. ; Department of Neuropathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK. ; NINDS Center for SUDEP Research, University Hospitals Case Medical Center, Department of Neurology Cleveland, OH. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 463 EP - 476 VL - 42 IS - 5 KW - Index Medicus KW - neuropathology KW - post mortem KW - SUDEP KW - audit KW - Sudden unexpected death in epilepsy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806077836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropathology+and+applied+neurobiology&rft.atitle=Audit+of+practice+in+sudden+unexpected+death+in+epilepsy+%28SUDEP%29+post+mortems+and+neuropathological+findings.&rft.au=Thom%2C+Maria%3BMichalak%2C+Zuzanna%3BWright%2C+Gabriella%3BDawson%2C+Timothy%3BHilton%2C+David%3BJoshi%2C+Abhijit%3BDiehl%2C+Beate%3BKoepp%2C+Matthias%3BLhatoo%2C+Samden%3BSander%2C+Josemir+W%3BSisodiya%2C+Sanjay+M&rft.aulast=Thom&rft.aufirst=Maria&rft.date=2016-08-01&rft.volume=42&rft.issue=5&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Neuropathology+and+applied+neurobiology&rft.issn=1365-2990&rft_id=info:doi/10.1111%2Fnan.12265 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/nan.12265 ER - TY - JOUR T1 - Dysfunctional representation of expected value is associated with reinforcement-based decision-making deficits in adolescents with conduct problems AN - 1806065957 AB - Background Previous work has shown that patients with conduct problems (CP) show impairments in reinforcement-based decision-making. However, studies with patients have not previously demonstrated any relationships between impairment in any of the neurocomputations underpinning reinforcement-based decision-making and specific symptom sets [e.g. level of CP and/or callous-unemotional (CU) traits]. Methods Seventy-two youths [20 female, mean age = 13.81 (SD = 2.14), mean IQ = 102.34 (SD = 10.99)] from a residential treatment program and the community completed a passive avoidance task while undergoing functional MRI. Results Greater levels of CP were associated with poorer task performance. Reduced representation of expected values (EV) when making avoidance responses within bilateral anterior insula cortex/inferior frontal gyrus (AIC/iFG) and striatum was associated with greater levels of CP but not CU traits. Conclusions The current data indicate that difficulties in the use of value information to motivate decisions to avoid suboptimal choices are associated with increased levels of CP (though not severity of CU traits). Moreover, they account for the behavioral deficits observed during reinforcement-based decision-making in youth with CP. In short, an individual's relative failure to utilize value information within AIC/iFG to avoid bad choices is associated with elevated levels of CP. JF - Journal of Child Psychology and Psychiatry AU - White, Stuart F AU - Tyler, Patrick M AU - Erway, Anna K AU - Botkin, Mary L AU - Kolli, Venkata AU - Meffert, Harma AU - Pope, Kayla AU - Blair, James R AD - Section on Affective Cognitive Neuroscience, NIMH, NIH, Bethesda, MD, USA; Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA ; Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, NE, USA ; Creighton University School of Medicine, Omaha, NE, USA ; Section on Affective Cognitive Neuroscience, NIMH, NIH, Bethesda, MD, USA Y1 - 2016/08// PY - 2016 DA - Aug 2016 SP - 938 EP - 946 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 8 KW - Psychology KW - Dysfunctional KW - Decision making KW - Cortex KW - Task performance KW - Residential treatment KW - Severity KW - Conduct disorders KW - Magnetic resonance imaging KW - Passive avoidance KW - Functional magnetic resonance imaging KW - Reinforcement KW - Avoidance KW - Intelligence quotient UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806065957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Dysfunctional+representation+of+expected+value+is+associated+with+reinforcement-based+decision-making+deficits+in+adolescents+with+conduct+problems&rft.au=White%2C+Stuart+F%3BTyler%2C+Patrick+M%3BErway%2C+Anna+K%3BBotkin%2C+Mary+L%3BKolli%2C+Venkata%3BMeffert%2C+Harma%3BPope%2C+Kayla%3BBlair%2C+James+R&rft.aulast=White&rft.aufirst=Stuart&rft.date=2016-08-01&rft.volume=57&rft.issue=8&rft.spage=938&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12557 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-08-17 DO - http://dx.doi.org/10.1111/jcpp.12557 ER - TY - JOUR T1 - Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study. AN - 1805484612; 26666433 AB - Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R-B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12-71 months). Toxicity was moderate, mainly grades 1 and 2. R-B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs. JF - Leukemia & lymphoma AU - Arcari, Annalisa AU - Chiappella, Annalisa AU - Spina, Michele AU - Zanlari, Luca AU - Bernuzzi, Patrizia AU - Valenti, Vanessa AU - Tani, Monica AU - Marasca, Roberto AU - Cabras, Maria Giuseppina AU - Zambello, Renato AU - Santagostino, Alberto AU - Ilariucci, Fiorella AU - Carli, Giuseppe AU - Musto, Pellegrino AU - Savini, Paolo AU - Marino, Dario AU - Ghio, Francesco AU - Gentile, Massimo AU - Cox, Maria Christina AU - Vallisa, Daniele AD - a Hematology Unit, Department of Onco-Hematology , Guglielmo da Saliceto Hospital , Piacenza , Italy ; ; b Department of Hematology , Città della Salute e della Scienza University Hospital , Torino , Italy ; ; c Department of Medical Oncology A , National Cancer Institute , Aviano , Italy ; ; d Day Hospital of Internal Medicine, Fiorenzuola d'Arda , Piacenza , Italy ; ; e Department of Hematology , Santa Maria delle Croci Hospital , Ravenna , Italy ; ; f Division of Hematology, Department of Medical and Surgical Sciences , University of Modena and Reggio Emilia , Italy ; ; g Department of Hematology , Businco Hospital , Cagliari , Italy ; ; h Hematology, Padua University School of Medicine , Padova , Italy ; ; i Onco-Hematology Unit, S. Andrea Hospital , Vercelli , Italy ; ; j Hematology Unit, Arcispedale Santa Maria Nuova-IRCCS , Reggio Emilia , Italy ; ; k Department of Medicine , Section of Hematology, University of Verona , Italy ; ; l Scientific Direction, IRCCS, Referral Cancer Center of Basilicata , Rionero in Vulture , Italy ; ; m Medicine Department , Ospedale degli Infermi , Faenza , Italy ; ; n Division of Medical Oncology 1 , Istituto Oncologico Veneto-IRCCS , Padova , Italy ; ; o Department of Clinical and Experimental Medicine , Hematology, University of Pisa , Italy ; ; p Department of Hematology Unit , Ospedale Annunziata , Cosenza , Italy ; ; q Department of Hematology , Azienda Ospedaliera S. Andrea , Rome , Italy. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1823 EP - 1830 VL - 57 IS - 8 KW - Index Medicus KW - rituximab KW - elderly KW - diffuse large B-cell lymphoma KW - Bendamustine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1805484612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=Safety+and+efficacy+of+rituximab+plus+bendamustine+in+relapsed+or+refractory+diffuse+large+B-cell+lymphoma+patients%3A+an+Italian+retrospective+multicenter+study.&rft.au=Arcari%2C+Annalisa%3BChiappella%2C+Annalisa%3BSpina%2C+Michele%3BZanlari%2C+Luca%3BBernuzzi%2C+Patrizia%3BValenti%2C+Vanessa%3BTani%2C+Monica%3BMarasca%2C+Roberto%3BCabras%2C+Maria+Giuseppina%3BZambello%2C+Renato%3BSantagostino%2C+Alberto%3BIlariucci%2C+Fiorella%3BCarli%2C+Giuseppe%3BMusto%2C+Pellegrino%3BSavini%2C+Paolo%3BMarino%2C+Dario%3BGhio%2C+Francesco%3BGentile%2C+Massimo%3BCox%2C+Maria+Christina%3BVallisa%2C+Daniele&rft.aulast=Arcari&rft.aufirst=Annalisa&rft.date=2016-08-01&rft.volume=57&rft.issue=8&rft.spage=1823&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=1029-2403&rft_id=info:doi/10.3109%2F10428194.2015.1106536 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.3109/10428194.2015.1106536 ER - TY - JOUR T1 - Amoxicillin-Clavulanate-Induced Liver Injury. AN - 1804859776; 27003146 AB - Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. AC-DILI causes a moderately severe, mixed hepatocellular-cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation. JF - Digestive diseases and sciences AU - deLemos, Andrew S AU - Ghabril, Marwan AU - Rockey, Don C AU - Gu, Jiezhun AU - Barnhart, Huiman X AU - Fontana, Robert J AU - Kleiner, David E AU - Bonkovsky, Herbert L AU - Drug-Induced Liver Injury Network (DILIN) AD - Department of Medicine, Carolinas Medical Center, 1025 Morehead Medical Drive, Suite 600, Charlotte, NC, 28204, USA. Andrew.deLemos@carolinashealthcare.org. ; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. ; Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. ; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. ; Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA. ; Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. ; Department of Medicine, Wake Forest Baptist Medical Center, Winston Salem, NC, USA. ; Drug-Induced Liver Injury Network (DILIN) Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 2406 EP - 2416 VL - 61 IS - 8 KW - Abridged Index Medicus KW - Index Medicus KW - Amoxicillin KW - Liver toxicity KW - Allergy KW - Clavulanic acid KW - Augmentin KW - Drug-induced liver injury UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804859776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Digestive+diseases+and+sciences&rft.atitle=Amoxicillin-Clavulanate-Induced+Liver+Injury.&rft.au=deLemos%2C+Andrew+S%3BGhabril%2C+Marwan%3BRockey%2C+Don+C%3BGu%2C+Jiezhun%3BBarnhart%2C+Huiman+X%3BFontana%2C+Robert+J%3BKleiner%2C+David+E%3BBonkovsky%2C+Herbert+L%3BDrug-Induced+Liver+Injury+Network+%28DILIN%29&rft.aulast=deLemos&rft.aufirst=Andrew&rft.date=2016-08-01&rft.volume=61&rft.issue=8&rft.spage=2406&rft.isbn=&rft.btitle=&rft.title=Digestive+diseases+and+sciences&rft.issn=1573-2568&rft_id=info:doi/10.1007%2Fs10620-016-4121-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-14 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1007/s10620-016-4121-6 ER - TY - JOUR T1 - Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population. AN - 1802744706; 27393504 AB - Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2. In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans. Published by Elsevier Ireland Ltd. JF - Lung cancer (Amsterdam, Netherlands) AU - Zanetti, Krista A AU - Wang, Zhaoming AU - Aldrich, Melinda AU - Amos, Christopher I AU - Blot, William J AU - Bowman, Elise D AU - Burdette, Laurie AU - Cai, Qiuyin AU - Caporaso, Neil AU - Chung, Charles C AU - Gillanders, Elizabeth M AU - Haiman, Christopher A AU - Hansen, Helen M AU - Henderson, Brian E AU - Kolonel, Laurence N AU - Marchand, Loic Le AU - Li, Shengchao AU - McNeill, Lorna Haughton AU - Ryan, Bríd M AU - Schwartz, Ann G AU - Sison, Jennette D AU - Spitz, Margaret R AU - Tucker, Margaret AU - Wenzlaff, Angela S AU - Wiencke, John K AU - Wilkens, Lynne AU - Wrensch, Margaret R AU - Wu, Xifeng AU - Zheng, Wei AU - Zhou, Weiyin AU - Christiani, David AU - Palmer, Julie R AU - Penning, Trevor M AU - Rieber, Alyssa G AU - Rosenberg, Lynn AU - Ruiz-Narvaez, Edward A AU - Su, Li AU - Vachani, Anil AU - Wei, Yongyue AU - Whitehead, Alexander S AU - Chanock, Stephen J AU - Harris, Curtis C AD - Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: zanettik@mail.nih.gov. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: wangzha@mail.nih.gov. ; Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA; Department of Thoracic Surgery, Vanderbilt University Medical Center, 609 Oxford House, 1313 21st Ave South, Nashville, TN 37232-4682, USA. Electronic address: melinda.aldrich@Vanderbilt.Edu. ; Department of Biomedical Data Science, Geisel School of Medicine, 1 Rope Ferry Road, Dartmouth, Lebanon, NH 03755-1404, USA. Electronic address: Christopher.I.Amos@Dartmouth.edu. ; Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: blotw@iei.us. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3068A, Bethesda, MD 20892, USA. Electronic address: bowmane@intra.nci.nih.gov. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: burdettl@mail.nih.gov. ; Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: qiuyin.cai@Vanderbilt.Edu. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: caporasn@mail.nih.gov. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: chungcc@mail.nih.gov. ; Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: lgilland@mail.nih.gov. ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California and Norris Comprehensive Cancer Center, 1975 Zonal Avenue, Los Angeles, CA 90033, USA. Electronic address: haiman@usc.edu. ; Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: helen.hansen@ucsf.edu. ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California and Norris Comprehensive Cancer Center, 1975 Zonal Avenue, Los Angeles, CA 90033, USA. ; Epidemiology Program, Cancer Research Center, University of Hawaii, 701 Ilalo Street, Honolulu, HI 96813, USA. Electronic address: lkolonel@cc.hawaii.edu. ; Epidemiology Program, Cancer Research Center, University of Hawaii, 701 Ilalo Street, Honolulu, HI 96813, USA. Electronic address: Loic@cc.hawaii.edu. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: shengchao.li@nih.gov. ; Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 91, Houston, TX 77030, USA. Electronic address: lmcneill@mdanderson.org. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3068A, Bethesda, MD 20892, USA. Electronic address: ryanb@mail.nih.gov. ; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R, Detroit, MI 48201, USA. Electronic address: schwarta@karmanos.org. ; Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: jennette.sison@ucsf.edu. ; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM225, Houston, TX 77030, USA. Electronic address: spitz@bcm.edu. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: tuckerp@mail.nih.gov. ; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R, Detroit, MI 48201, USA. Electronic address: wenzlaff@karmanos.org. ; Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: john.wiencke@ucsf.edu. ; Epidemiology Program, Cancer Research Center, University of Hawaii, 701 Ilalo Street, Honolulu, HI 96813, USA. Electronic address: lynne@cc.hawaii.edu. ; Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: Margaret.Wrensch@ucsf.edu. ; Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Unit 1340, PO Box 301439, Houston, TX 77230-1439, USA. Electronic address: xwu@mdanderson.org. ; Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: wei.zheng@vanderbilt.edu. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: zhouw@mail.nih.gov. ; Harvard School of Public Health, Massachusetts General Hospital/Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: dchris@hsph.harvard.edu. ; Slone Epidemiology Cancer Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. Electronic address: jpalmer@bu.edu. ; Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA. Electronic address: PENNING@UPENN.EDU. ; Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Electronic address: arieber@mdanderson.org. ; Slone Epidemiology Cancer Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. Electronic address: lrosenbe@bu.edu. ; Slone Epidemiology Cancer Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. Electronic address: eruiznar@bu.edu. ; Harvard School of Public Health, Massachusetts General Hospital/Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: lisu@hsph.harvard.edu. ; Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia, PA 19104, USA. Electronic address: avachani@mail.med.upenn.edu. ; Harvard School of Public Health, Massachusetts General Hospital/Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: ywei@hsph.harvard.edu. ; Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA. Electronic address: aswhiteh@mail.med.upenn.edu. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: chanocks@mail.nih.gov. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3068A, Bethesda, MD 20892, USA. Electronic address: Curtis_Harris@nih.gov. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 33 EP - 42 VL - 98 KW - Index Medicus KW - Smoking KW - Telomerase KW - Genome-wide association study KW - Lung neoplasms KW - African Americans KW - Receptors, Cholinergic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802744706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Genome-wide+association+study+confirms+lung+cancer+susceptibility+loci+on+chromosomes+5p15+and+15q25+in+an+African-American+population.&rft.au=Zanetti%2C+Krista+A%3BWang%2C+Zhaoming%3BAldrich%2C+Melinda%3BAmos%2C+Christopher+I%3BBlot%2C+William+J%3BBowman%2C+Elise+D%3BBurdette%2C+Laurie%3BCai%2C+Qiuyin%3BCaporaso%2C+Neil%3BChung%2C+Charles+C%3BGillanders%2C+Elizabeth+M%3BHaiman%2C+Christopher+A%3BHansen%2C+Helen+M%3BHenderson%2C+Brian+E%3BKolonel%2C+Laurence+N%3BMarchand%2C+Loic+Le%3BLi%2C+Shengchao%3BMcNeill%2C+Lorna+Haughton%3BRyan%2C+Br%C3%ADd+M%3BSchwartz%2C+Ann+G%3BSison%2C+Jennette+D%3BSpitz%2C+Margaret+R%3BTucker%2C+Margaret%3BWenzlaff%2C+Angela+S%3BWiencke%2C+John+K%3BWilkens%2C+Lynne%3BWrensch%2C+Margaret+R%3BWu%2C+Xifeng%3BZheng%2C+Wei%3BZhou%2C+Weiyin%3BChristiani%2C+David%3BPalmer%2C+Julie+R%3BPenning%2C+Trevor+M%3BRieber%2C+Alyssa+G%3BRosenberg%2C+Lynn%3BRuiz-Narvaez%2C+Edward+A%3BSu%2C+Li%3BVachani%2C+Anil%3BWei%2C+Yongyue%3BWhitehead%2C+Alexander+S%3BChanock%2C+Stephen+J%3BHarris%2C+Curtis+C&rft.aulast=Zanetti&rft.aufirst=Krista&rft.date=2016-08-01&rft.volume=98&rft.issue=&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=1872-8332&rft_id=info:doi/10.1016%2Fj.lungcan.2016.05.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.lungcan.2016.05.008 ER - TY - JOUR T1 - Quantitative Detection and Genotyping of Helicobacter pylori from Stool using Droplet Digital PCR Reveals Variation in Bacterial Loads that Correlates with cagA Virulence Gene Carriage. AN - 1802737329; 26667241 AB - Epidemiologic studies of the carcinogenic stomach bacterium Helicobacter pylori have been limited by the lack of noninvasive detection and genotyping methods. We developed a new stool-based method for detection, quantification, and partial genotyping of H. pylori using droplet digital PCR (ddPCR), which allows for increased sensitivity and absolute quantification by PCR partitioning. Stool-based ddPCR assays for H. pylori 16S gene detection and cagA virulence gene typing were tested using a collection of 50 matched stool and serum samples from Costa Rican volunteers and 29 H. pylori stool antigen-tested stool samples collected at a US hospital. The stool-based H. pylori 16S ddPCR assay had a sensitivity of 84% and 100% and a specificity of 100% and 71% compared to serology and stool antigen tests, respectively. The stool-based cagA genotyping assay detected cagA in 22 (88%) of 25 stools from CagA antibody-positive individuals and four (16%) of 25 stools from CagA antibody-negative individuals from Costa Rica. All 26 of these samples had a Western-type cagA allele. Presence of serum CagA antibodies was correlated with a significantly higher load of H. pylori in the stool. The stool-based ddPCR assays are a sensitive, noninvasive method for detection, quantification, and partial genotyping of H. pylori. The quantitative nature of ddPCR-based H. pylori detection revealed significant variation in bacterial load among individuals that correlates with presence of the cagA virulence gene. These stool-based ddPCR assays will facilitate future population-based epidemiologic studies of this important human pathogen. © 2015 John Wiley & Sons Ltd. JF - Helicobacter AU - Talarico, Sarah AU - Safaeian, Mahboobeh AU - Gonzalez, Paula AU - Hildesheim, Allan AU - Herrero, Rolando AU - Porras, Carolina AU - Cortes, Bernal AU - Larson, Ann AU - Fang, Ferric C AU - Salama, Nina R AD - Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; National Cancer Institute, NIH, Rockville, MD, USA. ; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica. ; Clinical Microbiology Laboratory, Harborview Medical Center, Seattle, WA, USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 325 EP - 333 VL - 21 IS - 4 KW - Index Medicus KW - H. pylori KW - Droplet digital PCR KW - cagA gene KW - stool-based assay KW - bacterial load UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802737329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Helicobacter&rft.atitle=Quantitative+Detection+and+Genotyping+of+Helicobacter+pylori+from+Stool+using+Droplet+Digital+PCR+Reveals+Variation+in+Bacterial+Loads+that+Correlates+with+cagA+Virulence+Gene+Carriage.&rft.au=Talarico%2C+Sarah%3BSafaeian%2C+Mahboobeh%3BGonzalez%2C+Paula%3BHildesheim%2C+Allan%3BHerrero%2C+Rolando%3BPorras%2C+Carolina%3BCortes%2C+Bernal%3BLarson%2C+Ann%3BFang%2C+Ferric+C%3BSalama%2C+Nina+R&rft.aulast=Talarico&rft.aufirst=Sarah&rft.date=2016-08-01&rft.volume=21&rft.issue=4&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Helicobacter&rft.issn=1523-5378&rft_id=info:doi/10.1111%2Fhel.12289 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/hel.12289 ER - TY - JOUR T1 - The Greatest Priority for Genetic Counseling: Effectively Meeting Our Clients' Needs 2014 NSGC Natalie Weissberger Paul National Achievement Award AN - 1802713168 AB - Issue Title: Genetic Counselor Professional Development Receipt of the 2014 Natalie Weissberger Paul (NWP) National Achievement Award was a highlight of my career. Thank you to all who nominated me for this prestigious NSGC recognition. I am humbled to join past NWP award winners many of whom are admired mentors, treasured colleagues and friends. I would like to express what a privilege it is to honor Natalie Weissberger Paul for whom this award is named. Twenty-nine years ago I co-edited a volume of the Birth Defects Original Article Series with Natalie summarizing a conference co-funded by the March of Dimes and NSGC (Biesecker et al., 1987 ). Natalie demonstrated her devotion to children with special needs through her work at the March of Dimes. As such I believe she would concur with the focus of my remarks on the partners in our work: our clients. JF - Journal of Genetic Counseling AU - Biesecker, Barbara Bowles AD - Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/08// PY - 2016 DA - Aug 2016 SP - 621 EP - 624 CY - New York PB - Springer Science & Business Media VL - 25 IS - 4 SN - 1059-7700 KW - Psychology KW - Psychotherapeutic genetic counseling KW - Client centered care KW - Paradigm shift in genetic counseling KW - Friends KW - Special needs children KW - Prestigious KW - Birth defects KW - Counselling KW - Defects KW - Mentors KW - Winners KW - Privilege KW - Professional development KW - Genetic counselling KW - Childbirth UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802713168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Genetic+Counseling&rft.atitle=The+Greatest+Priority+for+Genetic+Counseling%3A+Effectively+Meeting+Our+Clients%27+Needs+2014+NSGC+Natalie+Weissberger+Paul+National+Achievement+Award&rft.au=Biesecker%2C+Barbara+Bowles&rft.aulast=Biesecker&rft.aufirst=Barbara&rft.date=2016-08-01&rft.volume=25&rft.issue=4&rft.spage=621&rft.isbn=&rft.btitle=&rft.title=Journal+of+Genetic+Counseling&rft.issn=10597700&rft_id=info:doi/10.1007%2Fs10897-016-9962-9 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Name - March of Dimes N1 - Copyright - National Society of Genetic Counselors, Inc. 2016 N1 - Last updated - 2016-08-16 DO - http://dx.doi.org/10.1007/s10897-016-9962-9 ER - TY - JOUR T1 - Epidemiology of Injury-Related Emergency Department Visits in the US Among Youth with Autism Spectrum Disorder AN - 1802570621 AB - Several reports suggest children with autism spectrum disorder (ASD) are more likely to be seen for injury-related ED visits; however, no nationally representative study has examined this question. Using data from the 2008 Nationwide Emergency Department Sample, over a quarter of all visits among those with ASD were related to injury. In the multivariate analyses, the odds of an injury-related visit was 54 % greater among those with ASD compared to youth with intellectual disability (ID), but 48 % less compared to youth without ID or ASD. Compared to all other pediatric injury-visits in the US, visits among children with ASD were more likely to be due to self-inflicted injury and poisoning and were more likely to result in hospitalization (all p < 0.001). JF - Journal of Autism and Developmental Disorders AU - Kalb, Luther G AU - Vasa, Roma A AU - Ballard, Elizabeth D AU - Woods, Steven AU - Goldstein, Mitchell AU - Wilcox, Holly C AD - Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA ; Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA ; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Y1 - 2016/08// PY - 2016 DA - Aug 2016 SP - 2756 EP - 2763 CY - New York PB - Springer Science & Business Media VL - 46 IS - 8 SN - 0162-3257 KW - Children And Youth - About KW - Autistic disorder KW - Injury KW - Epidemiology KW - Intellectual disability KW - Emergency medicine KW - Accident and emergency departments KW - Autistic spectrum disorders KW - Learning disabled young people KW - Hospitalization KW - Autistic children KW - Disability KW - Young people KW - Selfinjury KW - Visits KW - Learning disabilities KW - Poisoning KW - Injuries KW - United States--US UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802570621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Autism+and+Developmental+Disorders&rft.atitle=Epidemiology+of+Injury-Related+Emergency+Department+Visits+in+the+US+Among+Youth+with+Autism+Spectrum+Disorder&rft.au=Kalb%2C+Luther+G%3BVasa%2C+Roma+A%3BBallard%2C+Elizabeth+D%3BWoods%2C+Steven%3BGoldstein%2C+Mitchell%3BWilcox%2C+Holly+C&rft.aulast=Kalb&rft.aufirst=Luther&rft.date=2016-08-01&rft.volume=46&rft.issue=8&rft.spage=2756&rft.isbn=&rft.btitle=&rft.title=Journal+of+Autism+and+Developmental+Disorders&rft.issn=01623257&rft_id=info:doi/10.1007%2Fs10803-016-2820-7 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10803-016-2820-7 ER - TY - JOUR T1 - Quercetin targets the interaction of calcineurin with LxVP-type motifs in immunosuppression. AN - 1801859926; 27109380 AB - Calcineurin (CN) is a unique calcium/calmodulin (CaM)-activated serine/threonine phosphatase. To perform its diverse biological functions, CN communicates with many substrates and other proteins. In the physiological activation of T cells, CN acts through transcriptional factors belonging to the NFAT family and other transcriptional effectors. The classic immunosuppressive drug cyclosporin A (CsA) can bind to cyclophilin (CyP) and compete with CN for the NFAT LxVP motif. CsA has debilitating side effects, including nephrotoxicity, hypertension and tremor. It is desirable to develop alternative immunosuppressive agents. To this end, we first tested the interactions between CN and the LxVP-type substrates, including endogenous regulators of calcineurin (RCAN1) and NFAT. Interestingly, we found that quercetin, the primary dietary flavonol, can inhibit the activity of CN and significantly disrupt the associations between CN and its LxVP-type substrates. We then validated the inhibitory effects of quercetin on the CN-NFAT interactions in cell-based assays. Further, quercetin also shows dose-dependent suppression of cytokine gene expression in mouse spleen cells. These data raise the possibility that the interactions of CN with its LxVP-type substrates are potential targets for immunosuppressive agents. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved. JF - Biochimie AU - Zhao, Yane AU - Zhang, Jin AU - Shi, Xiaoyu AU - Li, Jing AU - Wang, Rui AU - Song, Ruiwen AU - Wei, Qun AU - Cai, Huaibin AU - Luo, Jing AD - Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology Beijing Key Laboratory, Life Science Institute, Beijing Normal University, 100875 Beijing, China. ; Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology Beijing Key Laboratory, Life Science Institute, Beijing Normal University, 100875 Beijing, China. Electronic address: luojing@bnu.edu.cn. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 50 EP - 58 VL - 127 KW - Cytokines KW - 0 KW - Immunosuppressive Agents KW - NFATC Transcription Factors KW - Quercetin KW - 9IKM0I5T1E KW - Calcineurin KW - EC 3.1.3.16 KW - Index Medicus KW - Cyclosporine A KW - NFAT KW - Cytokine expression KW - LxVP-motif KW - RCAN1 KW - Animals KW - Cytokines -- genetics KW - Active Transport, Cell Nucleus -- drug effects KW - Cell Nucleus -- metabolism KW - Models, Molecular KW - HEK293 Cells KW - Humans KW - Amino Acid Sequence KW - Mice KW - Amino Acid Motifs KW - Protein Binding -- drug effects KW - Gene Expression Regulation -- drug effects KW - Male KW - Protein Conformation KW - Calcineurin -- metabolism KW - Calcineurin -- chemistry KW - NFATC Transcription Factors -- chemistry KW - NFATC Transcription Factors -- metabolism KW - Quercetin -- pharmacology KW - Immunosuppressive Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801859926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimie&rft.atitle=Quercetin+targets+the+interaction+of+calcineurin+with+LxVP-type+motifs+in+immunosuppression.&rft.au=Zhao%2C+Yane%3BZhang%2C+Jin%3BShi%2C+Xiaoyu%3BLi%2C+Jing%3BWang%2C+Rui%3BSong%2C+Ruiwen%3BWei%2C+Qun%3BCai%2C+Huaibin%3BLuo%2C+Jing&rft.aulast=Zhao&rft.aufirst=Yane&rft.date=2016-08-01&rft.volume=127&rft.issue=&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=Biochimie&rft.issn=1638-6183&rft_id=info:doi/10.1016%2Fj.biochi.2016.04.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-23 N1 - Date created - 2016-07-04 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.biochi.2016.04.011 ER - TY - JOUR T1 - Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review). AN - 1801432086; 27349723 AB - Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age. JF - Oncology reports AU - Del Pup, Lino AU - Mantovani, Alberto AU - Cavaliere, Carla AU - Facchini, Gaetano AU - Luce, Amalia AU - Sperlongano, Pasquale AU - Caraglia, Michele AU - Berretta, Massimiliano AD - Division of Gynecological Oncology, CRO Aviano, National Cancer Institute, I-33081 Aviano, Italy. ; National Institute of Health, I-00161 Rome, Italy. ; Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori 'Fondazione G. Pascale' - IRCCS, I-80131 Naples, Italy. ; Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, I-80138 Naples, Italy. ; Unit of General and Geriatric Surgery, School of Medicine, Second University of Naples, I-80137 Naples, Italy. ; Department of Medical Oncology, CRO Aviano, National Cancer Institute, I-33081 Aviano, Italy. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 603 EP - 612 VL - 36 IS - 2 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801432086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+reports&rft.atitle=Carcinogenetic+mechanisms+of+endocrine+disruptors+in+female+cancers+%28Review%29.&rft.au=Del+Pup%2C+Lino%3BMantovani%2C+Alberto%3BCavaliere%2C+Carla%3BFacchini%2C+Gaetano%3BLuce%2C+Amalia%3BSperlongano%2C+Pasquale%3BCaraglia%2C+Michele%3BBerretta%2C+Massimiliano&rft.aulast=Del+Pup&rft.aufirst=Lino&rft.date=2016-08-01&rft.volume=36&rft.issue=2&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1791-2431&rft_id=info:doi/10.3892%2For.2016.4886 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.3892/or.2016.4886 ER - TY - JOUR T1 - Age and Social Context Modulate the Effect of Anxiety on Risk-taking in Pediatric Samples AN - 1800975403 AB - Although risk-taking has been studied from a developmental perspective, no study has examined how anxiety, age, risk-valence and social context interact to modulate decision-making in youths. This study probes this question using a risk-taking task, the Stunt Task, in clinically anxious children (n=17, 10 F, age=8.3-12.1 years), healthy children (n=13, 4 F, age=9.3-12.2 years), clinically anxious adolescents (n=18, 6 F, age=12.3-17.7 years), and healthy adolescents (n =14, 10 F, age=12.5-17.3 years). Social context was manipulated: in one condition, participants were led to believe that a group of peers were observing and judging their performance (peer-judge), while, in the other condition, they were led to believe that peers were not observing them (control). Only anxious children showed an influence of social context on their risk-taking behavior. Specifically, anxious children bet significantly less and had slower reaction times (RT) during the peer-judge than control condition. However, across social conditions, risk-valence modulated RT differently in function of age and diagnosis. Anxious children were slower on the positive-valence risky trial, whereas anxious adolescents were slower on the negative-valence risky trials relative to their respective healthy peers. In conclusion, clinically anxious children were the only group that was sensitive (risk-averse) to the effect of a negative peer-judge context. The negative peer-judge context did not affect risky decision-making in adolescents, whether they were anxious or healthy. Future work using a stronger aversive social context might be more effective at influencing risky behavior in this age group. JF - Journal of Abnormal Child Psychology AU - Rosen, Dana AU - Patel, Nilam AU - Pavletic, Nevia AU - Grillon, Christian AU - Pine, Daniel S AU - Ernst, Monique AD - The National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/08// PY - 2016 DA - Aug 2016 SP - 1161 EP - 1171 CY - New York PB - Springer Science & Business Media VL - 44 IS - 6 SN - 0091-0627 KW - Medical Sciences--Physical Medicine And Rehabilitation KW - Peer judgement KW - Adolescents KW - Children KW - Clinical anxiety KW - Anxiety disorders KW - Decision making KW - Aversive KW - Social anxiety KW - Diagnosis KW - Reaction times KW - Risk taking KW - Social context KW - Risk behaviour KW - Age KW - Social conditions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800975403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Abnormal+Child+Psychology&rft.atitle=Age+and+Social+Context+Modulate+the+Effect+of+Anxiety+on+Risk-taking+in+Pediatric+Samples&rft.au=Rosen%2C+Dana%3BPatel%2C+Nilam%3BPavletic%2C+Nevia%3BGrillon%2C+Christian%3BPine%2C+Daniel+S%3BErnst%2C+Monique&rft.aulast=Rosen&rft.aufirst=Dana&rft.date=2016-08-01&rft.volume=44&rft.issue=6&rft.spage=1161&rft.isbn=&rft.btitle=&rft.title=Journal+of+Abnormal+Child+Psychology&rft.issn=00910627&rft_id=info:doi/10.1007%2Fs10802-015-0098-4 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-16 DO - http://dx.doi.org/10.1007/s10802-015-0098-4 ER - TY - JOUR T1 - Development and calibration of a dietary nitrate and nitrite database in the NIH-AARP Diet and Health Study. AN - 1800702913; 26626817 AB - Nitrate and nitrite are probable human carcinogens when ingested under conditions that increase the formation of N-nitroso compounds. There have been limited efforts to develop US databases of dietary nitrate and nitrite for standard FFQ. Here we describe the development of a dietary nitrate and nitrite database and its calibration. We analysed data from a calibration study of 1942 members of the NIH-AARP (NIH-AARP, National Institutes of Health-AARP) Diet and Health Study who reported all foods and beverages consumed on the preceding day in two non-consecutive 24 h dietary recalls (24HR) and completed an FFQ. Based on a literature review, we developed a database of nitrate and nitrite contents for foods reported on these 24HR and for food category line items on the FFQ. We calculated daily nitrate and nitrite intakes for both instruments, and used a measurement error model to compute correlation coefficients and attenuation factors for the FFQ-based intake estimates using 24HR-based values as reference data. FFQ-based median nitrate intake was 68·9 and 74·1 mg/d, and nitrite intake was 1·3 and 1·0 mg/d, in men and women, respectively. These values were similar to 24HR-based intake estimates. Energy-adjusted correlation coefficients between FFQ- and 24HR-based values for men and women respectively were 0·59 and 0·57 for nitrate and 0·59 and 0·58 for nitrite; energy-adjusted attenuation factors were 0·59 and 0·57 for nitrate and 0·47 and 0·38 for nitrite. The performance of the FFQ in assessing dietary nitrate and nitrite intakes is comparable to that for many other macro- and micronutrients. JF - Public health nutrition AU - Inoue-Choi, Maki AU - Virk-Baker, Mandeep K AU - Aschebrook-Kilfoy, Briseis AU - Cross, Amanda J AU - Subar, Amy F AU - Thompson, Frances E AU - Sinha, Rashmi AU - Ward, Mary H AD - 1Occupational and Environmental Epidemiology Branch,Division of Cancer Epidemiology & Genetics,National Cancer Institute,National Institutes of Health,Department of Health and Human Services,9609 Medical Center Drive,6E314,Rockville,MD 20850,USA. ; 3Cancer Prevention Fellowship Program,Division of Cancer Prevention,National Cancer Institute,National Institutes of Health,Rockville,MD,USA. ; 5Department of Epidemiology and Biostatistics,School of Public Health,Imperial College London,London,UK. ; 6Epidemiology and Genomics Research Program,Risk Factor Assessment Branch,Division of Cancer Control and Population Sciences,National Cancer Institute,Rockville,MD,USA. ; 7Nutritional Epidemiology Branch,Division of Cancer Epidemiology & Genetics,National Cancer Institute,National Institutes of Health,Department of Health and Human Services,Rockville,MD,USA. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1934 EP - 1943 VL - 19 IS - 11 KW - Index Medicus KW - Nitrate KW - FFQ KW - Nitrite KW - Dietary database UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800702913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+nutrition&rft.atitle=Development+and+calibration+of+a+dietary+nitrate+and+nitrite+database+in+the+NIH-AARP+Diet+and+Health+Study.&rft.au=Inoue-Choi%2C+Maki%3BVirk-Baker%2C+Mandeep+K%3BAschebrook-Kilfoy%2C+Briseis%3BCross%2C+Amanda+J%3BSubar%2C+Amy+F%3BThompson%2C+Frances+E%3BSinha%2C+Rashmi%3BWard%2C+Mary+H&rft.aulast=Inoue-Choi&rft.aufirst=Maki&rft.date=2016-08-01&rft.volume=19&rft.issue=11&rft.spage=1934&rft.isbn=&rft.btitle=&rft.title=Public+health+nutrition&rft.issn=1475-2727&rft_id=info:doi/10.1017%2FS1368980015003407 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1017/S1368980015003407 ER - TY - JOUR T1 - Assessing exposure risks for freshwater tilapia species posed by mercury and methylmercury. AN - 1800132568; 27207496 AB - Waterborne and dietborne exposures of freshwater fish to mercury (Hg) in the forms of inorganic (Hg(II)) and organic (methylmercury or MeHg) affect their growth, development, and reproduction. However, an integrated mechanistic risk model framework to predict the impact of Hg(II)/MeHg on freshwater fish is lacking. Here, we integrated biokinetic, physiological and biogeographic data to calibrate and then establish key risk indices-hazardous quotient and exceedance risk-for freshwater tilapia species across geographic ranges of several major rivers in Taiwan. We found that Hg(II) burden was highest in kidney followed by gill, intestine, liver, blood, and muscle. Our results showed that Hg was less likely to pose mortality risk (mortality rate less than 5 %) for freshwater tilapia species. However, Hg is likely to pose the potential hazard to aquatic environments constrained by safety levels for aquatic organisms. Sensitivity analysis showed that amount of Hg accumulated in tilapia was most influenced by sediment uptake rate. Our approach opens up new possibilities for predicting future fish population health with the impacts of continued Hg exposure to provide information on which fish are deemed safe for human consumption. JF - Ecotoxicology (London, England) AU - Cheng, Yi-Hsien AU - Lin, Yi-Jun AU - You, Shu-Han AU - Yang, Ying-Fei AU - How, Chun Ming AU - Tseng, Yi-Ting AU - Chen, Wei-Yu AU - Liao, Chung-Min AD - Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 10617, Taiwan, Republic of China. ; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, 35053, Taiwan, Republic of China. ; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan, Republic of China. ; Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 10617, Taiwan, Republic of China. cmliao@ntu.edu.tw. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1181 EP - 1193 VL - 25 IS - 6 KW - Methylmercury Compounds KW - 0 KW - Water Pollutants, Chemical KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Environmental risk assessment KW - Freshwater tilapia KW - Modeling KW - Rivers KW - Animals KW - Taiwan KW - Risk Assessment KW - Tilapia -- physiology KW - Environmental Monitoring KW - Water Pollutants, Chemical -- analysis KW - Mercury -- analysis KW - Water Pollution, Chemical -- statistics & numerical data KW - Mercury -- toxicity KW - Methylmercury Compounds -- toxicity KW - Methylmercury Compounds -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800132568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ecotoxicology+%28London%2C+England%29&rft.atitle=Assessing+exposure+risks+for+freshwater+tilapia+species+posed+by+mercury+and+methylmercury.&rft.au=Cheng%2C+Yi-Hsien%3BLin%2C+Yi-Jun%3BYou%2C+Shu-Han%3BYang%2C+Ying-Fei%3BHow%2C+Chun+Ming%3BTseng%2C+Yi-Ting%3BChen%2C+Wei-Yu%3BLiao%2C+Chung-Min&rft.aulast=Cheng&rft.aufirst=Yi-Hsien&rft.date=2016-08-01&rft.volume=25&rft.issue=6&rft.spage=1181&rft.isbn=&rft.btitle=&rft.title=Ecotoxicology+%28London%2C+England%29&rft.issn=1573-3017&rft_id=info:doi/10.1007%2Fs10646-016-1672-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-05 N1 - Date created - 2016-06-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10646-016-1672-4 ER - TY - JOUR T1 - A cell-based quantitative high-throughput image screening identified novel autophagy modulators. AN - 1798721379; 27168224 AB - Macroautophagy is a major cellular degradation pathway for long-lived proteins and cellular organelles to maintain cellular homeostasis. Reduced autophagy has been implicated in neurodegenerative diseases, metabolic syndrome, and tumorigenesis. In contrast, increased autophagy has been shown to protect against tissue injury and aging. Here we employed a cell-based quantitative high-throughput image screening (qHTS) for autophagy modulators using mouse embryonic fibroblasts (MEFs) that are stably expressing GFP-LC3. The library of pharmacologically active compounds (LOPAC) was used to screen for the autophagy modulators in compounds alone or in combination with the lysosome inhibitor chloroquine (CQ). The GFP-LC3 puncta were then quantified to measure autophagic flux. The primary screening revealed 173 compounds with efficacy more than 40%. These compounds were cherry-picked and re-tested at multiple different concentrations using the same assay. A number of novel autophagy inducers, inhibitors, and modulators with dual-effects on autophagy were identified from the cherry-pick screening. Interestingly, we found a group of compounds that induce autophagy are related to dopamine receptors and are commonly used as clinical psychiatric drugs. Among them, indatraline hydrochloride (IND), a dopamine inhibitor, and chlorpromazine hydrochloride (CPZ) and fluphenazine dihydrochloride (FPZ), two dopamine receptor antagonists, were further evaluated. We found that FPZ-induced autophagy through mTOR inhibition but IND and CPZ induced autophagy in an mTOR-independent manner. Our data suggest that image-based autophagic flux qHTS can efficiently identify autophagy inducers and inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Pharmacological research AU - Li, Yuan AU - McGreal, Steven AU - Zhao, Jean AU - Huang, Ruili AU - Zhou, Yan AU - Zhong, Hua AU - Xia, Menghang AU - Ding, Wen-Xing AD - Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA. ; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030 China. ; Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: wxding@kumc.edu. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 35 EP - 49 VL - 110 KW - Index Medicus KW - Dopamine receptor KW - High-throughput screening KW - Autophagy KW - mTOR KW - GFP-LC3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1798721379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=A+cell-based+quantitative+high-throughput+image+screening+identified+novel+autophagy+modulators.&rft.au=Li%2C+Yuan%3BMcGreal%2C+Steven%3BZhao%2C+Jean%3BHuang%2C+Ruili%3BZhou%2C+Yan%3BZhong%2C+Hua%3BXia%2C+Menghang%3BDing%2C+Wen-Xing&rft.aulast=Li&rft.aufirst=Yuan&rft.date=2016-08-01&rft.volume=110&rft.issue=&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=1096-1186&rft_id=info:doi/10.1016%2Fj.phrs.2016.05.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.phrs.2016.05.004 ER - TY - JOUR T1 - Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect. AN - 1797873044; 26467344 AB - Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1β, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone. JF - Cellular and molecular neurobiology AU - Salem, Neveen A AU - Assaf, Naglaa AU - Ismail, Manal F AU - Khadrawy, Yasser A AU - Samy, Mohga AD - Department of Narcotics, Ergogenics and Poisons, National Research Centre, Cairo, Egypt. dr_nsalem@yahoo.com. ; Department of Pharmacology and Toxicology, Faculty of Pharmacy, MISR for Science and Technology University, Cairo, Egypt. ; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt. ; Department of Physiology, National Research Centre, Cairo, Egypt. ; Department of Anesthesia and Pain Management, National Cancer Institute, Cairo University, Cairo, Egypt. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 943 EP - 954 VL - 36 IS - 6 KW - Index Medicus KW - Rat KW - Oxidative stress KW - Multiple sclerosis KW - Methylprednisolone KW - P53 KW - Ethidium bromide KW - Cox-2 KW - Ozone UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797873044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Ozone+Therapy+in+Ethidium+Bromide-Induced+Demyelination+in+Rats%3A+Possible+Protective+Effect.&rft.au=Salem%2C+Neveen+A%3BAssaf%2C+Naglaa%3BIsmail%2C+Manal+F%3BKhadrawy%2C+Yasser+A%3BSamy%2C+Mohga&rft.aulast=Salem&rft.aufirst=Neveen&rft.date=2016-08-01&rft.volume=36&rft.issue=6&rft.spage=943&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=1573-6830&rft_id=info:doi/10.1007%2Fs10571-015-0279-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10571-015-0279-2 ER - TY - JOUR T1 - The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17β-estradiol. AN - 1797870158; 27278606 AB - MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate their target mRNAs at a posttranscriptional level, thereby affecting crucial processes in cancer development. However, little is known about the molecular events that control expression of miRNAs in cervical cancer (CC). HPV16 E7 oncoprotein in conjunction with estrogen are sufficient to produce high grade cervical dysplasia and invasive cervical malignancies in a mouse model. In the present study, we determined the potential role that the E7 oncoprotein and 17β-estradiol (E2) play in the deregulation of miR-21 and miR-143 expression levels by these two risk factors. We found that, while the expression of miR-21 was upregulated and the expression of miR-143 was downregulated by the HPV16 E7 oncoprotein in vivo, and in vitro and that E2 treatment is also implicated in the deregulation of these important miRNAs in vivo. Sustained upregulation of miR-21 resulted in suppression of PTEN expression, and repression of miR-143 increased the mRNA and protein levels from Bcl-2. These results suggested that HPV type 16 E7 oncoprotein and E2 play an important role in regulating miR-21 and miR-143 expression. We have observed similar results in CC patients containing HPV16 sequences, suggesting that these miRNAs could serve as diagnostic biomarkers in CC. The present study highlights the roles of miRNAs in cervical tissue and implicates these important molecules in cervical carcinogenesis. JF - International journal of oncology AU - Gómez-Gómez, Yazmín AU - Organista-Nava, Jorge AU - Ocadiz-Delgado, Rodolfo AU - García-Villa, Enrique AU - Leyva-Vazquez, Marco Antonio AU - Illades-Aguiar, Berenice AU - Lambert, Paul F AU - García-Carrancá, Alejandro AU - Gariglio, Patricio AD - Programa de Doctorado en Ciencias Biomédicas, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico. ; Department of Genetics and Molecular Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico city 07360, Mexico. ; Laboratory of Molecular Biomedicine, Academic Unit of Chemical-Biological Sciences, Guerrero State University, Chilpancingo 39090, Guerrero, Mexico. ; McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA. ; Cancer Biomedical Research Unit, National Cancer Institute and Biomedical Research Institute, Biomedical Research Institute, National Autonomous University of Mexico and Division of Basic Research, National Cancer Institute (INCan), Mexico city 14080, Mexico. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 549 EP - 558 VL - 49 IS - 2 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797870158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=The+expression+of+miR-21+and+miR-143+is+deregulated+by+the+HPV16+E7+oncoprotein+and+17%CE%B2-estradiol.&rft.au=G%C3%B3mez-G%C3%B3mez%2C+Yazm%C3%ADn%3BOrganista-Nava%2C+Jorge%3BOcadiz-Delgado%2C+Rodolfo%3BGarc%C3%ADa-Villa%2C+Enrique%3BLeyva-Vazquez%2C+Marco+Antonio%3BIllades-Aguiar%2C+Berenice%3BLambert%2C+Paul+F%3BGarc%C3%ADa-Carranc%C3%A1%2C+Alejandro%3BGariglio%2C+Patricio&rft.aulast=G%C3%B3mez-G%C3%B3mez&rft.aufirst=Yazm%C3%ADn&rft.date=2016-08-01&rft.volume=49&rft.issue=2&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=1791-2423&rft_id=info:doi/10.3892%2Fijo.2016.3575 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.3892/ijo.2016.3575 ER - TY - JOUR T1 - Expression of Evc2 in craniofacial tissues and craniofacial bone defects in Evc2 knockout mouse. AN - 1795879294; 27164562 AB - Our objectives were to determine the expression of EVC2 in craniofacial tissues and investigate the effect of Evc2 deficiency on craniofacial bones using Evc2 knockout (KO) mouse model. Evc2 KO mice were generated by introducing a premature stop codon followed by the Internal Ribosomal Entry Site fused to β-galactosidase (LacZ). Samples from wild-type (WT), heterozygous (Het) and homozygous Evc2 KO mice were prepared. LacZ staining and immunohistochemistry (IHC) with anti-β-galactosidase, anti-EVC2 and anti-SOX9 antibodies were performed. The craniofacial bones were stained with alcian blue and alizarin red. The LacZ activity in KO was mainly observed in the anterior parts of viscerocranium. The Evc2-expressing cells were identified in many cartilageous regions by IHC with anti-β-galactosidase antibody in KO and Het embryos. The endogenous EVC2 protein was observed in these areas in WT embryos. Double labeling with anti-SOX9 antibody showed that these cells were mainly chondrocytes. At adult stages, the expression of EVC2 was found in chondrocytes of nasal bones and spheno-occipital synchondrosis, and osteocytes and endothelial-like cells of the premaxilla and mandible. The skeletal double staining demonstrated that craniofacial bones, where the expression of EVC2 was observed, in KO had the morphological defects as compared to WT. To our knowledge, our study was the first to identify the types of Evc2-expressing cells in craniofacial tissues. Consistent with the expression pattern, abnormal craniofacial bone morphology was found in the Evc2 KO mice, suggesting that EVC2 may be important during craniofacial growth and development. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Archives of oral biology AU - Badri, Mohammed K AU - Zhang, Honghao AU - Ohyama, Yoshio AU - Venkitapathi, Sundharamani AU - Alamoudi, Ahmed AU - Kamiya, Nobuhiro AU - Takeda, Haruko AU - Ray, Manas AU - Scott, Greg AU - Tsuji, Takehito AU - Kunieda, Tetsuo AU - Mishina, Yuji AU - Mochida, Yoshiyuki AD - Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, 700 Albany Street, Boston, MA 02118, USA; Department of Pediatric Dentistry and Orthodontics, College of Dentistry, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia. ; Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA. ; Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, 700 Albany Street, Boston, MA 02118, USA. ; Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27009, USA. ; Unit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of Liège, 1 Avenue de l'Hôpital, 4000-Liège, Belgium. ; Knock Out Core, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27009, USA. ; Graduate School of Environmental and Life Science, Okayama University, Okayama City, Japan. ; Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27009, USA; Knock Out Core, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27009, USA. ; Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, 700 Albany Street, Boston, MA 02118, USA. Electronic address: mochida@bu.edu. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 142 EP - 152 VL - 68 KW - Dentistry KW - Index Medicus KW - Craniofacial bone KW - EVC2 KW - Ellis-van Creveld syndrome KW - Knockout (KO) mouse KW - Expression KW - Development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795879294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+oral+biology&rft.atitle=Expression+of+Evc2+in+craniofacial+tissues+and+craniofacial+bone+defects+in+Evc2+knockout+mouse.&rft.au=Badri%2C+Mohammed+K%3BZhang%2C+Honghao%3BOhyama%2C+Yoshio%3BVenkitapathi%2C+Sundharamani%3BAlamoudi%2C+Ahmed%3BKamiya%2C+Nobuhiro%3BTakeda%2C+Haruko%3BRay%2C+Manas%3BScott%2C+Greg%3BTsuji%2C+Takehito%3BKunieda%2C+Tetsuo%3BMishina%2C+Yuji%3BMochida%2C+Yoshiyuki&rft.aulast=Badri&rft.aufirst=Mohammed&rft.date=2016-08-01&rft.volume=68&rft.issue=&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Archives+of+oral+biology&rft.issn=1879-1506&rft_id=info:doi/10.1016%2Fj.archoralbio.2016.05.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.archoralbio.2016.05.002 ER - TY - JOUR T1 - High sensitivity, loop-mediated isothermal amplification combined with colorimetric gold-nanoparticle probes for visual detection of high risk human papillomavirus genotypes 16 and 18. AN - 1795862794; 27086727 AB - High-risk human papillomavirus (HR-HPV) causes cervical cancer. HPV16 and HPV18 are the most prevalent strains of the virus reported in women worldwide. Loop-mediated isothermal amplification (LAMP) is an alternative method for DNA detection under isothermal conditions. However, it results in a turbid amplified product which is not easily detected by the naked eye. This study aimed to develop an improved technique by using gold nanoparticles (AuNPs) attached to a single-stranded DNA probe for the detection of HPV16 and HPV18. Detection of the LAMP product by AuNP color change was compared with detection by visual turbidity. The optimal conditions for this new LAMP-AuNP assay were an incubation time of 20min and a temperature of 65°C. After LAMP amplification was complete, its products were hybridized with the AuNP probe for 5min and then detected by the addition of magnesium salt. The color changed from red to blue as a result of aggregation of the AuNP probe under high ionic strength conditions produced by the addition of the salt. The sensitivity of the LAMP-AuNP assay was greater than the LAMP turbidity assay by up to 10-fold for both HPV genotypes. The LAMP-AuNP assay showed higher sensitivity and ease of visualization than did the LAMP turbidity for the detection of HPV16 and HPV18. Additionally, AuNP-HPV16 and AuNP-HPV18 probes were stable for over 1year. The combination of LAMP and the AuNP-probe colorimetric assay offers a simple, rapid and highly sensitive alternative diagnostic tool for the detection of HPV16 and HPV18 in district hospitals or field studies. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Journal of virological methods AU - Kumvongpin, Ratchanida AU - Jearanaikool, Patcharee AU - Wilailuckana, Chotechana AU - Sae-Ung, Nattaya AU - Prasongdee, Prinya AU - Daduang, Sakda AU - Wongsena, Metee AU - Boonsiri, Patcharee AU - Kiatpathomchai, Wansika AU - Swangvaree, Sukumarn Sanersak AU - Sandee, Alisa AU - Daduang, Jureerut AD - Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. ; Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. ; Ubon Ratchathani Cancer Center, Ubon Ratchathani, Thailand. ; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Bioengineering and Sensing Technology Laboratory, BIOTEC, National Science and Technology Development Agency (NSTDA), 113 Thailand Science Park, Pathum Thani, Thailand. ; Gynecological Oncology Division, National Cancer Institute, Bangkok, Thailand. ; Chulabhorn Research Institute, Bangkok, Thailand. ; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand. Electronic address: jurpoo@kku.ac.th. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 90 EP - 95 VL - 234 KW - Index Medicus KW - HPV18 KW - HPV16 KW - AuNPs KW - LAMP UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795862794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virological+methods&rft.atitle=High+sensitivity%2C+loop-mediated+isothermal+amplification+combined+with+colorimetric+gold-nanoparticle+probes+for+visual+detection+of+high+risk+human+papillomavirus+genotypes+16+and+18.&rft.au=Kumvongpin%2C+Ratchanida%3BJearanaikool%2C+Patcharee%3BWilailuckana%2C+Chotechana%3BSae-Ung%2C+Nattaya%3BPrasongdee%2C+Prinya%3BDaduang%2C+Sakda%3BWongsena%2C+Metee%3BBoonsiri%2C+Patcharee%3BKiatpathomchai%2C+Wansika%3BSwangvaree%2C+Sukumarn+Sanersak%3BSandee%2C+Alisa%3BDaduang%2C+Jureerut&rft.aulast=Kumvongpin&rft.aufirst=Ratchanida&rft.date=2016-08-01&rft.volume=234&rft.issue=&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Journal+of+virological+methods&rft.issn=1879-0984&rft_id=info:doi/10.1016%2Fj.jviromet.2016.04.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jviromet.2016.04.008 ER - TY - JOUR T1 - Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+ activated mitochondrial transporters (CaMCs). AN - 1794472235; 27060251 AB - Glutamate elicits Ca(2+) signals and workloads that regulate neuronal fate both in physiological and pathological circumstances. Oxidative phosphorylation is required in order to respond to the metabolic challenge caused by glutamate. In response to physiological glutamate signals, cytosolic Ca(2+) activates respiration by stimulation of the NADH malate-aspartate shuttle through Ca(2+)-binding to the mitochondrial aspartate/glutamate carrier (Aralar/AGC1/Slc25a12), and by stimulation of adenine nucleotide uptake through Ca(2+) binding to the mitochondrial ATP-Mg/Pi carrier (SCaMC-3/Slc25a23). In addition, after Ca(2+) entry into the matrix through the mitochondrial Ca(2+) uniporter (MCU), it activates mitochondrial dehydrogenases. In response to pathological glutamate stimulation during excitotoxicity, Ca(2+) overload, reactive oxygen species (ROS), mitochondrial dysfunction and delayed Ca(2+) deregulation (DCD) lead to neuronal death. Glutamate-induced respiratory stimulation is rapidly inactivated through a mechanism involving Poly (ADP-ribose) Polymerase-1 (PARP-1) activation, consumption of cytosolic NAD(+), a decrease in matrix ATP and restricted substrate supply. Glutamate-induced Ca(2+)-activation of SCaMC-3 imports adenine nucleotides into mitochondria, counteracting the depletion of matrix ATP and the impaired respiration, while Aralar-dependent lactate metabolism prevents substrate exhaustion. A second mechanism induced by excitotoxic glutamate is permeability transition pore (PTP) opening, which critically depends on ROS production and matrix Ca(2+) entry through the MCU. By increasing matrix content of adenine nucleotides, SCaMC-3 activity protects against glutamate-induced PTP opening and lowers matrix free Ca(2+), resulting in protracted appearance of DCD and protection against excitotoxicity in vitro and in vivo, while the lack of lactate protection during in vivo excitotoxicity explains increased vulnerability to kainite-induced toxicity in Aralar +/- mice. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. Copyright © 2016 Elsevier B.V. All rights reserved. JF - Biochimica et biophysica acta AU - Rueda, Carlos B AU - Llorente-Folch, Irene AU - Traba, Javier AU - Amigo, Ignacio AU - Gonzalez-Sanchez, Paloma AU - Contreras, Laura AU - Juaristi, Inés AU - Martinez-Valero, Paula AU - Pardo, Beatriz AU - Del Arco, Araceli AU - Satrustegui, Jorgina AD - Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain; CIBER de Enfermedades Raras (CIBERER), Spain; Instituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD), Spain. ; Cardiovascular and Pulmonary Branch, NHLBI, NIH, 20892 Bethesda, MD, USA. ; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 13560-970 São Paulo, Brazil. ; Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain; CIBER de Enfermedades Raras (CIBERER), Spain; Instituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD), Spain; Facultad de Ciencias Ambientales y Bioquímica, Universidad de Castilla la Mancha, Toledo 45071, Spain. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 1158 EP - 1166 VL - 1857 IS - 8 SN - 0006-3002, 0006-3002 KW - ATP-Mg-Pi carrier proteins, mitochondria KW - 0 KW - Antiporters KW - Calcium Channels KW - Mitochondrial Membrane Transport Proteins KW - Mitochondrial Proteins KW - Reactive Oxygen Species KW - Slc25a12 protein, mouse KW - mitochondrial calcium uniporter KW - mitochondrial permeability transition pore KW - Glutamic Acid KW - 3KX376GY7L KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Parp1 protein, mouse KW - EC 2.4.2.30 KW - Poly (ADP-Ribose) Polymerase-1 KW - Poly(ADP-ribose) Polymerases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Aralar KW - SCaMC-3 KW - Aspartate/glutamate carrier KW - ATP-Mg/Pi carrier KW - PARP-1 KW - Mitochondria KW - Excitotoxicity KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Neurons -- metabolism KW - Cell Respiration -- drug effects KW - Neurons -- drug effects KW - Gene Expression KW - Primary Cell Culture KW - Mice KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Poly(ADP-ribose) Polymerases -- genetics KW - Oxidative Phosphorylation -- drug effects KW - Adenosine Triphosphate -- metabolism KW - Neurons -- cytology KW - Signal Transduction KW - Calcium -- metabolism KW - Mitochondrial Membrane Transport Proteins -- metabolism KW - Calcium Channels -- metabolism KW - Glutamic Acid -- metabolism KW - Antiporters -- metabolism KW - Mitochondria -- drug effects KW - Mitochondrial Proteins -- genetics KW - Mitochondria -- metabolism KW - Calcium Channels -- genetics KW - Mitochondrial Proteins -- metabolism KW - Antiporters -- genetics KW - Mitochondrial Membrane Transport Proteins -- genetics KW - Glutamic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794472235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Glutamate+excitotoxicity+and+Ca2%2B-regulation+of+respiration%3A+Role+of+the+Ca2%2B+activated+mitochondrial+transporters+%28CaMCs%29.&rft.au=Rueda%2C+Carlos+B%3BLlorente-Folch%2C+Irene%3BTraba%2C+Javier%3BAmigo%2C+Ignacio%3BGonzalez-Sanchez%2C+Paloma%3BContreras%2C+Laura%3BJuaristi%2C+In%C3%A9s%3BMartinez-Valero%2C+Paula%3BPardo%2C+Beatriz%3BDel+Arco%2C+Araceli%3BSatrustegui%2C+Jorgina&rft.aulast=Rueda&rft.aufirst=Carlos&rft.date=2016-08-01&rft.volume=1857&rft.issue=8&rft.spage=1158&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/10.1016%2Fj.bbabio.2016.04.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-18 N1 - Date created - 2016-06-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bbabio.2016.04.003 ER - TY - JOUR T1 - Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping. AN - 1792538092; 27203617 AB - The accurate and sensitive detection of biological free radicals in a reliable manner is required to define the mechanistic roles of such species in biochemistry, medicine and toxicology. Most of the techniques currently available are either not appropriate to detect free radicals in cells and tissues due to sensitivity limitations (electron spin resonance, ESR) or subject to artifacts that make the validity of the results questionable (fluorescent probe-based analysis). The development of the immuno-spin trapping technique overcomes all these difficulties. This technique is based on the reaction of amino acid- and DNA base-derived radicals with the spin trap 5, 5-dimethyl-1-pyrroline N-oxide (DMPO) to form protein- and DNA-DMPO nitroxide radical adducts, respectively. These adducts have limited stability and decay to produce the very stable macromolecule-DMPO-nitrone product. This stable product can be detected by mass spectrometry, NMR or immunochemistry by the use of anti-DMPO nitrone antibodies. The formation of macromolecule-DMPO-nitrone adducts is based on the selective reaction of free radical addition to the spin trap and is thus not subject to artifacts frequently encountered with other methods for free radical detection. The selectivity of spin trapping for free radicals in biological systems has been proven by ESR. Immuno-spin trapping is proving to be a potent, sensitive (a million times higher sensitivity than ESR), and easy (not quantum mechanical) method to detect low levels of macromolecule-derived radicals produced in vitro and in vivo. Anti-DMPO antibodies have been used to determine the distribution of free radicals in cells and tissues and even in living animals. In summary, the invention of the immuno-spin trapping technique has had a major impact on the ability to accurately and sensitively detect biological free radicals and, subsequently, on our understanding of the role of free radicals in biochemistry, medicine and toxicology. Published by Elsevier B.V. JF - Redox biology AU - Mason, Ronald Paul AD - Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Electronic address: mason4@niehs.nih.gov. Y1 - 2016/08// PY - 2016 DA - August 2016 SP - 422 EP - 429 VL - 8 KW - Index Medicus KW - Free radical detection KW - Immuno-spin trapping KW - Confocal microscopy KW - Mass spectrometry KW - Spin trap KW - Molecular resonance imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1792538092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Redox+biology&rft.atitle=Imaging+free+radicals+in+organelles%2C+cells%2C+tissue%2C+and+in+vivo+with+immuno-spin+trapping.&rft.au=Mason%2C+Ronald+Paul&rft.aulast=Mason&rft.aufirst=Ronald&rft.date=2016-08-01&rft.volume=8&rft.issue=&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=Redox+biology&rft.issn=2213-2317&rft_id=info:doi/10.1016%2Fj.redox.2016.04.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-29 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Free Radic Biol Med. 2013 Mar;56:64-71 [23142572] Free Radic Biol Med. 2013 Oct;63:351-60 [23722162] Biochim Biophys Acta. 2013 Dec;1832(12):2153-61 [23959048] Biochim Biophys Acta. 2014 Feb;1840(2):722-9 [23644035] Free Radic Biol Med. 2013 Dec;65:828-37 [23978375] Free Radic Biol Med. 2002 Aug 1;33(3):364-9 [12126758] Free Radic Biol Med. 2001 Jan 15;30(2):187-97 [11163536] Free Radic Biol Med. 2015 Aug;85:259-68 [25933590] Free Radic Biol Med. 2003 Apr 1;34(7):830-9 [12654471] Free Radic Biol Med. 2003 Jun 1;34(11):1473-81 [12757857] J Biol Chem. 2004 Mar 19;279(12):11600-7 [14699100] Free Radic Biol Med. 2004 May 15;36(10):1214-23 [15110386] Biochim Biophys Acta. 1993 Oct 6;1202(2):173-81 [8399378] Free Radic Res. 1995 Jan;22(1):11-21 [7889144] Free Radic Biol Med. 1996;21(4):427-36 [8886792] Biochem J. 1998 Mar 15;330 ( Pt 3):1293-9 [9494099] Nat Methods. 2006 Feb;3(2):123-7 [16432522] Free Radic Biol Med. 2007 Feb 15;42(4):530-40 [17275685] Nat Protoc. 2007;2(3):512-22 [17406615] J Am Chem Soc. 2007 Nov 7;129(44):13493-501 [17939657] J Neurosci. 2008 Apr 16;28(16):4115-22 [18417691] Free Radic Biol Med. 2009 Apr 1;46(7):853-65 [19159679] J Biol Chem. 2010 Jul 30;285(31):24195-205 [20501663] Free Radic Biol Med. 2011 Jun 1;50(11):1536-45 [21382477] Nucleic Acids Res. 2012 Jul;40(12):5477-86 [22387463] Diabetes. 2012 Oct;61(10):2405-13 [22698922] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.redox.2016.04.003 ER - TY - JOUR T1 - Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats. AN - 1789038016; 27083855 AB - MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity (median lethal dose, LD50) in Wistar rats. Pharmacokinetics of MDAI was rapid, maximum median concentration in serum and brain was attained 30min and almost returned to zero 6h after subcutaneous (sc.) administration of 10mg/kg MDAI; brain/serum ratio was ~4. MDAI particularly accumulated in lung tissue. In the open field, MDAI (5, 10, 20 and 40mg/kg sc.) increased exploratory activity, induced signs of behavioural serotonin syndrome and reduced locomotor habituation, although by 60min some effects had diminished. All doses of MDAI significantly disrupted PPI and the effect was present during the onset of its action as well as 60min after treatment. Unexpectedly, 40mg/kg MDAI killed 90% of animals in the first behavioural test, hence LD50 tests were conducted which yielded 28.33mg/kg sc. and 35mg/kg intravenous but was not established up to 40mg/kg after gastric administration. Disseminated intravascular coagulopathy (DIC) with brain oedema was concluded as a direct cause of death in sc. treated animals. Finally, MDAI (10, 20mg/kg sc.) caused hyperthermia and perspiration in group-housed rats. In conclusion, the drug had fast pharmacokinetics and accumulated in lipohilic tissues. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3,4-metyhlenedioxymethamphetamine (MDMA, ecstasy) and paramethoxymethamphetamine (PMMA). Surprisingly subcutaneous MDAI appears to be more lethal than previously thought and its serotonergic toxicity is likely exacerbated by group housing conditions. MDAI therefore poses greater risks to physical and mental health than recognised hitherto. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Progress in neuro-psychopharmacology & biological psychiatry AU - Páleníček, Tomáš AU - Lhotková, Eva AU - Žídková, Monika AU - Balíková, Marie AU - Kuchař, Martin AU - Himl, Michal AU - Mikšátková, Petra AU - Čegan, Martin AU - Valeš, Karel AU - Tylš, Filip AU - Horsley, Rachel R AD - National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic; 3(rd) Medical faculty, Charles University in Prague, Ruská 87, 110 00 Prague 10, Czech Republic. Electronic address: tomas.palenicek@nudz.cz. ; National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic. ; Institute of Forensic Medicine and Toxicology, Charles University in Prague, Studničkova 4, 128 21 Prague 2, Czech Republic. ; National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic; Faculty of Food and Biochemical Technology & Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic. ; Faculty of Food and Biochemical Technology & Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic. ; Masaryk hospital in Ústí nad Labem, Sociální péče 3316/12A, 401 13 Ústí nad Labem, Czech Republic. ; National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic; 3(rd) Medical faculty, Charles University in Prague, Ruská 87, 110 00 Prague 10, Czech Republic. Y1 - 2016/08/01/ PY - 2016 DA - 2016 Aug 01 SP - 49 EP - 59 VL - 69 KW - Index Medicus KW - Wistar rat KW - Median lethal dose KW - Body temperature KW - Locomotion KW - Prepulse inhibition KW - Open field KW - 5,6-methylenedioxy-2-aminoindane KW - MDAI KW - Toxicology KW - Sensory gating KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789038016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.atitle=Emerging+toxicity+of+5%2C6-methylenedioxy-2-aminoindane+%28MDAI%29%3A+Pharmacokinetics%2C+behaviour%2C+thermoregulation+and+LD50+in+rats.&rft.au=P%C3%A1len%C3%AD%C4%8Dek%2C+Tom%C3%A1%C5%A1%3BLhotkov%C3%A1%2C+Eva%3B%C5%BD%C3%ADdkov%C3%A1%2C+Monika%3BBal%C3%ADkov%C3%A1%2C+Marie%3BKucha%C5%99%2C+Martin%3BHiml%2C+Michal%3BMik%C5%A1%C3%A1tkov%C3%A1%2C+Petra%3B%C4%8Cegan%2C+Martin%3BVale%C5%A1%2C+Karel%3BTyl%C5%A1%2C+Filip%3BHorsley%2C+Rachel+R&rft.aulast=P%C3%A1len%C3%AD%C4%8Dek&rft.aufirst=Tom%C3%A1%C5%A1&rft.date=2016-08-01&rft.volume=69&rft.issue=&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.issn=1878-4216&rft_id=info:doi/10.1016%2Fj.pnpbp.2016.04.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.pnpbp.2016.04.004 ER - TY - JOUR T1 - Targeting a Cancer-Specific Epitope of the Epidermal Growth Factor Receptor in Triple-Negative Breast Cancer. AN - 1781532920; 27075852 AB - Triple-negative breast cancers (TNBCs) are typically more aggressive and result in poorer outcomes than other breast cancers because treatment options are limited due to lack of hormone receptors or amplified human epidermal growth factor receptor 2 (HER2). Many TNBCs overexpress the epidermal growth factor receptor (EGFR) or manifest amplification of theEGFRgene, supporting EGFR as a therapeutic target. While EGFR-directed small molecule inhibitors have shown limited effectiveness in clinical settings, use of EGFR as a mechanism of delivering enzymatic cytotoxins to TNBC has not been demonstrated. Using the single-chain variable fragment (scFv) of the 806 antibody that binds only cells with overexpressed, misfolded, or mutant variants of the EGFR, a recombinant immunotoxin was engineered through gene fusion withPseudomonas aeruginosaExotoxin A (806-PE38). The potency of 806-PE38 on reducing TNBC cell growth in vitro and in xenograft models (n ≥ 6) was examined for six TNBC cell lines. All statistical tests were two-sided. 806-PE38 statistically significantly reduced the viability of all tested TNBC lines, with IC50values below 10 ng/mL for three of six cell lines, while not affecting cells with wild-type EGFR (IC50>300 ng/mL). Systemic treatments with 806-PE38 vs vehicle resulted in statistically significantly reduced tumor burdens (806-PE38 mean = 128 mm(3)[SD = 46 mm(3)] vs vehicle mean = 749 mm(3)[SD = 395 mm(3)], P = .001) and increased median survival (806-PE38 median = 82 days vs vehicle median = 50 days,P= .01) in a MDA-MB-468 TNBC mouse xenograft. Deletion of the catalytic residue eliminated both cytotoxic activity in vitro and the reduction in tumor burden and survival (P= .52). These data support the further development of the 806-PE38 immunotoxin as a therapeutic agent for the treatment of patients with EGFR-positive TNBC. Follow-up experiments with combination therapies will be attempted to achieve full remissions. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States. JF - Journal of the National Cancer Institute AU - Simon, Nathan AU - Antignani, Antonella AU - Sarnovsky, Robert AU - Hewitt, Stephen M AU - FitzGerald, David AD - Biotherapy Section, Laboratory of Molecular Biology (NS, AA, RS, DF), and Experimental Pathology Laboratory, Laboratory of Pathology (SMH), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. ; Biotherapy Section, Laboratory of Molecular Biology (NS, AA, RS, DF), and Experimental Pathology Laboratory, Laboratory of Pathology (SMH), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. fitzgerd@helix.nih.gov. Y1 - 2016/08// PY - 2016 DA - August 2016 VL - 108 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781532920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Targeting+a+Cancer-Specific+Epitope+of+the+Epidermal+Growth+Factor+Receptor+in+Triple-Negative+Breast+Cancer.&rft.au=Simon%2C+Nathan%3BAntignani%2C+Antonella%3BSarnovsky%2C+Robert%3BHewitt%2C+Stephen+M%3BFitzGerald%2C+David&rft.aulast=Simon&rft.aufirst=Nathan&rft.date=2016-08-01&rft.volume=108&rft.issue=8&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/10.1093%2Fjnci%2Fdjw028 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/jnci/djw028 ER - TY - JOUR T1 - An Integrated Experimental Design for the Assessment of Multiple Toxicological End Points in Rat Bioassays. AN - 1859718168; 27448388 AB - For nearly five decades long-term studies in rodents have been the accepted benchmark for assessing chronic long-term toxic effects, particularly carcinogenicity, of chemicals. The European Food Safety Authority (EFSA) and the World Health Organization (WHO) have pointed out that the current set of internationally utilized test methods capture only some of the potential adverse effects associated with exposures to these agents over the lifetime. In this paper we propose the adaption of the carcinogenicity bioassay to integrate additional protocols for comprehensive long-term toxicity assessment that includes developmental exposures and long-term outcomes, capable of generating information on a broad spectrum of different endpoints. An integrated study design based on a stepwise process is described, that includes the priority endpoints of the OECD and NTP guidelines on carcinogenicity/toxicity and developmental/reproductive toxicity. Integrating a comprehensive set of relevant toxicological endpoints in a single protocol represents an efficient opportunity, reducing animal use in accordance with the 3Rs (replacement, reduction and refinement). This strategy has the potential to provide sufficient data on multiple windows of susceptibility of specific interest for risk assessments and public health decision making by including prenatal, lactational, neonatal exposures and evaluating outcomes over the lifespan. This integrated study design is efficient in that the same generational cohort of rats used for evaluating long-term outcomes can be monitored in satellite parallel experiments to measure biomarkers and other parameters related to system-specific responses including metabolic alterations and endocrine disturbances. JF - Environmental health perspectives AU - Manservisi, Fabiana AU - Babot Marquillas, Clara AU - Buscaroli, Annalisa AU - Huff, James AU - Lauriola, Michelina AU - Mandrioli, Daniele AU - Manservigi, Marco AU - Panzacchi, Simona AU - Silbergeld, Ellen K AU - Belpoggi, Fiorella AD - Cesare Maltoni Cancer Research Center, Ramazzini Institute, Bentivoglio 40010, Bologna, Italy. ; Visiting Researcher from University of Barcelona, Leonardo da Vinci Programme at the Cesare Maltoni Cancer Research Center, Ramazzini Institute, Bentivoglio 40010, Bologna, Italy. ; National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA 27709. ; Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, USA 21205. Y1 - 2016/07/22/ PY - 2016 DA - 2016 Jul 22 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859718168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=An+Integrated+Experimental+Design+for+the+Assessment+of+Multiple+Toxicological+End+Points+in+Rat+Bioassays.&rft.au=Manservisi%2C+Fabiana%3BBabot+Marquillas%2C+Clara%3BBuscaroli%2C+Annalisa%3BHuff%2C+James%3BLauriola%2C+Michelina%3BMandrioli%2C+Daniele%3BManservigi%2C+Marco%3BPanzacchi%2C+Simona%3BSilbergeld%2C+Ellen+K%3BBelpoggi%2C+Fiorella&rft.aulast=Manservisi&rft.aufirst=Fabiana&rft.date=2016-07-22&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model. AN - 1806437093; 27443489 AB - Angiogenesis, the formation of new blood vessels, is essential for tumor growth, stabilization and progression. Angiogenesis inhibitors are now widely used in the clinic; however, there are relatively few published studies on the mechanism of their presumed teratogenic effects. To address this issue, we screened a variety of angiogenesis inhibitors in developing zebrafish and chicken embryo models to assess for developmental defects and potential teratogenic effects. We confirmed previous reports that sunitinib, sorafenib and TNP-470 are teratogenic and demonstrate that axitinib, pazopanib, vandetanib, and everolimus are also teratogens in these models. A dose response study identified the drugs inhibit HUVEC cell proliferation in vitro, and also target the developing blood vessels of embryos in vivo. This provides further evidence for the potential risk of fetal toxicity when using these drugs in a clinical setting, and emphasizes the importance of the development and maintenance of the vasculature in the embryo. We conclude that angiogenesis inhibitors, regardless of the molecular target, are teratogenic when exposed to chicken embryos. JF - Scientific reports AU - Beedie, Shaunna L AU - Mahony, Chris AU - Walker, Heather M AU - Chau, Cindy H AU - Figg, William D AU - Vargesson, Neil AD - School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. ; Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2016/07/22/ PY - 2016 DA - 2016 Jul 22 SP - 30038 VL - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806437093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Shared+mechanism+of+teratogenicity+of+anti-angiogenic+drugs+identified+in+the+chicken+embryo+model.&rft.au=Beedie%2C+Shaunna+L%3BMahony%2C+Chris%3BWalker%2C+Heather+M%3BChau%2C+Cindy+H%3BFigg%2C+William+D%3BVargesson%2C+Neil&rft.aulast=Beedie&rft.aufirst=Shaunna&rft.date=2016-07-22&rft.volume=6&rft.issue=&rft.spage=30038&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep30038 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep30038 ER - TY - JOUR T1 - Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer. AN - 1805761430; 27216424 AB - P-Glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance in cancer cells. Although various screening procedures have been practiced so far to develop first three generations of P-gp inhibitors, their toxicity and drug interaction profiles are still a matter of concern. To address the above important problem of developing safe and effective P-gp inhibitors, we have made systematic computational and experimental studies on the interaction of natural phytochemicals with human P-gp. Molecular docking and QSAR studies were carried out for 40 dietary phytochemicals in the drug-binding site of the transmembrane domains (TMDs) of P-gp. Dietary flavonoids exhibit better interactions with homology modeled human P-gp. Based on the computational analysis, selected flavonoids were tested for their inhibitory potential against P-gp transport function in drug resistant cell lines using calcein-AM and rhodamine 123 efflux assays. It has been found that quercetin and rutin were the highly desirable flavonoids for the inhibition of P-gp transport function and they significantly reduced resistance in cytotoxicity assays to paclitaxel in P-gp overexpressing MDR cell lines. Hence, quercetin and rutin may be considered as potential chemosensitizing agents to overcome multidrug resistance in cancer. JF - Molecular bioSystems AU - Mohana, S AU - Ganesan, M AU - Agilan, B AU - Karthikeyan, R AU - Srithar, G AU - Beaulah Mary, R AU - Ananthakrishnan, D AU - Velmurugan, D AU - Rajendra Prasad, N AU - Ambudkar, Suresh V AD - Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar-608 002, Tamilnadu, India. drprasadnr@gmail.com. ; Bioinformatics Infrastructure Facility (BIF), University of Madras, Guindy Campus, Chennai, Tamil Nadu, India. ; Bioinformatics Infrastructure Facility (BIF), University of Madras, Guindy Campus, Chennai, Tamil Nadu, India and CAS in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India. ; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, Maryland 20892-4256, USA. ambudkar@mail.nih.gov. Y1 - 2016/07/19/ PY - 2016 DA - 2016 Jul 19 SP - 2458 EP - 2470 VL - 12 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1805761430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+bioSystems&rft.atitle=Screening+dietary+flavonoids+for+the+reversal+of+P-glycoprotein-mediated+multidrug+resistance+in+cancer.&rft.au=Mohana%2C+S%3BGanesan%2C+M%3BAgilan%2C+B%3BKarthikeyan%2C+R%3BSrithar%2C+G%3BBeaulah+Mary%2C+R%3BAnanthakrishnan%2C+D%3BVelmurugan%2C+D%3BRajendra+Prasad%2C+N%3BAmbudkar%2C+Suresh+V&rft.aulast=Mohana&rft.aufirst=S&rft.date=2016-07-19&rft.volume=12&rft.issue=8&rft.spage=2458&rft.isbn=&rft.btitle=&rft.title=Molecular+bioSystems&rft.issn=1742-2051&rft_id=info:doi/10.1039%2Fc6mb00187d LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1039/c6mb00187d ER - TY - JOUR T1 - Distinguishing ventricular septal bulge versus hypertrophic cardiomyopathy in the elderly AN - 1808702737; PQ0003343394 AB - The burgeoning evidence of patients diagnosed with sigmoidal hypertrophic cardiomyopathy (HCM) later in life has revived the quest for distinctive features that may help discriminate it from more benign forms of isolated septal hypertrophy often labelled ventricular septal bulge (VSB). HCM is diagnosed less frequently than VSB at older ages, with a reversed female predominance. Most patients diagnosed with HCM at older ages suffer from hypertension, similar to those with VSB. A positive family history of HCM and/or sudden cardiac death and the presence of exertional symptoms usually support HCM, though they are less likely in older patients with HCM, and poorly investigated in individuals with VSB. A more severe hypertrophy and the presence of left ventricular outflow obstruction are considered diagnostic of HCM, though stress echocardiography has not been consistently used in VSB. Mitral annulus calcification is very prevalent in both conditions, whereas a restrictive filling pattern is found in a minority of older patients with HCM. Genetic testing has low applicability in this differential diagnosis at the current time, given that a causative mutation is found in less than 10% of elderly patients with suspected HCM. Emerging imaging modalities that allow non-invasive detection of myocardial fibrosis and disarray may help, but have not been fully investigated. Nonetheless, there remains a considerable morphological overlap between the two conditions. Comprehensive studies, particularly imaging based, are warranted to offer a more evidence-based approach to elderly patients with focal septal thickening. JF - Heart AU - Canepa, Marco AU - Pozios, Iraklis AU - Vianello, Pier Filippo AU - Ameri, Pietro AU - Brunelli, Claudio AU - Ferrucci, Luigi AU - Abraham, Theodore P AD - Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, , Maryland, USA Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 1087 EP - 1094 PB - British Medical Association, BMA House Square London WC1H 9JP United Kingdom VL - 102 IS - 14 SN - 1355-6037, 1355-6037 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Fibrosis KW - Echocardiography KW - Stress KW - imaging KW - Cardiomyopathy KW - Ventricle KW - Hypertrophy KW - Differential diagnosis KW - Calcification KW - Geriatrics KW - Genetic screening KW - Mutation KW - Hypertension KW - Benign KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808702737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Heart&rft.atitle=Distinguishing+ventricular+septal+bulge+versus+hypertrophic+cardiomyopathy+in+the+elderly&rft.au=Canepa%2C+Marco%3BPozios%2C+Iraklis%3BVianello%2C+Pier+Filippo%3BAmeri%2C+Pietro%3BBrunelli%2C+Claudio%3BFerrucci%2C+Luigi%3BAbraham%2C+Theodore+P&rft.aulast=Canepa&rft.aufirst=Marco&rft.date=2016-07-15&rft.volume=102&rft.issue=14&rft.spage=1087&rft.isbn=&rft.btitle=&rft.title=Heart&rft.issn=13556037&rft_id=info:doi/10.1136%2Fheartjnl-2015-308764 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Heart; Fibrosis; Echocardiography; Stress; imaging; Cardiomyopathy; Hypertrophy; Ventricle; Calcification; Differential diagnosis; Geriatrics; Genetic screening; Mutation; Benign; Hypertension DO - http://dx.doi.org/10.1136/heartjnl-2015-308764 ER - TY - JOUR T1 - Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays AN - 1808700775; PQ0003476510 AB - Purpose: Rational development of targeted MET inhibitors for cancer treatment requires a quantitative understanding of target pharmacodynamics, including molecular target engagement, mechanism of action, and duration of effect.Experimental Design: Sandwich immunoassays and specimen handling procedures were developed and validated for quantifying full-length MET and its key phosphospecies (pMET) in core tumor biopsies. MET was captured using an antibody to the extracellular domain and then probed using antibodies to its C-terminus (full-length) and epitopes containing pY1234/1235, pY1235, and pY1356. Using pMET:MET ratios as assay endpoints, MET inhibitor pharmacodynamics were characterized in MET-amplified and -compensated (VEGFR blockade) models.Results: By limiting cold ischemia time to less than two minutes, the pharmacodynamic effects of the MET inhibitors PHA665752 and PF02341066 (crizotinib) were quantifiable using core needle biopsies of human gastric carcinoma xenografts (GTL-16 and SNU5). One dose decreased pY1234/1235 MET:MET, pY1235-MET:MET, and pY1356-MET:MET ratios by 60% to 80% within 4 hours, but this effect was not fully sustained despite continued daily dosing. VEGFR blockade by pazopanib increased pY1235-MET:MET and pY1356-MET:MET ratios, which was reversed by tivantinib. Full-length MET was quantifiable in 5 of 5 core needle samples obtained from a resected hereditary papillary renal carcinoma, but the levels of pMET species were near the assay lower limit of quantitation.Conclusions: These validated immunoassays for pharmacodynamic biomarkers of MET signaling are suitable for studying MET responses in amplified cancers as well as compensatory responses to VEGFR blockade. Incorporating pharmacodynamic biomarker studies into clinical trials of MET inhibitors could provide critical proof of mechanism and proof of concept for the field. Clin Cancer Res; 22(14); 3683-94. copyright 2016 AACR. JF - Clinical Cancer Research AU - Srivastava, Apurva K AU - Hollingshead, Melinda G AU - Weiner, Jennifer AU - Navas, Tony AU - Evrard, Yvonne A AU - Khin, Sonny A AU - Ji, Jiuping Jay AU - Zhang, Yiping AU - Borgel, Suzanne AU - Pfister, Thomas D AU - Kinders, Robert J AU - Bottaro, Donald P AU - Linehan, WMarston AU - Tomaszewski, Joseph E AU - Doroshow, James H AU - Parchment, Ralph E AD - Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, parchmentr@mail.nih.gov Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 3683 EP - 3694 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 14 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - C-Terminus KW - Biopsy KW - Ischemia KW - Tumors KW - Clinical trials KW - biomarkers KW - c-Met protein KW - Antibodies KW - renal cell carcinoma KW - Protein-tyrosine kinase KW - Vascular endothelial growth factor receptors KW - Xenografts KW - Gastric cancer KW - Immunoassays KW - Pharmacodynamics KW - Epitopes KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808700775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Pharmacodynamic+Response+of+the+MET%2FHGF+Receptor+to+Small-Molecule+Tyrosine+Kinase+Inhibitors+Examined+with+Validated%2C+Fit-for-Clinic+Immunoassays&rft.au=Srivastava%2C+Apurva+K%3BHollingshead%2C+Melinda+G%3BWeiner%2C+Jennifer%3BNavas%2C+Tony%3BEvrard%2C+Yvonne+A%3BKhin%2C+Sonny+A%3BJi%2C+Jiuping+Jay%3BZhang%2C+Yiping%3BBorgel%2C+Suzanne%3BPfister%2C+Thomas+D%3BKinders%2C+Robert+J%3BBottaro%2C+Donald+P%3BLinehan%2C+WMarston%3BTomaszewski%2C+Joseph+E%3BDoroshow%2C+James+H%3BParchment%2C+Ralph+E&rft.aulast=Srivastava&rft.aufirst=Apurva&rft.date=2016-07-15&rft.volume=22&rft.issue=14&rft.spage=3683&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2323 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - C-Terminus; Biopsy; Tumors; Ischemia; c-Met protein; biomarkers; Clinical trials; Antibodies; renal cell carcinoma; Protein-tyrosine kinase; Vascular endothelial growth factor receptors; Xenografts; Gastric cancer; Immunoassays; Epitopes; Pharmacodynamics DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2323 ER - TY - JOUR T1 - Synthetic Amphipathic Helical Peptides Targeting CD36 Attenuate Lipopolysaccharide-Induced Inflammation and Acute Lung Injury AN - 1808696435; PQ0003408298 AB - Synthetic amphipathic helical peptides (SAHPs) designed as apolipoprotein A-I mimetics are known to bind to class B scavenger receptors (SR-Bs), SR-BI, SR-BII, and CD36, receptors that mediate lipid transport and facilitate pathogen recognition. In this study, we evaluated SAHPs, selected for targeting human CD36, by their ability to attenuate LPS-induced inflammation, endothelial barrier dysfunction, and acute lung injury (ALI). L37pA, which targets CD36 and SR-BI equally, inhibited LPS-induced IL-8 secretion and barrier dysfunction in cultured endothelial cells while reducing lung neutrophil infiltration by 40% in a mouse model of LPS-induced ALI. A panel of 20 SAHPs was tested in HEK293 cell lines stably transfected with various SR-Bs to identify SAHPs with preferential selectivity toward CD36. Among several SAHPs targeting both SR-BI/BII and CD36 receptors, ELK-B acted predominantly through CD36. Compared with L37pA, 5A, and ELK SAHPs, ELK-B was most effective in reducing the pulmonary barrier dysfunction, neutrophil migration into the lung, and lung inflammation induced by LPS. We conclude that SAHPs with relative selectivity toward CD36 are more potent at inhibiting acute pulmonary inflammation and dysfunction. These data indicate that therapeutic strategies using SAHPs targeting CD36, but not necessarily mimicking all apolipoprotein A-I functions, may be considered a possible new treatment approach for inflammation-induced ALI and pulmonary edema. JF - Journal of Immunology AU - Bocharov, Alexander V AU - Wu, Tinghuai AU - Baranova, Irina N AU - Birukova, Anna A AU - Sviridov, Denis AU - Vishnyakova, Tatyana G AU - Remaley, Alan T AU - Eggerman, Thomas L AU - Patterson, Amy P AU - Birukov, Konstantin G AD - National Heart, Lung, and Blood Institute, Bethesda, MD 20892 Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 611 EP - 619 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 United States VL - 197 IS - 2 SN - 0022-1767, 0022-1767 KW - Toxicology Abstracts; Immunology Abstracts KW - Protein transport KW - Mimicry KW - CD36 antigen KW - Data processing KW - Injuries KW - Lipids KW - Animal models KW - Leukocytes (neutrophilic) KW - Edema KW - Apolipoprotein A-I KW - Pathogens KW - Interleukin 8 KW - Inflammation KW - Endothelial cells KW - Leukocyte migration KW - Lung KW - Lipopolysaccharides KW - scavenger receptors KW - X 24370:Natural Toxins KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808696435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Synthetic+Amphipathic+Helical+Peptides+Targeting+CD36+Attenuate+Lipopolysaccharide-Induced+Inflammation+and+Acute+Lung+Injury&rft.au=Bocharov%2C+Alexander+V%3BWu%2C+Tinghuai%3BBaranova%2C+Irina+N%3BBirukova%2C+Anna+A%3BSviridov%2C+Denis%3BVishnyakova%2C+Tatyana+G%3BRemaley%2C+Alan+T%3BEggerman%2C+Thomas+L%3BPatterson%2C+Amy+P%3BBirukov%2C+Konstantin+G&rft.aulast=Bocharov&rft.aufirst=Alexander&rft.date=2016-07-15&rft.volume=197&rft.issue=2&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/10.4049%2Fjimmunol.1401028 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Mimicry; Protein transport; Data processing; CD36 antigen; Injuries; Lipids; Leukocytes (neutrophilic); Animal models; Edema; Pathogens; Apolipoprotein A-I; Interleukin 8; Inflammation; Leukocyte migration; Endothelial cells; Lung; Lipopolysaccharides; scavenger receptors DO - http://dx.doi.org/10.4049/jimmunol.1401028 ER - TY - JOUR T1 - High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma AN - 1808681853; PQ0003476489 AB - Purpose: Elevated IgA antibodies indicative of ongoing exposure to Epstein-Barr virus (EBV) are high-risk biomarkers for nasopharyngeal carcinoma (NPC), an EBV-related epithelial tumor. However, protective biomarkers that limit exposure to the virus have not been defined. We evaluated whether antibodies that can neutralize EBV infection by targeting glycoproteins involved in viral cell entry, including EBV vaccine candidate glycoprotein 350 (gp350), were associated with lower NPC risk.Experimental Design: In a prospective cohort of 2,557 individuals from 358 high-risk NPC multiplex families in Taiwan, we identified 21 incident NPC cases and 50 disease-free controls. To complement data from high-risk families, we further identified 30 prevalent NPC cases and 50 healthy controls from the general Taiwanese population. We quantified EBV-neutralizing antibody, antibodies against EBV glycoproteins involved in B-cell and epithelial cell entry, and anti-EBNA1 IgA, a high-risk NPC biomarker.Results: EBV-neutralizing antibodies blocking B-cell infection and anti-gp350 antibodies were present at significantly higher levels in disease-free controls compared with incident NPC cases (P < 0.03). Family members with both low EBV-neutralizing potential and elevated EBNA1 IgA had a 7-fold increased risk of NPC (95% CI, 1.9-28.7). Neutralizing antibodies against epithelial cell infection did not differ between incident cases and disease-free controls. Anti-glycoprotein antibody levels measured at diagnosis (prevalent NPC) were significantly higher than levels measured prior to diagnosis (P < 0.01).Conclusions: Elevated titers of EBV-neutralizing antibody and anti-gp350 antibody were low-risk biomarkers for NPC. These data suggest that a vaccine that induces potent EBV gp350 and B-cell-neutralizing antibodies could reduce the risk of EBV-related cancers such as NPC. Clin Cancer Res; 22(14); 3451-7. copyright 2016 AACR. JF - Clinical Cancer Research AU - Coghill, Anna E AU - Bu, Wei AU - Nguyen, Hanh AU - Hsu, Wan-Lun AU - Yu, Kelly J AU - Lou, Pei-Jen AU - Wang, Cheng-Ping AU - Chen, Chien-Jen AU - Hildesheim, Allan AU - Cohen, Jeffrey I AD - Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland, anna.coghill@nih.gov Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 3451 EP - 3457 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 14 SN - 1078-0432, 1078-0432 KW - Virology & AIDS Abstracts; Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Epithelial cells KW - Data processing KW - Lymphocytes B KW - Tumors KW - Infection KW - biomarkers KW - Epstein-Barr virus KW - Immunoglobulin A KW - Nasopharyngeal carcinoma KW - Risk factors KW - Risk groups KW - Glycoproteins KW - Vaccines KW - W 30915:Pharmaceuticals & Vaccines KW - V 22370:Oncology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808681853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=High+Levels+of+Antibody+that+Neutralize+B-cell+Infection+of+Epstein-Barr+Virus+and+that+Bind+EBV+gp350+Are+Associated+with+a+Lower+Risk+of+Nasopharyngeal+Carcinoma&rft.au=Coghill%2C+Anna+E%3BBu%2C+Wei%3BNguyen%2C+Hanh%3BHsu%2C+Wan-Lun%3BYu%2C+Kelly+J%3BLou%2C+Pei-Jen%3BWang%2C+Cheng-Ping%3BChen%2C+Chien-Jen%3BHildesheim%2C+Allan%3BCohen%2C+Jeffrey+I&rft.aulast=Coghill&rft.aufirst=Anna&rft.date=2016-07-15&rft.volume=22&rft.issue=14&rft.spage=3451&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2299 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-11-09 N1 - SubjectsTermNotLitGenreText - Epithelial cells; Immunoglobulin A; Nasopharyngeal carcinoma; Data processing; Lymphocytes B; Risk factors; Risk groups; Tumors; Vaccines; Glycoproteins; Infection; biomarkers; Epstein-Barr virus DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2299 ER - TY - JOUR T1 - Identification of Niclosamide as a Novel Anticancer Agent for Adrenocortical Carcinoma AN - 1808651309; PQ0003476490 AB - Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer, and no current effective therapy is available for locally advanced and metastatic ACC. Drug repurposing is an emerging approach for identifying new indications for existing drugs, especially for rare cancers such as ACC. The objective of this study was to use quantitative high-throughput screening to identify agents with antineoplastic activity against ACC.Experimental Design: A screening of 4,292 compounds was performed on three ACC cell lines: BD140A, SW-13, and NCI-H295R.Results: Twenty-one active compounds were identified, with an efficacy of >80% in all three cell lines. Of these, niclosamide showed higher efficacy and lower IC50 than established anti-ACC drugs. We then validated niclosamide-inhibited cellular proliferation in all three ACC cell lines. Next, we investigated the mechanism by which niclosamide inhibited ACC cell proliferation, and found that it induced caspase-dependent apoptosis and G1 cell-cycle arrest. Niclosamide also decreased cellular migration and reduced the level of mediators of epithelial-to-mesenchymal transition, such as N-cadherin and vimentin. Furthermore, niclosamide treatment resulted in decreased expression of beta -catenin. We also evaluated the effect of niclosamide on energy metabolism in ACC cell lines and found it resulted in mitochondrial uncoupling. Niclosamide treatment inhibited ACC tumor growth with no observed toxicity in mice in vivo.Conclusions: Our findings suggest that niclosamide has anti-ACC activity through its inhibition of multiple altered cellular pathways and cellular metabolism in ACC. Our results provide a preclinical rationale for evaluating niclosamide therapy in a clinical trial for ACC. Clin Cancer Res; 22(14); 3458-66. copyright 2016 AACR. JF - Clinical Cancer Research AU - Satoh, Kei AU - Zhang, Lisa AU - Zhang, Yaqin AU - Chelluri, Raju AU - Boufraqech, Myriem AU - Nilubol, Naris AU - Patel, Dhaval AU - Shen, Min AU - Kebebew, Electron AD - Icahn School of Medicine at Mount Sinai, New York, New York, kebebewe@mail.nih.gov Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 3458 EP - 3466 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 14 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Apoptosis KW - Energy metabolism KW - Mitochondria KW - Tumors KW - Toxicity KW - Antitumor agents KW - Clinical trials KW - Vimentin KW - Carcinoma KW - Niclosamide KW - Metastases KW - catenin KW - N-Cadherin KW - high-throughput screening KW - Cell migration KW - Cell proliferation KW - Drugs KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808651309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Identification+of+Niclosamide+as+a+Novel+Anticancer+Agent+for+Adrenocortical+Carcinoma&rft.au=Satoh%2C+Kei%3BZhang%2C+Lisa%3BZhang%2C+Yaqin%3BChelluri%2C+Raju%3BBoufraqech%2C+Myriem%3BNilubol%2C+Naris%3BPatel%2C+Dhaval%3BShen%2C+Min%3BKebebew%2C+Electron&rft.aulast=Satoh&rft.aufirst=Kei&rft.date=2016-07-15&rft.volume=22&rft.issue=14&rft.spage=3458&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2256 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Apoptosis; Energy metabolism; Mitochondria; Toxicity; Tumors; Clinical trials; Antitumor agents; Vimentin; Carcinoma; Metastases; Niclosamide; catenin; N-Cadherin; high-throughput screening; Cell migration; Cell proliferation; Drugs DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2256 ER - TY - JOUR T1 - Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer: Results of a Randomized Study at 15-Year Follow-Up. AN - 1800705627; 27209504 AB - To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery. From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years). Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (<8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic) scale (OR, 3.75; 95% CI, 1.19-11.79; P=.018), as well as grade 2 or 3 breast atrophy or retraction (OR, 3.87; 95% CI, 1.42-10.56; P=.008). No effect on telangiectasia was detected. At long-term follow-up, concomitant chemoradiation therapy has a detrimental effect on both fibrosis and retraction with an approximately 4-fold increase in the odds of grade 2 or 3 toxicity. Copyright © 2016 Elsevier Inc. All rights reserved. JF - International journal of radiation oncology, biology, physics AU - Pinnarò, Paola AU - Giordano, Carolina AU - Farneti, Alessia AU - Strigari, Lidia AU - Landoni, Valeria AU - Marucci, Laura AU - Petrongari, Maria Grazia AU - Sanguineti, Giuseppe AD - Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Physics, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: sanguineti@ifo.it. Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 1201 EP - 1209 VL - 95 IS - 4 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800705627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Impact+of+Sequencing+Radiation+Therapy+and+Chemotherapy+on+Long-Term+Local+Toxicity+for+Early+Breast+Cancer%3A+Results+of+a+Randomized+Study+at+15-Year+Follow-Up.&rft.au=Pinnar%C3%B2%2C+Paola%3BGiordano%2C+Carolina%3BFarneti%2C+Alessia%3BStrigari%2C+Lidia%3BLandoni%2C+Valeria%3BMarucci%2C+Laura%3BPetrongari%2C+Maria+Grazia%3BSanguineti%2C+Giuseppe&rft.aulast=Pinnar%C3%B2&rft.aufirst=Paola&rft.date=2016-07-15&rft.volume=95&rft.issue=4&rft.spage=1201&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=1879-355X&rft_id=info:doi/10.1016%2Fj.ijrobp.2016.03.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ijrobp.2016.03.016 ER - TY - JOUR T1 - Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft. AN - 1796245946; 27262595 AB - Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally verified their selective inhibitory activity. Three inhibitors exhibited low-micromolar IC50 values. Molecular dynamics simulations revealed a common binding mode for these inhibitors, involving association to the TDP2 DNA-binding cleft. MM-PBSA per-residue energy decomposition identified important interactions of the compounds with specific TDP2 residues. These interactions could provide new avenues for synthetic optimization of these scaffolds. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Bioorganic & medicinal chemistry letters AU - Kossmann, Bradley R AU - Abdelmalak, Monica AU - Lopez, Sophia AU - Tender, Gabrielle AU - Yan, Chunli AU - Pommier, Yves AU - Marchand, Christophe AU - Ivanov, Ivaylo AD - Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, United States. ; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States. ; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: marchanc@mail.nih.gov. ; Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, United States. Electronic address: iivanov@gsu.edu. Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 3232 EP - 3236 VL - 26 IS - 14 KW - Index Medicus KW - Tyrosyl-DNA phosphodiesterase 2 KW - TDP2 KW - Virtual screening KW - Inhibitor KW - Rational drug design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1796245946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Discovery+of+selective+inhibitors+of+tyrosyl-DNA+phosphodiesterase+2+by+targeting+the+enzyme+DNA-binding+cleft.&rft.au=Kossmann%2C+Bradley+R%3BAbdelmalak%2C+Monica%3BLopez%2C+Sophia%3BTender%2C+Gabrielle%3BYan%2C+Chunli%3BPommier%2C+Yves%3BMarchand%2C+Christophe%3BIvanov%2C+Ivaylo&rft.aulast=Kossmann&rft.aufirst=Bradley&rft.date=2016-07-15&rft.volume=26&rft.issue=14&rft.spage=3232&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=1464-3405&rft_id=info:doi/10.1016%2Fj.bmcl.2016.05.065 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bmcl.2016.05.065 ER - TY - JOUR T1 - Polymorphisms in DNA repair genes, traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence. AN - 1788226427; 26946191 AB - Vehicular traffic polycyclic aromatic hydrocarbons (PAHs) have been associated with breast cancer incidence in epidemiologic studies, including our own. Because PAHs damage DNA by forming adducts and oxidative lesions, genetic polymorphisms that alter DNA repair capacity may modify associations between PAH-related exposures and breast cancer risk. Our goal was to examine the association between vehicular traffic exposure and breast cancer incidence within strata of a panel of nine biologically plausible nucleotide excision repair (NER) and base excision repair (BER) genotypes. Residential histories of 1,508 cases and 1,556 controls were assessed in the Long Island Breast Cancer Study Project between 1996 and 1997 and used to reconstruct residential traffic exposures to benzo[a]pyrene, as a proxy for traffic-related PAHs. Likelihood ratio tests from adjusted unconditional logistic regression models were used to assess multiplicative interactions. A gene-traffic interaction was evident (p = 0.04) for ERCC2 (Lys751); when comparing the upper and lower tertiles of 1995 traffic exposure estimates, the odds ratio (95% confidence interval) was 2.09 (1.13, 3.90) among women with homozygous variant alleles. Corresponding odds ratios for 1960-1990 traffic were also elevated nearly 2-3-fold for XRCC1(Arg194Trp), XRCC1(Arg399Gln) and OGG1(Ser326Cys), but formal multiplicative interaction was not evident. When DNA repair variants for ERCC2, XRCC1 and OGG1 were combined, among women with 4-6 variants, the odds ratios were 2.32 (1.22, 4.49) for 1995 traffic and 2.96 (1.06, 8.21) for 1960-1990 traffic. Our study is first to report positive associations between traffic-related PAH exposure and breast cancer incidence among women with select biologically plausible DNA repair genotypes. © 2016 UICC. JF - International journal of cancer AU - Mordukhovich, Irina AU - Beyea, Jan AU - Herring, Amy H AU - Hatch, Maureen AU - Stellman, Steven D AU - Teitelbaum, Susan L AU - Richardson, David B AU - Millikan, Robert C AU - Engel, Lawrence S AU - Shantakumar, Sumitra AU - Steck, Susan E AU - Neugut, Alfred I AU - Rossner, Pavel AU - Santella, Regina M AU - Gammon, Marilie D AD - Department of Epidemiology, Lambertville, NJ. ; Consulting in the Public Interest, Lambertville, NJ. ; Biostatistics, University of North Carolina, Chapel Hill, NC. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. ; Department of Epidemiology, Columbia University, New York, NY. ; Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY. ; Glaxo-Smith Kline, Inc, Singapore. ; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, South Carolina, CA. ; Environmental Health Sciences, Columbia University, New York, NY. Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 310 EP - 321 VL - 139 IS - 2 KW - Index Medicus KW - breast cancer KW - traffic KW - polycyclic aromatic hydrocarbons KW - DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1788226427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Polymorphisms+in+DNA+repair+genes%2C+traffic-related+polycyclic+aromatic+hydrocarbon+exposure+and+breast+cancer+incidence.&rft.au=Mordukhovich%2C+Irina%3BBeyea%2C+Jan%3BHerring%2C+Amy+H%3BHatch%2C+Maureen%3BStellman%2C+Steven+D%3BTeitelbaum%2C+Susan+L%3BRichardson%2C+David+B%3BMillikan%2C+Robert+C%3BEngel%2C+Lawrence+S%3BShantakumar%2C+Sumitra%3BSteck%2C+Susan+E%3BNeugut%2C+Alfred+I%3BRossner%2C+Pavel%3BSantella%2C+Regina+M%3BGammon%2C+Marilie+D&rft.aulast=Mordukhovich&rft.aufirst=Irina&rft.date=2016-07-15&rft.volume=139&rft.issue=2&rft.spage=310&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.30079 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.30079 ER - TY - JOUR T1 - Colorectal cancer risk and nitrate exposure through drinking water and diet. AN - 1788225635; 26954527 AB - Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research. © 2016 UICC. JF - International journal of cancer AU - Espejo-Herrera, Nadia AU - Gràcia-Lavedan, Esther AU - Boldo, Elena AU - Aragonés, Nuria AU - Pérez-Gómez, Beatriz AU - Pollán, Marina AU - Molina, Antonio J AU - Fernández, Tania AU - Martín, Vicente AU - La Vecchia, Carlo AU - Bosetti, Cristina AU - Tavani, Alessandra AU - Polesel, Jerry AU - Serraino, Diego AU - Gómez Acebo, Inés AU - Altzibar, Jone M AU - Ardanaz, Eva AU - Burgui, Rosana AU - Pisa, Federica AU - Fernández-Tardón, Guillermo AU - Tardón, Adonina AU - Peiró, Rosana AU - Navarro, Carmen AU - Castaño-Vinyals, Gemma AU - Moreno, Victor AU - Righi, Elena AU - Aggazzotti, Gabriella AU - Basagaña, Xavier AU - Nieuwenhuijsen, Mark AU - Kogevinas, Manolis AU - Villanueva, Cristina M AD - ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. ; Research Group on Gene-Environment Interactions and Health, , University of León, León, Spain. ; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. ; Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. ; Unit of Epidemiology and Biostatistics, IRCCS, CRO Aviano National Cancer Institute, Aviano, Italy. ; SOC Igiene ed Epidemiologia Clinica, Azienda Ospedaliera Universitaria, Udine, Italy. ; University of Modena and Reggio Emilia, Modena, Italy. Y1 - 2016/07/15/ PY - 2016 DA - 2016 Jul 15 SP - 334 EP - 346 VL - 139 IS - 2 KW - Index Medicus KW - diet KW - nitrate KW - colorectal cancer KW - drinking water KW - case-control studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1788225635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Colorectal+cancer+risk+and+nitrate+exposure+through+drinking+water+and+diet.&rft.au=Espejo-Herrera%2C+Nadia%3BGr%C3%A0cia-Lavedan%2C+Esther%3BBoldo%2C+Elena%3BAragon%C3%A9s%2C+Nuria%3BP%C3%A9rez-G%C3%B3mez%2C+Beatriz%3BPoll%C3%A1n%2C+Marina%3BMolina%2C+Antonio+J%3BFern%C3%A1ndez%2C+Tania%3BMart%C3%ADn%2C+Vicente%3BLa+Vecchia%2C+Carlo%3BBosetti%2C+Cristina%3BTavani%2C+Alessandra%3BPolesel%2C+Jerry%3BSerraino%2C+Diego%3BG%C3%B3mez+Acebo%2C+In%C3%A9s%3BAltzibar%2C+Jone+M%3BArdanaz%2C+Eva%3BBurgui%2C+Rosana%3BPisa%2C+Federica%3BFern%C3%A1ndez-Tard%C3%B3n%2C+Guillermo%3BTard%C3%B3n%2C+Adonina%3BPeir%C3%B3%2C+Rosana%3BNavarro%2C+Carmen%3BCasta%C3%B1o-Vinyals%2C+Gemma%3BMoreno%2C+Victor%3BRighi%2C+Elena%3BAggazzotti%2C+Gabriella%3BBasaga%C3%B1a%2C+Xavier%3BNieuwenhuijsen%2C+Mark%3BKogevinas%2C+Manolis%3BVillanueva%2C+Cristina+M&rft.aulast=Espejo-Herrera&rft.aufirst=Nadia&rft.date=2016-07-15&rft.volume=139&rft.issue=2&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.30083 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.30083 ER - TY - JOUR T1 - Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. AN - 1804857057; 27410922 AB - We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.). JF - The New England journal of medicine AU - Navari, Rudolph M AU - Qin, Rui AU - Ruddy, Kathryn J AU - Liu, Heshan AU - Powell, Steven F AU - Bajaj, Madhuri AU - Dietrich, Leah AU - Biggs, David AU - Lafky, Jacqueline M AU - Loprinzi, Charles L AD - From Indiana University School of Medicine-South Bend, South Bend (R.M.N.); Alliance Statistics and Data Center, Mayo Clinic (R.Q., H.L.), and Mayo Clinic (K.J.R., J.M.L., C.L.L.), Rochester, MN; Sanford NCORP (National Cancer Institute Community Oncology Research Program) of the North Central Plains, Sioux Falls, SD (S.F.P.); Illinois Cancer Care-Peoria, Peoria (M.B.); Gundersen Lutheran Medical Center, La Crosse, WI (L.D.); and Delaware-Christiana Care NCORP, Newark, DE (D.B.). Y1 - 2016/07/14/ PY - 2016 DA - 2016 Jul 14 SP - 134 EP - 142 VL - 375 IS - 2 KW - Antiemetics KW - 0 KW - Antineoplastic Agents KW - Morpholines KW - Benzodiazepines KW - 12794-10-4 KW - aprepitant KW - 1NF15YR6UY KW - fosaprepitant KW - 6L8OF9XRDC KW - Dexamethasone KW - 7S5I7G3JQL KW - olanzapine KW - N7U69T4SZR KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Dexamethasone -- therapeutic use KW - Double-Blind Method KW - Morpholines -- therapeutic use KW - Aged, 80 and over KW - Humans KW - Intention to Treat Analysis KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Nausea -- chemically induced KW - Benzodiazepines -- therapeutic use KW - Antiemetics -- therapeutic use KW - Vomiting -- prevention & control KW - Nausea -- prevention & control KW - Benzodiazepines -- adverse effects KW - Vomiting -- chemically induced KW - Antiemetics -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804857057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Olanzapine+for+the+Prevention+of+Chemotherapy-Induced+Nausea+and+Vomiting.&rft.au=Navari%2C+Rudolph+M%3BQin%2C+Rui%3BRuddy%2C+Kathryn+J%3BLiu%2C+Heshan%3BPowell%2C+Steven+F%3BBajaj%2C+Madhuri%3BDietrich%2C+Leah%3BBiggs%2C+David%3BLafky%2C+Jacqueline+M%3BLoprinzi%2C+Charles+L&rft.aulast=Navari&rft.aufirst=Rudolph&rft.date=2016-07-14&rft.volume=375&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/10.1056%2FNEJMoa1515725 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-20 N1 - Date created - 2016-07-14 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT02116530; ClinicalTrials.gov N1 - SuppNotes - Comment In: N Engl J Med. 2016 Oct 6;375(14 ):1395-1396 [27705262] N Engl J Med. 2016 Oct 6;375(14 ):1395-1396 [27705263] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1056/NEJMoa1515725 ER - TY - JOUR T1 - Ipilimumab for Patients with Relapse after Allogeneic Transplantation. AN - 1804856995; 27410923 AB - Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.). JF - The New England journal of medicine AU - Davids, Matthew S AU - Kim, Haesook T AU - Bachireddy, Pavan AU - Costello, Caitlin AU - Liguori, Rebecca AU - Savell, Alexandra AU - Lukez, Alexander P AU - Avigan, David AU - Chen, Yi-Bin AU - McSweeney, Peter AU - LeBoeuf, Nicole R AU - Rooney, Michael S AU - Bowden, Michaela AU - Zhou, Chensheng W AU - Granter, Scott R AU - Hornick, Jason L AU - Rodig, Scott J AU - Hirakawa, Masahiro AU - Severgnini, Mariano AU - Hodi, F Stephen AU - Wu, Catherine J AU - Ho, Vincent T AU - Cutler, Corey AU - Koreth, John AU - Alyea, Edwin P AU - Antin, Joseph H AU - Armand, Philippe AU - Streicher, Howard AU - Ball, Edward D AU - Ritz, Jerome AU - Bashey, Asad AU - Soiffer, Robert J AU - Leukemia and Lymphoma Society Blood Cancer Research Partnership AD - From the Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School (M.S.D., H.T.K., P.B., R.L., A.S., A.P.L., M.H., M.S., F.S.H., C.J.W., V.T.H., C. Cutler, J.K., E.P.A., J.H.A., P.A., J.R., R.J.S.), the Bone Marrow Transplant Program, Beth Israel Deaconess Medical Center and Harvard Medical School (D.A.), the Bone Marrow Transplant Program, Massachusetts General Hospital Cancer Center and Harvard Medical School (Y.-B.C.), the Departments of Dermatology (N.R.L.) and Pathology (S.R.G., J.L.H., S.J.R.), Dana-Farber and Brigham and Women's Cancer Center, and the Dana-Farber Cancer Institute, Center for Molecular Oncologic Pathology (M.B., C.W.Z.) - all in Boston; Broad Institute of Massachusetts Institute of Technology and Harvard (P.B., C.J.W.) and Neon Therapeutics (M.S.R.) - both in Cambridge; the Blood and Marrow Transplant Program, University of California, San Diego, Moores Cancer Center, La Jolla (C. Costello, E.D.B.); Colorado Blood Cancer Institute, Denver (P.M.); Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (H.S.); and the Blood and Marrow Transplant Group of Georgia at Northside Hospital, Atlanta (A.B.). ; Leukemia and Lymphoma Society Blood Cancer Research Partnership Y1 - 2016/07/14/ PY - 2016 DA - 2016 Jul 14 SP - 143 EP - 153 VL - 375 IS - 2 KW - Antibodies, Monoclonal KW - 0 KW - ipilimumab KW - 6T8C155666 KW - Abridged Index Medicus KW - Index Medicus KW - Myeloproliferative Disorders -- therapy KW - T-Lymphocytes, Regulatory KW - Leukemia -- therapy KW - Humans KW - Induction Chemotherapy KW - Aged KW - Transplantation, Homologous KW - CD4 Lymphocyte Count KW - Recurrence KW - Transplantation Immunology KW - Lymphoma -- therapy KW - Adult KW - Middle Aged KW - Female KW - Male KW - Hematologic Neoplasms -- therapy KW - Hematologic Neoplasms -- pathology KW - Hematopoietic Stem Cell Transplantation KW - Antibodies, Monoclonal -- adverse effects KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804856995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Ipilimumab+for+Patients+with+Relapse+after+Allogeneic+Transplantation.&rft.au=Davids%2C+Matthew+S%3BKim%2C+Haesook+T%3BBachireddy%2C+Pavan%3BCostello%2C+Caitlin%3BLiguori%2C+Rebecca%3BSavell%2C+Alexandra%3BLukez%2C+Alexander+P%3BAvigan%2C+David%3BChen%2C+Yi-Bin%3BMcSweeney%2C+Peter%3BLeBoeuf%2C+Nicole+R%3BRooney%2C+Michael+S%3BBowden%2C+Michaela%3BZhou%2C+Chensheng+W%3BGranter%2C+Scott+R%3BHornick%2C+Jason+L%3BRodig%2C+Scott+J%3BHirakawa%2C+Masahiro%3BSevergnini%2C+Mariano%3BHodi%2C+F+Stephen%3BWu%2C+Catherine+J%3BHo%2C+Vincent+T%3BCutler%2C+Corey%3BKoreth%2C+John%3BAlyea%2C+Edwin+P%3BAntin%2C+Joseph+H%3BArmand%2C+Philippe%3BStreicher%2C+Howard%3BBall%2C+Edward+D%3BRitz%2C+Jerome%3BBashey%2C+Asad%3BSoiffer%2C+Robert+J%3BLeukemia+and+Lymphoma+Society+Blood+Cancer+Research+Partnership&rft.aulast=Davids&rft.aufirst=Matthew&rft.date=2016-07-14&rft.volume=375&rft.issue=2&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/10.1056%2FNEJMoa1601202 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-20 N1 - Date created - 2016-07-14 N1 - Date revised - 2017-01-24 N1 - Genetic sequence - NCT01822509; ClinicalTrials.gov N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1056/NEJMoa1601202 ER - TY - JOUR T1 - Calling in sick: impacts of fever on intra-urban human mobility AN - 1808685447; PQ0003476363 AB - Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A retrospective, semi-structured interview allowed us to quantify multiple aspects of mobility during the two-week period preceding each interview. We fitted nested models of each aspect of mobility to data from interviews and compared models using likelihood ratio tests to determine whether there were statistically distinguishable differences in mobility attributable to fever or its aetiology. Compared with afebrile individuals, febrile study participants spent more time at home, visited fewer locations, and, in some cases, visited locations closer to home and spent less time at certain types of locations. These multifaceted impacts are consistent with the possibility that disease-mediated changes in host mobility generate dynamic and complex changes in host contact network structure. JF - Proceedings of the Royal Society of London, Series B: Biological Sciences AU - Perkins, TAlex AU - Paz-Soldan, Valerie A AU - Stoddard, Steven T AU - Morrison, Amy C AU - Forshey, Brett M AU - Long, Kanya C AU - Halsey, Eric S AU - Kochel, Tadeusz J AU - Elder, John P AU - Kitron, Uriel AU - Scott, Thomas W AU - Vazquez-Prokopec, Gonzalo M AD - Fogarty International Center, National Institutes of Health, , Bethesda, MD, USA, taperkins@nd.edu Y1 - 2016/07/13/ PY - 2016 DA - 2016 Jul 13 SP - 20160390 PB - Royal Society of London, 6 Carlton House Terrace London SW1Y 5AG United Kingdom VL - 283 IS - 1834 SN - 0962-8452, 0962-8452 KW - Ecology Abstracts KW - activity space KW - contact KW - dengue KW - infection KW - movement KW - network KW - Fever KW - Mathematical models KW - Data processing KW - Mobility KW - Statistical analysis KW - Pathogens KW - Disease transmission KW - D 04040:Ecosystem and Ecology Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808685447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.atitle=Calling+in+sick%3A+impacts+of+fever+on+intra-urban+human+mobility&rft.au=Perkins%2C+TAlex%3BPaz-Soldan%2C+Valerie+A%3BStoddard%2C+Steven+T%3BMorrison%2C+Amy+C%3BForshey%2C+Brett+M%3BLong%2C+Kanya+C%3BHalsey%2C+Eric+S%3BKochel%2C+Tadeusz+J%3BElder%2C+John+P%3BKitron%2C+Uriel%3BScott%2C+Thomas+W%3BVazquez-Prokopec%2C+Gonzalo+M&rft.aulast=Perkins&rft.aufirst=TAlex&rft.date=2016-07-13&rft.volume=283&rft.issue=1834&rft.spage=20160390&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Royal+Society+of+London%2C+Series+B%3A+Biological+Sciences&rft.issn=09628452&rft_id=info:doi/10.1098%2Frspb.2016.0390 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Fever; Data processing; Mathematical models; Mobility; Statistical analysis; Pathogens; Disease transmission DO - http://dx.doi.org/10.1098/rspb.2016.0390 ER - TY - JOUR T1 - Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites. AN - 1826717123; 27401914 AB - 1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. 4. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. 5. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Židková, Monika AU - Linhart, Igor AU - Balíková, Marie AU - Himl, Michal AU - Váňa, Lubomír AU - Vetýška, Michal AU - Páleníček, Tomáš AU - Lhotková, Eva AU - Dušek, Martin AD - a Institute of Forensic Medicine and Toxicology, 1st Faculty of Medicine, Charles University , Prague , Czech Republic . ; b National Institute of Mental Health , Klecany , Czech Republic . ; c Department of Organic Chemistry , Faculty of Chemical Technology, University of Chemistry and Technology , Prague , Czech Republic , and. ; d Research Institute of Brewing and Malting, PLC , Prague , Czech Republic. Y1 - 2016/07/12/ PY - 2016 DA - 2016 Jul 12 SP - 1 EP - 10 KW - new designer drugs KW - LC-HRMS KW - GC–MS KW - urinary metabolites KW - Biotransformation in rats KW - MDAI UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826717123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Study+on+the+metabolism+of+5%2C6-methylenedioxy-2-aminoindane+%28MDAI%29+in+rats%3A+identification+of+urinary+metabolites.&rft.au=%C5%BDidkov%C3%A1%2C+Monika%3BLinhart%2C+Igor%3BBal%C3%ADkov%C3%A1%2C+Marie%3BHiml%2C+Michal%3BV%C3%A1%C5%88a%2C+Lubom%C3%ADr%3BVet%C3%BD%C5%A1ka%2C+Michal%3BP%C3%A1len%C3%AD%C4%8Dek%2C+Tom%C3%A1%C5%A1%3BLhotkov%C3%A1%2C+Eva%3BDu%C5%A1ek%2C+Martin&rft.aulast=%C5%BDidkov%C3%A1&rft.aufirst=Monika&rft.date=2016-07-12&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=1366-5928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Polybrominated Diphenyl Ethers in Human Milk and Serum from the US EPA MAMA Study: Modeled Predictions of Infant Exposure and Considerations for Risk Assessment. AN - 1826714990; 27405099 AB - Serum concentrations of polybrominated diphenyl ethers (PBDEs) in U.S. women are believed to be among the world's highest, however, little information exists on the partitioning of PBDEs between serum and breast milk and how this may impact infant exposure. Paired milk and serum samples were measured for PBDE concentrations in 34 women who participated in the US EPA MAMA Study. Computational models for predicting milk PBDE concentrations from serum were evaluated. Samples were analyzed using gas chromatography isotope-dilution high-resolution mass spectrometry. Observed milk PBDE concentrations were compared to model predictions and models were applied to NHANES serum data to predict milk PBDE concentrations and infant intakes for the U.S. population. Serum and milk samples had detectable concentrations of most PBDEs. BDE-47 was found in the highest concentrations (median serum: 18.6; milk: 31.5 ng/g lipid) and BDE-28 had the highest milk:serum partitioning ratio (2.1 ± 0.2). No evidence of depuration was found. Models demonstrated high reliability and, as of 2007-2008, predicted U.S. milk concentrations of BDE-47, BDE-99, and BDE-100 appear to be declining but BDE-153 may be rising. Predicted infant intakes (ng/kg/day) were below threshold reference doses (RfDs) for BDE-99 and BDE-153 but above the suggested RfD for BDE-47. Concentrations and partitioning ratios of PBDEs in milk and serum from women in the U.S. EPA MAMA Study are presented for the first time; modeled predictions of milk PBDE concentrations using serum concentrations appear to be a valid method for estimating PBDE exposure in U.S. infants. JF - Environmental health perspectives AU - Marchitti, Satori A AU - Fenton, Suzanne E AU - Mendola, Pauline AU - Kenneke, John F AU - Hines, Erin P AD - ORISE Fellow, National Exposure Research Laboratory, U.S. EPA, Athens, GA, USA. ; National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, RTP, NC, USA. ; Eunice Kennedy Shriver National Institute for Child Health and Development, Rockville, MD, USA. ; National Exposure Research Laboratory, U.S. EPA, Athens, GA, USA. ; National Center for Environmental Assessment, U.S. EPA, RTP, NC, USA. Y1 - 2016/07/12/ PY - 2016 DA - 2016 Jul 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826714990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Polybrominated+Diphenyl+Ethers+in+Human+Milk+and+Serum+from+the+US+EPA+MAMA+Study%3A+Modeled+Predictions+of+Infant+Exposure+and+Considerations+for+Risk+Assessment.&rft.au=Marchitti%2C+Satori+A%3BFenton%2C+Suzanne+E%3BMendola%2C+Pauline%3BKenneke%2C+John+F%3BHines%2C+Erin+P&rft.aulast=Marchitti&rft.aufirst=Satori&rft.date=2016-07-12&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Serum Estrogens and Estrogen Metabolites and Endometrial Cancer Risk among Postmenopausal Women AN - 1808681431; PQ0003376070 AB - Background: Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogen metabolites.Methods: We conducted a nested case-control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95% confidence intervals (CI) for overall and subtype-specific endometrial cancer risk.Results: Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95% CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m2, BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01).Conclusions: Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens.Impact: These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity. Cancer Epidemiol Biomarkers Prev; 25(7); 1081-9. copyright 2016 AACR. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Brinton, Louise A AU - Trabert, Britton AU - Anderson, Garnet L AU - Falk, Roni T AU - Felix, Ashley S AU - Fuhrman, Barbara J AU - Gass, Margery L AU - Kuller, Lewis H AU - Pfeiffer, Ruth M AU - Rohan, Thomas E AU - Strickler, Howard D AU - Xu, Xia AU - Wentzensen, Nicolas AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, brintonl@exchange.nih.gov Y1 - 2016/07/12/ PY - 2016 DA - 2016 Jul 12 SP - 1081 EP - 1089 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 25 IS - 7 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - High-performance liquid chromatography KW - Obesity KW - Endometrium KW - Estrogens KW - Metabolites KW - Tumors KW - biomarkers KW - Hormones KW - Estradiol KW - Cancer KW - Post-menopause KW - Risk factors KW - Carcinogenesis KW - Body mass index KW - Estrone KW - B 26660:Miscellaneous Oncogenes & Growth Factors KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808681431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Serum+Estrogens+and+Estrogen+Metabolites+and+Endometrial+Cancer+Risk+among+Postmenopausal+Women&rft.au=Brinton%2C+Louise+A%3BTrabert%2C+Britton%3BAnderson%2C+Garnet+L%3BFalk%2C+Roni+T%3BFelix%2C+Ashley+S%3BFuhrman%2C+Barbara+J%3BGass%2C+Margery+L%3BKuller%2C+Lewis+H%3BPfeiffer%2C+Ruth+M%3BRohan%2C+Thomas+E%3BStrickler%2C+Howard+D%3BXu%2C+Xia%3BWentzensen%2C+Nicolas&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2016-07-12&rft.volume=25&rft.issue=7&rft.spage=1081&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&rft_id=info:doi/10.1158%2F1055-9965.EPI-16-0225 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - High-performance liquid chromatography; Obesity; Estrogens; Endometrium; Metabolites; Tumors; Hormones; biomarkers; Cancer; Estradiol; Post-menopause; Risk factors; Carcinogenesis; Body mass index; Estrone DO - http://dx.doi.org/10.1158/1055-9965.EPI-16-0225 ER - TY - JOUR T1 - Trajectories of maternal gestational weight gain and child cognition assessed at 5years of age in a prospective cohort study AN - 1808670684; PQ0003313420 AB - BackgroundThere has been concern that low gestational weight gain may cause poor fetal neurodevelopment.MethodsThe association between maternal weight gain and child IQ was examined using serial antenatal weight measurements (median 12) from a prospective cohort of non-obese Scandinavian women (1986-1988). Linear mixed models with piecewise regression were used to estimate participants' (n=552) trimester-specific average rate of weight gain. Linear regression was used to assess the association between weight gain and children's (n=344) full-scale, performance and verbal IQ measured at age 5 using the Wechsler Preschool and Primary Scales of Intelligence-Revised.ResultsChildren born to mothers who gained below versus within the 2nd trimester 2009 recommendations tended to have lower IQ scores (Full-scale: 106.6 (SD 15.1) vs 110.2 (15.2), p=0.04; verbal: 102.5 (14.3) vs 105.0 (14.9), p=0.10; performance: 109.5 (15.4) vs 113.4 (14.5), p=0.03). After adjustment there were no differences in child IQ by weight gain adequacy (full-scale: beta below=-1.1 (95% CI -5.1 to 2.9), beta above=1.5 (-3.8 to 6.8); verbal: beta below=-0.2 (-3.1 to 2.6), beta above=1.8 (-3.6 to 7.3); performance beta below=-1.2 (-4.6 to 2.2), beta above=1.0 (-4.6 to 6.7)). No differences were observed based on 3rd trimester adequacy. No differences were observed in IQ scores by quintile of weight gain for any trimester, particularly after adjustment for maternal IQ.ConclusionsOur findings are reassuring that among normal weight women, pregnancy weight gain is not associated with child cognitive development. Further investigation should be conducted in contemporary cohorts that also include obese mothers, who are at the greatest risk for low weight gain. JF - Journal of Epidemiology and Community Health AU - Hinkle, Stefanie N AU - Albert, Paul S AU - Sjaarda, Lindsey A AU - Grewal, Jagteshwar AU - Grantz, Katherine L AD - Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, , Bethesda, Maryland, USA Y1 - 2016/07/12/ PY - 2016 DA - 2016 Jul 12 SP - 696 EP - 703 PB - British Medical Association, BMA House Square London WC1H 9JP United Kingdom VL - 70 IS - 7 SN - 0143-005X, 0143-005X KW - Health & Safety Science Abstracts KW - PREGNANCY KW - CHILD HEALTH KW - COGNITION KW - MATERNAL HEALTH KW - MEASUREMENT KW - Risk assessment KW - Obesity KW - Intelligence KW - Age KW - Body weight KW - Cognitive ability KW - Children KW - Pregnancy KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808670684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Epidemiology+and+Community+Health&rft.atitle=Trajectories+of+maternal+gestational+weight+gain+and+child+cognition+assessed+at+5years+of+age+in+a+prospective+cohort+study&rft.au=Hinkle%2C+Stefanie+N%3BAlbert%2C+Paul+S%3BSjaarda%2C+Lindsey+A%3BGrewal%2C+Jagteshwar%3BGrantz%2C+Katherine+L&rft.aulast=Hinkle&rft.aufirst=Stefanie&rft.date=2016-07-12&rft.volume=70&rft.issue=7&rft.spage=696&rft.isbn=&rft.btitle=&rft.title=Journal+of+Epidemiology+and+Community+Health&rft.issn=0143005X&rft_id=info:doi/10.1136%2Fjech-2014-205108 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Risk assessment; Intelligence; Obesity; Age; Body weight; Cognitive ability; Children; Pregnancy DO - http://dx.doi.org/10.1136/jech-2014-205108 ER - TY - JOUR T1 - Pesticides Are Associated with Allergic and Non-Allergic Wheeze among Male Farmers. AN - 1826716877; 27384423 AB - Growing evidence suggests that pesticide use may contribute to respiratory symptoms. To evaluate the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. Using the 2005-2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n=1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n=3,939, 18%); men without wheeze were the referent. In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p<0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure-response models with up to five exposure categories, we saw evidence of an exposure-response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl and the rodenticide warfarin. These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects. JF - Environmental health perspectives AU - Hoppin, Jane A AU - Umbach, David M AU - Long, Stuart AU - London, Stephanie J AU - Henneberger, Paul K AU - Blair, Aaron AU - Alavanja, Michael AU - Beane Freeman, Laura E AU - Sandler, Dale P AD - Department of Biological Sciences and Center for Human Health and the Environment, North Carolina State University, Raleigh, NC. ; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, RTP, NC. ; Westat, Durham, NC. ; Epidemiology Branch, National Institute of Environmental Health Sciences, RTP, NC. ; Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV. ; National Cancer Institute, Rockville, MD. Y1 - 2016/07/06/ PY - 2016 DA - 2016 Jul 06 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826716877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Pesticides+Are+Associated+with+Allergic+and+Non-Allergic+Wheeze+among+Male+Farmers.&rft.au=Hoppin%2C+Jane+A%3BUmbach%2C+David+M%3BLong%2C+Stuart%3BLondon%2C+Stephanie+J%3BHenneberger%2C+Paul+K%3BBlair%2C+Aaron%3BAlavanja%2C+Michael%3BBeane+Freeman%2C+Laura+E%3BSandler%2C+Dale+P&rft.aulast=Hoppin&rft.aufirst=Jane&rft.date=2016-07-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study. AN - 1826716666; 27384818 AB - Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence. We evaluated use of 43 pesticides and 654 lung cancer cases after ten years of additional follow-up in the AHS, a prospective cohort study comprised of 57,310 pesticide applicators from Iowa and North Carolina. Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for smoking (smoking status and pack-years), gender, and lifetime days of use of any pesticides. Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI = 0.98-2.31), dieldrin (1.93; 95% CI = 0.70-5.30), and chlorimuron-ethyl (1.74; 95% CI = 1.02-2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p=0.049) and borderline for lifetime days (p=0.073). None of the remaining pesticides evaluated were associated with lung cancer incidence. These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron-ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted. JF - Environmental health perspectives AU - Bonner, Matthew R AU - Beane Freeman, Laura E AU - Hoppin, Jane A AU - Koutros, Stella AU - Sandler, Dale P AU - Lynch, Charles F AU - Hines, Cynthia J AU - Thomas, Kent AU - Blair, Aaron AU - Alavanja, Michael C R AD - Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York. ; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. ; Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina. ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina. ; College of Public Health, University of Iowa, Iowa City, Iowa. ; Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, Ohio. ; National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina. Y1 - 2016/07/06/ PY - 2016 DA - 2016 Jul 06 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826716666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Occupational+Exposure+to+Pesticides+and+the+Incidence+of+Lung+Cancer+in+the+Agricultural+Health+Study.&rft.au=Bonner%2C+Matthew+R%3BBeane+Freeman%2C+Laura+E%3BHoppin%2C+Jane+A%3BKoutros%2C+Stella%3BSandler%2C+Dale+P%3BLynch%2C+Charles+F%3BHines%2C+Cynthia+J%3BThomas%2C+Kent%3BBlair%2C+Aaron%3BAlavanja%2C+Michael+C+R&rft.aulast=Bonner&rft.aufirst=Matthew&rft.date=2016-07-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Biomonitoring in the Era of the Exposome. AN - 1826713122; 27385067 AB - The term "exposome" was coined in 2005 to underscore the importance of the environment to human health and bring research efforts in line with those on the human genome. The ability to characterize environmental exposures through biomonitoring is key to exposome research efforts. Our objective was to describe why traditional and non-traditional (exposomic) biomonitoring are both critical in studies aiming to capture the exposome and make recommendations on how to transition exposure research toward exposomic approaches. We describe the biomonitoring needs of exposome research and approaches and recommendations that will help fill the gaps in the current science. Traditional and exposomic biomonitoring approaches have key advantages and disadvantages for assessing exposure. Exposomic approaches differ from traditional biomonitoring methods in that they can include all exposures of potential health significance, whether from endogenous or exogenous sources. Issues of sample availability and quality, identification of unknown analytes, capture of non-persistent chemicals, integration of methods and statistical assessment of increasingly complex datasets remain as challenges that must continue to be addressed. To understand the complexity of exposures faced across the lifespan, traditional and nontraditional biomonitoring methods should both be used. Through hybrid approaches and integration of emerging techniques, biomonitoring strategies can be maximized in research to define the exposome. JF - Environmental health perspectives AU - Dennis, Kristine K AU - Marder, Elizabeth AU - Balshaw, David M AU - Cui, Yuxia AU - Lynes, Michael A AU - Patti, Gary J AU - Rappaport, Stephen M AU - Shaughnessy, Daniel T AU - Vrijheid, Martine AU - Barr, Dana Boyd AD - Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA. ; Exposure, Response, and Technology Branch, Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Research Triangle Park, NC. ; Department of Molecular and Cell Biology, College of Liberal Arts and Sciences, University of Connecticut, Storrs, CT. ; Departments of Chemistry and Medicine, Washington University, St. Louis, MO. ; Department of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA. ; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. Y1 - 2016/07/06/ PY - 2016 DA - 2016 Jul 06 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826713122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Biomonitoring+in+the+Era+of+the+Exposome.&rft.au=Dennis%2C+Kristine+K%3BMarder%2C+Elizabeth%3BBalshaw%2C+David+M%3BCui%2C+Yuxia%3BLynes%2C+Michael+A%3BPatti%2C+Gary+J%3BRappaport%2C+Stephen+M%3BShaughnessy%2C+Daniel+T%3BVrijheid%2C+Martine%3BBarr%2C+Dana+Boyd&rft.aulast=Dennis&rft.aufirst=Kristine&rft.date=2016-07-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Small cell lung cancer: Time to revisit DNA-damaging chemotherapy AN - 1815697333; PQ0003609839 AB - Rational use of DNA-damaging chemotherapy, with new combinations to heighten DNA replication stress, could improve outcomes in small cell lung cancer. JF - Science Translational Medicine AU - Thomas, Anish AU - Pommier, Yves AD - Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA, anish.thomas@mail.nih.gov Y1 - 2016/07/06/ PY - 2016 DA - 2016 Jul 06 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 United States VL - 8 IS - 346 SN - 1946-6234, 1946-6234 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Translation KW - DNA biosynthesis KW - Replication KW - Chemotherapy KW - Stress KW - New combinations KW - Lung cancer KW - W 30940:Products KW - N 14820:DNA Metabolism & Structure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1815697333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+Translational+Medicine&rft.atitle=Small+cell+lung+cancer%3A+Time+to+revisit+DNA-damaging+chemotherapy&rft.au=Thomas%2C+Anish%3BPommier%2C+Yves&rft.aulast=Thomas&rft.aufirst=Anish&rft.date=2016-07-06&rft.volume=8&rft.issue=346&rft.spage=346fs12&rft.isbn=&rft.btitle=&rft.title=Science+Translational+Medicine&rft.issn=19466234&rft_id=info:doi/10.1126%2Fscitranslmed.aaf6282 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - DNA biosynthesis; Translation; Replication; Chemotherapy; Stress; New combinations; Lung cancer DO - http://dx.doi.org/10.1126/scitranslmed.aaf6282 ER - TY - JOUR T1 - Differential Role of Leptin as an Immunomodulator in Controlling Visceral Leishmaniasis in Normal and Leptin-Deficient Mice. AN - 1802735362; 27114296 AB - Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani There are no vaccines and available drugs against leishmaniasis are toxic. Immunomodulators that specifically boost the anti-microbial activities of the immune cells could alleviate several of these limitations. Therefore, finding novel immunomodulators for VL therapy is a pressing need. This study is aimed to evaluate the immunomodulatory role of leptin, an adipocyte-derived hormone capable of regulating the immune response, in L. donovani-infected mice. We observed that recombinant leptin treatment reduced splenic parasite burden compared with non-treated infected normal mice. Decrease in parasite burden correlated with an induction of innate immune response in antigen-presenting cells that showed an increase in nitric oxide, enhanced pro-inflammatory cytokine (interferon gamma [IFNγ], interleukin12 [IL]12, and IL1β) response in the splenocytes, indicating host-protecting Th1 response mediated by leptin. Moreover, in infected normal mice, leptin treatment induced IFNγ production from both CD4(+) and CD8(+) T cells, compared with non-treated infected mice. Alternatively, leptin-deficient (Ob/Ob) mice had higher splenic and liver parasite burden compared with the infected normal mice. However, leptin treatment failed to reduce the splenic parasite burden and improve a host-protective cytokine response in these mice. In addition, in contrast to dendritic cells (DCs) from a normal mouse, Ob/Ob mouse-derived DCs showed a defect in the induction of innate immune response on Leishmania infection that could not be reversed by leptin treatment. Therefore, our findings reveal that leptin has a differential immunomodulatory effect in controlling VL in normal and Ob/Ob mice. © The American Society of Tropical Medicine and Hygiene. JF - The American journal of tropical medicine and hygiene AU - Maurya, Radheshyam AU - Bhattacharya, Parna AU - Ismail, Nevien AU - Dagur, Pradeep K AU - Joshi, Amritanshu B AU - Razdan, Kundan AU - McCoy, J Philip AU - Ascher, Jill AU - Dey, Ranadhir AU - Nakhasi, Hira L AD - Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. Department of Animal Biology, School of Life Science, University of Hyderabad, Hyderabad, India. rmusl@uohyd.ernet.in ranadhir.dey@fda.hhs.gov. ; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. ; Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. ; Division of Veterinary Services, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. ; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland. rmusl@uohyd.ernet.in ranadhir.dey@fda.hhs.gov. Y1 - 2016/07/06/ PY - 2016 DA - 2016 Jul 06 SP - 109 EP - 119 VL - 95 IS - 1 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802735362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+tropical+medicine+and+hygiene&rft.atitle=Differential+Role+of+Leptin+as+an+Immunomodulator+in+Controlling+Visceral+Leishmaniasis+in+Normal+and+Leptin-Deficient+Mice.&rft.au=Maurya%2C+Radheshyam%3BBhattacharya%2C+Parna%3BIsmail%2C+Nevien%3BDagur%2C+Pradeep+K%3BJoshi%2C+Amritanshu+B%3BRazdan%2C+Kundan%3BMcCoy%2C+J+Philip%3BAscher%2C+Jill%3BDey%2C+Ranadhir%3BNakhasi%2C+Hira+L&rft.aulast=Maurya&rft.aufirst=Radheshyam&rft.date=2016-07-06&rft.volume=95&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+tropical+medicine+and+hygiene&rft.issn=1476-1645&rft_id=info:doi/10.4269%2Fajtmh.15-0804 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.4269/ajtmh.15-0804 ER - TY - JOUR T1 - Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease. AN - 1814655115; 27463540 AB - Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model. JF - Prion AU - Race, Brent AU - Phillips, Katie AU - Kraus, Allison AU - Chesebro, Bruce AD - a Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH , Hamilton , MT , USA. Y1 - 2016/07/03/ PY - 2016 DA - 2016 Jul 03 SP - 319 EP - 330 VL - 10 IS - 4 KW - Index Medicus KW - P-tau KW - prion KW - mouse model KW - tau KW - survival KW - amyloid KW - scrapie UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814655115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prion&rft.atitle=Phosphorylated+human+tau+associates+with+mouse+prion+protein+amyloid+in+scrapie-infected+mice+but+does+not+increase+progression+of+clinical+disease.&rft.au=Race%2C+Brent%3BPhillips%2C+Katie%3BKraus%2C+Allison%3BChesebro%2C+Bruce&rft.aulast=Race&rft.aufirst=Brent&rft.date=2016-07-03&rft.volume=10&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Prion&rft.issn=1933-690X&rft_id=info:doi/10.1080%2F19336896.2016.1199313 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/19336896.2016.1199313 ER - TY - JOUR T1 - An Update on the Streptococcus bovis Group: Classification, Identification, and Disease Associations AN - 1827928723; PQ0003494235 AB - The Streptococcus bovis group has undergone significant taxonomic changes over the past 2 decades with the advent of new identification methods with higher discriminatory power. Although the current classification system is not yet embraced by all researchers in the field and debate remains over the performance of molecular techniques for identification to the species level within the group, important disease associations for several members of the group have been clarified. Here, we provide a brief overview of the history of the S. bovis group, an outline of the currently accepted classification scheme, a review of associated clinical syndromes, and a summary of the performance and diagnostic accuracy of currently available identification methods. JF - Journal of Clinical Microbiology AU - Dekker, John P AU - Lau, Anna F Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1694 EP - 1699 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 54 IS - 7 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - Classification systems KW - Streptococcus bovis KW - Classification KW - Reviews KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1827928723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=An+Update+on+the+Streptococcus+bovis+Group%3A+Classification%2C+Identification%2C+and+Disease+Associations&rft.au=Dekker%2C+John+P%3BLau%2C+Anna+F&rft.aulast=Dekker&rft.aufirst=John&rft.date=2016-07-01&rft.volume=54&rft.issue=7&rft.spage=1694&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.02977-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-10-01 N1 - Number of references - 40 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Classification systems; Classification; Reviews; Streptococcus bovis DO - http://dx.doi.org/10.1128/JCM.02977-15 ER - TY - JOUR T1 - The IntXO-PSL Recombination System Is a Key Component of the Second Maintenance System for Bacillus anthracis Plasmid pXO1 AN - 1811906350; PQ0003494188 AB - We previously identified three noncontiguous regions on Bacillus anthracis plasmid pXO1 that comprise a system for accurate plasmid partitioning and maintenance. However, deletion of these regions did not decrease retention of certain shortened pXO1 plasmids during vegetative growth. Using two genetic tools developed for DNA manipulation in B. anthracis (the Cre-loxP and Flp-FRT systems), we found two other noncontiguous pXO1 regions that together are sufficient for plasmid stability. This second pXO1 maintenance system includes the tubZ and tubR genes, characteristic of a type III partitioning system, and the IntXO recombinase gene (GBAA_RS29165), encoding a tyrosine recombinase, along with its adjacent 37-bp perfect stem-loop (PSL) target. Insertion of either the tubZ and tubR genes or the IntXO-PSL system into an unstable mini-pXO1 plasmid did not restore plasmid stability. The need for the two components of the second pXO1 maintenance system follows from the sequential roles of IntXO-PSL in generating monomeric circular daughter pXO1 molecules (thereby presumably preventing dimer catastrophe) and of TubZ/TubR in partitioning the monomers during cell division. We show that the IntXO recombinase deletes DNA regions located between two PSL sites in a manner similar to the actions of the Cre-loxP and Flp-FRT systems. IMPORTANCE Tyrosine recombinases catalyze cutting and joining reactions between short specific DNA sequences. Three types of reactions occur: integration and excision of DNA segments, inversion of DNA segments, and separation of monomeric forms from replicating circular DNA molecules. Here we show that the newly discovered site-specific IntXO-PSL recombinase system that contributes to the maintenance of the B. anthracis plasmid pXO1 can be used for genome engineering in a manner similar to that of the Cre-loxP or Flp-FRT system. JF - Journal of Bacteriology AU - Pomerantsev, Andrei P AU - Rappole, Catherine AU - Chang, Zanetta AU - Chahoud, Margaret AU - Leppla, Stephen H Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1939 EP - 1951 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 198 IS - 14 SN - 0021-9193, 0021-9193 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Genomes KW - Circular DNA KW - recombinase KW - Nucleotide sequence KW - Tyrosine KW - Bacillus anthracis KW - Plasmids KW - Monomers KW - Recombination KW - Integration KW - Cell division KW - Inversion KW - Insertion KW - J 02320:Cell Biology KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811906350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+IntXO-PSL+Recombination+System+Is+a+Key+Component+of+the+Second+Maintenance+System+for+Bacillus+anthracis+Plasmid+pXO1&rft.au=Pomerantsev%2C+Andrei+P%3BRappole%2C+Catherine%3BChang%2C+Zanetta%3BChahoud%2C+Margaret%3BLeppla%2C+Stephen+H&rft.aulast=Pomerantsev&rft.aufirst=Andrei&rft.date=2016-07-01&rft.volume=198&rft.issue=14&rft.spage=1939&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.01004-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 36 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Genomes; Monomers; Integration; Recombination; Cell division; Circular DNA; Insertion; Inversion; Nucleotide sequence; recombinase; Tyrosine; Plasmids; Bacillus anthracis DO - http://dx.doi.org/10.1128/JB.01004-15 ER - TY - JOUR T1 - A bimodal fluorescent and photocytotoxic naphthalene diimide for theranostic applications AN - 1811892664; PQ0003522695 AB - We report on the potential of a water-soluble tetracationic quaternary ammonium naphthalene diimide (NDI) as multifunctional agent of interest for theranostic applications. The DNA binding ability of this NDI has been investigated. NDI exhibits high binding constants for G-quadruplex DNA but it is not selective for this type of DNA. Taking advantage of its intrinsic fluorescence and singlet oxygen sensitizing ability, cellular uptake, cytotoxicity and photocytotoxicity have been investigated. The intense emission in the red/NIR allows monitoring of the cell permeability of this charged tetracationic NDI, accumulating into the cell nuclei. No dark cytotoxicity has been observed on selected tumor cell lines. Irradiation of the NDI loaded cells with red light reduces cell viability up to 40% and causes a significant increase of the percentage of cells expressing gamma H2AX foci indicating DNA damage. The presence of distinct DNA damage foci inside the nucleus suggests that the NDI molecule might induce DNA damage in specific sites. To the best of our knowledge this is the first NDI exhibiting PDT activity at mu M concentration combined with low dark cytotoxicity. JF - Organic & Biomolecular Chemistry AU - Salvati, Erica AU - Doria, Filippo AU - Manoli, Francesco AU - D'Angelo, Carmen AU - Biroccio, Annamaria AU - Freccero, Mauro AU - Manet, Ilse AD - Oncogenomic and Epigenetic Unit; Regina Elena National Cancer Institute; Via Elio Chianesi; 53 Rome; Italy Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 7238 EP - 7249 PB - Royal Society of Chemistry VL - 14 IS - 30 SN - 1477-0520, 1477-0520 KW - Biotechnology and Bioengineering Abstracts KW - DNA damage KW - Oxygen KW - Ammonium KW - Cytotoxicity KW - Tumor cell lines KW - Fluorescence KW - Radiation KW - Naphthalene KW - Cell permeability KW - Nuclei KW - W 30935:Food Biotechnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811892664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Organic+%26+Biomolecular+Chemistry&rft.atitle=A+bimodal+fluorescent+and+photocytotoxic+naphthalene+diimide+for+theranostic+applications&rft.au=Salvati%2C+Erica%3BDoria%2C+Filippo%3BManoli%2C+Francesco%3BD%27Angelo%2C+Carmen%3BBiroccio%2C+Annamaria%3BFreccero%2C+Mauro%3BManet%2C+Ilse&rft.aulast=Salvati&rft.aufirst=Erica&rft.date=2016-07-01&rft.volume=14&rft.issue=30&rft.spage=7238&rft.isbn=&rft.btitle=&rft.title=Organic+%26+Biomolecular+Chemistry&rft.issn=14770520&rft_id=info:doi/10.1039%2Fc6ob00987e LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 38 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Ammonium; Oxygen; DNA damage; Tumor cell lines; Cytotoxicity; Fluorescence; Radiation; Naphthalene; Cell permeability; Nuclei DO - http://dx.doi.org/10.1039/c6ob00987e ER - TY - JOUR T1 - Discovery, Development, and Adoption of Medications to Treat Alcohol Use Disorder: Goals for the Phases of Medications Development AN - 1808733306; PQ0003372071 AB - For more than 25 years, advances have been made in developing medications to treat alcohol use disorder (AUD), highlighted by the U.S. Food and Drug Administration's approval of naltrexone (oral and long-acting) and acamprosate. Despite this progress, more work remains to be done in this area because these medications, although effective for some people, do not work for everyone. A high priority for the National Institute on Alcohol Abuse and Alcohol is to put into place a solid infrastructure to aid in the development of medications that are more effective than those currently available and with few side effects. Medication development, especially for a disorder as complex as AUD, is challenging and involves multiple phases, including discovery of "druggable" targets, preclinical studies, human clinical trials, and the adoption and implementation of the new medication into mainstream medicine. A successful medications development program requires clearly established goals for each phase to ensure that a candidate compound is not trapped in one particular phase, a condition known as "the valley of death." In this article, the phases of medication development are described as they apply to AUD, and specific goals of each phase are identified for the next decade. In addition, several important crosscutting themes are outlined for each phase, all of which are essential for advancing medications development. These include identifying and validating screening models and druggable targets, making use of precision medicine, and establishing partnerships among key stakeholders. Our goal in writing this article is to provide a guide on medications development that will aid the alcohol research community in planning, testing, and developing medications for AUD. A successful medications development program for the treatment of alcohol use disorder (AUD) requires clearly established goals for each phase of development to ensure that a candidate compound is not trapped in one particular phase. In this article, the phases of medication development are described as they apply to AUD, and specific goals of each phase are identified for the next decade. We hope this will aid the alcohol research community in planning, testing, and developing medications for AUD. JF - Alcoholism: Clinical and Experimental Research AU - Litten, Raye Z AU - Falk, Daniel E AU - Ryan, Megan L AU - Fertig, Joanne B AD - NIAAA's Clinical Investigations Group (NCIG), Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1368 EP - 1379 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 40 IS - 7 SN - 0145-6008, 0145-6008 KW - Toxicology Abstracts KW - Alcoholism KW - Naltrexone KW - alcohols KW - Adoption KW - Drug abuse KW - Clinical trials KW - Side effects KW - Ethanol KW - Models KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808733306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%3A+Clinical+and+Experimental+Research&rft.atitle=Discovery%2C+Development%2C+and+Adoption+of+Medications+to+Treat+Alcohol+Use+Disorder%3A+Goals+for+the+Phases+of+Medications+Development&rft.au=Litten%2C+Raye+Z%3BFalk%2C+Daniel+E%3BRyan%2C+Megan+L%3BFertig%2C+Joanne+B&rft.aulast=Litten&rft.aufirst=Raye&rft.date=2016-07-01&rft.volume=40&rft.issue=7&rft.spage=1368&rft.isbn=&rft.btitle=&rft.title=Alcoholism%3A+Clinical+and+Experimental+Research&rft.issn=01456008&rft_id=info:doi/10.1111%2Facer.13093 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Naltrexone; Alcoholism; alcohols; Adoption; Drug abuse; Clinical trials; Side effects; Models; Ethanol DO - http://dx.doi.org/10.1111/acer.13093 ER - TY - JOUR T1 - First metabolic profile of PV8, a novel synthetic cathinone, in human hepatocytes and urine by high-resolution mass spectrometry AN - 1808729464; PQ0003331340 AB - Novel psychoactive substances (NPS) are ever changing on the drug market, making it difficult for toxicology laboratory methods to stay current with so many new drugs. Recently, PV8, a synthetic pyrrolidinophenone, was detected in seized products in Japan (2013), The Netherlands (2014), and Germany (2014). There are no controlled PV8 administration studies, and no pharmacodynamic and pharmacokinetic data. The objective was to determine PV8's metabolic stability in human liver microsome (HLM) incubation and its metabolism following human hepatocyte incubation and high-resolution mass spectrometry (HRMS) with a Thermo Scientific Q-Exactive. Data were acquired with a full-scan data-dependent mass spectrometry method. Scans were thoroughly data mined with different data processing algorithms and analyzed in WebMetaBase. PV8 exhibited a relatively short 28.8 min half-life, with an intrinsic 24.2 mu L/min/mg microsomal clearance. This compound is predicted to be an intermediate clearance drug with an estimated human 22.7 mL/min/kg hepatic clearance. Metabolic pathways identified in vitro included: hydroxylation, ketone reduction, carboxylation, N-dealkylation, iminium formation, dehydrogenation, N-oxidation, and carbonylation. The top three in vitro metabolic pathways were di-hydroxylation > ketone reduction > gamma -lactam formation. Authentic urine specimen analyses revealed the top three metabolic pathways were aliphatic hydroxylation > ketone reduction + aliphatic hydroxylation > aliphatic carboxylation, although the most prominent peak was parent PV8. These data provide useful urinary metabolite targets (aliphatic hydroxylation, aliphatic hydroxylation + ketone reduction, aliphatic carboxylation, and di-hydroxylation) for forensic and clinical testing, and focus reference standard companies' synthetic efforts to provide commercially available standards needed for PV8 biological specimen testing. [Figure not available: see fulltext.] JF - Analytical and Bioanalytical Chemistry AU - Swortwood, Madeleine J AU - Ellefsen, Kayla N AU - Wohlfarth, Ariane AU - Diao, Xingxing AU - Concheiro-Guisan, Marta AU - Kronstrand, Robert AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd. Suite 05A721, Baltimore, MD, 21224, USA, marilyn.huestis@gmail.com Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 4845 EP - 4856 PB - Springer Science+Business Media, Berlin/Heidelberg Germany VL - 408 IS - 18 SN - 1618-2642, 1618-2642 KW - Toxicology Abstracts; Biotechnology and Bioengineering Abstracts KW - Microsomes KW - Data processing KW - Hepatocytes KW - Carboxylation KW - Algorithms KW - Metabolites KW - Mass spectroscopy KW - Pharmacokinetics KW - Hydroxylation KW - Urine KW - Forensic science KW - Liver KW - Metabolic pathways KW - Dehydrogenation KW - Drugs KW - Pharmacodynamics KW - ketones KW - W 30960:Bioinformatics & Computer Applications KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808729464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+and+Bioanalytical+Chemistry&rft.atitle=First+metabolic+profile+of+PV8%2C+a+novel+synthetic+cathinone%2C+in+human+hepatocytes+and+urine+by+high-resolution+mass+spectrometry&rft.au=Swortwood%2C+Madeleine+J%3BEllefsen%2C+Kayla+N%3BWohlfarth%2C+Ariane%3BDiao%2C+Xingxing%3BConcheiro-Guisan%2C+Marta%3BKronstrand%2C+Robert%3BHuestis%2C+Marilyn+A&rft.aulast=Swortwood&rft.aufirst=Madeleine&rft.date=2016-07-01&rft.volume=408&rft.issue=18&rft.spage=4845&rft.isbn=&rft.btitle=&rft.title=Analytical+and+Bioanalytical+Chemistry&rft.issn=16182642&rft_id=info:doi/10.1007%2Fs00216-016-9599-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 42 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Microsomes; Data processing; Hepatocytes; Carboxylation; Algorithms; Metabolites; Pharmacokinetics; Mass spectroscopy; Hydroxylation; Urine; Dehydrogenation; Metabolic pathways; Liver; Forensic science; Drugs; Pharmacodynamics; ketones DO - http://dx.doi.org/10.1007/s00216-016-9599-4 ER - TY - JOUR T1 - Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease AN - 1808725628; PQ0003404477 AB - Head and neck irradiation (IR) during cancer treatment causes by-stander effects on the salivary glands leading to irreversible loss of saliva secretion. The mechanism underlying loss of fluid secretion is not understood and no adequate therapy is currently available. Delivery of an adenoviral vector encoding human aquaporin-1 (hAQP1) into the salivary glands of human subjects and animal models with radiation-induced salivary hypofunction leads to significant recovery of saliva secretion and symptomatic relief in subjects. To elucidate the mechanism underlying loss of salivary secretion and the basis for AdhAQP1-dependent recovery of salivary gland function we assessed submandibular gland function in control mice and mice 2 and 8 months after treatment with a single 15-Gy dose of IR (delivered to the salivary gland region). Salivary secretion and neurotransmitter-stimulated changes in acinar cell volume, an in vitro read-out for fluid secretion, were monitored. Consistent with the sustained 60% loss of fluid secretion following IR, a carbachol (CCh)-induced decrease in acinar cell volume from the glands of mice post IR was transient and attenuated as compared with that in cells from non-IR age-matched mice. The hAQP1 expression in non-IR mice induced no significant effect on salivary fluid secretion or CCh-stimulated cell volume changes, except in acinar cells from 8-month group where the initial rate of cell shrinkage was increased. Importantly, the expression of hAQP1 in the glands of mice post IR induced recovery of salivary fluid secretion and a volume decrease in acinar cells to levels similar to those in cells from non-IR mice. The initial rates of CCh-stimulated cell volume reduction in acinar cells from hAQP1-expressing glands post IR were similar to those from control cells. Altogether, the data suggest that expression of hAQP1 increases the water permeability of acinar cells, which underlies the recovery of fluid secretion in the salivary glands functionally compromised post IR. JF - Gene Therapy AU - Teos, L Y AU - Zheng, C-Y AU - Liu, X AU - Swaim, W D AU - Goldsmith, C M AU - Cotrim, A P AU - Baum, B J AU - Ambudkar, I S AD - Secretory and Physiology Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, Bethesda, MD, USA Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 572 EP - 579 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 23 IS - 7 SN - 0969-7128, 0969-7128 KW - Virology & AIDS Abstracts; Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - I.R. radiation KW - Data processing KW - Gene therapy KW - Secretion KW - Animal models KW - Salivary gland KW - Cancer KW - Acinar cells KW - Expression vectors KW - Permeability KW - Cell size KW - Submandibular gland KW - Atrophy KW - Carbachol KW - Saliva KW - W 30905:Medical Applications KW - V 22410:Animal Diseases KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808725628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Adenovirus-mediated+hAQP1+expression+in+irradiated+mouse+salivary+glands+causes+recovery+of+saliva+secretion+by+enhancing+acinar+cell+volume+decrease&rft.au=Teos%2C+L+Y%3BZheng%2C+C-Y%3BLiu%2C+X%3BSwaim%2C+W+D%3BGoldsmith%2C+C+M%3BCotrim%2C+A+P%3BBaum%2C+B+J%3BAmbudkar%2C+I+S&rft.aulast=Teos&rft.aufirst=L&rft.date=2016-07-01&rft.volume=23&rft.issue=7&rft.spage=572&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fgt.2016.29 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Data processing; I.R. radiation; Gene therapy; Secretion; Animal models; Salivary gland; Acinar cells; Cancer; Expression vectors; Permeability; Cell size; Atrophy; Submandibular gland; Saliva; Carbachol DO - http://dx.doi.org/10.1038/gt.2016.29 ER - TY - JOUR T1 - Significance of preoperative radiographic pancreatic density in predicting pancreatic fistula after surgery for pancreatic neuroendocrine tumors AN - 1808715570; PQ0003321027 AB - Background Postoperative pancreatic fistula remains the most severe and worrisome complication after surgery. Predictive preoperative assessment remains challenging. The authors examine the role of pancreatic computed tomography density in predicting postoperative pancreatic fistula after surgery for pancreatic neuroendocrine tumors. Methods A single institutional retrospective review of pancreatic surgery for neuroendocrine tumors between 1998 and 2010 was conducted. Preoperative contrast-enhanced computed tomography scans were reviewed, with mean region of interest measurements of pancreatic parenchymal density obtained from 10-mm thick axial computed tomography images. Results A total of 119 patients were identified: 59 with enucleations and 60 with resections. Decreased preoperative pancreatic density was significantly associated with an increased grade of postoperative pancreatic fistula (P < .01). Subgroup analyses revealed that decreased gland density was associated with increased grade of postoperative pancreatic fistula in the resection (P < .01) but not in the enucleation group (P = .34). Conclusions A significant association between postoperative pancreatic fistula grade and preoperative pancreatic computed tomography density is observed in patients undergoing resection for pancreatic neuroendocrine tumors. JF - American Journal of Surgery AU - Assadipour, Yasmine AU - Azoury, Said C AU - Schaub, Nicholas N AU - Hong, Young AU - Eil, Robert AU - Inchauste, Suzanne M AU - Steinberg, Seth M AU - Venkatesan, Aradhana M AU - Libutti, Steven K AU - Hughes, Marybeth S AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 40 EP - 46 PB - Elsevier B.V., Radarweg 29 Amsterdam 1043 NX Netherlands VL - 212 IS - 1 SN - 0002-9610, 0002-9610 KW - Biotechnology and Bioengineering Abstracts KW - Pancreatic fistula KW - Neuroendocrine tumors KW - Pancreaticoduodenectomy KW - Pancreatic resection KW - Pancreatic enucleation KW - Pancreas KW - Surgery KW - Glands KW - Computed tomography KW - Enucleation KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808715570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Surgery&rft.atitle=Significance+of+preoperative+radiographic+pancreatic+density+in+predicting+pancreatic+fistula+after+surgery+for+pancreatic+neuroendocrine+tumors&rft.au=Assadipour%2C+Yasmine%3BAzoury%2C+Said+C%3BSchaub%2C+Nicholas+N%3BHong%2C+Young%3BEil%2C+Robert%3BInchauste%2C+Suzanne+M%3BSteinberg%2C+Seth+M%3BVenkatesan%2C+Aradhana+M%3BLibutti%2C+Steven+K%3BHughes%2C+Marybeth+S&rft.aulast=Assadipour&rft.aufirst=Yasmine&rft.date=2016-07-01&rft.volume=212&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Surgery&rft.issn=00029610&rft_id=info:doi/10.1016%2Fj.amjsurg.2015.07.031 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 23 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Glands; Surgery; Pancreas; Computed tomography; Enucleation; Neuroendocrine tumors DO - http://dx.doi.org/10.1016/j.amjsurg.2015.07.031 ER - TY - JOUR T1 - Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation AN - 1808708145; PQ0003316690 AB - Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer's disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity of Alzheimer's neuropathology. Using a prospective population-based cohort, Baltimore Longitudinal Study of Aging (BLSA), this study aims to examine the relationships between midlife body mass index (BMI) and (1) AAO of AD (2) severity of Alzheimer's neuropathology and (3) fibrillar brain amyloid deposition during aging. We analyzed data on 1394 cognitively normal individuals at baseline (8643 visits; average follow-up interval 13.9 years), among whom 142 participants developed incident AD. In two subsamples of BLSA, 191 participants underwent autopsy and neuropathological assessment, and 75 non-demented individuals underwent brain amyloid imaging. Midlife adiposity was derived from BMI data at 50 years of age. We find that each unit increase in midlife BMI predicts earlier onset of AD by 6.7 months (P=0.013). Higher midlife BMI was associated with greater Braak neurofibrillary but not CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuritic plaque scores at autopsy overall. Associations between midlife BMI and brain amyloid burden approached statistical significance. Thus, higher midlife BMI was also associated with greater fibrillar amyloid measured by global mean cortical distribution volume ratio (P=0.075) and within the precuneus (left, P=0.061; right, P=0.079). In conclusion, midlife overweight predicts earlier onset of AD and greater burden of Alzheimer's neuropathology. A healthy BMI at midlife may delay the onset of AD. JF - Molecular Psychiatry AU - Chuang, Y-F AU - An, Y AU - Bilgel, M AU - Wong, D F AU - Troncoso, J C AU - O'Brien, R J AU - Breitner, J C AU - Ferruci, L AU - Resnick, S M AU - Thambisetty, M AD - Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA; Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 910 EP - 915 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 21 IS - 7 SN - 1359-4184, 1359-4184 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Autopsy KW - Neuroimaging KW - Statistics KW - Data processing KW - Aging KW - Alzheimer's disease KW - Brain KW - Cortex (parietal) KW - Neurodegenerative diseases KW - Body weight KW - Risk factors KW - Dementia disorders KW - Adipose tissue KW - Plaques KW - beta -Amyloid KW - Body mass index KW - Neuropathology KW - Amyloid KW - N3 11001:Behavioral and Cognitive Neuroscience KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808708145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Psychiatry&rft.atitle=Midlife+adiposity+predicts+earlier+onset+of+Alzheimer%27s+dementia%2C+neuropathology+and+presymptomatic+cerebral+amyloid+accumulation&rft.au=Chuang%2C+Y-F%3BAn%2C+Y%3BBilgel%2C+M%3BWong%2C+D+F%3BTroncoso%2C+J+C%3BO%27Brien%2C+R+J%3BBreitner%2C+J+C%3BFerruci%2C+L%3BResnick%2C+S+M%3BThambisetty%2C+M&rft.aulast=Chuang&rft.aufirst=Y-F&rft.date=2016-07-01&rft.volume=21&rft.issue=7&rft.spage=910&rft.isbn=&rft.btitle=&rft.title=Molecular+Psychiatry&rft.issn=13594184&rft_id=info:doi/10.1038%2Fmp.2015.129 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Autopsy; Neuroimaging; Data processing; Statistics; Alzheimer's disease; Aging; Brain; Cortex (parietal); Neurodegenerative diseases; Body weight; Risk factors; Dementia disorders; Adipose tissue; Plaques; beta -Amyloid; Body mass index; Neuropathology; Amyloid DO - http://dx.doi.org/10.1038/mp.2015.129 ER - TY - JOUR T1 - Amarogentin regulates self renewal pathways to restrict liver carcinogenesis in experimental mouse model AN - 1808692407; PQ0003271521 AB - Amarogentin, a secoiridoid glycoside isolated from medicinal plant Swertia chirata, was found to restrict CCl sub(4)/N-nitrosodiethyl amine (NDEA) induced mouse liver carcinogenesis by modulating G1/S cell cycle check point and inducing apoptosis. To understand its therapeutic efficacy on stem cell self renewal pathways, prevalence of CD44 positive cancer stem cell (CSC) population, expressions (mRNA/protein) of some key regulatory genes of self renewal Wnt and Hedgehog pathways along with expressions of E-cadherin and EGFR were analyzed during the liver carcinogenesis and in liver cancer cell line HepG2. It was observed that amarogentin could significantly reduce CD44 positive CSCs in both pre and post initiation stages of carcinogenesis than carcinogen control mice. In Wnt pathway, amarogentin could inhibit expressions of beta -catenin, phospho beta -catenin (Y-654) and activate expressions of antagonists sFRP1/2 and APC in the liver lesions. In Hedgehog pathway, decreased expressions of Gli1, sonic hedgehog ligand, and SMO along with up-regulation of PTCH1 were seen in the liver lesions due to amarogentin treatment. Moreover, amarogentin could up-regulate E-cadherin expression and down-regulate expression of EGFR in the liver lesions. Similarly, amarogentin could inhibit HepG2 cell growth along with expression and prevalence of CD44 positive CSCs. Similar to in vivo analysis, amarogentin could modulate the expressions of the key regulatory genes of the Wnt and hedgehog pathways and EGFR in HepG2 cells. Thus, our data suggests that the restriction of liver carcinogenesis by amarogentin might be due to reduction of CD44 positive CSCs and modulation of the self renewal pathways. JF - Molecular Carcinogenesis AU - Sur, Subhayan AU - Pal, Debolina AU - Banerjee, Kaustav AU - Mandal, Suvra AU - Das, Ashes AU - Roy, Anup AU - Panda, Chinmay Kumar AD - Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1138 EP - 1149 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 55 IS - 7 SN - 0899-1987, 0899-1987 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Apoptosis KW - Wnt protein KW - Hepatocytes KW - CD44 antigen KW - Liver cancer KW - Cell cycle KW - Medicinal plants KW - Animal models KW - Self KW - Epidermal growth factor receptors KW - Carcinogens KW - Antagonists KW - Swertia chirata KW - Hedgehog protein KW - amines KW - Tumor cell lines KW - Stem cells KW - adenomatous polyposis coli KW - glycosides KW - Data processing KW - E-Cadherin KW - mRNA KW - catenin KW - Frizzled-related protein 1 KW - Carcinogenesis KW - Proteins KW - B 26670:Tumor Suppressors KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808692407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Amarogentin+regulates+self+renewal+pathways+to+restrict+liver+carcinogenesis+in+experimental+mouse+model&rft.au=Sur%2C+Subhayan%3BPal%2C+Debolina%3BBanerjee%2C+Kaustav%3BMandal%2C+Suvra%3BDas%2C+Ashes%3BRoy%2C+Anup%3BPanda%2C+Chinmay+Kumar&rft.aulast=Sur&rft.aufirst=Subhayan&rft.date=2016-07-01&rft.volume=55&rft.issue=7&rft.spage=1138&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/10.1002%2Fmc.22356 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Wnt protein; Apoptosis; Hepatocytes; Liver cancer; CD44 antigen; Medicinal plants; Cell cycle; Animal models; Self; Epidermal growth factor receptors; Carcinogens; Antagonists; Stem cells; Tumor cell lines; amines; Hedgehog protein; adenomatous polyposis coli; glycosides; Data processing; E-Cadherin; mRNA; catenin; Frizzled-related protein 1; Carcinogenesis; Proteins; Swertia chirata DO - http://dx.doi.org/10.1002/mc.22356 ER - TY - JOUR T1 - Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas AN - 1808690156; PQ0003376464 AB - Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes.Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations plus or minus recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS).Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7.Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. copyright 2016 AACR. JF - Clinical Cancer Research AU - Merchant, Melinda S AU - Bernstein, Donna AU - Amoako, Martha AU - Baird, Kristin AU - Fleisher, Thomas A AU - Morre, Michel AU - Steinberg, Seth M AU - Sabatino, Marianna AU - Stroncek, Dave F AU - Venkatasan, Aradhana M AU - Wood, Bradford J AU - Wright, Matthew AU - Zhang, Hua AU - Mackall, Crystal L AD - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland, mackallc@mail.nih.gov Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 3182 EP - 3191 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 13 SN - 1078-0432, 1078-0432 KW - Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Cell survival KW - Leukocytes (mononuclear) KW - Apheresis KW - Pediatrics KW - Immunotherapy KW - Biopsy KW - Toxicity KW - Lymphocytes KW - Tumors KW - Adjuvants KW - Immune reconstitution KW - Metastases KW - Dendritic cells KW - CD4 antigen KW - Sarcoma KW - Lymphocytes T KW - Immune response KW - Vaccines KW - Rhabdomyosarcoma KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808690156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Adjuvant+Immunotherapy+to+Improve+Outcome+in+High-Risk+Pediatric+Sarcomas&rft.au=Merchant%2C+Melinda+S%3BBernstein%2C+Donna%3BAmoako%2C+Martha%3BBaird%2C+Kristin%3BFleisher%2C+Thomas+A%3BMorre%2C+Michel%3BSteinberg%2C+Seth+M%3BSabatino%2C+Marianna%3BStroncek%2C+Dave+F%3BVenkatasan%2C+Aradhana+M%3BWood%2C+Bradford+J%3BWright%2C+Matthew%3BZhang%2C+Hua%3BMackall%2C+Crystal+L&rft.aulast=Merchant&rft.aufirst=Melinda&rft.date=2016-07-01&rft.volume=22&rft.issue=13&rft.spage=3182&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2550 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Cell survival; Leukocytes (mononuclear); Apheresis; Pediatrics; Immunotherapy; Biopsy; Adjuvants; Tumors; Lymphocytes; Toxicity; Metastases; Immune reconstitution; Dendritic cells; CD4 antigen; Lymphocytes T; Sarcoma; Vaccines; Immune response; Rhabdomyosarcoma DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2550 ER - TY - JOUR T1 - Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials AN - 1808685489; PQ0003376459 AB - There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy. For in vitro research, the clonogenic assay remains the current state-of-the-art of preclinical assays, whereas newer moderate and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient-derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies; for example, regrowth delay measures bulk tumor killing, whereas local tumor control assesses effects on CSCs. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radiochemotherapy for most tumors. Radiation models are compatible with but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapeutic agent may be different from its interaction with radiation and/or radiochemotherapy. This provides an opportunity to expand the use of molecular-targeted agents. Clin Cancer Res; 22(13); 3138-47. copyright 2016 AACR. JF - Clinical Cancer Research AU - Coleman, CNorman AU - Higgins, Geoff S AU - Brown, JMartin AU - Baumann, Michael AU - Kirsch, David G AU - Willers, Henning AU - Prasanna, Pataje GS AU - Dewhirst, Mark W AU - Bernhard, Eric J AU - Ahmed, Mansoor M AD - Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI), NIH, Bethesda, Maryland, ccoleman@mail.nih.gov Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 3138 EP - 3147 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 13 SN - 1078-0432, 1078-0432 KW - Biotechnology and Bioengineering Abstracts KW - Molecular modelling KW - Data processing KW - Chemotherapy KW - Animal models KW - Radiotherapy KW - Cell culture KW - Tumors KW - Drug screening KW - Immunomodulation KW - biomarkers KW - Clinical trials KW - Cancer KW - Standardization KW - Stem cells KW - Radiation KW - Genetic engineering KW - Microenvironments KW - Xenografts KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808685489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Improving+the+Predictive+Value+of+Preclinical+Studies+in+Support+of+Radiotherapy+Clinical+Trials&rft.au=Coleman%2C+CNorman%3BHiggins%2C+Geoff+S%3BBrown%2C+JMartin%3BBaumann%2C+Michael%3BKirsch%2C+David+G%3BWillers%2C+Henning%3BPrasanna%2C+Pataje+GS%3BDewhirst%2C+Mark+W%3BBernhard%2C+Eric+J%3BAhmed%2C+Mansoor+M&rft.aulast=Coleman&rft.aufirst=CNorman&rft.date=2016-07-01&rft.volume=22&rft.issue=13&rft.spage=3138&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-16-0069 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Molecular modelling; Data processing; Chemotherapy; Animal models; Radiotherapy; Cell culture; Tumors; Drug screening; Clinical trials; biomarkers; Immunomodulation; Cancer; Standardization; Stem cells; Radiation; Genetic engineering; Microenvironments; Xenografts DO - http://dx.doi.org/10.1158/1078-0432.CCR-16-0069 ER - TY - JOUR T1 - Clinical and pharmacologic evaluation of two dosing schedules of indotecan (LMP400), a novel indenoisoquinoline, in patients with advanced solid tumors AN - 1808684418; PQ0003351798 AB - Indenoisoquinolines are non-camptothecin topoisomerase I (TopI) inhibitors that overcome the limitations of camptothecins: chemical instability and camptothecin resistance. Two dosing schedules of the novel indenoisoquinoline, indotecan (LMP400), were evaluated in patients with advanced solid tumors. The maximum tolerated dose (MTD), toxicities, and pharmacokinetics of two indotecan drug administration schedules (daily for 5 days or weekly) were investigated. Modulation of TopI and the phosphorylation of histone H2AX ( gamma H2AX) were assayed in tumor biopsies; gamma H2AX levels were also evaluated in circulating tumor cells (CTCs) and hair follicles to assess DNA damage response. An MTD of 60 mg/m super(2)/day was established for the daily regimen, compared to 90 mg/m super(2) for the weekly regimen. The TopI response to drug showed target engagement in a subset of tumor biopsies. Pharmacokinetics profiles demonstrated a prolonged terminal half-life and tissue accumulation compared to topotecan. Dose-dependent decreases in total CTCs were measured in seven patients. Formation of gamma H2AX-positive foci in CTCs (day 3) and hair follicles (4-6 h) was observed following treatment. We established the MTD of two dosing schedules for a novel TopI inhibitor, indotecan. Target engagement was demonstrated as Top1 downregulation and gamma H2AX response. No objective responses were observed on either schedule in this small patient cohort. The principal toxicity of both schedules was myelosuppression; no significant gastrointestinal problems were observed. Increased DNA damage response was observed in CTCs, hair follicles, and a subset of tumor biopsies. JF - Cancer Chemotherapy and Pharmacology AU - Kummar, Shivaani AU - Chen, Alice AU - Gutierrez, Martin AU - Pfister, Thomas D AU - Wang, Lihua AU - Redon, Christophe AU - Bonner, William M AU - Yutzy, William AU - Zhang, Yiping AU - Kinders, Robert J AU - Ji, Jiuping AU - Allen, Deborah AU - Covey, Joseph M AU - Eiseman, Julie L AU - Holleran, Julianne L AU - Beumer, Jan H AU - Rubinstein, Larry AU - Collins, Jerry AU - Tomaszewski, Joseph AU - Parchment, Ralph AU - Pommier, Yves AU - Doroshow, James H AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 31 Center Drive, Room 3A44, Bethesda, MD, 20814, USA, doroshoj@mail.nih.gov Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 73 EP - 81 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 78 IS - 1 SN - 0344-5704, 0344-5704 KW - Toxicology Abstracts KW - Follicles KW - Solid tumors KW - DNA topoisomerase KW - Biopsy KW - Toxicity KW - Tumors KW - Tumor cells KW - Hair KW - Pharmacokinetics KW - Camptothecin KW - DNA damage KW - Phosphorylation KW - Myelosuppression KW - Topotecan KW - Histone H2A KW - Drugs KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808684418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Chemotherapy+and+Pharmacology&rft.atitle=Clinical+and+pharmacologic+evaluation+of+two+dosing+schedules+of+indotecan+%28LMP400%29%2C+a+novel+indenoisoquinoline%2C+in+patients+with+advanced+solid+tumors&rft.au=Kummar%2C+Shivaani%3BChen%2C+Alice%3BGutierrez%2C+Martin%3BPfister%2C+Thomas+D%3BWang%2C+Lihua%3BRedon%2C+Christophe%3BBonner%2C+William+M%3BYutzy%2C+William%3BZhang%2C+Yiping%3BKinders%2C+Robert+J%3BJi%2C+Jiuping%3BAllen%2C+Deborah%3BCovey%2C+Joseph+M%3BEiseman%2C+Julie+L%3BHolleran%2C+Julianne+L%3BBeumer%2C+Jan+H%3BRubinstein%2C+Larry%3BCollins%2C+Jerry%3BTomaszewski%2C+Joseph%3BParchment%2C+Ralph%3BPommier%2C+Yves%3BDoroshow%2C+James+H&rft.aulast=Kummar&rft.aufirst=Shivaani&rft.date=2016-07-01&rft.volume=78&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Cancer+Chemotherapy+and+Pharmacology&rft.issn=03445704&rft_id=info:doi/10.1007%2Fs00280-016-2998-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 18 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Follicles; Solid tumors; DNA topoisomerase; Biopsy; Tumors; Toxicity; Hair; Tumor cells; Camptothecin; Pharmacokinetics; DNA damage; Phosphorylation; Myelosuppression; Topotecan; Drugs; Histone H2A DO - http://dx.doi.org/10.1007/s00280-016-2998-6 ER - TY - JOUR T1 - Vav1 Regulates Mesenchymal Stem Cell Differentiation Decision Between Adipocyte and Chondrocyte via Sirt1 AN - 1808681955; PQ0003374589 AB - Abstract Mesenchymal stem cells (MSCs) are multipotent stromal cells residing in the bone marrow. MSCs have the potential to differentiate to adipocytes, chondrocytes, and other types of cells. In this study, we investigated the molecular mechanism that controls MSC cell fate decisions for differentiation. We found that Vav1, a guanine nucleotide exchange factor for Rho GTPase, was highly expressed in MSCs. Interestingly, loss of Vav1 in MSCs led to spontaneous adipogenic but impaired chondrogenic differentiation, and accordingly Vav1 null mice displayed an increase in fat content and a decrease in cartilage. Conversely, ectopic expression of Vav1 in MSCs reversed this phenotype, and led to enhanced MSC differentiation into chondrocyte but retarded adipogenesis. Mechanistically, loss of Vav1 reduced the level of Sirt1, which was responsible for an increase of acetylated PPAR gamma . As acetylation activates PPAR gamma , it increased C/EBP alpha expression and promoted adipogenesis. On the other hand, loss of Vav1 resulted in an increase of acetylated Sox9, a target of Sirt1. As acetylation represses Sox9 activity, it led to a dramatic reduction of collagen 2 alpha 1, a key regulator in chondrocyte differentiation. Finally, we found that Vav1 regulates Sirt1 in MSCs through Creb. Together this study reveals a novel function of Vav1 in regulating MSC cell fate decisions for differentiation through Sirt1. Sirt1 deacetylates PPAR gamma and Sox9, two key mediators that control adipocyte and chondrocyte differentiation. The acetylation status of PPAR gamma and Sox9 has opposite effects on its activity, thereby controlling cell fate decision. Stem Cells 2016; 34:1934-1946 JF - Stem Cells AU - Qu, Peng AU - Wang, Lizhen AU - Min, Yongfen AU - McKennett, Lois AU - Keller, Jonathan R AU - Lin, PCharles AD - Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1934 EP - 1946 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 7 SN - 1066-5099, 1066-5099 KW - Calcium & Calcified Tissue Abstracts; Biotechnology and Bioengineering Abstracts KW - Molecular modelling KW - SIRT1 protein KW - stromal cells KW - Cartilage KW - Bone marrow KW - Chondrocytes KW - Sox9 protein KW - Collagen KW - Acetylation KW - Stem cells KW - guanine nucleotide exchange factor KW - Adipocytes KW - Cell fate KW - Mesenchyme KW - adipogenesis KW - Guanosinetriphosphatase KW - Cyclic AMP response element-binding protein KW - Chondrogenesis KW - T 2030:Cartilage and Cartilage Diseases KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808681955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Vav1+Regulates+Mesenchymal+Stem+Cell+Differentiation+Decision+Between+Adipocyte+and+Chondrocyte+via+Sirt1&rft.au=Qu%2C+Peng%3BWang%2C+Lizhen%3BMin%2C+Yongfen%3BMcKennett%2C+Lois%3BKeller%2C+Jonathan+R%3BLin%2C+PCharles&rft.aulast=Qu&rft.aufirst=Peng&rft.date=2016-07-01&rft.volume=34&rft.issue=7&rft.spage=1934&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2365 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Molecular modelling; SIRT1 protein; stromal cells; Cartilage; Bone marrow; Chondrocytes; Sox9 protein; Collagen; Acetylation; guanine nucleotide exchange factor; Stem cells; Adipocytes; Cell fate; adipogenesis; Mesenchyme; Chondrogenesis; Cyclic AMP response element-binding protein; Guanosinetriphosphatase DO - http://dx.doi.org/10.1002/stem.2365 ER - TY - JOUR T1 - Dermal Exposure to Cumene Hydroperoxide: Assessing Its Toxic Relevance and Oxidant Potential AN - 1808667404; PQ0003318200 AB - Cumene hydroperoxide (CHP) is a high production volume chemical that is used to generate phenol and acetone. Dermal exposure to CHP was hypothesized to result in systemic tissue toxicity, production of free radicals, and consequent decrease in plasma antioxidant levels. To evaluate the hypothesis and characterize the toxicity of CHP, male and female B6C3F1/N mice and F344/N rats were exposed to varying doses of CHP applied topically for 14 or 90 days. No significant changes in survival or body weight of mice and rats were observed following 14 days of exposure. However, 90 days of CHP exposure at the high dose (12 mg/kg) triggered a significant decrease (-15%) in the body weight of the male rat group only. Irritation of the skin was observed at the site of application and was characterized by inflammation and epidermal hyperplasia. In treated animals, histology of liver tissue, free radical generation, and antioxidant levels in blood plasma were not significantly changed as compared to the corresponding controls. Consistent with the lack of systemic damage, no increase in micronucleated erythrocytes was seen in peripheral blood. In conclusion, topical CHP application caused skin damage only at the application site and did not cause systemic tissue impairment. JF - Toxicologic Pathology AU - Rider, Cynthia V AU - Chan, Po AU - Herbert, Ron A AU - Kissling, Grace E AU - Fomby, Laurene M AU - Hejtmancik, Milton R AU - Witt, Kristine L AU - Waidyanatha, Suramya AU - Travlos, Greg S AU - Kadiiska, Maria B AD - 1 .Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA, cynthia.rider@nih.gov Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 749 EP - 762 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - skin irritant KW - oxidizing agent KW - Ames assay KW - industrial chemical KW - Antioxidants KW - Skin KW - Free radicals KW - Erythrocytes KW - Survival KW - Peripheral blood KW - Toxicity KW - cumene hydroperoxide KW - Phenols KW - Irritation KW - Inflammation KW - Hyperplasia KW - Body weight KW - Liver KW - Acetone KW - Oxidants KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808667404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Dermal+Exposure+to+Cumene+Hydroperoxide%3A+Assessing+Its+Toxic+Relevance+and+Oxidant+Potential&rft.au=Rider%2C+Cynthia+V%3BChan%2C+Po%3BHerbert%2C+Ron+A%3BKissling%2C+Grace+E%3BFomby%2C+Laurene+M%3BHejtmancik%2C+Milton+R%3BWitt%2C+Kristine+L%3BWaidyanatha%2C+Suramya%3BTravlos%2C+Greg+S%3BKadiiska%2C+Maria+B&rft.aulast=Rider&rft.aufirst=Cynthia&rft.date=2016-07-01&rft.volume=44&rft.issue=5&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316636712 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 46 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Skin; Antioxidants; Free radicals; Erythrocytes; Survival; Peripheral blood; Toxicity; cumene hydroperoxide; Irritation; Phenols; Inflammation; Hyperplasia; Body weight; Liver; Acetone; Oxidants DO - http://dx.doi.org/10.1177/0192623316636712 ER - TY - JOUR T1 - Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development AN - 1808658769; PQ0003318197 AB - A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular development is dependent upon normal vasculogenesis, angiogenesis, and the transformation of vessels into their adult counterparts. Any alteration in vascular development has the potential to cause deformities or embryonic death. Numerous publications describe specific stages of vascular development relating to various organs, but a single resource detailing the stage-by-stage development of the vasculature pertaining to the hepatobiliary system has not been available. This comprehensive histology atlas provides hematoxylin & eosin and immunohistochemical-stained sections of the developing mouse blood and lymphatic vasculature with emphasis on the hepatobiliary system between embryonic days (E) 11.5-18.5 and the early postnatal period. Additionally, this atlas includes a 3-dimensional video representation of the E18.5 mouse venous vasculature. One of the most noteworthy findings of this atlas is the identification of the portal sinus within the mouse, which has been erroneously misinterpreted as the ductus venosus in previous publications. Although the primary purpose of this atlas is to identify normal hepatobiliary vascular development, potential embryonic abnormalities are also described. JF - Toxicologic Pathology AU - Swartley, Olivia M AU - Foley, Julie F AU - Livingston, David P, III AU - Cullen, John M AU - Elmore, Susan A AD - 1 .College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA, elmore@niehs.nih.gov Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 705 EP - 725 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - vascular development KW - lymphatic development KW - hepatobiliary development KW - portal sinus KW - embryo KW - mouse KW - atlas KW - Transformation KW - Blood KW - Embryogenesis KW - Atlases KW - Angiogenesis KW - Developmental stages KW - Embryos KW - Sinus KW - Development KW - Transgenic mice KW - Vascular system KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808658769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Histology+Atlas+of+the+Developing+Mouse+Hepatobiliary+Hemolymphatic+Vascular+System+with+Emphasis+on+Embryonic+Days+11.5-18.5+and+Early+Postnatal+Development&rft.au=Swartley%2C+Olivia+M%3BFoley%2C+Julie+F%3BLivingston%2C+David+P%2C+III%3BCullen%2C+John+M%3BElmore%2C+Susan+A&rft.aulast=Swartley&rft.aufirst=Olivia&rft.date=2016-07-01&rft.volume=44&rft.issue=5&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316630836 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 58 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Transformation; Blood; Embryogenesis; Atlases; Angiogenesis; Developmental stages; Sinus; Embryos; Development; Transgenic mice; Vascular system DO - http://dx.doi.org/10.1177/0192623316630836 ER - TY - JOUR T1 - Contribution of inorganic arsenic sources to population exposure risk on a regional scale AN - 1808651492; PQ0003488997 AB - Chronic exposure to inorganic arsenic (iAs) in the human population is associated with various internal cancers and other adverse outcomes. The purpose of this study was to estimate a population-scale exposure risk attributable to iAs consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK) model and biomonitoring data of iAs in urine. The urinary As concentrations were obtained from a total of 1,043 subjects living in an industrial area of Taiwan. The results showed that the study subjects had an iAs exposure risk of 27 % (the daily iAs intake for 27 % study subjects exceeded the WHO-recommended value, 2.1 mu g iAs day super(-1) kg super(-1) body weight). Moreover, drinking water and cooked rice contributed to the iAs exposure risk by 10 and 41 %, respectively. The predicted risks in the current study were 4.82, 27.21, 34.69, and 64.17 %, respectively, among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh reported in the literature. In conclusion, we developed a population-scale-based risk model that covered the broad range of iAS exposure by integrating stochastic PBPK modeling and reverse dosimetry to generate probabilistic distribution of As intake corresponding to urinary As measured from the cohort study. The model can also be updated as new urinary As information becomes available. JF - Environmental Science and Pollution Research International AU - Chou, Wei-Chun AU - Chen, Jein-Wen AU - Liao, Chung-Min AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, 35053, Taiwan, Republic of China, cmliao@ntu.edu.tw Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 14173 EP - 14182 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 23 IS - 14 SN - 0944-1344, 0944-1344 KW - Toxicology Abstracts; Pollution Abstracts; Ecology Abstracts KW - ISW, Bangladesh KW - Models KW - Body weight KW - Chronic exposure KW - biomonitoring KW - Korea, Rep. KW - Industrial areas KW - Bioindicators KW - Arsenic KW - Data processing KW - Human populations KW - Dosimetry KW - Pollution research KW - Stochasticity KW - Pharmacokinetics KW - Cancer KW - Health risks KW - ISEW, Taiwan KW - Mexico KW - Stochastic models KW - Urine KW - Drinking water KW - D 04070:Pollution KW - P 2000:FRESHWATER POLLUTION KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808651492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Science+and+Pollution+Research+International&rft.atitle=Contribution+of+inorganic+arsenic+sources+to+population+exposure+risk+on+a+regional+scale&rft.au=Chou%2C+Wei-Chun%3BChen%2C+Jein-Wen%3BLiao%2C+Chung-Min&rft.aulast=Chou&rft.aufirst=Wei-Chun&rft.date=2016-07-01&rft.volume=23&rft.issue=14&rft.spage=14173&rft.isbn=&rft.btitle=&rft.title=Environmental+Science+and+Pollution+Research+International&rft.issn=09441344&rft_id=info:doi/10.1007%2Fs11356-016-6557-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 36 N1 - Last updated - 2016-09-29 N1 - SubjectsTermNotLitGenreText - Arsenic; Data processing; Dosimetry; Pollution research; Stochasticity; Cancer; Pharmacokinetics; Models; Body weight; Urine; Chronic exposure; biomonitoring; Drinking water; Bioindicators; Health risks; Stochastic models; Human populations; Industrial areas; ISW, Bangladesh; Mexico; ISEW, Taiwan; Korea, Rep. DO - http://dx.doi.org/10.1007/s11356-016-6557-9 ER - TY - JOUR T1 - Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function AN - 1808650437; PQ0003319645 AB - Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down-regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure. Cover image for this issue: doi: . We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down-regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure. JF - Journal of Neurochemistry AU - Sunitha, Balaraju AU - Gayathri, Narayanappa AU - Kumar, Manish AU - Keshava Prasad, Thottethodi Subrahmanya AU - Nalini, Atchayaram AU - Padmanabhan, Balasundaram AU - Srinivas Bharath, Muchukunte Mukunda AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 174 EP - 191 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 138 IS - 1 SN - 0022-3042, 0022-3042 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Cardiotoxins KW - Tryptophan KW - Data processing KW - Animal models KW - Muscles KW - Enzymes KW - Mitochondria KW - Biopsy KW - Inflammation KW - Oxidative stress KW - Vacuoles KW - Oxidation KW - Polymyositis KW - Muscular dystrophy KW - proteomics KW - Tricarboxylic acid cycle KW - Histochemistry KW - Electron transport chain KW - Myopathy KW - X 24310:Pharmaceuticals KW - N3 11008:Neurochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808650437?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurochemistry&rft.atitle=Muscle+biopsies+from+human+muscle+diseases+with+myopathic+pathology+reveal+common+alterations+in+mitochondrial+function&rft.au=Sunitha%2C+Balaraju%3BGayathri%2C+Narayanappa%3BKumar%2C+Manish%3BKeshava+Prasad%2C+Thottethodi+Subrahmanya%3BNalini%2C+Atchayaram%3BPadmanabhan%2C+Balasundaram%3BSrinivas+Bharath%2C+Muchukunte+Mukunda&rft.aulast=Sunitha&rft.aufirst=Balaraju&rft.date=2016-07-01&rft.volume=138&rft.issue=1&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurochemistry&rft.issn=00223042&rft_id=info:doi/10.1111%2Fjnc.13626 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Cardiotoxins; Tryptophan; Data processing; Muscles; Animal models; Mitochondria; Enzymes; Biopsy; Inflammation; Oxidative stress; Oxidation; Vacuoles; Polymyositis; proteomics; Muscular dystrophy; Tricarboxylic acid cycle; Histochemistry; Myopathy; Electron transport chain DO - http://dx.doi.org/10.1111/jnc.13626 ER - TY - JOUR T1 - Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice: An NTP Retrospective Study AN - 1808645752; PQ0003318192 AB - Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine whether HG had occurred in prior NTP studies and, if so, whether these 2 glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid-positive control mice, 2 HG-positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Congo red (CR), and Masson's trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally, the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining and/or ultraviolet evaluation. JF - Toxicologic Pathology AU - Hoane, Jessica S AU - Johnson, Crystal L AU - Morrison, James P AU - Elmore, Susan A AD - 1 .Charles River Laboratories, Inc., Durham, North Carolina, USA, elmore@niehs.nih.gov Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 687 EP - 704 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 5 SN - 0192-6233, 0192-6233 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - renal glomerulus KW - amyloid KW - hyaline glomerulopathy KW - transmission electron microscopy KW - B6C3F1 mice KW - pulegone KW - autofluorescence KW - Deposits KW - Amyloidosis KW - U.V. radiation KW - Transmission electron microscopy KW - Kidney diseases KW - Kidney KW - beta -Amyloid KW - Stains KW - Amyloid KW - N3 11028:Neuropharmacology & toxicology KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808645752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Comparison+of+Renal+Amyloid+and+Hyaline+Glomerulopathy+in+B6C3F1+Mice%3A+An+NTP+Retrospective+Study&rft.au=Hoane%2C+Jessica+S%3BJohnson%2C+Crystal+L%3BMorrison%2C+James+P%3BElmore%2C+Susan+A&rft.aulast=Hoane&rft.aufirst=Jessica&rft.date=2016-07-01&rft.volume=44&rft.issue=5&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623316630625 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 19 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Deposits; Amyloidosis; U.V. radiation; Transmission electron microscopy; Kidney; Kidney diseases; Stains; beta -Amyloid; Amyloid DO - http://dx.doi.org/10.1177/0192623316630625 ER - TY - JOUR T1 - Air pollution exposure and preeclampsia among US women with and without asthma AN - 1808636588; PQ0003166127 AB - Maternal asthma and air pollutants have been independently associated with preeclampsia but rarely studied together. Our objective was to comprehensively evaluate preeclampsia risk based on the interaction of maternal asthma and air pollutants. Preeclampsia and asthma diagnoses, demographic and clinical data came from electronic medical records for 210,508 singleton deliveries. Modified Community Multiscale Air Quality models estimated preconception, first and second trimester and whole pregnancy exposure to: particulate matter (PM)<2.5 and <10 mu m, ozone, nitrogen oxides (NOx), sulfur dioxide (SO2) and carbon monoxide (CO); PM2.5 constituents; volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). Asthma-pollutant interaction adjusted relative risks (RR) and 95% confidence intervals (CI) for preeclampsia were calculated by interquartile range for criteria pollutants and high exposure ( greater than or equal to 75th percentile) for PAHs and VOCs. Asthmatics had higher risk associated with first trimester NOx and SO2 and whole pregnancy elemental carbon (EC) exposure than non-asthmatics, but only EC significantly increased risk (RR=1.11, CI:1.03-1.21). Asthmatics also had a 10% increased risk associated with second trimester CO. Significant interactions were observed for nearly all VOCs and asthmatics had higher risk during all time windows for benzene, ethylbenzene, m-xylene, o-xylene, p-xylene and toluene while most PAHs did not increase risk. JF - Environmental Research AU - Mendola, Pauline AU - Wallace, Maeve AU - Liu, Danping AU - Robledo, Candace AU - Mo"nnisto, Tuija AU - Grantz, Katherine L AD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Intramural Population Health Research, Epidemiology Branch, Rockville, MD 20852, United States Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 248 EP - 255 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 148 SN - 0013-9351, 0013-9351 KW - Toxicology Abstracts; Pollution Abstracts; Environment Abstracts KW - PM2.5 Particulate Matter <2.5 mu m KW - NO2 nitrogen dioxide KW - NOx nitrogen oxides KW - PM10, Particulate Matter <10 mu m KW - CO carbon monoxide KW - O3, ozone KW - PAHs polycyclic aromatic hydrocarbons KW - VOCs volatile organic compounds KW - ICD-9 International Classification of Diseases, Ninth Revision KW - CMAQ Community Multiscale Air Quality KW - IQR interquartile range KW - BMI body mass index KW - Preeclampsia KW - Pregnancy KW - Hypertension KW - Asthma KW - Air pollution KW - Risk assessment KW - Particulate matter KW - Air quality KW - Particulates KW - Respiratory diseases KW - Benzene KW - Carbon monoxide KW - Demography KW - Carbon KW - Sulfur dioxide KW - Pollutants KW - Risk factors KW - Pre-eclampsia KW - oxides KW - Ozone KW - Polycyclic aromatic hydrocarbons KW - Data processing KW - Nitrogen oxides KW - Photochemicals KW - volatile organic compounds KW - Ethylbenzene KW - Volatile organic compounds KW - electronic medical records KW - p-Xylene KW - P 0000:AIR POLLUTION KW - X 24360:Metals KW - ENA 01:Air Pollution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808636588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=Air+pollution+exposure+and+preeclampsia+among+US+women+with+and+without+asthma&rft.au=Mendola%2C+Pauline%3BWallace%2C+Maeve%3BLiu%2C+Danping%3BRobledo%2C+Candace%3BMo%22nnisto%2C+Tuija%3BGrantz%2C+Katherine+L&rft.aulast=Mendola&rft.aufirst=Pauline&rft.date=2016-07-01&rft.volume=148&rft.issue=&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1016%2Fj.envres.2016.04.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Risk assessment; Polycyclic aromatic hydrocarbons; Data processing; Particulate matter; Asthma; Benzene; Pregnancy; Air pollution; Demography; Sulfur dioxide; Pollutants; Risk factors; Pre-eclampsia; volatile organic compounds; oxides; Ethylbenzene; electronic medical records; Ozone; p-Xylene; Air quality; Respiratory diseases; Particulates; Nitrogen oxides; Carbon monoxide; Carbon; Photochemicals; Volatile organic compounds DO - http://dx.doi.org/10.1016/j.envres.2016.04.004 ER - TY - JOUR T1 - Optically controlled switch-mode current-source amplifiers for on-coil implementation in high-field parallel transmission AN - 1808630493; PQ0003293789 AB - Purpose We tested the feasibility of implementing parallel transmission (pTX) for high-field MRI using a radiofrequency (RF) amplifier design to be located on or in the immediate vicinity of an RF transmit coil. Method We designed a current-source switch-mode amplifier based on miniaturized, nonmagnetic electronics. Optical RF carrier and envelope signals to control the amplifier were derived, through a custom-built interface, from the RF source accessible in the scanner control. Amplifier performance was tested by benchtop measurements as well as with imaging at 7T (300 MHz) and 11.7 T (500 MHz). The ability to perform pTX was evaluated by measuring interchannel coupling and phase adjustment in a two-channel setup. Results The amplifier delivered in excess of 44 W RF power and caused minimal interference with MRI. The interface derived accurate optical control signals with carrier frequencies ranging from 64 to 750 MHz. Decoupling better than 14 dB was obtained between two coil loops separated by only 1 cm. Application to MRI was demonstrated by acquiring artifact-free images at 7 T and 11.7 T. Conclusion We propose an optically controlled miniaturized RF amplifier for on-coil implementation at high fields that should facilitate implementation of high-density pTX arrays. Magn Reson Med 76:340-349, 2016. JF - Magnetic Resonance in Medicine AU - Gudino, Natalia AU - Duan, Qi AU - de Zwart, Jacco A AU - Murphy-Boesch, Joe AU - Dodd, Stephen J AU - Merkle, Hellmut AU - van Gelderen, Peter AU - Duyn, Jeff H AD - Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 340 EP - 349 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 76 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Envelopes KW - Magnetic resonance imaging KW - N.M.R. KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808630493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Optically+controlled+switch-mode+current-source+amplifiers+for+on-coil+implementation+in+high-field+parallel+transmission&rft.au=Gudino%2C+Natalia%3BDuan%2C+Qi%3Bde+Zwart%2C+Jacco+A%3BMurphy-Boesch%2C+Joe%3BDodd%2C+Stephen+J%3BMerkle%2C+Hellmut%3Bvan+Gelderen%2C+Peter%3BDuyn%2C+Jeff+H&rft.aulast=Gudino&rft.aufirst=Natalia&rft.date=2016-07-01&rft.volume=76&rft.issue=1&rft.spage=340&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25857 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Envelopes; Magnetic resonance imaging; N.M.R. DO - http://dx.doi.org/10.1002/mrm.25857 ER - TY - JOUR T1 - Arsenic and Environmental Health: State of the Science and Future Research Opportunities. AN - 1808606878; 26587579 AB - Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer and noncancer effects in nearly every organ in the body, and evidence is mounting for health effects at lower levels of arsenic exposure than previously thought. Building from a tremendous knowledge base with > 1,000 scientific papers published annually with "arsenic" in the title, the question becomes, what questions would best drive future research directions? The objective is to discuss emerging issues in arsenic research and identify data gaps across disciplines. The National Institutes of Health's National Institute of Environmental Health Sciences Superfund Research Program convened a workshop to identify emerging issues and research needs to address the multi-faceted challenges related to arsenic and environmental health. This review summarizes information captured during the workshop. More information about aggregate exposure to arsenic is needed, including the amount and forms of arsenic found in foods. New strategies for mitigating arsenic exposures and related health effects range from engineered filtering systems to phytogenetics and nutritional interventions. Furthermore, integration of omics data with mechanistic and epidemiological data is a key step toward the goal of linking biomarkers of exposure and susceptibility to disease mechanisms and outcomes. Promising research strategies and technologies for arsenic exposure and adverse health effect mitigation are being pursued, and future research is moving toward deeper collaborations and integration of information across disciplines to address data gaps. Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, Lee JS, Thomas DJ, Thompson C, Tokar EJ, Waalkes MP, Birnbaum LS, Suk WA. 2016. Arsenic and environmental health: state of the science and future research opportunities. Environ Health Perspect 124:890-899; http://dx.doi.org/10.1289/ehp.1510209. JF - Environmental health perspectives AU - Carlin, Danielle J AU - Naujokas, Marisa F AU - Bradham, Karen D AU - Cowden, John AU - Heacock, Michelle AU - Henry, Heather F AU - Lee, Janice S AU - Thomas, David J AU - Thompson, Claudia AU - Tokar, Erik J AU - Waalkes, Michael P AU - Birnbaum, Linda S AU - Suk, William A AD - Superfund Research Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 890 EP - 899 VL - 124 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808606878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Arsenic+and+Environmental+Health%3A+State+of+the+Science+and+Future+Research+Opportunities.&rft.au=Carlin%2C+Danielle+J%3BNaujokas%2C+Marisa+F%3BBradham%2C+Karen+D%3BCowden%2C+John%3BHeacock%2C+Michelle%3BHenry%2C+Heather+F%3BLee%2C+Janice+S%3BThomas%2C+David+J%3BThompson%2C+Claudia%3BTokar%2C+Erik+J%3BWaalkes%2C+Michael+P%3BBirnbaum%2C+Linda+S%3BSuk%2C+William+A&rft.aulast=Carlin&rft.aufirst=Danielle&rft.date=2016-07-01&rft.volume=124&rft.issue=7&rft.spage=890&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1510209 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-08-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1510209 ER - TY - JOUR T1 - Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond. AN - 1807878556; 27467575 AB - A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts. JF - PLoS pathogens AU - Van Voorhis, Wesley C AU - Adams, John H AU - Adelfio, Roberto AU - Ahyong, Vida AU - Akabas, Myles H AU - Alano, Pietro AU - Alday, Aintzane AU - Alemán Resto, Yesmalie AU - Alsibaee, Aishah AU - Alzualde, Ainhoa AU - Andrews, Katherine T AU - Avery, Simon V AU - Avery, Vicky M AU - Ayong, Lawrence AU - Baker, Mark AU - Baker, Stephen AU - Ben Mamoun, Choukri AU - Bhatia, Sangeeta AU - Bickle, Quentin AU - Bounaadja, Lotfi AU - Bowling, Tana AU - Bosch, Jürgen AU - Boucher, Lauren E AU - Boyom, Fabrice F AU - Brea, Jose AU - Brennan, Marian AU - Burton, Audrey AU - Caffrey, Conor R AU - Camarda, Grazia AU - Carrasquilla, Manuela AU - Carter, Dee AU - Belen Cassera, Maria AU - Chih-Chien Cheng, Ken AU - Chindaudomsate, Worathad AU - Chubb, Anthony AU - Colon, Beatrice L AU - Colón-López, Daisy D AU - Corbett, Yolanda AU - Crowther, Gregory J AU - Cowan, Noemi AU - D'Alessandro, Sarah AU - Le Dang, Na AU - Delves, Michael AU - DeRisi, Joseph L AU - Du, Alan Y AU - Duffy, Sandra AU - Abd El-Salam El-Sayed, Shimaa AU - Ferdig, Michael T AU - Fernández Robledo, José A AU - Fidock, David A AU - Florent, Isabelle AU - Fokou, Patrick V T AU - Galstian, Ani AU - Gamo, Francisco Javier AU - Gokool, Suzanne AU - Gold, Ben AU - Golub, Todd AU - Goldgof, Gregory M AU - Guha, Rajarshi AU - Guiguemde, W Armand AU - Gural, Nil AU - Guy, R Kiplin AU - Hansen, Michael A E AU - Hanson, Kirsten K AU - Hemphill, Andrew AU - Hooft van Huijsduijnen, Rob AU - Horii, Takaaki AU - Horrocks, Paul AU - Hughes, Tyler B AU - Huston, Christopher AU - Igarashi, Ikuo AU - Ingram-Sieber, Katrin AU - Itoe, Maurice A AU - Jadhav, Ajit AU - Naranuntarat Jensen, Amornrat AU - Jensen, Laran T AU - Jiang, Rays H Y AU - Kaiser, Annette AU - Keiser, Jennifer AU - Ketas, Thomas AU - Kicka, Sebastien AU - Kim, Sunyoung AU - Kirk, Kiaran AU - Kumar, Vidya P AU - Kyle, Dennis E AU - Lafuente, Maria Jose AU - Landfear, Scott AU - Lee, Nathan AU - Lee, Sukjun AU - Lehane, Adele M AU - Li, Fengwu AU - Little, David AU - Liu, Liqiong AU - Llinás, Manuel AU - Loza, Maria I AU - Lubar, Aristea AU - Lucantoni, Leonardo AU - Lucet, Isabelle AU - Maes, Louis AU - Mancama, Dalu AU - Mansour, Nuha R AU - March, Sandra AU - McGowan, Sheena AU - Medina Vera, Iset AU - Meister, Stephan AU - Mercer, Luke AU - Mestres, Jordi AU - Mfopa, Alvine N AU - Misra, Raj N AU - Moon, Seunghyun AU - Moore, John P AU - Morais Rodrigues da Costa, Francielly AU - Müller, Joachim AU - Muriana, Arantza AU - Nakazawa Hewitt, Stephen AU - Nare, Bakela AU - Nathan, Carl AU - Narraidoo, Nathalie AU - Nawaratna, Sujeevi AU - Ojo, Kayode K AU - Ortiz, Diana AU - Panic, Gordana AU - Papadatos, George AU - Parapini, Silvia AU - Patra, Kailash AU - Pham, Ngoc AU - Prats, Sarah AU - Plouffe, David M AU - Poulsen, Sally-Ann AU - Pradhan, Anupam AU - Quevedo, Celia AU - Quinn, Ronald J AU - Rice, Christopher A AU - Abdo Rizk, Mohamed AU - Ruecker, Andrea AU - St Onge, Robert AU - Salgado Ferreira, Rafaela AU - Samra, Jasmeet AU - Robinett, Natalie G AU - Schlecht, Ulrich AU - Schmitt, Marjorie AU - Silva Villela, Filipe AU - Silvestrini, Francesco AU - Sinden, Robert AU - Smith, Dennis A AU - Soldati, Thierry AU - Spitzmüller, Andreas AU - Stamm, Serge Maximilian AU - Sullivan, David J AU - Sullivan, William AU - Suresh, Sundari AU - Suzuki, Brian M AU - Suzuki, Yo AU - Swamidass, S Joshua AU - Taramelli, Donatella AU - Tchokouaha, Lauve R Y AU - Theron, Anjo AU - Thomas, David AU - Tonissen, Kathryn F AU - Townson, Simon AU - Tripathi, Abhai K AU - Trofimov, Valentin AU - Udenze, Kenneth O AU - Ullah, Imran AU - Vallieres, Cindy AU - Vigil, Edgar AU - Vinetz, Joseph M AU - Voong Vinh, Phat AU - Vu, Hoan AU - Watanabe, Nao-Aki AU - Weatherby, Kate AU - White, Pamela M AU - Wilks, Andrew F AU - Winzeler, Elizabeth A AU - Wojcik, Edward AU - Wree, Melanie AU - Wu, Wesley AU - Yokoyama, Naoaki AU - Zollo, Paul H A AU - Abla, Nada AU - Blasco, Benjamin AU - Burrows, Jeremy AU - Laleu, Benoît AU - Leroy, Didier AU - Spangenberg, Thomas AU - Wells, Timothy AU - Willis, Paul A AD - Departments of Medicine, Microbiology, and Global Health, Center for Emerging and Re-emerging Infectious Diseases (CERID) University of Washington, Seattle, Washington, United States of America. ; Center for Global Health and Infectious Diseases Research, Department of Global Health, University of South Florida, Tampa, Florida, United States of America. ; Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. ; Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, California, United States of America. ; Departments of Physiology & Biophysics, Neuroscience and Medicine, Albert Einstein College of Medicine, New York, New York, United States of America. ; Dipartimento Malattie Infettive, Parassitarie ed Immunomediate Istituto Superiore di Sanità, Roma, Italia. ; BBD BioPhenix SL-BIOBIDE, Donostia, Gipuzkoa, Spain. ; Bigelow Laboratory for Ocean Sciences, East Boothbay, Maine, United States of America. ; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland. ; Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia. ; School of Life Sciences, University of Nottingham, Nottingham, Nottinghamshire, England, United Kingdom. ; Institut Pasteur Korea, Pangyo Techno-Valley, Gyeonggi Province, Korea. ; Clinical Pharmacology, Novartis Consumer Health, Nyon, Switzerland. ; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. ; Internal Medicine, Yale University, New Haven, Connecticut, United States of America. ; Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America. ; Department of Immunology & Infection, London School of Hygiene and Tropical Medicine, London, England, United Kingdom. ; Museum of National History, Sorbonne Universities, Paris, France. ; SCYNEXIS, Inc., Durham, North Carolina, United States of America. ; Department of Biochemistry and Molecular Biology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, Untied States of America. ; Department of Biochemistry, University of Yaoundé, Yaoundé, Cameroon. ; CIMUS Research Centre, University of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain. ; Center for Discovery and Innovation in Parasitic Diseases, Department of Pathology, University of California San Francisco, San Francisco, California, United States of America. ; Department of Biochemistry and Molecular Biology and Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America. ; School of Life and Environmental Sciences, University of Sydney, Darlington New South Wales, Australia. ; Department of Biochemistry and Virginia Tech Center for Drug Discovery, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America. ; National Center of Advancing Translational Sciences, NIH, Bethesda, Maryland, United States of America. ; Department of Biochemistry, Mahidol University, Bangkok, Thailand. ; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America. ; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. ; Department of Pathology and Immunology, Washington University in St Louis, St. Louis, Missouri, United States of America. ; Department of Life Sciences, Imperial College London, London, England, United Kingdom. ; Division of Pharmacology and Drug Discovery, Department of Pediatrics, School of Medicine University of California San Diego, La Jolla, California, United States of America. ; National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. ; Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame Indiana, United States of America. ; Department of Microbiology & Immunology and Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York, United States of America. ; Broad Institute, Cambridge, Massachusetts, United States of America. ; Biochemistry and Parasitology Department, Malaria DPU, Diseases of the Developing World (DDW), GlaxoSmithKline R&D, Tres Cantos, Madrid, Spain. ; Tropical Parasitic Diseases Unit, Northwick Park Institute for Medical Research, Harrow, Middlesex, England, United Kingdom. ; Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America. ; Medical Scientist Training Program, University of California, San Diego, San Diego, California, United States of America. ; Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America. ; Dept. of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, San Antonio, Texas, United States of America. ; Institute of Parasitology, University of Berne, Bern, Switzerland. ; Medicines for Malaria Venture, Geneva, Switzerland. ; Global Health Research Section, hhc Data Creation Center, Eisai Co., Ltd, Tsukuba-shi, Ibaraki, Japan. ; Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire, United Kingdom. ; Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont, United States of America. ; Instituto de Medicina Molecular, Lisboa, Portugal. ; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok Thailand. ; Medical Research Centre, Institute for Pharmacogenetics, Essen, Germany. ; Department of Biochemistry, University of Geneva, Geneva, Switzerland. ; Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, New Orleans, Louisiana, United States of America. ; Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia. ; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America. ; Department of Medicine, University of California San Diego, San Diego, California, United States of America. ; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. ; University of Antwerp, Department of Biomedical Sciences, Antwerp, Belgium. ; Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, South Africa. ; Department of Microbiology, Monash University, Clayton, Australia. ; Chemotargets S.L. and Research Group on Systems Pharmacology, Research Program on Biomedical Informatics (GRIB), IMIM Hospital del Mar Institute of Medical Research and University Pompeu Fabra, Barcelona, Catalonia, Spain. ; Division of Cancer Therapeutics and Diagnosis, Drug Synthesis and Chemistry Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. ; Graduate Program in Bioinformatics, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. ; ChEMBL group, European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, United Kingdom. ; Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America. ; Department of Biochemistry and Stanford Genome Technology Center, Stanford University, Palo Alto, Calilfornia, United States of America. ; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. ; Laboratoire de Chimie Moléculaire, CNRS,-UMR 7509, COB-IRJBD, Mulhouse Cedex, France. ; The Jenner Institute, University of Oxford, Oxford, England, United Kingdom. ; Department of Chemistry, University of Capetown, Capetown, South Africa. ; H. Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America. ; Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, United States of America. ; Department of Synthetic Biology and Bioenergy, J. Craig Venter Institute, La Jolla, California, United States of America. ; Hudson Institute of Medical Research; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1 VL - 12 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1807878556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+pathogens&rft.atitle=Open+Source+Drug+Discovery+with+the+Malaria+Box+Compound+Collection+for+Neglected+Diseases+and+Beyond.&rft.au=Van+Voorhis%2C+Wesley+C%3BAdams%2C+John+H%3BAdelfio%2C+Roberto%3BAhyong%2C+Vida%3BAkabas%2C+Myles+H%3BAlano%2C+Pietro%3BAlday%2C+Aintzane%3BAlem%C3%A1n+Resto%2C+Yesmalie%3BAlsibaee%2C+Aishah%3BAlzualde%2C+Ainhoa%3BAndrews%2C+Katherine+T%3BAvery%2C+Simon+V%3BAvery%2C+Vicky+M%3BAyong%2C+Lawrence%3BBaker%2C+Mark%3BBaker%2C+Stephen%3BBen+Mamoun%2C+Choukri%3BBhatia%2C+Sangeeta%3BBickle%2C+Quentin%3BBounaadja%2C+Lotfi%3BBowling%2C+Tana%3BBosch%2C+J%C3%BCrgen%3BBoucher%2C+Lauren+E%3BBoyom%2C+Fabrice+F%3BBrea%2C+Jose%3BBrennan%2C+Marian%3BBurton%2C+Audrey%3BCaffrey%2C+Conor+R%3BCamarda%2C+Grazia%3BCarrasquilla%2C+Manuela%3BCarter%2C+Dee%3BBelen+Cassera%2C+Maria%3BChih-Chien+Cheng%2C+Ken%3BChindaudomsate%2C+Worathad%3BChubb%2C+Anthony%3BColon%2C+Beatrice+L%3BCol%C3%B3n-L%C3%B3pez%2C+Daisy+D%3BCorbett%2C+Yolanda%3BCrowther%2C+Gregory+J%3BCowan%2C+Noemi%3BD%27Alessandro%2C+Sarah%3BLe+Dang%2C+Na%3BDelves%2C+Michael%3BDeRisi%2C+Joseph+L%3BDu%2C+Alan+Y%3BDuffy%2C+Sandra%3BAbd+El-Salam+El-Sayed%2C+Shimaa%3BFerdig%2C+Michael+T%3BFern%C3%A1ndez+Robledo%2C+Jos%C3%A9+A%3BFidock%2C+David+A%3BFlorent%2C+Isabelle%3BFokou%2C+Patrick+V+T%3BGalstian%2C+Ani%3BGamo%2C+Francisco+Javier%3BGokool%2C+Suzanne%3BGold%2C+Ben%3BGolub%2C+Todd%3BGoldgof%2C+Gregory+M%3BGuha%2C+Rajarshi%3BGuiguemde%2C+W+Armand%3BGural%2C+Nil%3BGuy%2C+R+Kiplin%3BHansen%2C+Michael+A+E%3BHanson%2C+Kirsten+K%3BHemphill%2C+Andrew%3BHooft+van+Huijsduijnen%2C+Rob%3BHorii%2C+Takaaki%3BHorrocks%2C+Paul%3BHughes%2C+Tyler+B%3BHuston%2C+Christopher%3BIgarashi%2C+Ikuo%3BIngram-Sieber%2C+Katrin%3BItoe%2C+Maurice+A%3BJadhav%2C+Ajit%3BNaranuntarat+Jensen%2C+Amornrat%3BJensen%2C+Laran+T%3BJiang%2C+Rays+H+Y%3BKaiser%2C+Annette%3BKeiser%2C+Jennifer%3BKetas%2C+Thomas%3BKicka%2C+Sebastien%3BKim%2C+Sunyoung%3BKirk%2C+Kiaran%3BKumar%2C+Vidya+P%3BKyle%2C+Dennis+E%3BLafuente%2C+Maria+Jose%3BLandfear%2C+Scott%3BLee%2C+Nathan%3BLee%2C+Sukjun%3BLehane%2C+Adele+M%3BLi%2C+Fengwu%3BLittle%2C+David%3BLiu%2C+Liqiong%3BLlin%C3%A1s%2C+Manuel%3BLoza%2C+Maria+I%3BLubar%2C+Aristea%3BLucantoni%2C+Leonardo%3BLucet%2C+Isabelle%3BMaes%2C+Louis%3BMancama%2C+Dalu%3BMansour%2C+Nuha+R%3BMarch%2C+Sandra%3BMcGowan%2C+Sheena%3BMedina+Vera%2C+Iset%3BMeister%2C+Stephan%3BMercer%2C+Luke%3BMestres%2C+Jordi%3BMfopa%2C+Alvine+N%3BMisra%2C+Raj+N%3BMoon%2C+Seunghyun%3BMoore%2C+John+P%3BMorais+Rodrigues+da+Costa%2C+Francielly%3BM%C3%BCller%2C+Joachim%3BMuriana%2C+Arantza%3BNakazawa+Hewitt%2C+Stephen%3BNare%2C+Bakela%3BNathan%2C+Carl%3BNarraidoo%2C+Nathalie%3BNawaratna%2C+Sujeevi%3BOjo%2C+Kayode+K%3BOrtiz%2C+Diana%3BPanic%2C+Gordana%3BPapadatos%2C+George%3BParapini%2C+Silvia%3BPatra%2C+Kailash%3BPham%2C+Ngoc%3BPrats%2C+Sarah%3BPlouffe%2C+David+M%3BPoulsen%2C+Sally-Ann%3BPradhan%2C+Anupam%3BQuevedo%2C+Celia%3BQuinn%2C+Ronald+J%3BRice%2C+Christopher+A%3BAbdo+Rizk%2C+Mohamed%3BRuecker%2C+Andrea%3BSt+Onge%2C+Robert%3BSalgado+Ferreira%2C+Rafaela%3BSamra%2C+Jasmeet%3BRobinett%2C+Natalie+G%3BSchlecht%2C+Ulrich%3BSchmitt%2C+Marjorie%3BSilva+Villela%2C+Filipe%3BSilvestrini%2C+Francesco%3BSinden%2C+Robert%3BSmith%2C+Dennis+A%3BSoldati%2C+Thierry%3BSpitzm%C3%BCller%2C+Andreas%3BStamm%2C+Serge+Maximilian%3BSullivan%2C+David+J%3BSullivan%2C+William%3BSuresh%2C+Sundari%3BSuzuki%2C+Brian+M%3BSuzuki%2C+Yo%3BSwamidass%2C+S+Joshua%3BTaramelli%2C+Donatella%3BTchokouaha%2C+Lauve+R+Y%3BTheron%2C+Anjo%3BThomas%2C+David%3BTonissen%2C+Kathryn+F%3BTownson%2C+Simon%3BTripathi%2C+Abhai+K%3BTrofimov%2C+Valentin%3BUdenze%2C+Kenneth+O%3BUllah%2C+Imran%3BVallieres%2C+Cindy%3BVigil%2C+Edgar%3BVinetz%2C+Joseph+M%3BVoong+Vinh%2C+Phat%3BVu%2C+Hoan%3BWatanabe%2C+Nao-Aki%3BWeatherby%2C+Kate%3BWhite%2C+Pamela+M%3BWilks%2C+Andrew+F%3BWinzeler%2C+Elizabeth+A%3BWojcik%2C+Edward%3BWree%2C+Melanie%3BWu%2C+Wesley%3BYokoyama%2C+Naoaki%3BZollo%2C+Paul+H+A%3BAbla%2C+Nada%3BBlasco%2C+Benjamin%3BBurrows%2C+Jeremy%3BLaleu%2C+Beno%C3%AEt%3BLeroy%2C+Didier%3BSpangenberg%2C+Thomas%3BWells%2C+Timothy%3BWillis%2C+Paul+A&rft.aulast=Van+Voorhis&rft.aufirst=Wesley&rft.date=2016-07-01&rft.volume=12&rft.issue=7&rft.spage=e1005763&rft.isbn=&rft.btitle=&rft.title=PLoS+pathogens&rft.issn=1553-7374&rft_id=info:doi/10.1371%2Fjournal.ppat.1005763 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1371/journal.ppat.1005763 ER - TY - JOUR T1 - Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships. AN - 1806442683; 26257143 AB - Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r≥0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. JF - Drug testing and analysis AU - Hartman, Rebecca L AU - Brown, Timothy L AU - Milavetz, Gary AU - Spurgin, Andrew AU - Gorelick, David A AU - Gaffney, Gary AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, USA. ; National Advanced Driving Simulator, University of Iowa, Iowa City, IA, USA. ; College of Pharmacy, University of Iowa, Iowa City, IA, USA. ; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. ; Carver College of Medicine, University of Iowa, Iowa City, IA, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 690 EP - 701 VL - 8 IS - 7 KW - Index Medicus KW - cannabis KW - alcohol KW - subjective KW - blood KW - oral fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806442683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+testing+and+analysis&rft.atitle=Controlled+vaporized+cannabis%2C+with+and+without+alcohol%3A+subjective+effects+and+oral+fluid-blood+cannabinoid+relationships.&rft.au=Hartman%2C+Rebecca+L%3BBrown%2C+Timothy+L%3BMilavetz%2C+Gary%3BSpurgin%2C+Andrew%3BGorelick%2C+David+A%3BGaffney%2C+Gary%3BHuestis%2C+Marilyn+A&rft.aulast=Hartman&rft.aufirst=Rebecca&rft.date=2016-07-01&rft.volume=8&rft.issue=7&rft.spage=690&rft.isbn=&rft.btitle=&rft.title=Drug+testing+and+analysis&rft.issn=1942-7611&rft_id=info:doi/10.1002%2Fdta.1839 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/dta.1839 ER - TY - JOUR T1 - Right on Q: genetics begin to unravel Coxiella burnetii host cell interactions. AN - 1806441934; 27418426 AB - Invasion of macrophages and replication within an acidic and degradative phagolysosome-like vacuole are essential for disease pathogenesis by Coxiella burnetii, the bacterial agent of human Q fever. Previous experimental constraints imposed by the obligate intracellular nature of Coxiella limited knowledge of pathogen strategies that promote infection. Fortunately, new genetic tools facilitated by axenic culture now allow allelic exchange and transposon mutagenesis approaches for virulence gene discovery. Phenotypic screens have illuminated the critical importance of Coxiella's type 4B secretion system in host cell subversion and discovered genes encoding translocated effector proteins that manipulate critical infection events. Here, we highlight the cellular microbiology and genetics of Coxiella and how recent technical advances now make Coxiella a model organism to study macrophage parasitism. JF - Future microbiology AU - Larson, Charles L AU - Martinez, Eric AU - Beare, Paul A AU - Jeffrey, Brendan AU - Heinzen, Robert A AU - Bonazzi, Matteo AD - Coxiella Pathogenesis Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy & Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA. ; CNRS, FRE3698, CPBS, 1919 Route de Mende, 34293 Montpellier, France. ; Bioinformatics & Computational Biosciences Branch, Rocky Mountain Laboratories, National Institute of Allergy & Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 919 EP - 939 VL - 11 KW - Index Medicus KW - Coxiella burnetii KW - apoptosis KW - vacuole remodeling KW - mutagenesis KW - autophagy KW - type 4B secretion KW - macrophages KW - phagolysosome KW - effector protein KW - host cell invasion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806441934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Future+microbiology&rft.atitle=Right+on+Q%3A+genetics+begin+to+unravel+Coxiella+burnetii+host+cell+interactions.&rft.au=Larson%2C+Charles+L%3BMartinez%2C+Eric%3BBeare%2C+Paul+A%3BJeffrey%2C+Brendan%3BHeinzen%2C+Robert+A%3BBonazzi%2C+Matteo&rft.aulast=Larson&rft.aufirst=Charles&rft.date=2016-07-01&rft.volume=11&rft.issue=&rft.spage=919&rft.isbn=&rft.btitle=&rft.title=Future+microbiology&rft.issn=1746-0921&rft_id=info:doi/10.2217%2Ffmb-2016-0044 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.2217/fmb-2016-0044 ER - TY - JOUR T1 - A 24-Weeks Toxicity Study of Eryngium foetidum Linn. Leaves in Mice. AN - 1806076513; 27437090 AB - Eryngium foetidum Linn. leaves (EF) are widely used in Thailand and many countries throughout Asia as a culinary seasoning and a traditional medicine. However, adverse effect of high dose consumption in long duration has not been evaluated. The aim of this study was to investigate chronic toxicity of EF in mice. Thirty-two ICR male mice were divided into 4 groups of 8 mice each. The mice were fed AIN-76 rodent diet, or AIN-76 rodent diet supplemented with ground freeze-dried EF at 0.8%, 1.6% and 3.2% that is equivalent to approximately 35, 73 and 155 times that of human consumption, respectively, at 97.5 percentile for a period of 24 weeks. At the end of experiment, the mice were euthanized and blood samples were collected for hematological and biochemical evaluations. Necropsy was performed while visceral organs such as lung, liver, kidneys, spleen etc. were collected, weighed and histopathologically examined. Blood urea nitrogen (BUN) results of mice in 1.6% and 3.2% EF diet groups were significantly higher than the BUN of control group. No significant difference was noted in other biochemical and hematological properties between the treatment groups and control; all results were within normal range. Histopathology of almost all visceral organs showed no significant changes. However, tubulonephrosis and chronic interstitial nephritis were observed in the groups treated with 1.6% and 3.2% EF diet. Body weight was reduced significantly at week 12 to week 20 when compared to the control group while relative kidney weights were significantly increased. In conclusion, the consumption of EF in diet at high doses illustrated the adverse effect on some biochemical parameters and histopathology in mice. Our findings suggested that EF daily consumption for 24 weeks, at higher doses than the 0.8% EF diet (35 times of human consumption), might cause adverse effect on kidney function in mice. JF - Toxicological research AU - Janwitthayanuchit, Kanittha AU - Kupradinun, Piengchai AU - Rungsipipat, Anudep AU - Kettawan, Aikkarach AU - Butryee, Chaniphun AD - Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand. ; Research Division, National Cancer Institute, Bangkok, Thailand. ; Department of Veterinary Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 231 EP - 237 VL - 32 IS - 3 SN - 1976-8257, 1976-8257 KW - AIN-76 diet KW - Chronic toxicity KW - Eryngium foetidum Linn. KW - Kidney KW - Mice UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1806076513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+research&rft.atitle=A+24-Weeks+Toxicity+Study+of+Eryngium+foetidum+Linn.+Leaves+in+Mice.&rft.au=Janwitthayanuchit%2C+Kanittha%3BKupradinun%2C+Piengchai%3BRungsipipat%2C+Anudep%3BKettawan%2C+Aikkarach%3BButryee%2C+Chaniphun&rft.aulast=Janwitthayanuchit&rft.aufirst=Kanittha&rft.date=2016-07-01&rft.volume=32&rft.issue=3&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Toxicological+research&rft.issn=19768257&rft_id=info:doi/10.5487%2FTR.2016.32.3.231 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-20 N1 - Date created - 2016-07-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.5487/TR.2016.32.3.231 ER - TY - JOUR T1 - Identification of cooperative genes for E2A-PBX1 to develop acute lymphoblastic leukemia. AN - 1804866839; 27088431 AB - E2A-PBX1 is a chimeric gene product detected in t(1;19)-bearing acute lymphoblastic leukemia (ALL) with B-cell lineage. To investigate the leukemogenic process, we generated conditional knock-in (cKI) mice for E2A-PBX1, in which E2A-PBX1 is inducibly expressed under the control of the endogenous E2A promoter. Despite the induced expression of E2A-PBX1, no hematopoietic disease was observed, strongly suggesting that additional genetic alterations are required to develop leukemia. To address this possibility, retroviral insertional mutagenesis was used. Virus infection efficiently induced T-cell, B-cell, and biphenotypic ALL in E2A-PBX1 cKI mice. Inverse PCR identified eight retroviral common integration sites, in which enhanced expression was observed in the Gfi1, Mycn, and Pim1 genes. In addition, it is of note that viral integration and overexpression of the Zfp521 gene was detected in one tumor with B-cell lineage; we previously identified Zfp521 as a cooperative gene with E2A-HLF, another E2A-involving fusion gene with B-lineage ALL. The cooperative oncogenicity of E2A-PBX1 with overexpressed Zfp521 in B-cell tumorigenesis was indicated by the finding that E2A-PBX1 cKI, Zfp521 transgenic compound mice developed B-lineage ALL. Moreover, upregulation of ZNF521, the human counterpart of Zfp521, was found in several human leukemic cell lines bearing t(1;19). These results indicate that E2A-PBX1 cooperates with additional gene alterations to develop ALL. Among them, enhanced expression of ZNF521 may play a clinically relevant role in E2A fusion genes to develop B-lineage ALL. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. JF - Cancer science AU - Sera, Yasuyuki AU - Yamasaki, Norimasa AU - Oda, Hideaki AU - Nagamachi, Akiko AU - Wolff, Linda AU - Inukai, Takeshi AU - Inaba, Toshiya AU - Honda, Hiroaki AD - Department of Disease Model, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. ; Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan. ; Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. ; Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. ; Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 890 EP - 898 VL - 107 IS - 7 KW - Index Medicus KW - conditional knock-in mice KW - E2A-PBX1 KW - Zfp521/ZNF521 KW - Acute lymphoblastic leukemia KW - retroviral insertional mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804866839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+science&rft.atitle=Identification+of+cooperative+genes+for+E2A-PBX1+to+develop+acute+lymphoblastic+leukemia.&rft.au=Sera%2C+Yasuyuki%3BYamasaki%2C+Norimasa%3BOda%2C+Hideaki%3BNagamachi%2C+Akiko%3BWolff%2C+Linda%3BInukai%2C+Takeshi%3BInaba%2C+Toshiya%3BHonda%2C+Hiroaki&rft.aulast=Sera&rft.aufirst=Yasuyuki&rft.date=2016-07-01&rft.volume=107&rft.issue=7&rft.spage=890&rft.isbn=&rft.btitle=&rft.title=Cancer+science&rft.issn=1349-7006&rft_id=info:doi/10.1111%2Fcas.12945 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cas.12945 ER - TY - JOUR T1 - Phase I biomarker modulation study of atorvastatin in women at increased risk for breast cancer. AN - 1802740801; 27287781 AB - Selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene that reduce the risk of breast cancer are limited to only estrogen receptor-positive (ER(+)) breast cancer. In addition, patient acceptance of SERMs is low due to toxicity and intolerability. New agents with improved toxicity profile that reduce risk of ER-negative breast cancer are urgently needed. Observational studies show that statins can reduce breast cancer incidence and recurrence. The objective of this prospective short-term prevention study was to evaluate the effect of a lipophilic statin, atorvastatin, on biomarkers in breast tissue and serum of women at increased risk. Eligible participants included women with previous history of carcinoma in situ, or atypical hyperplasia, or 5 year breast cancer projected Gail risk >1.67 %, or lifetime breast cancer risk >20 % calculated by models including Claus, Tyrer-Cuzick, Boadicea, or BRCAPRO. Patients underwent baseline fine needle aspiration (FNA) of the breast, blood collection for biomarker analysis, and were randomized to either no treatment or atorvastatin at 10, 20, or 40 mg/day dose for 3 months. At 3 months, blood collection and breast FNA were repeated. Biomarkers included C-reactive protein (CRP), lipid profile, atorvastatin, and its metabolites, Ki-67, bcl-2, EGFR, and pEGFR. Baseline genotype for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) was also measured. Among 60 patients evaluated, a significant reduction in serum CRP, cholesterol and low-density lipoprotein (LDL), and increase in atorvastatin metabolites in serum and breast FNAs was demonstrated. No changes were observed in other tissue biomarkers. This study shows that atorvastatin and its metabolites are detectable in breast samples and may lower serum CRP among women without hyperlipidemia. JF - Breast cancer research and treatment AU - Arun, Banu K AU - Gong, Yun AU - Liu, Diane AU - Litton, Jennifer K AU - Gutierrez-Barrera, Angelica M AU - Jack Lee, J AU - Vornik, Lana AU - Ibrahim, Nuhad K AU - Cornelison, Terri AU - Hortobagyi, Gabriel N AU - Heckman-Stoddard, Brandy M AU - Koenig, Kimberly B AU - Alvarez, Ricardo R AU - Murray, James L AU - Valero, Vicente AU - Lippman, Scott M AU - Brown, Powel AU - Sneige, Nour AD - Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA. barun@mdanderson.org. ; Breast Medical Oncology and Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, CPB 5., Box 1354, Houston, TX, 77030, USA. ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ; Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ; Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA. ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 67 EP - 77 VL - 158 IS - 1 KW - Index Medicus KW - Statins KW - Breast cancer biomarkers KW - Breast cancer risk KW - Atorvastatin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802740801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Phase+I+biomarker+modulation+study+of+atorvastatin+in+women+at+increased+risk+for+breast+cancer.&rft.au=Arun%2C+Banu+K%3BGong%2C+Yun%3BLiu%2C+Diane%3BLitton%2C+Jennifer+K%3BGutierrez-Barrera%2C+Angelica+M%3BJack+Lee%2C+J%3BVornik%2C+Lana%3BIbrahim%2C+Nuhad+K%3BCornelison%2C+Terri%3BHortobagyi%2C+Gabriel+N%3BHeckman-Stoddard%2C+Brandy+M%3BKoenig%2C+Kimberly+B%3BAlvarez%2C+Ricardo+R%3BMurray%2C+James+L%3BValero%2C+Vicente%3BLippman%2C+Scott+M%3BBrown%2C+Powel%3BSneige%2C+Nour&rft.aulast=Arun&rft.aufirst=Banu&rft.date=2016-07-01&rft.volume=158&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=1573-7217&rft_id=info:doi/10.1007%2Fs10549-016-3849-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-08 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10549-016-3849-1 ER - TY - JOUR T1 - Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions AN - 1801951629 AB - This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing. JF - Journal of Clinical Child and Adolescent Psychology AU - Sherrill, Joel T AD - Division of Services & Intervention Research, National Institute of Mental Health Y1 - 2016///Jul/Aug PY - 2016 DA - Jul/Aug 2016 SP - 522 EP - 527 CY - Mahwah PB - Taylor & Francis Ltd. VL - 45 IS - 4 SN - 1537-4416 KW - Psychology KW - Advantages KW - Mental health KW - Intervention KW - Early intervention programmes KW - Interventions KW - Comments KW - Individualized KW - Approaches KW - Identification KW - Mental health services KW - Moderators UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801951629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Child+and+Adolescent+Psychology&rft.atitle=Adaptive+Treatment+Strategies+in+Youth+Mental+Health%3A+A+Commentary+on+Advantages%2C+Challenges%2C+and+Potential+Directions&rft.au=Sherrill%2C+Joel+T&rft.aulast=Sherrill&rft.aufirst=Joel&rft.date=2016-07-01&rft.volume=45&rft.issue=4&rft.spage=522&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Child+and+Adolescent+Psychology&rft.issn=15374416&rft_id=info:doi/10.1080%2F15374416.2016.1169539 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - This article not subject to U.S. copyright law. N1 - Last updated - 2016-08-17 DO - http://dx.doi.org/10.1080/15374416.2016.1169539 ER - TY - JOUR T1 - Attentional bias to threat in children at-risk for emotional disorders: role of gender and type of maternal emotional disorder AN - 1801607376 AB - Previous studies suggested that threat biases underlie familial risk for emotional disorders in children. However, major questions remain concerning the moderating role of the offspring gender and the type of parental emotional disorder on this association. This study addresses these questions in a large sample of boys and girls. Participants were 6-12 years old (at screening) typically developing children participating in the High Risk Cohort Study for Psychiatric Disorders (n = 1280; 606 girls, 674 boys). Children were stratified according to maternal emotional disorder (none; mood disorder; anxiety disorder; comorbid anxiety/mood disorder) and gender. Attention biases were assessed using a dot-probe paradigm with threat, happy and neutral faces. A significant gender-by-parental emotional disorder interaction predicted threat bias, independent of anxiety and depression symptoms in children. Daughters of mothers with an emotional disorder showed increased attention to threat compared with daughters of disorder-free mothers, irrespective of the type of maternal emotion disorder. In contrast, attention bias to threat in boys only occurred in mothers with a non-comorbid mood disorder. No group differences were found for biases for happy-face cues. Gender and type of maternal emotional disorder predict attention bias in disorder-free children. This highlights the need for longitudinal research to clarify whether this pattern of threat-attention bias in children relates to the risk of developing anxiety and mood disorders later in life. JF - European Child & Adolescent Psychiatry AU - Montagner, Rachel AU - Mogg, Karin AU - Bradley, Brendan P AU - Pine, Daniel S AU - Czykiel, Marcelo S AU - Miguel, Euripedes Constantino AU - Rohde, Luis A AU - Manfro, Gisele G AU - Salum, Giovanni A AD - Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Southampton University, Southampton, UK ; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA ; São Paulo University, São Paulo, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents (INPD, CNPq), São Paulo, Brazil ; Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; São Paulo University, São Paulo, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents (INPD, CNPq), São Paulo, Brazil ; Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents (INPD, CNPq), São Paulo, Brazil Y1 - 2016/07// PY - 2016 DA - Jul 2016 SP - 735 EP - 742 CY - Dordrecht PB - Springer Science & Business Media VL - 25 IS - 7 SN - 1018-8827 KW - Medical Sciences--Psychiatry And Neurology KW - Attention KW - Threat KW - Mother-child KW - Anxiety KW - Depression KW - Cues KW - Daughters KW - High risk KW - Emotional disorders KW - At risk KW - Facial expressions KW - Comorbidity KW - Anxiety-Depression KW - Parents KW - Gender differences KW - Mothers KW - Screening KW - Attentional bias KW - Cohort analysis KW - Affective disorders KW - Familial factors KW - Children KW - Psychiatric disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801607376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Child+%26+Adolescent+Psychiatry&rft.atitle=Attentional+bias+to+threat+in+children+at-risk+for+emotional+disorders%3A+role+of+gender+and+type+of+maternal+emotional+disorder&rft.au=Montagner%2C+Rachel%3BMogg%2C+Karin%3BBradley%2C+Brendan+P%3BPine%2C+Daniel+S%3BCzykiel%2C+Marcelo+S%3BMiguel%2C+Euripedes+Constantino%3BRohde%2C+Luis+A%3BManfro%2C+Gisele+G%3BSalum%2C+Giovanni+A&rft.aulast=Montagner&rft.aufirst=Rachel&rft.date=2016-07-01&rft.volume=25&rft.issue=7&rft.spage=735&rft.isbn=&rft.btitle=&rft.title=European+Child+%26+Adolescent+Psychiatry&rft.issn=10188827&rft_id=info:doi/10.1007%2Fs00787-015-0792-3 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer-Verlag Berlin Heidelberg 2016 N1 - Last updated - 2016-08-16 DO - http://dx.doi.org/10.1007/s00787-015-0792-3 ER - TY - JOUR T1 - Inflammatory-Related Genetic Variants in Non-Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment. AN - 1801434917; 27197286 AB - Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammation-related genes with non-muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression. We considered 822 NMIBC included in the SBC/EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures. While no SNP was found to be associated with risk-of-recurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of-progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 × 10(-5)) and two SNPs in MASP1 and AIRE, showed a posterior probability ≥80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively. Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC. This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1144-50. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Masson-Lecomte, Alexandra AU - López de Maturana, Evangelina AU - Goddard, Michael E AU - Picornell, Antoni AU - Rava, Marta AU - González-Neira, Anna AU - Márquez, Mirari AU - Carrato, Alfredo AU - Tardon, Adonina AU - Lloreta, Josep AU - Garcia-Closas, Montserrat AU - Silverman, Debra AU - Rothman, Nathaniel AU - Kogevinas, Manolis AU - Allory, Yves AU - Chanock, Stephen J AU - Real, Francisco X AU - Malats, Núria AU - SBC/EPICURO Study Investigators AD - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Urology Department, Henri Mondor Academic Hospital, Paris Est Créteil University, Créteil, France. ; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ; Biosciences Research Division, Department of Environment and Primary Industries, Agribio, Bundoora, Victoria, Australia. Department of Food and Agricultural Systems, University of Melbourne, Melbourne, Australia. ; Human Genotyping-CEGEN Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ; Servicio de Oncología, Hospital Universitario Ramon y Cajal, Madrid, and Servicio de Oncología, Hospital Universitario de Elche, Elche, Spain. ; Department of Preventive Medicine, Universidad de Oviedo, Oviedo, Spain. ; Institut Municipal d'Investigació Mèdica - Hospital del Mar and Departament de Patologia, Hospital del Mar - IMAS, Barcelona, Spain. ; Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland. ; Centre for Research in Environmental Epidemiology (CREAL) and Institut Municipal d'Investigació Mèdica - Hospital del Mar, Barcelona, Spain. ; Pathology Department, Henri Mondor Academic Hospital, Paris Est Créteil University, INSERM, Créteil, France. ; Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. ; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. nmalats@cnio.es. ; SBC/EPICURO Study Investigators Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1144 EP - 1150 VL - 25 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801434917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Inflammatory-Related+Genetic+Variants+in+Non-Muscle-Invasive+Bladder+Cancer+Prognosis%3A+A+Multimarker+Bayesian+Assessment.&rft.au=Masson-Lecomte%2C+Alexandra%3BL%C3%B3pez+de+Maturana%2C+Evangelina%3BGoddard%2C+Michael+E%3BPicornell%2C+Antoni%3BRava%2C+Marta%3BGonz%C3%A1lez-Neira%2C+Anna%3BM%C3%A1rquez%2C+Mirari%3BCarrato%2C+Alfredo%3BTardon%2C+Adonina%3BLloreta%2C+Josep%3BGarcia-Closas%2C+Montserrat%3BSilverman%2C+Debra%3BRothman%2C+Nathaniel%3BKogevinas%2C+Manolis%3BAllory%2C+Yves%3BChanock%2C+Stephen+J%3BReal%2C+Francisco+X%3BMalats%2C+N%C3%BAria%3BSBC%2FEPICURO+Study+Investigators&rft.aulast=Masson-Lecomte&rft.aufirst=Alexandra&rft.date=2016-07-01&rft.volume=25&rft.issue=7&rft.spage=1144&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=1538-7755&rft_id=info:doi/10.1158%2F1055-9965.EPI-15-0894 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1055-9965.EPI-15-0894 ER - TY - JOUR T1 - Diallyl Disulfide (DADS), a Constituent of Garlic, Inactivates NF-κB and Prevents Colitis-Induced Colorectal Cancer by Inhibiting GSK-3β. AN - 1801434861; 27138790 AB - There is a strong belief that garlic has medicinal properties and may even reduce the risk of developing certain cancers including those of the gastrointestinal tract. The chemopreventive effects of garlic may be attributed to the anti-inflammatory properties of the sulfur-containing constituents of garlic, which includes diallyl disulfide (DADS). Here, we demonstrate that DADS prevented colorectal tumorigenesis in a mouse model of colitis-induced colorectal cancer. Supplementation with 85 ppm of DADS (60 mg daily human equivalent dose) in the diet of FVB/N mice treated with chemical carcinogen azoxymethane (AOM) and colonic irritant dextran sodium sulfate (DSS) resulted in the reduction in tumor incidence, tumor number, and tumor burden by 21.54%, 47.3%, and 66.4%, respectively. Further analysis revealed that mice fed the DADS-supplemented diet resolved the initial DSS-induced inflammation faster than those on the control diet, preventing prolonged inflammation and cellular transformation. Subsequent mechanistic studies in vitro suggest that DADS chemopreventive effects are mediated through NF-κB signaling. When SW480 colorectal cancer cells were treated with DADS, NF-κB nuclear localization and activity were diminished. Interestingly, NF-κB suppression was found to be dependent on DADS inhibition of GSK-3β, a positive regulator of NF-κB. Inhibition of GSK-3β and loss of nuclear NF-κB activity were also observed in vivo in AOM/DSS-treated mice fed a diet supplemented with 85 ppm DADS. Our results indicate that DADS can prevent tumorigenesis by suppressing inflammation, a process largely involving GSK-3β inhibition and consequential reduction in NF-κB nuclear localization. Cancer Prev Res; 9(7); 607-15. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer prevention research (Philadelphia, Pa.) AU - Saud, Shakir M AU - Li, Weidong AU - Gray, Zane AU - Matter, Matthias S AU - Colburn, Nancy H AU - Young, Matthew R AU - Kim, Young S AD - Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland. Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland. ; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland. Department of Infectious Disease, Guang'anmen Hospital, Beijing, China. ; Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, Maryland. ; Institute of Pathology, University Hospital of Basel, Basel, Switzerland. ; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland. ; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland. Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland. ; Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland. yk47s@nih.gov. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 607 EP - 615 VL - 9 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801434861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.atitle=Diallyl+Disulfide+%28DADS%29%2C+a+Constituent+of+Garlic%2C+Inactivates+NF-%CE%BAB+and+Prevents+Colitis-Induced+Colorectal+Cancer+by+Inhibiting+GSK-3%CE%B2.&rft.au=Saud%2C+Shakir+M%3BLi%2C+Weidong%3BGray%2C+Zane%3BMatter%2C+Matthias+S%3BColburn%2C+Nancy+H%3BYoung%2C+Matthew+R%3BKim%2C+Young+S&rft.aulast=Saud&rft.aufirst=Shakir&rft.date=2016-07-01&rft.volume=9&rft.issue=7&rft.spage=607&rft.isbn=&rft.btitle=&rft.title=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.issn=1940-6215&rft_id=info:doi/10.1158%2F1940-6207.CAPR-16-0044 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1940-6207.CAPR-16-0044 ER - TY - JOUR T1 - The Discovery and Early Days of TGF-β: A Historical Perspective. AN - 1801433497; 27328871 AB - Transforming growth factors (TGFs) were discovered as activities that were secreted by cancer cells, and later by normal cells, and had the ability to phenotypically and reversibly transform immortalized fibroblasts. TGF-β distinguished itself from TGF-α because it did not bind to the same epidermal growth factor (EGF) receptor as TGF-α and, therefore, acted through different cell-surface receptors and signaling mediators. This review summarizes the discovery of TGF-β, the early developments in its molecular and biological characterization with its many biological activities in different cell and tissue contexts and its roles in disease, the realization that there is a family of secreted TGF-β-related proteins with many differentiation functions in development and activities in normal cell and tissue physiology, and the subsequent identification and characterization of the receptors and effectors that mediate TGF-β family signaling responses. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved. JF - Cold Spring Harbor perspectives in biology AU - Moses, Harold L AU - Roberts, Anita B AU - Derynck, Rik AD - Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232. ; Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. ; Department of Cell and Tissue Biology, University of California, San Francisco, California 94143. Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 VL - 8 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801433497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+perspectives+in+biology&rft.atitle=The+Discovery+and+Early+Days+of+TGF-%CE%B2%3A+A+Historical+Perspective.&rft.au=Moses%2C+Harold+L%3BRoberts%2C+Anita+B%3BDerynck%2C+Rik&rft.aulast=Moses&rft.aufirst=Harold&rft.date=2016-07-01&rft.volume=8&rft.issue=7&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+perspectives+in+biology&rft.issn=1943-0264&rft_id=info:doi/10.1101%2Fcshperspect.a021865 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1101/cshperspect.a021865 ER - TY - JOUR T1 - Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. AN - 1801432810; 26842236 AB - PARP is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitor-mediated DNA damage. This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan. Patients with advanced solid tumors were treated with 100 mg/m(2) irinotecan on days 1 and 8 of a 21-day cycle. Twice-daily oral dosing of veliparib (10-50 mg) occurred on days 3 to 14 (cycle 1) and days -1 to 14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Paired tumor biopsies were obtained after irinotecan alone and veliparib/irinotecan to evaluate PARP1/2 inhibition and explore DNA damage signals (nuclear γ-H2AX and pNBS1). Thirty-five patients were treated. DLTs included fatigue, diarrhea, febrile neutropenia, and neutropenia. The MTD was 100 mg/m(2) irinotecan (days 1 and 8) combined with veliparib 40 mg twice daily (days -1-14) on a 21-day cycle. Of 31 response-evaluable patients, there were six (19%) partial responses. Veliparib exhibited linear PK, and there were no apparent PK interactions between veliparib and irinotecan. At all dose levels, veliparib reduced tumor poly(ADP-ribose) (PAR) content in the presence of irinotecan. Several samples showed increases in γ-H2AX and pNBS1 after veliparib/irinotecan compared with irinotecan alone. Veliparib can be safely combined with irinotecan at doses that inhibit PARP catalytic activity. Preliminary antitumor activity justifies further evaluation of the combination. Clin Cancer Res; 22(13); 3227-37. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - LoRusso, Patricia M AU - Li, Jing AU - Burger, Angelika AU - Heilbrun, Lance K AU - Sausville, Edward A AU - Boerner, Scott A AU - Smith, Daryn AU - Pilat, Mary Jo AU - Zhang, Jie AU - Tolaney, Sara M AU - Cleary, James M AU - Chen, Alice P AU - Rubinstein, Lawrence AU - Boerner, Julie L AU - Bowditch, Adam AU - Cai, Dongpo AU - Bell, Tracy AU - Wolanski, Andrew AU - Marrero, Allison M AU - Zhang, Yiping AU - Ji, Jiuping AU - Ferry-Galow, Katherine AU - Kinders, Robert J AU - Parchment, Ralph E AU - Shapiro, Geoffrey I AD - Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. geoffrey_shapiro@dfci.harvard.edu. ; Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. ; University of Maryland Greenebaum Cancer Center, Baltimore, Maryland. ; Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. Wayne State University, Detroit, Michigan. ; Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. ; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland. ; Clinical Pharmacodynamics Biomarker Program, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland. Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 3227 EP - 3237 VL - 22 IS - 13 SN - 1078-0432, 1078-0432 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801432810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+I+Safety%2C+Pharmacokinetic%2C+and+Pharmacodynamic+Study+of+the+Poly%28ADP-ribose%29+Polymerase+%28PARP%29+Inhibitor+Veliparib+%28ABT-888%29+in+Combination+with+Irinotecan+in+Patients+with+Advanced+Solid+Tumors.&rft.au=LoRusso%2C+Patricia+M%3BLi%2C+Jing%3BBurger%2C+Angelika%3BHeilbrun%2C+Lance+K%3BSausville%2C+Edward+A%3BBoerner%2C+Scott+A%3BSmith%2C+Daryn%3BPilat%2C+Mary+Jo%3BZhang%2C+Jie%3BTolaney%2C+Sara+M%3BCleary%2C+James+M%3BChen%2C+Alice+P%3BRubinstein%2C+Lawrence%3BBoerner%2C+Julie+L%3BBowditch%2C+Adam%3BCai%2C+Dongpo%3BBell%2C+Tracy%3BWolanski%2C+Andrew%3BMarrero%2C+Allison+M%3BZhang%2C+Yiping%3BJi%2C+Jiuping%3BFerry-Galow%2C+Katherine%3BKinders%2C+Robert+J%3BParchment%2C+Ralph+E%3BShapiro%2C+Geoffrey+I&rft.aulast=LoRusso&rft.aufirst=Patricia&rft.date=2016-07-01&rft.volume=22&rft.issue=13&rft.spage=3227&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-0652 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-0652 ER - TY - JOUR T1 - A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2. AN - 1801432435; 27197190 AB - Pancreatic cancers with aberrant expression of macrophage migration inhibitory factor (MIF) are particularly aggressive. To identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression, we analyzed the expression of coding and noncoding genes in high and low MIF-expressing tumors in multiple cohorts of pancreatic ductal adenocarcinoma (PDAC) patients. The key genes and pathways identified were linked to patient survival and were mechanistically, functionally, and clinically characterized using cell lines, a genetically engineered mouse model, and PDAC patient cohorts. Here, we report evidence of a novel MIF-driven signaling pathway that inhibits the orphan nuclear receptor NR3C2, a previously undescribed tumor suppressor that impacts aggressiveness and survival in PDAC. Mechanistically, MIF upregulated miR-301b that targeted NR3C2 and suppressed its expression. PDAC tumors expressing high levels of MIF displayed elevated levels of miR-301b and reduced levels of NR3C2. In addition, reduced levels of NR3C2 expression correlated with poorer survival in multiple independent cohorts of PDAC patients. Functional analysis showed that NR3C2 inhibited epithelial-to-mesenchymal transition and enhanced sensitivity to the gemcitabine, a chemotherapeutic drug used in PDAC standard of care. Furthermore, genetic deletion of MIF disrupted a MIF-mir-301b-NR3C2 signaling axis, reducing metastasis and prolonging survival in a genetically engineered mouse model of PDAC. Taken together, our results offer a preclinical proof of principle for candidate therapies to target a newly described MIF-miR-301b-NR3C2 signaling axis for PDAC management. Cancer Res; 76(13); 3838-50. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer research AU - Yang, Shouhui AU - He, Peijun AU - Wang, Jian AU - Schetter, Aaron AU - Tang, Wei AU - Funamizu, Naotake AU - Yanaga, Katsuhiko AU - Uwagawa, Tadashi AU - Satoskar, Abhay R AU - Gaedcke, Jochen AU - Bernhardt, Markus AU - Ghadimi, B Michael AU - Gaida, Matthias M AU - Bergmann, Frank AU - Werner, Jens AU - Ried, Thomas AU - Hanna, Nader AU - Alexander, H Richard AU - Hussain, S Perwez AD - Pancreatic Cancer Unit, National Cancer Institute, Bethesda, Maryland. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. ; Department of Surgery, Jikei University School of Medicine, Tokyo, Japan. ; Department Pathology and Microbiology, Ohio State University, Columbus, Ohio. ; Department of General, Visceral and Pediatric Surgery, University Medicine, Göttingen, Germany. ; Institute of Pathology, University of Heidelberg, Heidelberg, Germany. ; Department of Surgery, Ludwig-Maximillians University, Munich, Germany. ; Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. ; Division of Surgical Oncology, University of Maryland School of Medicine, Baltimore, Maryland. ; Pancreatic Cancer Unit, National Cancer Institute, Bethesda, Maryland. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. hussainp@mail.nih.gov. Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 3838 EP - 3850 VL - 76 IS - 13 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801432435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=A+Novel+MIF+Signaling+Pathway+Drives+the+Malignant+Character+of+Pancreatic+Cancer+by+Targeting+NR3C2.&rft.au=Yang%2C+Shouhui%3BHe%2C+Peijun%3BWang%2C+Jian%3BSchetter%2C+Aaron%3BTang%2C+Wei%3BFunamizu%2C+Naotake%3BYanaga%2C+Katsuhiko%3BUwagawa%2C+Tadashi%3BSatoskar%2C+Abhay+R%3BGaedcke%2C+Jochen%3BBernhardt%2C+Markus%3BGhadimi%2C+B+Michael%3BGaida%2C+Matthias+M%3BBergmann%2C+Frank%3BWerner%2C+Jens%3BRied%2C+Thomas%3BHanna%2C+Nader%3BAlexander%2C+H+Richard%3BHussain%2C+S+Perwez&rft.aulast=Yang&rft.aufirst=Shouhui&rft.date=2016-07-01&rft.volume=76&rft.issue=13&rft.spage=3838&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=1538-7445&rft_id=info:doi/10.1158%2F0008-5472.CAN-15-2841 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/0008-5472.CAN-15-2841 ER - TY - JOUR T1 - 5MeCDDO Blocks Metabolic Activation but not Progression of Breast, Intestine, and Tongue Cancers. Is Antioxidant Response Element a Prevention Target? AN - 1801431533; 27150634 AB - The preventive efficacy of the triterpenoid 5MeCDDO was tested in two models of mammary cancer, the Min model of intestinal cancer, and a chemically induced model of head and neck cancer. In one model of mammary cancer, female Sprague-Dawley rats were administered MNU at 50 days of age, and 5MeCDDO (27 ppm) was administered in the diet beginning 5 days later for the duration of the study; 5MeCDDO was ineffective. In contrast, in a model examining initiation of mammary cancers by the procarcinogen dimethyl-benzanthracene, 5, 6-benzoflavone (500 ppm, an Ah receptor agonist) or 5MeCDDO (27 or 2.7 ppm) decreased tumor multiplicity by 90%, 80%, and 50%, respectively. This anti-initiating effect which is presumably mediated by altered metabolic activation parallels our observation that 5MeCDDO induced proteins of various antioxidant response element (ARE)-related phase II drug-metabolizing enzymes [e.g., GST Pi, AKR 7A3 (aflatoxicol), epoxide hydrolase, and quinone reductase] in the liver. 5MeCDDO tested in the 4-nitroquinoline-l-oxide (4-NQO) head and neck cancer model failed to decrease tumor incidence or invasiveness. In the Min mouse model of intestinal cancer, a high dose of 5MeCDDO (80 ppm) was weakly effective in reducing adenoma multiplicity [∼30% (P < 0.05)]; however, a lower dose was totally ineffective. These findings question whether measuring increased levels of certain ARE-related genes (e.g., quinone reductase, GST Pi), indicating decreased carcinogen activation are sufficient to imply general chemopreventive efficacy of a given agent or mixture. Cancer Prev Res; 9(7); 616-23. ©2016 AACR. ©2016 American Association for Cancer Research. JF - Cancer prevention research (Philadelphia, Pa.) AU - Lubet, Ronald A AU - Townsend, Reid AU - Clapper, Margie L AU - Juliana, M Margaret AU - Steele, Vernon E AU - McCormick, David L AU - Grubbs, Clinton J AD - Division of Cancer Prevention, Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, Maryland. ; Department of Cell Biology & Physiology and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. ; Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania. ; Chemoprevention Center, University of Alabama at Birmingham, Birmingham, Alabama. ; Life Sciences Group, IIT Research Institute, Chicago, Illinois. ; Chemoprevention Center, University of Alabama at Birmingham, Birmingham, Alabama. clintongrubbs@uabmc.edu. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 616 EP - 623 VL - 9 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801431533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.atitle=5MeCDDO+Blocks+Metabolic+Activation+but+not+Progression+of+Breast%2C+Intestine%2C+and+Tongue+Cancers.+Is+Antioxidant+Response+Element+a+Prevention+Target%3F&rft.au=Lubet%2C+Ronald+A%3BTownsend%2C+Reid%3BClapper%2C+Margie+L%3BJuliana%2C+M+Margaret%3BSteele%2C+Vernon+E%3BMcCormick%2C+David+L%3BGrubbs%2C+Clinton+J&rft.aulast=Lubet&rft.aufirst=Ronald&rft.date=2016-07-01&rft.volume=9&rft.issue=7&rft.spage=616&rft.isbn=&rft.btitle=&rft.title=Cancer+prevention+research+%28Philadelphia%2C+Pa.%29&rft.issn=1940-6215&rft_id=info:doi/10.1158%2F1940-6207.CAPR-15-0294 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1940-6207.CAPR-15-0294 ER - TY - JOUR T1 - SAHA-induced loss of tumor suppressor Pten gene promotes thyroid carcinogenesis in a mouse model. AN - 1801431304; 27267120 AB - Thyroid cancer is on the rise. Novel approaches are needed to improve the outcome of patients with recurrent and advanced metastatic thyroid cancers. FDA approval of suberoylanilide hydroxamic acid (SAHA; vorinostat), an inhibitor of histone deacetylase, for the treatment of hematological malignancies led to the clinical trials of vorinostat for advanced thyroid cancer. However, patients were resistant to vorinostat treatment. To understand the molecular basis of resistance, we tested the efficacy of SAHA in two mouse models of metastatic follicular thyroid cancer: Thrb(PV/PV) and Thrb(PV/PV)Pten(+/-) mice. In both, thyroid cancer is driven by overactivation of PI3K-AKT signaling. However, the latter exhibit more aggressive cancer progression due to haplodeficiency of the tumor suppressor, the Pten gene. SAHA had no effects on thyroid cancer progression in Thrb(PV/PV) mice, indicative of resistance to SAHA. Unexpectedly, thyroid cancer progressed in SAHA-treated Thrb(PV/PV)Pten(+/-) mice with accelerated occurrence of vascular invasion, anaplastic foci, and lung metastasis. Molecular analyses showed further activated PI3K-AKT in thyroid tumors of SAHA-treated Thrb(PV/PV)Pten(+/-) mice, resulting in the activated effectors, p-Rb, CDK6, p21(Cip1), p-cSrc, ezrin, and matrix metalloproteinases, to increase proliferation and invasion of tumor cells. Single-molecule DNA analysis indicated that the wild-type allele of the Pten gene was progressively lost, whereas carcinogenesis progressed in SAHA-treated Thrb(PV/PV)Pten(+/-) mice. Thus, this study has uncovered a novel mechanism by which SAHA-induced loss of the tumor suppressor Pten gene to promote thyroid cancer progression. Effectors downstream of the Pten loss-induced signaling may be potential targets to overcome resistance of thyroid cancer to SAHA. © 2016 Society for Endocrinology. JF - Endocrine-related cancer AU - Zhu, Xuguang AU - Kim, Dong Wook AU - Zhao, Li AU - Willingham, Mark C AU - Cheng, Sheue-Yann AD - Laboratory of Molecular BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Laboratory of Molecular BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA chengs@mail.nih.gov. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 521 EP - 533 VL - 23 IS - 7 KW - Index Medicus KW - tumor suppressor PTEN KW - thyroid hormone receptors KW - tumorigenesis KW - thyroid cancer KW - genetically engineered mouse model KW - vorinostat KW - SAHA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801431304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrine-related+cancer&rft.atitle=SAHA-induced+loss+of+tumor+suppressor+Pten+gene+promotes+thyroid+carcinogenesis+in+a+mouse+model.&rft.au=Zhu%2C+Xuguang%3BKim%2C+Dong+Wook%3BZhao%2C+Li%3BWillingham%2C+Mark+C%3BCheng%2C+Sheue-Yann&rft.aulast=Zhu&rft.aufirst=Xuguang&rft.date=2016-07-01&rft.volume=23&rft.issue=7&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Endocrine-related+cancer&rft.issn=1479-6821&rft_id=info:doi/10.1530%2FERC-16-0103 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1530/ERC-16-0103 ER - TY - JOUR T1 - Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards. AN - 1800703721; 27208077 AB - A computational framework was developed to assist in screening and prioritizing chemicals based on their dosimetry, toxicity, and potential exposures. The overall strategy started with contextualizing chemical activity observed in high-throughput toxicity screening (HTS) by mapping these assays to biological events described in Adverse Outcome Pathways (AOPs). Next, in vitro to in vivo (IVIVE) extrapolation was used to convert an in vitro dose to an external exposure level, which was compared with potential exposure levels to derive an AOP-based margins of exposure (MOE). In this study, the framework was applied to estimate MOEs for chemicals that can potentially cause developmental toxicity following a putative AOP for fetal vasculogenesis/angiogenesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe chemical disposition during pregnancy, fetal, neonatal, and infant to adulthood stages. Using this life-stage PBPK model, maternal exposures were estimated that would yield fetal blood levels equivalent to the chemical concentration that altered in vitro activity of selected HTS assays related to the most sensitive vasculogenesis/angiogenesis putative AOP. The resulting maternal exposure estimates were then compared with potential exposure levels using literature data or exposure models to derive AOP-based MOEs. Published by Oxford University Press on behalf of the Society of Toxicology 2016. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - El-Masri, Hisham AU - Kleinstreuer, Nicole AU - Hines, Ronald N AU - Adams, Linda AU - Tal, Tamara AU - Isaacs, Kristin AU - Wetmore, Barbara A AU - Tan, Yu-Mei AD - *National Human and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, RTP, North Carolina el-masri.hisham@epa.gov. ; National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, North Carolina. ; *National Human and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, RTP, North Carolina. ; National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency. ; ScitoVation, Research Triangle Park, North Carolina, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 230 EP - 243 VL - 152 IS - 1 KW - Index Medicus KW - life-stage KW - PBPK KW - AOPs KW - developmental toxicology KW - environmental toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800703721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Integration+of+Life-Stage+Physiologically+Based+Pharmacokinetic+Models+with+Adverse+Outcome+Pathways+and+Environmental+Exposure+Models+to+Screen+for+Environmental+Hazards.&rft.au=El-Masri%2C+Hisham%3BKleinstreuer%2C+Nicole%3BHines%2C+Ronald+N%3BAdams%2C+Linda%3BTal%2C+Tamara%3BIsaacs%2C+Kristin%3BWetmore%2C+Barbara+A%3BTan%2C+Yu-Mei&rft.aulast=El-Masri&rft.aufirst=Hisham&rft.date=2016-07-01&rft.volume=152&rft.issue=1&rft.spage=230&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfw082 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/toxsci/kfw082 ER - TY - JOUR T1 - Sirtuin 3 Protects against Urban Particulate Matter-Induced Autophagy in Human Bronchial Epithelial Cells. AN - 1800703664; 27125970 AB - Urban particulate matter (urban PM) is a heterogeneous mixture of various types of particles originating from different sources. Exposure to high concentrations of urban PM leading to adverse health effects is evaluated by using in vitro cultures of human lung epithelial cells. However, the mechanism underlying the correlation between high concentrations of urban PM exposure and adverse health effects has not been fully elucidated; urban PM-induced oxidative stress is considered as an important mechanism of urban PM-mediated cytotoxicity. Sirtuin 3 (SIRT3), a primary mitrochondrial deacetylase, controls cellular reactive oxygen species (ROS) production, and expression of antioxidant enzymes. In this study, we examined the role of SIRT3 in the regulation of urban PM-induced oxidative stress in normal primary human bronchial epithelial cells (HBEpiCs). Cell viability showed a time- and concentration-dependent decrease when exposed to urban PM, which could indicate that the amount of lactate dehydrogenase released from the cell in response to urban PM is related to cell viability in HBEpiC. The effects of urban PM on morphological and biochemical markers of autophagy in HBEpiC were analyzed by electron microscopy and Western blotting. Overexpression of SIRT3 inhibited urban PM-induced ROS generation, while concomitantly increasing the expression of antioxidant enzymes, and decreasing NF-κB activation and release of inflammation factors. Up-regulation of SIRT3 significantly inhibited the expression of autophagy markers and autophagic vacuole formation. Our findings provide a valuable insight into the potential role of the SIRT3 enzyme in regulating urban PM-induced autophagy by mediating urban PM-induced oxidative stress, which may contribute to urban PM-induced impairment of airway epithelial cell function. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Chen, I-Chieh AU - Huang, Hsin-Hsiu AU - Chen, Pei-Fen AU - Chiang, Hung-Che AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan. ; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan Department of Occupational Medicine, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan hcchiang@nhri.org.tw. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 113 EP - 127 VL - 152 IS - 1 KW - Index Medicus KW - sirtuin 3 KW - human bronchial epithelial cells KW - urban particulate matter KW - reactive oxygen species UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800703664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Sirtuin+3+Protects+against+Urban+Particulate+Matter-Induced+Autophagy+in+Human+Bronchial+Epithelial+Cells.&rft.au=Chen%2C+I-Chieh%3BHuang%2C+Hsin-Hsiu%3BChen%2C+Pei-Fen%3BChiang%2C+Hung-Che&rft.aulast=Chen&rft.aufirst=I-Chieh&rft.date=2016-07-01&rft.volume=152&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfw073 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/toxsci/kfw073 ER - TY - JOUR T1 - The Emergence of Systematic Review in Toxicology. AN - 1800703660; 27208075 AB - The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward. We conclude with a recommendation that as various agencies and organizations adapt systematic review methods, they continue to work together to ensure that there is a harmonized process for how the basic elements of systematic review methods are applied in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Stephens, Martin L AU - Betts, Kellyn AU - Beck, Nancy B AU - Cogliano, Vincent AU - Dickersin, Kay AU - Fitzpatrick, Suzanne AU - Freeman, James AU - Gray, George AU - Hartung, Thomas AU - McPartland, Jennifer AU - Rooney, Andrew A AU - Scherer, Roberta W AU - Verloo, Didier AU - Hoffmann, Sebastian AD - Johns Hopkins Center for Alternatives to Animal Testing, Baltimore, Maryland msteph14@jhu.edu. ; Freelance Science and Technology Writer, Takoma Park, Maryland. ; American Chemistry Council, Washington, District of Columbia. ; US Environmental Protection Agency, Arlington, Virginia. ; Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. ; Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland. ; ExxonMobil Biomedical Sciences, Annandale, New Jersey. ; George Washington University Milken Institute School of Public Health, Washington, DC. ; Johns Hopkins Center for Alternatives to Animal Testing, Baltimore, Maryland University of Konstanz, CAAT-Europe, Germany. ; Environmental Defense Fund, Washington, District of Columbia. ; Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina. ; European Food Safety Authority, Parma 43126, Italy. ; seh consulting + services, Paderborn 33098, Germany. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 10 EP - 16 VL - 152 IS - 1 KW - Index Medicus KW - risk of bias KW - data integration. KW - systematic review UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800703660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=The+Emergence+of+Systematic+Review+in+Toxicology.&rft.au=Stephens%2C+Martin+L%3BBetts%2C+Kellyn%3BBeck%2C+Nancy+B%3BCogliano%2C+Vincent%3BDickersin%2C+Kay%3BFitzpatrick%2C+Suzanne%3BFreeman%2C+James%3BGray%2C+George%3BHartung%2C+Thomas%3BMcPartland%2C+Jennifer%3BRooney%2C+Andrew+A%3BScherer%2C+Roberta+W%3BVerloo%2C+Didier%3BHoffmann%2C+Sebastian&rft.aulast=Stephens&rft.aufirst=Martin&rft.date=2016-07-01&rft.volume=152&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfw059 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/toxsci/kfw059 ER - TY - JOUR T1 - A Buffered Alcohol-Based Fixative for Histomorphologic and Molecular Applications. AN - 1800700656; 27221702 AB - Formalin-fixed paraffin-embedded (FFPE) tissue is the predominant preparation for diagnostic histopathological evaluation and increasingly the biospecimen on which molecular diagnostics are performed. However, formalin is carcinogenic and results in cross-linking of proteins and nicking and alterations of nucleic acids. Alternative fixatives, including 70% ethanol, improved biomolecular integrity; however, they have yet to replace neutral-buffered formalin (NBF). Herein, we describe the phosphate-buffered ethanol 70% (BE70) fixative. The histomorphology of BE70-fixed tissue is very similar to that of NBF; however, it is a non-cross-linking fixative and lacks the carcinogenic profile of formaldehyde-based fixatives. RNA isolated from tissue fixed in BE70 was of substantially higher quality and quantity than that was recovered from formalin-fixed tissue. Furthermore, the BE70 fixative showed excellent RNA and DNA integrity compared with that of NBF fixative based on real-time polymerase chain reaction analysis results. Immunohistochemical staining was similar for the antigen tested. In conclusion, BE70 is a non-cross-linking fixative that is superior to NBF and 70% ethanol with reference to biomolecule recovery and quality from paraffin-embedded tissue. Additional studies to compare the histomorphologic and immunohistochemical performance and utility in a clinical setting are required. © 2016 The Histochemical Society. JF - The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society AU - Perry, Candice AU - Chung, Joon-Yong AU - Ylaya, Kris AU - Choi, Chel Hun AU - Simpson, Amari AU - Matsumoto, Kaipo T AU - Smith, William A AU - Hewitt, Stephen M AD - Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (CP, J-YC, KY, CHC, AS, KTM, WAS, SMH)Antibody Characterization Laboratory, Advanced Technology Program, Leidos Biomedical Research, Inc., Frederick, Maryland (CP)Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (CHC). ; Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (CP, J-YC, KY, CHC, AS, KTM, WAS, SMH)Antibody Characterization Laboratory, Advanced Technology Program, Leidos Biomedical Research, Inc., Frederick, Maryland (CP)Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (CHC) genejock@helix.nih.gov. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 425 EP - 440 VL - 64 IS - 7 KW - Index Medicus KW - fixation KW - formalin KW - alcohol KW - histomorphology KW - RNA integrity KW - tissue KW - real-time RT-PCR KW - paraffin embedded UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800700656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journal+of+histochemistry+and+cytochemistry+%3A+official+journal+of+the+Histochemistry+Society&rft.atitle=A+Buffered+Alcohol-Based+Fixative+for+Histomorphologic+and+Molecular+Applications.&rft.au=Perry%2C+Candice%3BChung%2C+Joon-Yong%3BYlaya%2C+Kris%3BChoi%2C+Chel+Hun%3BSimpson%2C+Amari%3BMatsumoto%2C+Kaipo+T%3BSmith%2C+William+A%3BHewitt%2C+Stephen+M&rft.aulast=Perry&rft.aufirst=Candice&rft.date=2016-07-01&rft.volume=64&rft.issue=7&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=The+journal+of+histochemistry+and+cytochemistry+%3A+official+journal+of+the+Histochemistry+Society&rft.issn=1551-5044&rft_id=info:doi/10.1369%2F0022155416649579 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1369/0022155416649579 ER - TY - JOUR T1 - Long-Term Effects of In Utero Antiretroviral Exposure: Systolic and Diastolic Function in HIV-Exposed Uninfected Youth. AN - 1800404062; 26794032 AB - The aim of this study was to evaluate the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children. A prospective, multisite cohort study in HEU children was conducted by the Pediatric HIV/AIDS Cohort Study (PHACS). Echocardiographic measures of LV systolic and diastolic function and cardiac structure were obtained from HEU subjects aged ≥6 years enrolled in the PHACS Surveillance Monitoring of ART Toxicities study. Echocardiographic Z-scores were calculated using normative data from an established reference cohort. We used adjusted linear regression models to compare Z-scores for echocardiographic measures from HEU children exposed in utero to HAART with those exposed to non-HAART, adjusting for demographic and maternal health characteristics. One hundred seventy-four HEU subjects with echocardiograms and maternal ARV information were included (mean age 10.9 years; 48% male, 56% black non-Hispanic). Among 156 HEU youth with any ARV exposure, we observed no differences in Z-scores for LV systolic function measures between youth exposed in utero to HAART (39%) and HAART-unexposed youth in either unadjusted or adjusted models. In adjusted models, those exposed to HAART had significantly lower mitral late diastolic inflow velocities (adjusted mean Z-score = 0.00 vs. 0.52, p = .04) and significantly higher adjusted mean LV mass-to-volume ratio Z-scores (adjusted mean Z-score = 0.47 vs. 0.11, p = .03) than HAART-unexposed youth. Uninfected children with perinatal exposure to HAART had no difference in LV systolic function. However, small but significant differences in LV diastolic function and cardiac structure were observed, suggesting that continued monitoring for cardiac outcomes is warranted in this population. JF - AIDS research and human retroviruses AU - Guerra, Vitor AU - Leister, Erin C AU - Williams, Paige L AU - Starc, Thomas J AU - Lipshultz, Steven E AU - Wilkinson, James D AU - Van Dyke, Russell B AU - Hazra, Rohan AU - Colan, Steven D AD - 1 Department of Pediatrics, Tulane University School of Medicine , New Orleans, Louisiana. ; 2 Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health , Boston, Massachusetts. ; 3 Columbia University Medical Center , New York, New York. ; 4 Wayne State University School of Medicine and Children's Hospital of Michigan , Detroit, Michigan. ; 5 Eunice Kennedy Shriver National Institute of Child Health and Human Development , Bethesda, Maryland. ; 6 Harvard Medical School and Boston Children's Hospital , Boston, Massachusetts. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 621 EP - 627 VL - 32 IS - 7 KW - Index Medicus KW - AIDS/HIV UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800404062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Long-Term+Effects+of+In+Utero+Antiretroviral+Exposure%3A+Systolic+and+Diastolic+Function+in+HIV-Exposed+Uninfected+Youth.&rft.au=Guerra%2C+Vitor%3BLeister%2C+Erin+C%3BWilliams%2C+Paige+L%3BStarc%2C+Thomas+J%3BLipshultz%2C+Steven+E%3BWilkinson%2C+James+D%3BVan+Dyke%2C+Russell+B%3BHazra%2C+Rohan%3BColan%2C+Steven+D&rft.aulast=Guerra&rft.aufirst=Vitor&rft.date=2016-07-01&rft.volume=32&rft.issue=7&rft.spage=621&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=1931-8405&rft_id=info:doi/10.1089%2FAID.2015.0281 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1089/AID.2015.0281 ER - TY - JOUR T1 - A phase I study of mTOR inhibitor everolimus in association with cisplatin and radiotherapy for the treatment of locally advanced cervix cancer: PHOENIX I. AN - 1800128827; 27206639 AB - Cervix cancer (CC) represents the fourth most common cancer in women. Treatment involving cisplatin and radiotherapy has been the standard for locally advanced disease. Everolimus inhibits the aberrant activity of mTOR that is part of carcinogenesis in CC. Further everolimus inactivates the HPV E7 oncoprotein and inhibits its proliferation. Preclinical models have suggested that everolimus sensitizes tumoral cells and vasculature to cisplatin and radiotherapy. In a 3 + 3 design, the trial aimed to treat three dose levels of at least three patients with daily doses of everolimus (2.5, 5 and 10 mg/day), cisplatin and radiotherapy delivered in a 9-week interval in CC patients, stage IIB, IIIA or IIIB. Patients received everolimus from day -7 up to the last day of brachytherapy. Primary objective was to evaluate safety, toxicity and the maximum-tolerated dose (MTD) of everolimus in association with cisplatin and radiotherapy. Pharmacokinetic (PK) parameters and response rates were analyzed as secondary objectives. Thirteen patients were enrolled, 6 at 2.5 mg, 3 at 5 mg and 4 at 10 mg. Four patients did not complete the planned schedule, 1 at 2.5 mg presented grade 4 acute renal failure interpreted as dose-limiting toxicity (DLT) and 3 at 10 mg: 1 with disease progression, and 2 with DLTs-1 grade 3 rash and 1 grade 4 neutropenia. PK results were characterized by dose-dependent increases in AUC and C max. The MTD of everolimus in combination with cisplatin and radiotherapy has been defined as 5 mg/day. The data regarding safety and response rates support further studies. JF - Cancer chemotherapy and pharmacology AU - de Melo, Andréia Cristina AU - Grazziotin-Reisner, Rachele AU - Erlich, Felipe AU - Fontes Dias, Mariane S AU - Moralez, Giulliana AU - Carneiro, Michel AU - Ingles Garces, Álvaro Henrique AU - Guerra Alves, Flávia Vieira AU - Novaes Neto, Bruna AU - Fuchshuber-Moraes, Mateus AU - Morando, Juliane AU - Suarez-Kurtz, Guilherme AU - Ferreira, Carlos Gil AD - Brazilian National Cancer Institute, Rio de Janeiro, Brazil. andreia.melo@inca.gov.br. ; Brazilian National Cancer Institute, Rio de Janeiro, Brazil. ; Novartis, São Paulo, Brazil. ; Brazilian Clinical Cancer Research Network (RNPCC) - INCA/Decit/MS, D'or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 101 EP - 109 VL - 78 IS - 1 KW - Index Medicus KW - Everolimus KW - Phase I KW - Cisplatin KW - Cervix cancer KW - Radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800128827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=A+phase+I+study+of+mTOR+inhibitor+everolimus+in+association+with+cisplatin+and+radiotherapy+for+the+treatment+of+locally+advanced+cervix+cancer%3A+PHOENIX+I.&rft.au=de+Melo%2C+Andr%C3%A9ia+Cristina%3BGrazziotin-Reisner%2C+Rachele%3BErlich%2C+Felipe%3BFontes+Dias%2C+Mariane+S%3BMoralez%2C+Giulliana%3BCarneiro%2C+Michel%3BIngles+Garces%2C+%C3%81lvaro+Henrique%3BGuerra+Alves%2C+Fl%C3%A1via+Vieira%3BNovaes+Neto%2C+Bruna%3BFuchshuber-Moraes%2C+Mateus%3BMorando%2C+Juliane%3BSuarez-Kurtz%2C+Guilherme%3BFerreira%2C+Carlos+Gil&rft.aulast=de+Melo&rft.aufirst=Andr%C3%A9ia&rft.date=2016-07-01&rft.volume=78&rft.issue=1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=1432-0843&rft_id=info:doi/10.1007%2Fs00280-016-3064-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00280-016-3064-0 ER - TY - JOUR T1 - Promoter SNPs rs116896264 and rs73933062 form a distinct haplotype and are associated with galectin-4 overexpression in colorectal cancer. AN - 1799563558; 26681582 AB - Galectin-4 is a member of the galectin family which consists of 15 galactoside-binding proteins. Previously, galectin-4 has been shown to have a role in cancer progression and metastasis and it is found upregulated in many solid tumours, including colorectal cancer (CRC). Recently, the role in the metastatic process was suggested to be via promoting cancer cells to adhere to blood vascular endothelium. In the present study, the regulatory region of LGALS4 (galectin-4) in seven colon cell lines was investigated with respect to genetic variation that could be linked to expression levels and therefore a tumourigenic effect. Interestingly, qRT-PCR and sequencing results revealed that galectin-4 upregulation is associated with SNPs rs116896264 and rs73933062. By use of luciferase reporter- and pull-down assays, we confirmed the association between the gene upregulation and the two SNPs. Also, using pull-down assay followed by mass spectrometry, we found that the presence rs116896264 and rs73933062 is changing transcription factors binding sites. In order to assess the frequencies of the two SNPs among colon cancer patients and healthy individuals, we genotyped 75 colon cancer patients, 12 patients with adenomatous polyposis and 17 patients with ulcerative colitis and we performed data mining in the 1000 genomes databank. We found the two SNPs co-occuring in 21% of 75 CRC patients, 0 out of 12 patients of adenomatous polyposis, and 6 out of 17 patients (35%) with ulcerative colitis. Both in the patient samples and in the 1000 genomes project, the two SNPs were found to co-occur whenever present (D' = 1). © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. JF - Mutagenesis AU - Helwa, Reham AU - Ramadan, Mohamed AU - Abdel-Wahab, Abdel-Hady A AU - Knappskog, Stian AU - Bauer, Andrea S AD - Molecular Cell Biology Lab, Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt, Division of Functional Genome Analysis, Deutsche Krebsforschungszentrum (DKFZ), Heidelberg, Germany, rehamhg@yahoo.com. ; Surgical Oncology Department and. ; Cancer Biology Department, Egyptian National Cancer Institute, Cairo University, Cairo, Egypt. ; Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway and Department of Oncology, Haukeland University Hospital, Bergen, Norway. ; Division of Functional Genome Analysis, Deutsche Krebsforschungszentrum (DKFZ), Heidelberg, Germany. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 401 EP - 408 VL - 31 IS - 4 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1799563558?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Promoter+SNPs+rs116896264+and+rs73933062+form+a+distinct+haplotype+and+are+associated+with+galectin-4+overexpression+in+colorectal+cancer.&rft.au=Helwa%2C+Reham%3BRamadan%2C+Mohamed%3BAbdel-Wahab%2C+Abdel-Hady+A%3BKnappskog%2C+Stian%3BBauer%2C+Andrea+S&rft.aulast=Helwa&rft.aufirst=Reham&rft.date=2016-07-01&rft.volume=31&rft.issue=4&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=1464-3804&rft_id=info:doi/10.1093%2Fmutage%2Fgev086 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/mutage/gev086 ER - TY - JOUR T1 - Systemic PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by eliminating activated hepatic stellate cells. AN - 1799561040; 26710118 AB - Liver fibrosis is a common outcome of chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. No US Food and Drug Administration-approved targeted antifibrotic therapy exists. Activated hepatic stellate cells (aHSCs) are the major cell types responsible for liver fibrosis; therefore, eradication of aHSCs, while preserving quiescent HSCs and other normal cells, is a logical strategy to stop and/or reverse liver fibrogenesis/fibrosis. However, there are no effective approaches to specifically deplete aHSCs during fibrosis without systemic toxicity. aHSCs are associated with elevated expression of death receptors and become sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. Treatment with recombinant TRAIL could be a potential strategy to ameliorate liver fibrosis; however, the therapeutic application of recombinant TRAIL is halted due to its very short half-life. To overcome this problem, we previously generated PEGylated TRAIL (TRAILPEG ) that has a much longer half-life in rodents than native-type TRAIL. In this study, we demonstrate that intravenous TRAILPEG has a markedly extended half-life over native-type TRAIL in nonhuman primates and has no toxicity in primary human hepatocytes. Intravenous injection of TRAILPEG directly induces apoptosis of aHSCs in vivo and ameliorates carbon tetrachloride-induced fibrosis/cirrhosis in rats by simultaneously down-regulating multiple key fibrotic markers that are associated with aHSCs. TRAIL-based therapies could serve as new therapeutics for liver fibrosis/cirrhosis and possibly other fibrotic diseases. (Hepatology 2016;64:209-223). © 2015 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Oh, Yumin AU - Park, Ogyi AU - Swierczewska, Magdalena AU - Hamilton, James P AU - Park, Jong-Sung AU - Kim, Tae Hyung AU - Lim, Sung-Mook AU - Eom, Hana AU - Jo, Dong Gyu AU - Lee, Choong-Eun AU - Kechrid, Raouf AU - Mastorakos, Panagiotis AU - Zhang, Clark AU - Hahn, Sei Kwang AU - Jeon, Ok-Cheol AU - Byun, Youngro AU - Kim, Kwangmeyung AU - Hanes, Justin AU - Lee, Kang Choon AU - Pomper, Martin G AU - Gao, Bin AU - Lee, Seulki AD - The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD. ; Divison of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. ; College of Pharmacy, Sungkyunkwan University, Suwon, Korea. ; Department of Biological Science, Sungkyunkwan University, Suwon, Korea. ; Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD. ; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD. ; Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang, Korea. ; College of Pharmacy, Seoul National University, Seoul, Korea. ; Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 209 EP - 223 VL - 64 IS - 1 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1799561040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Systemic+PEGylated+TRAIL+treatment+ameliorates+liver+cirrhosis+in+rats+by+eliminating+activated+hepatic+stellate+cells.&rft.au=Oh%2C+Yumin%3BPark%2C+Ogyi%3BSwierczewska%2C+Magdalena%3BHamilton%2C+James+P%3BPark%2C+Jong-Sung%3BKim%2C+Tae+Hyung%3BLim%2C+Sung-Mook%3BEom%2C+Hana%3BJo%2C+Dong+Gyu%3BLee%2C+Choong-Eun%3BKechrid%2C+Raouf%3BMastorakos%2C+Panagiotis%3BZhang%2C+Clark%3BHahn%2C+Sei+Kwang%3BJeon%2C+Ok-Cheol%3BByun%2C+Youngro%3BKim%2C+Kwangmeyung%3BHanes%2C+Justin%3BLee%2C+Kang+Choon%3BPomper%2C+Martin+G%3BGao%2C+Bin%3BLee%2C+Seulki&rft.aulast=Oh&rft.aufirst=Yumin&rft.date=2016-07-01&rft.volume=64&rft.issue=1&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28432 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28432 ER - TY - JOUR T1 - Delta-Like Ligand 4 Modulates Liver Damage by Down-Regulating Chemokine Expression. AN - 1799558554; 27171900 AB - Disrupting Notch signaling ameliorates experimental liver fibrosis. However, the role of individual Notch ligands in liver damage is unknown. We investigated the effects of Delta-like ligand 4 (Dll4) in liver disease. DLL4 expression was measured in 31 human liver tissues by immunohistochemistry. Dll4 function was examined in carbon tetrachloride- and bile duct ligation-challenged mouse models in vivo and evaluated in hepatic stellate cells, hepatocytes, and Kupffer cells in vitro. DLL4 was expressed in patients' Kupffer and liver sinusoidal endothelial cells. Recombinant Dll4 protein (rDll4) ameliorated hepatocyte apoptosis, inflammation, and fibrosis in mice after carbon tetrachloride challenge. In vitro, rDll4 significantly decreased lipopolysaccharide-dependent chemokine expression in both Kupffer and hepatic stellate cells. In bile duct ligation mice, rDll4 induced massive hepatic necrosis, resulting in the death of all animals within 1 week. Inflammatory cell infiltration and chemokine ligand 2 (Ccl2) expression were significantly reduced in rDll4-receiving bile duct ligation mice. Recombinant Ccl2 rescued bile duct ligation mice from rDll4-mediated death. In patients with acute-on-chronic liver failure, DLL4 expression was inversely associated with CCL2 abundance. Mechanistically, Dll4 regulated Ccl2 expression via NF-κB. Taken together, Dll4 modulates liver inflammatory response by down-regulating chemokine expression. rDll4 application results in opposing outcomes in two models of liver damage. Loss of DLL4 may be associated with CCL2-mediated cytokine storm in patients with acute-on-chronic liver failure. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. JF - The American journal of pathology AU - Shen, Zhe AU - Liu, Yan AU - Dewidar, Bedair AU - Hu, Junhao AU - Park, Ogyi AU - Feng, Teng AU - Xu, Chengfu AU - Yu, Chaohui AU - Li, Qi AU - Meyer, Christoph AU - Ilkavets, Iryna AU - Müller, Alexandra AU - Stump-Guthier, Carolin AU - Munker, Stefan AU - Liebe, Roman AU - Zimmer, Vincent AU - Lammert, Frank AU - Mertens, Peter R AU - Li, Hai AU - Ten Dijke, Peter AU - Augustin, Hellmut G AU - Li, Jun AU - Gao, Bin AU - Ebert, Matthias P AU - Dooley, Steven AU - Li, Youming AU - Weng, Hong-Lei AD - Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. ; Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Centre, RC Leiden, the Netherlands. ; Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. ; Division of Vascular Oncology and Metastasis, German Cancer Research Center, Center of Molecular Biology, Heidelberg University Alliance, Heidelberg, Germany. ; Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland. ; Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Division of Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany. ; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany. ; Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke-University, Magdeburg, Germany. ; Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. ; Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Centre, RC Leiden, the Netherlands. ; Division of Vascular Oncology and Metastasis, German Cancer Research Center, Center of Molecular Biology, Heidelberg University Alliance, Heidelberg, Germany; Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; German Cancer Consortium, Heidelberg, Germany. ; Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. ; Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address: zlym@zju.edu.cn. ; Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: honglei.weng@medma.uni-heidelberg.de. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1874 EP - 1889 VL - 186 IS - 7 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1799558554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Delta-Like+Ligand+4+Modulates+Liver+Damage+by+Down-Regulating+Chemokine+Expression.&rft.au=Shen%2C+Zhe%3BLiu%2C+Yan%3BDewidar%2C+Bedair%3BHu%2C+Junhao%3BPark%2C+Ogyi%3BFeng%2C+Teng%3BXu%2C+Chengfu%3BYu%2C+Chaohui%3BLi%2C+Qi%3BMeyer%2C+Christoph%3BIlkavets%2C+Iryna%3BM%C3%BCller%2C+Alexandra%3BStump-Guthier%2C+Carolin%3BMunker%2C+Stefan%3BLiebe%2C+Roman%3BZimmer%2C+Vincent%3BLammert%2C+Frank%3BMertens%2C+Peter+R%3BLi%2C+Hai%3BTen+Dijke%2C+Peter%3BAugustin%2C+Hellmut+G%3BLi%2C+Jun%3BGao%2C+Bin%3BEbert%2C+Matthias+P%3BDooley%2C+Steven%3BLi%2C+Youming%3BWeng%2C+Hong-Lei&rft.aulast=Shen&rft.aufirst=Zhe&rft.date=2016-07-01&rft.volume=186&rft.issue=7&rft.spage=1874&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=1525-2191&rft_id=info:doi/10.1016%2Fj.ajpath.2016.03.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ajpath.2016.03.010 ER - TY - JOUR T1 - Ring Catalog: A resource for designing self-assembling RNA nanostructures. AN - 1799556157; 27090005 AB - Designing self-assembling RNA ring structures based on known 3D structural elements connected via linker helices is a challenging task due to the immense number of motif combinations, many of which do not lead to ring-closure. We describe an in silico solution to this design problem by combinatorial assembly of RNA 3-way junctions, bulges, and kissing loops, and tabulating the cases that lead to ring formation. The solutions found are made available in the form of a web-accessible Ring Catalog. As an example of a potential use of this resource, we chose a predicted RNA square structure consisting of five RNA strands and demonstrate experimentally that the self-assembly of those five strands leads to the formation of a square-like complex. This is a demonstration of a novel "design by catalog" approach to RNA nano-structure generation. The URL https://rnajunction.ncifcrf.gov/ringdb can be used to access the resource. Copyright © 2016. Published by Elsevier Inc. JF - Methods (San Diego, Calif.) AU - Parlea, Lorena AU - Bindewald, Eckart AU - Sharan, Rishabh AU - Bartlett, Nathan AU - Moriarty, Daniel AU - Oliver, Jerome AU - Afonin, Kirill A AU - Shapiro, Bruce A AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Frederick, MD 21702, USA. ; Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. ; Department of Chemistry, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223, USA. ; Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: shabirbr@mail.nih.gov. Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 128 EP - 137 VL - 103 KW - Index Medicus KW - 3D structural elements KW - Self-assembly KW - RNA nanoparticle KW - RNA motifs KW - Nanoconstruct KW - Sequence design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1799556157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+%28San+Diego%2C+Calif.%29&rft.atitle=Ring+Catalog%3A+A+resource+for+designing+self-assembling+RNA+nanostructures.&rft.au=Parlea%2C+Lorena%3BBindewald%2C+Eckart%3BSharan%2C+Rishabh%3BBartlett%2C+Nathan%3BMoriarty%2C+Daniel%3BOliver%2C+Jerome%3BAfonin%2C+Kirill+A%3BShapiro%2C+Bruce+A&rft.aulast=Parlea&rft.aufirst=Lorena&rft.date=2016-07-01&rft.volume=103&rft.issue=&rft.spage=128&rft.isbn=&rft.btitle=&rft.title=Methods+%28San+Diego%2C+Calif.%29&rft.issn=1095-9130&rft_id=info:doi/10.1016%2Fj.ymeth.2016.04.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ymeth.2016.04.016 ER - TY - JOUR T1 - Should anti-mesothelin therapies be explored in lung cancer? AN - 1799207531; 27210575 JF - Expert review of anticancer therapy AU - Thomas, Anish AD - a Thoracic and GI Oncology Branch, Center for Cancer Research , National Cancer Institute , Bethesda , MD , USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 677 EP - 679 VL - 16 IS - 7 KW - Index Medicus KW - lung adenocarcinoma KW - NSCLC KW - immunotoxin KW - antibody-drug conjugate KW - Mesothelin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1799207531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+review+of+anticancer+therapy&rft.atitle=Should+anti-mesothelin+therapies+be+explored+in+lung+cancer%3F&rft.au=Thomas%2C+Anish&rft.aulast=Thomas&rft.aufirst=Anish&rft.date=2016-07-01&rft.volume=16&rft.issue=7&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+anticancer+therapy&rft.issn=1744-8328&rft_id=info:doi/10.1080%2F14737140.2016.1192472 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/14737140.2016.1192472 ER - TY - JOUR T1 - Chemical Reactivity and Respiratory Toxicity of the α-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione. AN - 1797879218; 27025954 AB - Occupational exposure to 2,3-butanedione (BD) vapors has been associated with severe respiratory disease leading to the use of potentially toxic substitutes. We compared the reactivity and respiratory toxicity of BD with that of two structurally related substitutes, 2,3-pentanedione (PD) and 2,3-hexanedione (HD). Chemical reactivity of the diketones with an arginine substrate decreased with increasing chain length (BD > PD > HD). Animals were evaluated the morning after a 2-week exposure to 0, 100, 150, or 200 ppm BD, PD, or HD (postexposure) or 2 weeks later (recovery). Bronchial fibrosis was observed in 5/5 BD and 5/5 PD rats at 200 ppm and in 4/6 BD and 6/6 PD rats at 150 ppm in the postexposure groups. Following recovery, bronchial fibrosis was observed in all surviving rats exposed to 200 ppm BD (5/5) or PD (3/3) and in 2/10 BD and 7/9 PD rats exposed to 150 ppm. Bronchial fibrosis was observed only in 2/12 HD-exposed rats in the 200 ppm postexposure group. Patchy interstitial fibrosis affected lungs of recovery groups exposed to 200 ppm PD (3/3) or BD (1/5) and to 150 ppm PD (4/9) or BD (7/10) and correlated with pulmonary function deficits. BD and PD were more reactive and produced more bronchial fibrosis than HD. © The Author(s) 2016. JF - Toxicologic pathology AU - Morgan, Daniel L AU - Jokinen, Micheal P AU - Johnson, Crystal L AU - Price, Herman C AU - Gwinn, William M AU - Bousquet, Ronald W AU - Flake, Gordon P AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA morgan3@niehs.nih.gov. ; Integrated Laboratory Systems, Morrisville, North Carolina, USA. ; Charles River Laboratories, Inc., Durham, North Carolina, USA. ; Alion Science and Technology, Research Triangle Park, North Carolina, USA. ; National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 763 EP - 783 VL - 44 IS - 5 KW - Index Medicus KW - 2,3-pentanedione (acetyl propionyl) KW - 2,3-hexanedione (acetyl butyryl) KW - pulmonary function KW - flavoring agents KW - fibrosis KW - 2,3-butanedione (diacetyl) KW - obliterative bronchiolitis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797879218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Chemical+Reactivity+and+Respiratory+Toxicity+of+the+%CE%B1-Diketone+Flavoring+Agents%3A+2%2C3-Butanedione%2C+2%2C3-Pentanedione%2C+and+2%2C3-Hexanedione.&rft.au=Morgan%2C+Daniel+L%3BJokinen%2C+Micheal+P%3BJohnson%2C+Crystal+L%3BPrice%2C+Herman+C%3BGwinn%2C+William+M%3BBousquet%2C+Ronald+W%3BFlake%2C+Gordon+P&rft.aulast=Morgan&rft.aufirst=Daniel&rft.date=2016-07-01&rft.volume=44&rft.issue=5&rft.spage=763&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=1533-1601&rft_id=info:doi/10.1177%2F0192623316638962 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0192623316638962 ER - TY - JOUR T1 - Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma. AN - 1797877815; 26709844 AB - Various grades of adverse events are associated with sorafenib and have recently been considered as a surrogate of response in patients with advanced hepatocellular carcinoma. The aim of this prospective study was to measure the efficacy of a sorafenib dose reduction regimen, adjusted on patient's tolerability, and aimed at increasing the exposure to the drug. A total of 73/140 patients with advanced hepatocellular carcinoma receiving sorafenib developed relevant adverse events (grade ≥2) and were managed with a tolerable-adverse-event-protocol consisting of a drug stepwise dose reduction adjusted on patient's tolerability. The remaining 67 patients with toxicity grade 0-1 (minor adverse event group) were managed conventionally with just symptomatic treatment. Median follow-up was 7 months. By adopting the tolerable-adverse-event-protocol, 48% of patients meant to transiently or definitively interrupt the drug were kept on treatment. Macrovascular invasion with/out extra-hepatic spread (HR = 1.9, 95% CI: 1.3-2.8; P = 0.001) and sorafenib exposure <2 months (HR = 4, 95% CI: 2.5-6.4; P < 0.0001) were independently related to a worse survival. Overall disease control rate, time to progression and survival were: 63.5%, 6 and 9.1 months respectively. The tolerable-adverse-event-protocol group experienced a more favourable outcome with respect to the minor adverse event group as for disease control rate (78% vs. 48%: P < 0.0001), time to progression (9.5 vs. 3 months; HR = 0.3, 95% CI: 0.2-0.5, P < 0.0001) and survival (12.5 vs. 5.7 months; HR = 0.4, 95% CI: 0.3-0.6; P < 0.0001). In patients with advanced hepatocellular carcinoma, sorafenib dose adjustments based on inducing tolerability of relevant adverse events prolong drug exposure and maximize survival. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. JF - Liver international : official journal of the International Association for the Study of the Liver AU - Ponziani, Francesca Romana AU - Bhoori, Sherrie AU - Germini, Alessandro AU - Bongini, Marco AU - Flores, Maria AU - Sposito, Carlo AU - Facciorusso, Antonio AU - Gasbarrini, Antonio AU - Mazzaferro, Vincenzo AD - Surgery, Hepatology and Hepato-Oncology Group, Istituto Nazionale Tumori (National Cancer Institute), Milan, Italy. ; Internal Medicine and Gastroenterology, Catholic University, Gemelli Hospital, Rome, Italy. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1033 EP - 1042 VL - 36 IS - 7 KW - Index Medicus KW - tumour response KW - toxicity KW - adverse events KW - tolerable adverse event protocol KW - sorafenib KW - hepatocellular carcinoma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797877815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+international+%3A+official+journal+of+the+International+Association+for+the+Study+of+the+Liver&rft.atitle=Inducing+tolerability+of+adverse+events+increases+sorafenib+exposure+and+optimizes+patient%27s+outcome+in+advanced+hepatocellular+carcinoma.&rft.au=Ponziani%2C+Francesca+Romana%3BBhoori%2C+Sherrie%3BGermini%2C+Alessandro%3BBongini%2C+Marco%3BFlores%2C+Maria%3BSposito%2C+Carlo%3BFacciorusso%2C+Antonio%3BGasbarrini%2C+Antonio%3BMazzaferro%2C+Vincenzo&rft.aulast=Ponziani&rft.aufirst=Francesca&rft.date=2016-07-01&rft.volume=36&rft.issue=7&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Liver+international+%3A+official+journal+of+the+International+Association+for+the+Study+of+the+Liver&rft.issn=1478-3231&rft_id=info:doi/10.1111%2Fliv.13052 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/liv.13052 ER - TY - JOUR T1 - Positive parenting and children's prosocial behavior in eight countries AN - 1797846369 AB - Background Research supports the beneficial role of prosocial behaviors on children's adjustment and successful youth development. Empirical studies point to reciprocal relations between negative parenting and children's maladjustment, but reciprocal relations between positive parenting and children's prosocial behavior are understudied. In this study reciprocal relations between two different dimensions of positive parenting (quality of the mother-child relationship and the use of balanced positive discipline) and children's prosocial behavior were examined in Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Methods Mother-child dyads (N = 1105) provided data over 2 years in two waves (Mage of child in wave 1 = 9.31 years, SD = 0.73; 50% female). Results A model of reciprocal relations between parenting dimensions, but not among parenting and children's prosocial behavior, emerged. In particular, children with higher levels of prosocial behavior at age 9 elicited higher levels of mother-child relationship quality in the following year. Conclusions Findings yielded similar relations across countries, evidencing that being prosocial in late childhood contributes to some degree to the enhancement of a nurturing and involved mother-child relationship in countries that vary widely on sociodemographic profiles and psychological characteristics. Policy and intervention implications of this study are discussed. JF - Journal of Child Psychology and Psychiatry AU - Pastorelli, Concetta AU - Lansford, Jennifer E AU - Luengo Kanacri, Bernadette Paula AU - Malone, Patrick S AU - Di Giunta, Laura AU - Bacchini, Dario AU - Bombi, Anna Silvia AU - Zelli, Arnaldo AU - Miranda, Maria Concetta AU - Bornstein, Marc H AU - Tapanya, Sombat AU - Uribe Tirado, Liliana Maria AU - Alampay, Liane Pena AU - Al-Hassan, Suha M AU - Chang, Lei AU - Deater-Deckard, Kirby AU - Dodge, Kenneth A AU - Oburu, Paul AU - Skinner, Ann T AU - Sorbring, Emma AD - Department of Psychology, Sapienza University of Rome, Rome, Italy ; Center for Child and Family Policy, Duke University, Durham, NC, USA ; Department of Psychology, University of South Carolina, Columbia, SC, USA ; Interuniversity Centre for Research in the Genesis and Development of Prosocial and Antisocial Motivations, Sapienza University of Rome, Rome, Italy ; Department of Psychology, Second University of Naples, Caserta, Italy ; Department of Developmental and Social Psychology, Sapienza University of Rome, Rome, Italy ; Department of Education Sciences, Foro Italico University of Rome, Rome, Italy ; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA ; Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand ; Facultad de Psicologia, Universidad San Buenaventura, Medellin, Colombia ; Department of Psychology, Ateneo de Manila University, Metropolitan Manila, Philippines ; Department of Special Education, Hashemite University, Zarqa, Jordan ; Department of Educational Psychology, Chinese University of Hong Kong, Hong Kong, China ; Department of Psychology, Virginia Tech, Blacksburg, VA, USA ; Department of Educational Psychology, Maseno University, Maseno, Kenya ; Department of Psychology, University West, Trollhättan, Sweden Y1 - 2016/07// PY - 2016 DA - Jul 2016 SP - 824 EP - 834 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 7 KW - Psychology KW - Parenting KW - Sociodemographic aspects KW - Behaviour KW - Emotionally disturbed children KW - Academic disciplines KW - Young people KW - Social development KW - Child development KW - Interpersonal relationships KW - Quality KW - Childhood KW - Discipline KW - Prosocial behaviour KW - Philippines KW - Kenya KW - Jordan KW - Thailand KW - United States--US KW - Colombia KW - Italy KW - Sweden UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797846369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Positive+parenting+and+children%27s+prosocial+behavior+in+eight+countries&rft.au=Pastorelli%2C+Concetta%3BLansford%2C+Jennifer+E%3BLuengo+Kanacri%2C+Bernadette+Paula%3BMalone%2C+Patrick+S%3BDi+Giunta%2C+Laura%3BBacchini%2C+Dario%3BBombi%2C+Anna+Silvia%3BZelli%2C+Arnaldo%3BMiranda%2C+Maria+Concetta%3BBornstein%2C+Marc+H%3BTapanya%2C+Sombat%3BUribe+Tirado%2C+Liliana+Maria%3BAlampay%2C+Liane+Pena%3BAl-Hassan%2C+Suha+M%3BChang%2C+Lei%3BDeater-Deckard%2C+Kirby%3BDodge%2C+Kenneth+A%3BOburu%2C+Paul%3BSkinner%2C+Ann+T%3BSorbring%2C+Emma&rft.aulast=Pastorelli&rft.aufirst=Concetta&rft.date=2016-07-01&rft.volume=57&rft.issue=7&rft.spage=824&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12477 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-06-21 N1 - SubjectsTermNotLitGenreText - Colombia; Sweden; United States--US; Philippines; Italy; Jordan; Kenya; Thailand DO - http://dx.doi.org/10.1111/jcpp.12477 ER - TY - JOUR T1 - Evaluating differences in Pavlovian fear acquisition and extinction as predictors of outcome from cognitive behavioural therapy for anxious children AN - 1797846360 AB - Background Extinction is a key theoretical model of exposure-based treatments, such as cognitive behavioural therapy (CBT). This study examined whether individual differences in physiological responses and subjective stimulus evaluations as indices of fear extinction predicted response to CBT. Methods Thirty-two nonanxious comparisons and 44 anxious, 7-to-13-year-old children completed a Pavlovian conditioning and extinction task. Anxious children then completed group-based CBT. Skin conductance responses (SCRs) as well as subjective arousal and valence evaluations were measured in response to a conditioned stimulus paired with an aversive tone (CS+) and another conditioned stimulus presented alone (CS-). Both stimuli were presented alone during extinction. Diagnostic and symptom measures were completed before and after treatment. Results Like nonanxious comparisons, treatment responders did not acquire conditioned negative stimulus evaluations and displayed elevated SCRs that declined significantly across extinction trials. Nonresponders, by contrast, showed elevated negative stimulus evaluations of both CSs that were sensitive to extinction trials but showed no change in SCRs during extinction. Change in physiological but not evaluative indices of fear extinction predicted better treatment outcomes. Conclusions Individual differences in evaluative and physiological indices of fear extinction might moderate response to CBT. Read the Commentary on this article at doi: 10.1111/jcpp.12553 JF - Journal of Child Psychology and Psychiatry AU - Waters, Allison M AU - Pine, Daniel S AD - School of Applied Psychology, Griffith University, Mt Gravatt, Qld, Australia ; Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD, USA Y1 - 2016/07// PY - 2016 DA - Jul 2016 SP - 869 EP - 876 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 7 KW - Psychology KW - Physiology KW - Stimulus KW - Anxiety disorders KW - Extinction KW - Aversive KW - Psychological extinction KW - Galvanic skin response KW - Classical conditioning KW - Clinical outcomes KW - Fear KW - Cognitive behaviour therapy KW - Arousal KW - Individual differences KW - Children UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797846360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Evaluating+differences+in+Pavlovian+fear+acquisition+and+extinction+as+predictors+of+outcome+from+cognitive+behavioural+therapy+for+anxious+children&rft.au=Waters%2C+Allison+M%3BPine%2C+Daniel+S&rft.aulast=Waters&rft.aufirst=Allison&rft.date=2016-07-01&rft.volume=57&rft.issue=7&rft.spage=869&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12522 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-06-21 DO - http://dx.doi.org/10.1111/jcpp.12522 ER - TY - JOUR T1 - Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells. AN - 1797544225; 27095671 AB - Etoposide and doxorubicin, topoisomerase II poisons, are important drugs for the treatment of tumors in the clinic. Topoisomerases contain several free sulfhydryl groups which are important for their activity and are also potential targets for nitric oxide (NO)-induced nitrosation. NO, a physiological signaling molecule nitrosates many cellular proteins, causing altered protein and cellular functions. Here, we have evaluated the roles of NO/NO-derived species in the activity/stability of topo II both in vitro and in human tumor cells, and in the cytotoxicity of topo II-poisons, etoposide and doxorubicin. Treatment of purified topo IIα with propylamine propylamine nonoate (PPNO), an NO donor, resulted in inhibition of both the catalytic and relaxation activity in vitro, and decreased etoposide-dependent cleavable complex formation in both human HT-29 colon and MCF-7 breast cancer cells. PPNO treatment also induced significant nitrosation of topo IIα protein in these human tumor cells. These events, taken together, caused a significant resistance to etoposide in both cell lines. However, PPNO had no effect on doxorubicin-induced cleavable complex formation, or doxorubicin cytotoxicity in these cell lines. Inhibition of topo II function by NO/NO-derived species induces significant resistance to etoposide, without affecting doxorubicin cytotoxicity in human tumor cells. As tumors express inducible nitric oxide synthase and generate significant amounts of NO, modulation of topo II functions by NO/NO-derived species could render tumors resistant to certain topo II-poisons in the clinic. Published by Elsevier B.V. JF - Biochimica et biophysica acta AU - Kumar, Ashutosh AU - Ehrenshaft, Marilyn AU - Tokar, Erik J AU - Mason, Ronald P AU - Sinha, Birandra K AD - Immunity, Inflammation and Disease Laboratory, NIH, Research Triangle Park, North Carolina, USA. ; National Toxicology Program National Institutes of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. ; Immunity, Inflammation and Disease Laboratory, NIH, Research Triangle Park, North Carolina, USA. Electronic address: sinha1@niehs.nih.gov. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1519 EP - 1527 VL - 1860 IS - 7 SN - 0006-3002, 0006-3002 KW - Nitric Oxide Donors KW - 0 KW - Topoisomerase II Inhibitors KW - Nitric Oxide KW - 31C4KY9ESH KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - Cytotoxicity KW - VP-16 KW - Resistance KW - Topoisomerase II KW - Nitric oxide KW - Doxorubicin -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Enzyme Stability KW - DNA -- metabolism KW - MCF-7 Cells KW - DNA -- chemistry KW - HT29 Cells KW - Nucleic Acid Conformation KW - Female KW - Protein Conformation KW - Catalysis KW - Nitric Oxide Donors -- pharmacology KW - Etoposide -- pharmacology KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Colorectal Neoplasms -- pathology KW - DNA Topoisomerases, Type II -- metabolism KW - Nitric Oxide -- metabolism KW - Colorectal Neoplasms -- enzymology KW - Breast Neoplasms -- enzymology KW - Colorectal Neoplasms -- drug therapy KW - Topoisomerase II Inhibitors -- pharmacology KW - Drug Resistance, Neoplasm -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797544225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Nitric+oxide+inhibits+topoisomerase+II+activity+and+induces+resistance+to+topoisomerase+II-poisons+in+human+tumor+cells.&rft.au=Kumar%2C+Ashutosh%3BEhrenshaft%2C+Marilyn%3BTokar%2C+Erik+J%3BMason%2C+Ronald+P%3BSinha%2C+Birandra+K&rft.aulast=Kumar&rft.aufirst=Ashutosh&rft.date=2016-07-01&rft.volume=1860&rft.issue=7&rft.spage=1519&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/10.1016%2Fj.bbagen.2016.04.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-10 N1 - Date created - 2016-06-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bbagen.2016.04.009 ER - TY - JOUR T1 - K-Ras4B/calmodulin/PI3Kα: A promising new adenocarcinoma-specific drug target? AN - 1797255630; 26873344 AB - Decades of efforts have yet to yield a safe and effective drug to target KRAS-driven pancreatic, colorectal and lung cancers; particularly those driven by the highly oncogenic splice variant KRAS4B. K-Ras4B's fairly smooth surface, cancer tissue/cell heterogeneity, tolerated lipid post-translational modification exchange, as well as drug-elicited toxicity present a daunting challenge. Within this framework, hee we focus on a new adenocarcinoma-specific drug concept. Calmodulin (CaM) binds to K-Ras4B but not to the H-Ras or N-Ras isoforms. Physiologically, in calcium- and calmodulin-rich environments such as ductal tissues, calmodulin can sequester K-Ras4B from the membrane; in cancer, CaM/Ca(2+) can replace the missing receptor tyrosine kinase (RTK) signal, acting to fully activate PI3Kα. An oncogenic GTP-bound K-Ras4B/CaM/PI3Kα complex is supported by available experimental and clinical data; therefore, targeting it may address a pressing therapeutic need. High resolution electron microscopy (EM) or crystal structure of the tripartite complex would allow orthosteric or allosteric drug discovery to disrupt the CaM/PI3Kα interface and thus Akt/mTOR signaling. However, since drug resistance is expected to develop, combining it with compensatory pathways, particularly those involved in cell-cycle control, appears a reasonable strategy. JF - Expert opinion on therapeutic targets AU - Nussinov, Ruth AU - Muratcioglu, Serena AU - Tsai, Chung-Jung AU - Jang, Hyunbum AU - Gursoy, Attila AU - Keskin, Ozlem AD - a Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , National Cancer Institute at Frederick , Frederick , MD , USA. ; c Department of Chemical and Biological Engineering , Koc University , Istanbul , Turkey. ; d Department of Computer Engineering , Koc University , Istanbul , Turkey. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 831 EP - 842 VL - 20 IS - 7 KW - Index Medicus KW - calcium KW - pancreatic cancer KW - orthosteric drugs KW - lung cancer KW - allosteric drugs KW - colorectal cancer KW - K-Ras dimers KW - KRAS KW - small molecule drug KW - pancreatic ductal adenocarcinomas (PDAC) KW - KRAS4B KW - KRAS4A KW - calmodulin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797255630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+therapeutic+targets&rft.atitle=K-Ras4B%2Fcalmodulin%2FPI3K%CE%B1%3A+A+promising+new+adenocarcinoma-specific+drug+target%3F&rft.au=Nussinov%2C+Ruth%3BMuratcioglu%2C+Serena%3BTsai%2C+Chung-Jung%3BJang%2C+Hyunbum%3BGursoy%2C+Attila%3BKeskin%2C+Ozlem&rft.aulast=Nussinov&rft.aufirst=Ruth&rft.date=2016-07-01&rft.volume=20&rft.issue=7&rft.spage=831&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+therapeutic+targets&rft.issn=1744-7631&rft_id=info:doi/10.1517%2F14728222.2016.1135131 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1517/14728222.2016.1135131 ER - TY - JOUR T1 - Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia. AN - 1795881515; 26851769 AB - Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. JF - Neuroscience research AU - Nie, Xingju AU - Lowe, Danielle W AU - Rollins, Laura Grace AU - Bentzley, Jessica AU - Fraser, Jamie L AU - Martin, Renee AU - Singh, Inderjit AU - Jenkins, Dorothea AD - Center for Biomedical Imaging, Medical University of South Carolina, 165 Ashley Ave, Charleston, SC 29425, United States. Electronic address: niexi@musc.edu. ; Department of Pediatrics, Medical University of South Carolina, 165 Ashley Ave, Charleston, SC 29425, United States. Electronic address: clarkdw@musc.edu. ; Department of Psychology, University of Massachusetts, 100 Morrissey Blvd, Boston, MA 02125, United States. Electronic address: lgrollins@gmail.com. ; Department of Pediatrics, Medical University of South Carolina, 165 Ashley Ave, Charleston, SC 29425, United States. Electronic address: perkel@musc.edu. ; Medical Genetics Training Program, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-2152, United States. Electronic address: jamie.fraser@nih.gov. ; Department of Biostatistics and Epidemiology, Medical University of South Carolina, 165 Ashley Ave, Charleston, SC 29425, United States. Electronic address: hebertrl@musc.edu. ; Department of Pediatrics, Medical University of South Carolina, 165 Ashley Ave, Charleston, SC 29425, United States. Electronic address: singhi@musc.edu. ; Department of Pediatrics, Medical University of South Carolina, 165 Ashley Ave, Charleston, SC 29425, United States. Electronic address: jenkd@musc.edu. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 24 EP - 33 VL - 108 KW - Antioxidants KW - 0 KW - Inflammation Mediators KW - Nitric Oxide Synthase Type II KW - EC 1.14.13.39 KW - Caspase 3 KW - EC 3.4.22.- KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - N-acetylcysteine KW - Neonatal hypoxia ischemia KW - Redox regulation KW - Neuroprotection KW - Sex KW - Animals KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Brain -- drug effects KW - Brain Infarction -- therapy KW - Brain -- metabolism KW - Inflammation Mediators -- metabolism KW - Brain Infarction -- pathology KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Motor Skills -- drug effects KW - Brain -- pathology KW - Cell Death KW - Nitric Oxide Synthase Type II -- metabolism KW - Time Factors KW - Male KW - Female KW - Caspase 3 -- metabolism KW - Hypoxia-Ischemia, Brain -- physiopathology KW - Hypoxia-Ischemia, Brain -- pathology KW - Acetylcysteine -- therapeutic use KW - Acetylcysteine -- administration & dosage KW - Antioxidants -- therapeutic use KW - Hypoxia-Ischemia, Brain -- therapy KW - Hypothermia, Induced KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795881515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+research&rft.atitle=Sex-specific+effects+of+N-acetylcysteine+in+neonatal+rats+treated+with+hypothermia+after+severe+hypoxia-ischemia.&rft.au=Nie%2C+Xingju%3BLowe%2C+Danielle+W%3BRollins%2C+Laura+Grace%3BBentzley%2C+Jessica%3BFraser%2C+Jamie+L%3BMartin%2C+Renee%3BSingh%2C+Inderjit%3BJenkins%2C+Dorothea&rft.aulast=Nie&rft.aufirst=Xingju&rft.date=2016-07-01&rft.volume=108&rft.issue=&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Neuroscience+research&rft.issn=1872-8111&rft_id=info:doi/10.1016%2Fj.neures.2016.01.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-26 N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neures.2016.01.008 ER - TY - JOUR T1 - Quantification of cannabinoids and their free and glucuronide metabolites in whole blood by disposable pipette extraction and liquid chromatography-tandem mass spectrometry. AN - 1795880822; 27236483 AB - Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1h for cannabidiol (CBD) and cannabinol (CBN) and Δ(9)-tetrahydrocannabinol (THC)-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200μL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100μg/L for THC and 11-nor-9-carboxy-THC (THCCOOH); 0.5-50μg/L for 11-hydroxy-THC (11-OH-THC), CBD, CBN, and THC-glucuronide; 1-50μg/L for CBG, THCV, and THCVCOOH; and 5-500μg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and -25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved. Published by Elsevier B.V. JF - Journal of chromatography. A AU - Scheidweiler, Karl B AU - Newmeyer, Matthew N AU - Barnes, Allan J AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. Electronic address: KScheidweiler@intra.nida.nih.gov. ; Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA; Program in Toxicology, University of Maryland, Baltimore, MD, USA. ; Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 34 EP - 42 VL - 1453 KW - Biomarkers KW - 0 KW - Cannabinoids KW - Glucuronides KW - Cannabidiol KW - 19GBJ60SN5 KW - tetrahydrocannabivarin 9 KW - 28172-17-0 KW - 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid KW - 4TPC9E4A32 KW - Dronabinol KW - 7J8897W37S KW - cannabigerol KW - J1K406072N KW - Index Medicus KW - Whole blood KW - Disposable pipette extraction KW - Recent use markers KW - Cannabidiol -- blood KW - Dronabinol -- analogs & derivatives KW - Humans KW - Dronabinol -- blood KW - Glucuronides -- blood KW - Biomarkers -- blood KW - Cannabinoids -- blood KW - Chromatography, Liquid -- methods KW - Cannabinoids -- isolation & purification KW - Tandem Mass Spectrometry -- methods KW - Marijuana Smoking KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795880822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+A&rft.atitle=Quantification+of+cannabinoids+and+their+free+and+glucuronide+metabolites+in+whole+blood+by+disposable+pipette+extraction+and+liquid+chromatography-tandem+mass+spectrometry.&rft.au=Scheidweiler%2C+Karl+B%3BNewmeyer%2C+Matthew+N%3BBarnes%2C+Allan+J%3BHuestis%2C+Marilyn+A&rft.aulast=Scheidweiler&rft.aufirst=Karl&rft.date=2016-07-01&rft.volume=1453&rft.issue=&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+A&rft.issn=1873-3778&rft_id=info:doi/10.1016%2Fj.chroma.2016.05.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-29 N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.chroma.2016.05.024 ER - TY - JOUR T1 - Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry. AN - 1795879683; 27122575 AB - Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses, including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Journal of virology AU - Rhein, Bethany A AU - Brouillette, Rachel B AU - Schaack, Grace A AU - Chiorini, John A AU - Maury, Wendy AD - Department of Microbiology, The University of Iowa, Iowa City, Iowa, USA. ; Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Microbiology, The University of Iowa, Iowa City, Iowa, USA wendy-maury@uiowa.edu. Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 6097 EP - 6111 VL - 90 IS - 13 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795879683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Characterization+of+Human+and+Murine+T-Cell+Immunoglobulin+Mucin+Domain+4+%28TIM-4%29+IgV+Domain+Residues+Critical+for+Ebola+Virus+Entry.&rft.au=Rhein%2C+Bethany+A%3BBrouillette%2C+Rachel+B%3BSchaack%2C+Grace+A%3BChiorini%2C+John+A%3BMaury%2C+Wendy&rft.aulast=Rhein&rft.aufirst=Bethany&rft.date=2016-07-01&rft.volume=90&rft.issue=13&rft.spage=6097&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/10.1128%2FJVI.00100-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1128/JVI.00100-16 ER - TY - JOUR T1 - Study sensitivity: Evaluating the ability to detect effects in systematic reviews of chemical exposures. AN - 1795870592; 27156196 AB - A critical step in systematic reviews of potential health hazards is the structured evaluation of the strengths and weaknesses of the included studies; risk of bias is a term often used to represent this process, specifically with respect to the evaluation of systematic errors that can lead to inaccurate (biased) results (i.e. focusing on internal validity). Systematic review methods developed in the clinical medicine arena have been adapted for use in evaluating environmental health hazards; this expansion raises questions about the scope of risk of bias tools and the extent to which they capture the elements that can affect the interpretation of results from environmental and occupational epidemiology studies and in vivo animal toxicology studies, (the studies typically available for assessment of risk of chemicals). One such element, described here as "sensitivity", is a measure of the ability of a study to detect a true effect or hazard. This concept is similar to the concept of the sensitivity of an assay; an insensitive study may fail to show a difference that truly exists, leading to a false conclusion of no effect. Factors relating to study sensitivity should be evaluated in a systematic manner with the same rigor as the evaluation of other elements within a risk of bias framework. We discuss the importance of this component for the interpretation of individual studies, examine approaches proposed or in use to address it, and describe how it relates to other evaluation components. The evaluation domains contained within a risk of bias tool can include, or can be modified to include, some features relating to study sensitivity; the explicit inclusion of these sensitivity criteria with the same rigor and at the same stage of study evaluation as other bias-related criteria can improve the evaluation process. In some cases, these and other features may be better addressed through a separate sensitivity domain. The combined evaluation of risk of bias and sensitivity can be used to identify the most informative studies, to evaluate the confidence of the findings from individual studies and to identify those study elements that may help to explain heterogeneity across the body of literature. Copyright © 2016. Published by Elsevier Ltd. JF - Environment international AU - Cooper, Glinda S AU - Lunn, Ruth M AU - Ågerstrand, Marlene AU - Glenn, Barbara S AU - Kraft, Andrew D AU - Luke, April M AU - Ratcliffe, Jennifer M AD - National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. Electronic address: cooper.glinda@epa.gov. ; Office of the Report on Carcinogens, Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, USA. ; Department of Environmental Science and Analytical Chemistry (ACES), Stockholm University, 106 91 Stockholm, Sweden. ; National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. ; Integrated Laboratory Systems (ILS), Research Triangle Park, NC, USA. PY - 2016 SP - 605 EP - 610 VL - 92-93 KW - Index Medicus KW - Study sensitivity KW - Validity KW - Chemical hazard assessment KW - Environmental health KW - Systematic review KW - Bias UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795870592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+international&rft.atitle=Study+sensitivity%3A+Evaluating+the+ability+to+detect+effects+in+systematic+reviews+of+chemical+exposures.&rft.au=Cooper%2C+Glinda+S%3BLunn%2C+Ruth+M%3B%C3%85gerstrand%2C+Marlene%3BGlenn%2C+Barbara+S%3BKraft%2C+Andrew+D%3BLuke%2C+April+M%3BRatcliffe%2C+Jennifer+M&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2016-07-01&rft.volume=92-93&rft.issue=&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Environment+international&rft.issn=1873-6750&rft_id=info:doi/10.1016%2Fj.envint.2016.03.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.envint.2016.03.017 ER - TY - JOUR T1 - The Association Between Post-traumatic Stress Disorder and Markers of Inflammation and Immune Activation in HIV-Infected Individuals With Controlled Viremia. AN - 1795870079; 27095586 AB - Post-traumatic stress disorder (PTSD) may be associated with chronic immune dysregulation and a proinflammatory state. Among HIV-infected individuals, PTSD is associated with greater morbidity and mortality, but the association with immune dysfunction has not been evaluated. This study explores the association between PTSD and selected markers of inflammation and immune activation in a cohort of HIV-infected, virally-suppressed individuals. HIV-infected adults who were virologically controlled on antiretroviral medications were recruited through a screening protocol for studies of HIV-related neurocognitive disorders. Each participant underwent blood draws, urine toxicology screen, and completed the Client Diagnostic Questionnaire, a semistructured psychiatric interview. Of 114 eligible volunteers, 72 (63%) were male, 77 (68%) African American, and 34 (30%) participants met criteria for PTSD. Participants with PTSD were more likely to be current smokers (79%) than those without (60%) (p = 0.05). The PTSD cohort had significantly higher total white blood cell counts (5318 and 6404 cells/uL, p = 0.03), absolute neutrophil count (2767 and 3577 cells/uL, p = 0.02), CD8% (43 and 48, p = 0.05), and memory CD8% (70 and 78%, p = 0.04); lower naïve CD8% (30 and 22%, p = 0.04) and higher rate of high-sensitivity C-reactive protein >3mg/L (29 and 20, p = 0.03). A high prevalence of PTSD was identified in this cohort of HIV-infected adults who were virally suppressed. These results suggest that PTSD may be associated with immune dysregulation even among antiretroviral therapy-adherent HIV-infected individuals. Published by Elsevier Inc. JF - Psychosomatics AU - Siyahhan Julnes, Peter AU - Auh, Sungyoung AU - Krakora, Rebecca AU - Withers, Keenan AU - Nora, Diana AU - Matthews, Lindsay AU - Steinbach, Sally AU - Snow, Joseph AU - Smith, Bryan AU - Nath, Avindra AU - Morse, Caryn AU - Kapetanovic, Suad AD - Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. Electronic address: peterselim.siyahhanjulnes@nih.gov. ; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. ; Critical Care Medicine Department, National Institutes of Health, Bethesda, MD. ; National Institute of Mental Health, National Institutes of Health, Bethesda, MD. ; Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Frederick, MD. ; Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. ; National Institute of Mental Health, National Institutes of Health, Bethesda, MD; Department of Psychiatry and The Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA. PY - 2016 SP - 423 EP - 430 VL - 57 IS - 4 KW - Index Medicus KW - client diagnostic questionnaire KW - PLWH KW - mental health KW - antiretroviral therapy KW - post-traumatic stress KW - immunophenotyping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795870079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychosomatics&rft.atitle=The+Association+Between+Post-traumatic+Stress+Disorder+and+Markers+of+Inflammation+and+Immune+Activation+in+HIV-Infected+Individuals+With+Controlled+Viremia.&rft.au=Siyahhan+Julnes%2C+Peter%3BAuh%2C+Sungyoung%3BKrakora%2C+Rebecca%3BWithers%2C+Keenan%3BNora%2C+Diana%3BMatthews%2C+Lindsay%3BSteinbach%2C+Sally%3BSnow%2C+Joseph%3BSmith%2C+Bryan%3BNath%2C+Avindra%3BMorse%2C+Caryn%3BKapetanovic%2C+Suad&rft.aulast=Siyahhan+Julnes&rft.aufirst=Peter&rft.date=2016-07-01&rft.volume=57&rft.issue=4&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Psychosomatics&rft.issn=1545-7206&rft_id=info:doi/10.1016%2Fj.psym.2016.02.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.psym.2016.02.015 ER - TY - JOUR T1 - Implementing systematic review techniques in chemical risk assessment: Challenges, opportunities and recommendations. AN - 1795867832; 26687863 AB - Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a "step change" in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved. JF - Environment international AU - Whaley, Paul AU - Halsall, Crispin AU - Ågerstrand, Marlene AU - Aiassa, Elisa AU - Benford, Diane AU - Bilotta, Gary AU - Coggon, David AU - Collins, Chris AU - Dempsey, Ciara AU - Duarte-Davidson, Raquel AU - FitzGerald, Rex AU - Galay-Burgos, Malyka AU - Gee, David AU - Hoffmann, Sebastian AU - Lam, Juleen AU - Lasserson, Toby AU - Levy, Len AU - Lipworth, Steven AU - Ross, Sarah Mackenzie AU - Martin, Olwenn AU - Meads, Catherine AU - Meyer-Baron, Monika AU - Miller, James AU - Pease, Camilla AU - Rooney, Andrew AU - Sapiets, Alison AU - Stewart, Gavin AU - Taylor, David AD - Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK. ; Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK. Electronic address: c.halsall@lancaster.ac.uk. ; Department of Environmental Science and Analytical Chemistry, Stockholm University, SE-106 91, Stockholm, Sweden. ; Assessment and Methodological Support Unit, European Food Safety Authority, Via Carlo Magno 1/a 43126, Parma, Italy. ; Food Standards Agency, Aviation House, 125 Kingsway, London WC2B 6NH, UK. ; Aquatic Research Centre, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK. ; MRC Lifecourse Epidemiology Unit, University of Southampton, MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton SO16 6YD, UK. ; Department of Geography and Environmental Science, School of Archaeology, Geography and Environmental Science, University of Reading, Reading, RG6 6DW, United Kingdom. ; Royal Society of Chemistry, Burlington House, Piccadilly, London W1J 0BA, UK. ; Centre for Radiation, Chemicals and Environmental Hazards, Public Health England, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0RQ, UK. ; Swiss Centre for Applied Human Toxicology, University of Basel, Missionsstrasse 64, 4055 Basel, Switzerland. ; European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Avenue Edmond Van Nieuwenhuyse 2 Bte 8B-1160 Brussels, Belgium. ; Institute for the Environment, Health and Societies, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UK. ; Evidence-Based Toxicology Collaboration (EBTC), Stembergring 15, 33106 Paderborn, Germany. ; University of California San Francisco, Program on Reproductive Health and the Environment, San Francisco, CA, USA. ; Cochrane Editorial Unit, Cochrane Central Executive, St Albans House, 57-9 Haymarket, London SW1Y 4QX, UK. ; Institute of Environment, Health, Risks and Futures, School of Energy, Environment and Agrifood, Cranfield University, Cranfield, Bedfordshire MK43 0AL, UK. ; Research Department of Clinical, Educational and Health Psychology, University College London, Gower Street, London WC1E 6BT, UK. ; Health Economics Research Group, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UK. ; Leibniz Research Centre for Working Environment and Human Factors (IfADo), Neurobehavioural Toxicology, Ardeystr 67, D-44139 Dortmund, Germany. ; Centre for Ecology and Hydrology, Wallingford, Oxfordshire 0X10 8BB, UK. ; Ramboll Environ, 1 Broad Gate, The Headrow, Leeds LS1 8EQ, UK. ; National Institute of Environmental Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, NC, USA. ; Syngenta Ltd., Jealott's Hill International Research Centre, Bracknell RG42 6EY, UK. ; Centre for Rural Economy, School of Agriculture, Food and Rural Development, University of Newcastle upon Tyne, UK. PY - 2016 SP - 556 EP - 564 VL - 92-93 KW - Index Medicus KW - Risk assessment KW - Environment KW - Chemicals KW - Research synthesis KW - Systematic review KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795867832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+international&rft.atitle=Implementing+systematic+review+techniques+in+chemical+risk+assessment%3A+Challenges%2C+opportunities+and+recommendations.&rft.au=Whaley%2C+Paul%3BHalsall%2C+Crispin%3B%C3%85gerstrand%2C+Marlene%3BAiassa%2C+Elisa%3BBenford%2C+Diane%3BBilotta%2C+Gary%3BCoggon%2C+David%3BCollins%2C+Chris%3BDempsey%2C+Ciara%3BDuarte-Davidson%2C+Raquel%3BFitzGerald%2C+Rex%3BGalay-Burgos%2C+Malyka%3BGee%2C+David%3BHoffmann%2C+Sebastian%3BLam%2C+Juleen%3BLasserson%2C+Toby%3BLevy%2C+Len%3BLipworth%2C+Steven%3BRoss%2C+Sarah+Mackenzie%3BMartin%2C+Olwenn%3BMeads%2C+Catherine%3BMeyer-Baron%2C+Monika%3BMiller%2C+James%3BPease%2C+Camilla%3BRooney%2C+Andrew%3BSapiets%2C+Alison%3BStewart%2C+Gavin%3BTaylor%2C+David&rft.aulast=Whaley&rft.aufirst=Paul&rft.date=2016-07-01&rft.volume=92-93&rft.issue=&rft.spage=556&rft.isbn=&rft.btitle=&rft.title=Environment+international&rft.issn=1873-6750&rft_id=info:doi/10.1016%2Fj.envint.2015.11.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.envint.2015.11.002 ER - TY - JOUR T1 - Safe use of high intakes of folic acid: research challenges and paths forward. AN - 1795867829; 27272334 AB - Adequate folic acid intake is an effective dietary-based prevention tool for reducing the risk of neural tube defects. Achieving adequate intake for the prevention of neural tube defects frequently requires the consumption of foods fortified with folic acid and/or the use of folic acid-containing dietary supplements. To date, research on the potential for adverse effects of high intakes of folic acid has been limited. Without such research, it is difficult to define a value for high intake. In May 2015, an expert panel was tasked with examining the available scientific literature and making research recommendations within 4 general categories of potential folate-related adverse health effects: cancer, cognition in conjunction with vitamin B12 deficiency, hypersensitivity-related outcomes, and thyroid and diabetes-related disorders. This article summarizes the expert panel's conclusions, outlines the challenges faced when reviewing the literature, and examines some of the panel's recommendations for research. Published by Oxford University Press on behalf of the International Life Sciences Institute 2016. This work is written by US Government employees and is in the public domain in the United States. JF - Nutrition reviews AU - Boyles, Abee L AU - Yetley, Elizabeth A AU - Thayer, Kristina A AU - Coates, Paul M AD - A.L. Boyles and K.A. Thayer are with the Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, North Carolina, USA. E.A. Yetley and P.M. Coates are with the Office of Dietary Supplements, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. abee.boyles@nih.gov. ; A.L. Boyles and K.A. Thayer are with the Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, North Carolina, USA. E.A. Yetley and P.M. Coates are with the Office of Dietary Supplements, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 469 EP - 474 VL - 74 IS - 7 KW - Index Medicus KW - folic acid KW - research recommendations KW - high vitamin intake KW - safety. UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795867829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=Safe+use+of+high+intakes+of+folic+acid%3A+research+challenges+and+paths+forward.&rft.au=Boyles%2C+Abee+L%3BYetley%2C+Elizabeth+A%3BThayer%2C+Kristina+A%3BCoates%2C+Paul+M&rft.aulast=Boyles&rft.aufirst=Abee&rft.date=2016-07-01&rft.volume=74&rft.issue=7&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=1753-4887&rft_id=info:doi/10.1093%2Fnutrit%2Fnuw015 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-09 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Erratum In: Nutr Rev. 2016 Sep;74(9):600 [27353599] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/nutrit/nuw015 ER - TY - JOUR T1 - Considerations for the combination of anticancer vaccines and immune checkpoint inhibitors. AN - 1795866492; 27010190 AB - Over the past few years, trials evaluating immunotherapies, particularly immune checkpoint inhibitors, have revolutionized the standard model of cancer treatment, demonstrating significant antitumor responses and improved clinical outcomes across a wide array of tumors types. Yet, despite these compelling data, a major limitation has been that only a fraction of patients mount a response to single-agent immune checkpoint inhibition. However, a growing amount of preclinical and clinical data suggests that combining immune checkpoint inhibition, either with other immune checkpoint inhibitors or with therapeutic cancer vaccines, has the potential to improve the proportion of patients seeing long-term durable responses with these therapies. We have reviewed the reported data on immune checkpoint inhibition as monotherapy and as combination therapy with other immune checkpoint inhibitors or therapeutic cancer vaccines. Data is reviewed on agents with FDA approval or breakthrough designation as of the writing of this manuscript. Particular focus is given to the combination of immune checkpoint inhibitors and therapeutic cancer vaccines which has the potential to increase efficacy compared to single agent immune checkpoint inhibition with minimal added toxicity. JF - Expert opinion on biological therapy AU - Strauss, Julius AU - Madan, Ravi A AU - Gulley, James L AD - a Genitourinary Malignancies Branch , Center for Cancer Research, National Cancer Institute , Bethesda , MD , USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 895 EP - 901 VL - 16 IS - 7 KW - Index Medicus KW - immunogenic intensification KW - Immune checkpoint inhibitors KW - therapeutic cancer vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795866492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+biological+therapy&rft.atitle=Considerations+for+the+combination+of+anticancer+vaccines+and+immune+checkpoint+inhibitors.&rft.au=Strauss%2C+Julius%3BMadan%2C+Ravi+A%3BGulley%2C+James+L&rft.aulast=Strauss&rft.aufirst=Julius&rft.date=2016-07-01&rft.volume=16&rft.issue=7&rft.spage=895&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+biological+therapy&rft.issn=1744-7682&rft_id=info:doi/10.1517%2F14712598.2016.1170805 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1517/14712598.2016.1170805 ER - TY - JOUR T1 - Subtilase cytotoxin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli induces stress granule formation. AN - 1795866168; 26749168 AB - Subtilase cytotoxin (SubAB) is mainly produced by locus of enterocyte effacement (LEE)-negative strains of Shiga-toxigenic Escherichia coli (STEC). SubAB cleaves an endoplasmic reticulum (ER) chaperone, BiP/Grp78, leading to induction of ER stress. This stress causes activation of ER stress sensor proteins and induction of caspase-dependent apoptosis. We found that SubAB induces stress granules (SG) in various cells. Aim of this study was to explore the mechanism by which SubAB induced SG formation. Here, we show that SubAB-induced SG formation is regulated by activation of double-stranded RNA-activated protein kinase (PKR)-like endoplasmic reticulum kinase (PERK). The culture supernatant of STEC O113:H21 dramatically induced SG in Caco2 cells, although subAB knockout STEC O113:H21 culture supernatant did not. Treatment with phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, and lysosomal inhibitors, NH4 Cl and chloroquine, suppressed SubAB-induced SG formation, which was enhanced by PKC and PKD inhibitors. SubAB attenuated the level of PKD1 phosphorylation. Depletion of PKCδ and PKD1 by siRNA promoted SG formation in response to SubAB. Furthermore, death-associated protein 1 (DAP1) knockdown increased basal phospho-PKD1(S916) and suppressed SG formation by SubAB. However, SG formation by an ER stress inducer, Thapsigargin, was not inhibited in PMA-treated cells. Our findings show that SubAB-induced SG formation is regulated by the PERK/DAP1 signalling pathway, which may be modulated by PKCδ/PKD1, and different from the signal transduction pathway that results in Thapsigargin-induced SG formation. © 2016 John Wiley & Sons Ltd. JF - Cellular microbiology AU - Tsutsuki, Hiroyasu AU - Yahiro, Kinnosuke AU - Ogura, Kohei AU - Ichimura, Kimitoshi AU - Iyoda, Sunao AU - Ohnishi, Makoto AU - Nagasawa, Sayaka AU - Seto, Kazuko AU - Moss, Joel AU - Noda, Masatoshi AD - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. ; Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan. ; Pathogenic Microbe Laboratory, Research Institute, National Centre for Global Health and Medicine, Tokyo, Japan. ; Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan. ; Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan. ; Division of Bacteriology, Osaka Prefectural Institute of Public Health, Osaka, Japan. ; Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1024 EP - 1040 VL - 18 IS - 7 KW - Index Medicus KW - subtilase cytotoxin KW - stress granule KW - protein kinases KW - ER stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795866168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+microbiology&rft.atitle=Subtilase+cytotoxin+produced+by+locus+of+enterocyte+effacement-negative+Shiga-toxigenic+Escherichia+coli+induces+stress+granule+formation.&rft.au=Tsutsuki%2C+Hiroyasu%3BYahiro%2C+Kinnosuke%3BOgura%2C+Kohei%3BIchimura%2C+Kimitoshi%3BIyoda%2C+Sunao%3BOhnishi%2C+Makoto%3BNagasawa%2C+Sayaka%3BSeto%2C+Kazuko%3BMoss%2C+Joel%3BNoda%2C+Masatoshi&rft.aulast=Tsutsuki&rft.aufirst=Hiroyasu&rft.date=2016-07-01&rft.volume=18&rft.issue=7&rft.spage=1024&rft.isbn=&rft.btitle=&rft.title=Cellular+microbiology&rft.issn=1462-5822&rft_id=info:doi/10.1111%2Fcmi.12565 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cmi.12565 ER - TY - JOUR T1 - Depression and Oral FTC/TDF Pre-exposure Prophylaxis (PrEP) Among Men and Transgender Women Who Have Sex With Men (MSM/TGW) AN - 1795753263 AB - We conducted a longitudinal and cross-sectional analysis of depressive symptomology in iPrEx, a randomized, placebo-controlled trial of daily, oral FTC/TDF HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. Depression-related adverse events (AEs) were the most frequently reported severe or life-threatening AEs and were not associated with being randomized to the FTC/TDF arm (152 vs. 144 respectively OR 0.66 95 % CI 0.35-1.25). Center for Epidemiologic Studies Depression scale (CES-D) and a four questions suicidal ideation scale scores did not differ by arm. Participants reporting forced sex at anal sexual debut had higher CES-D scores (coeff: 3.23; 95 % CI 1.24-5.23) and were more likely to have suicidal ideation (OR 2.2; 95 % CI 1.09-4.26). CES-D scores were higher among people reporting non-condom receptive anal intercourse (ncRAI) (OR 1.46; 95 % CI 1.09-1.94). We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services. JF - AIDS and Behavior AU - Defechereux, Patricia A AU - Mehrotra, Megha AU - Liu, Albert Y AU - Mcmahan, Vanessa M AU - Glidden, David V AU - Mayer, Kenneth H AU - Vargas, Lorena AU - Amico, K Rivet AU - Chodacki, Piotr AU - Fernandez, Telmo AU - Avelino-silva, Vivian I AU - Burns, David AU - Grant, Robert M AD - J. David Gladstone Institutes, San Francisco, CA, USA ; Bridge HIV, San Francisco Department of Public Health, San Francisco, CA, USA; University of California, San Francisco, CA, USA ; University of California, San Francisco, CA, USA ; Fenway Community Health, Boston, MA, USA ; Investigaciones Medicas en Salud, Lima, Peru ; School of Public Health, University of Michigan, Ann Arbor, MI, USA ; Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa ; Fundacion Ecuatoriana Equidad, Guayaquil, Ecuador ; University of Sao Paulo Medical School, Sao Paulo, Brazil ; National Institutes of Health, Bethesda, MD, USA ; J. David Gladstone Institutes, San Francisco, CA, USA; University of California, San Francisco, CA, USA; San Francisco AIDS Foundation, San Francisco, CA, USA Y1 - 2016/07// PY - 2016 DA - Jul 2016 SP - 1478 EP - 1488 CY - New York PB - Springer Science & Business Media VL - 20 IS - 7 SN - 1090-7165 KW - Psychology KW - Depression KW - Men who have sex with men KW - HIV prevention KW - PrEP KW - FTC/TDF KW - iPrEx KW - Acquired Immune Deficiency Syndrome KW - Delivery Systems KW - Health Care Services KW - Homosexuality KW - Methodology (Data Collection) KW - Sexual Intercourse KW - Health KW - Mental Health Services KW - Mental Health KW - Epidemiology KW - Depression (Psychology) KW - Transsexuality KW - 6126:acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795753263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=Depression+and+Oral+FTC%2FTDF+Pre-exposure+Prophylaxis+%28PrEP%29+Among+Men+and+Transgender+Women+Who+Have+Sex+With+Men+%28MSM%2FTGW%29&rft.au=Defechereux%2C+Patricia+A%3BMehrotra%2C+Megha%3BLiu%2C+Albert+Y%3BMcmahan%2C+Vanessa+M%3BGlidden%2C+David+V%3BMayer%2C+Kenneth+H%3BVargas%2C+Lorena%3BAmico%2C+K+Rivet%3BChodacki%2C+Piotr%3BFernandez%2C+Telmo%3BAvelino-silva%2C+Vivian+I%3BBurns%2C+David%3BGrant%2C+Robert+M&rft.aulast=Defechereux&rft.aufirst=Patricia&rft.date=2016-07-01&rft.volume=20&rft.issue=7&rft.spage=1478&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-015-1082-2 LA - English DB - Social Services Abstracts N1 - Name - Federal Trade Commission--FTC N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-06-22 DO - http://dx.doi.org/10.1007/s10461-015-1082-2 ER - TY - JOUR T1 - Passive Suicidal Ideation and Community Mental Health Resources in South Africa AN - 1794490958 AB - South African communities continue to experience elevated incidence and prevalence of HIV infection. Passive suicidal ideation (PSI) may be one expression of distress in high prevalence communities. We report the prevalence of PSI and examine the relationship between PSI and participation in community organizations in a semi-rural sample of South African adults (N = 594). The prevalence of PSI in the 2 weeks prior to the interview was 9.1 %. Members of burial societies ([Chi] 2 = 7.34; p = 0.01) and stokvels ([Chi] 2 = 4.1; p = 0.04) (community-based savings groups) reported significantly less PSI compared to other respondents. Using a multivariate model adjusted for demographic characteristics, psychological distress, and socioeconomic status, we found lower odds of reporting PSI for members of burial societies (OR 0.48, CI 0.25 -0.91). Participation in community organizations that provide contextually salient resources in settings with high levels of distress may be a resource for mental health. JF - Community Mental Health Journal AU - Collins, Pamela Y AU - Kondos, Leeza AU - Pillai, Aravind AU - Joestl, Sarah S AU - Frohlich, Janet AD - National Institute of Mental Health/NIH, Bethesda, MD, USA ; Public Health Institute, Global Health Bureau, United States Agency for International Development, Washington, DC, USA ; Mailman School of Public Health, Columbia University, New York, NY, USA ; National Center for Health Statistics, Center for Disease Control, Hyattsville, MD, USA ; Center for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa Y1 - 2016/07// PY - 2016 DA - Jul 2016 SP - 541 EP - 550 CY - New York PB - Springer Science & Business Media VL - 52 IS - 5 SN - 0010-3853 KW - Psychology KW - Passive suicidal ideation KW - Community resources KW - Community mental health KW - Africa KW - HIV/AIDS KW - Acquired Immune Deficiency Syndrome KW - Community Organizations KW - Participation KW - Methodology (Data Collection) KW - Rural Areas KW - Health KW - Community Mental Health KW - Psychological Distress KW - Socioeconomic Status KW - Mental Health KW - Community Involvement KW - Sociodemographic Factors KW - African communities KW - Savings KW - Socioeconomic status KW - Demographic aspects KW - Mental health KW - Rural communities KW - Suicidal ideation KW - Community organizations KW - Infection KW - HIV KW - Psychological distress KW - Community mental health services KW - Suicidal behaviour KW - South Africa KW - 6142:mental & emotional health problems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794490958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Community+Mental+Health+Journal&rft.atitle=Passive+Suicidal+Ideation+and+Community+Mental+Health+Resources+in+South+Africa&rft.au=Collins%2C+Pamela+Y%3BKondos%2C+Leeza%3BPillai%2C+Aravind%3BJoestl%2C+Sarah+S%3BFrohlich%2C+Janet&rft.aulast=Collins&rft.aufirst=Pamela&rft.date=2016-07-01&rft.volume=52&rft.issue=5&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Community+Mental+Health+Journal&rft.issn=00103853&rft_id=info:doi/10.1007%2Fs10597-016-0003-9 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA); Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-06-14 N1 - SubjectsTermNotLitGenreText - South Africa DO - http://dx.doi.org/10.1007/s10597-016-0003-9 ER - TY - JOUR T1 - Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis. AN - 1793905766; 26860770 AB - Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance. Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues. miR-484(-/-), Ifnar1(-/-) and Tgfbr2(△hep) mice were employed to determine the critical role of the interferon (IFN)-microRNA pathway in precancerous lesion formation and tumourigenesis. RNA immunoprecipitation (RIP), pull-down and chromatin immunoprecipitation (ChIP) assays were applied to explore the underlying mechanisms. miR-484 is highly expressed in over 88% liver samples clinically. DEN-induced precancerous lesions and hepatocellular carcinoma were dramatically impaired in miR-484(-/-) mice. Mechanistically, ectopic expression of miR-484 initiates tumourigenesis and cell malignant transformation through synergistic activation of the transforming growth factor-β/Gli and nuclear factor-κB/type I IFN pathways. Specific acetylation of H3K27 is indispensable for basal IFN-induced continuous transcription of miR-484 and cell transformation. Convincingly, formation of precancerous lesions were significantly attenuated in both Tgfbr2(△hep) and Ifnar1(-/-) mice. These findings demonstrate a new protumourigenic axis involving type I IFN-microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ JF - Gut AU - Yang, Yingcheng AU - Lin, Ximeng AU - Lu, Xinyuan AU - Luo, Guijuan AU - Zeng, Tao AU - Tang, Jing AU - Jiang, Feng AU - Li, Liang AU - Cui, Xiuliang AU - Huang, Wentao AU - Hou, Guojun AU - Chen, Xin AU - Ouyang, Qing AU - Tang, Shanhua AU - Sun, Huanlin AU - Chen, Luonan AU - Gonzalez, Frank J AU - Wu, Mengchao AU - Cong, Wenming AU - Chen, Lei AU - Wang, Hongyang AD - International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. ; Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. ; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China. ; Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. ; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. ; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China State Key Laboratory for Oncogenes and Related Genes, Cancer Institute of RenJi Hospital, Shanghai JiaoTong University, Shanghai, China. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1186 EP - 1201 VL - 65 IS - 7 KW - Abridged Index Medicus KW - Index Medicus KW - TGF-BETA KW - INTERFERON KW - HEPATOBILIARY CANCER KW - INFLAMMATION KW - CARCINOGENESIS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793905766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=Interferon-microRNA+signalling+drives+liver+precancerous+lesion+formation+and+hepatocarcinogenesis.&rft.au=Yang%2C+Yingcheng%3BLin%2C+Ximeng%3BLu%2C+Xinyuan%3BLuo%2C+Guijuan%3BZeng%2C+Tao%3BTang%2C+Jing%3BJiang%2C+Feng%3BLi%2C+Liang%3BCui%2C+Xiuliang%3BHuang%2C+Wentao%3BHou%2C+Guojun%3BChen%2C+Xin%3BOuyang%2C+Qing%3BTang%2C+Shanhua%3BSun%2C+Huanlin%3BChen%2C+Luonan%3BGonzalez%2C+Frank+J%3BWu%2C+Mengchao%3BCong%2C+Wenming%3BChen%2C+Lei%3BWang%2C+Hongyang&rft.aulast=Yang&rft.aufirst=Yingcheng&rft.date=2016-07-01&rft.volume=65&rft.issue=7&rft.spage=1186&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2015-310318 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/gutjnl-2015-310318 ER - TY - JOUR T1 - Dosing recommendations for pharmacogenetic interactions related to drug metabolism. AN - 1793904920; 27058883 AB - Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations. Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers. Eighty four gene-drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations. For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers. JF - Pharmacogenetics and genomics AU - Filipski, Kelly K AU - Pacanowski, Michael A AU - Ramamoorthy, Anuradha AU - Feero, William Gregory AU - Freedman, Andrew N AD - aEpidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville bOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland cMaine Dartmouth Family Medicine Residency Program, Augusta, Maine, USA. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 334 EP - 339 VL - 26 IS - 7 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793904920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics+and+genomics&rft.atitle=Dosing+recommendations+for+pharmacogenetic+interactions+related+to+drug+metabolism.&rft.au=Filipski%2C+Kelly+K%3BPacanowski%2C+Michael+A%3BRamamoorthy%2C+Anuradha%3BFeero%2C+William+Gregory%3BFreedman%2C+Andrew+N&rft.aulast=Filipski&rft.aufirst=Kelly&rft.date=2016-07-01&rft.volume=26&rft.issue=7&rft.spage=334&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics+and+genomics&rft.issn=1744-6880&rft_id=info:doi/10.1097%2FFPC.0000000000000220 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1097/FPC.0000000000000220 ER - TY - JOUR T1 - Linguistic validation of the Spanish version of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). AN - 1791331720; 26838022 AB - The U.S. NCI's PRO-CTCAE is a library of self-report items for assessing symptomatic adverse events in cancer clinical trials from the patient perspective. The aim of this study was to translate and linguistically validate a Spanish version. PRO-CTCAE's 124 items were translated from English into Spanish using multiple forward and back translations. Native Spanish speakers undergoing cancer treatment were enrolled at six cancer treatment sites. Participants each completed approximately 50 items and were then interviewed using cognitive probes. The interviews were analyzed at the item level by linguistic themes, and responses were examined for evidence of equivalence to English. Items for which ≥20 % of participants experienced difficulties were reviewed, and phrasing was revised and then retested in subsequent interviews. Items where <20 % of respondents experienced difficulties were also reviewed and were considered for rephrasing and retesting. One hundred nine participants from diverse Spanish-speaking countries were enrolled (77 in Round 1 and 32 in Round 2). A majority of items were well comprehended in Round 1. Two items presented difficulties in ≥20 % of participants and were revised/retested without further difficulties. Two items presented difficulties in <20 %, and when retested exhibited no further difficulties. Two items presented difficulties in <20 %, but were not revised due to lack of alternatives. Sixteen items presented difficulties in ≤12 % and were not revised because difficulties were minor. The Spanish PRO-CTCAE has been developed and refined for use in Spanish-speaking populations, with high levels of comprehension and equivalence to the English PRO-CTCAE. ClinicalTrials.gov:NCT01436240. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Arnold, Benjamin AU - Mitchell, Sandra A AU - Lent, Lauren AU - Mendoza, Tito R AU - Rogak, Lauren J AU - Barragán, Natalie M AU - Willis, Gordon AU - Medina, Mauricio AU - Lechner, Suzanne AU - Penedo, Frank J AU - Harness, Jay K AU - Basch, Ethan M AU - PRO-CTCAE Spanish Translation and Linguistic Validation Study Group AD - FACITtrans, LLC, 381 S. Cottage Hill Ave, Elmhurst, IL, 60126, USA. ; Division of Cancer Control and Population Sciences, Outcomes Research Branch, National Cancer Institute, 9609 Medical Center Drive, East Tower, Room 3-448, Rockville, MD, 20850, USA. mitchlls@mail.nih.gov. ; Department of Symptom Research, The University of Texas M. D. Anderson Cancer Center, 1400 Pressler Street, Unit 1450, Houston, TX, 77030, USA. ; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Avenue, 2nd Floor, New York, NY, 10017, USA. ; Division of Cancer Control and Population Sciences, Behavioral Research Program, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA. ; Health Education and Digital Information Dissemination Branch, Office of Science Policy, Engagement, Education and Communications (OSPEEC), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. ; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14 Street, C202, Miami, FL, 33136, USA. ; Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N., St. Clair, USA. ; The Center for Cancer Prevention and Treatment, St. Joseph Hospital of Orange, 1010 West La Veta Avenue, Suite 470, Orange, CA, 92868, USA. ; PRO-CTCAE Spanish Translation and Linguistic Validation Study Group Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 2843 EP - 2851 VL - 24 IS - 7 KW - Index Medicus KW - Translation KW - Spanish KW - Toxicity KW - Patient-Reported outcomes KW - PRO-CTCAE KW - Cancer KW - Adverse events UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791331720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=Linguistic+validation+of+the+Spanish+version+of+the+National+Cancer+Institute%27s+Patient-Reported+Outcomes+version+of+the+Common+Terminology+Criteria+for+Adverse+Events+%28PRO-CTCAE%29.&rft.au=Arnold%2C+Benjamin%3BMitchell%2C+Sandra+A%3BLent%2C+Lauren%3BMendoza%2C+Tito+R%3BRogak%2C+Lauren+J%3BBarrag%C3%A1n%2C+Natalie+M%3BWillis%2C+Gordon%3BMedina%2C+Mauricio%3BLechner%2C+Suzanne%3BPenedo%2C+Frank+J%3BHarness%2C+Jay+K%3BBasch%2C+Ethan+M%3BPRO-CTCAE+Spanish+Translation+and+Linguistic+Validation+Study+Group&rft.aulast=Arnold&rft.aufirst=Benjamin&rft.date=2016-07-01&rft.volume=24&rft.issue=7&rft.spage=2843&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=1433-7339&rft_id=info:doi/10.1007%2Fs00520-015-3062-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00520-015-3062-5 ER - TY - JOUR T1 - Precise quantification of cellular uptake of cell-penetrating peptides using fluorescence-activated cell sorting and fluorescence correlation spectroscopy. AN - 1789758022; 27033412 AB - Cell-penetrating peptides (CPPs) have emerged as a potentially powerful tool for drug delivery due to their ability to efficiently transport a whole host of biologically active cargoes into cells. Although concerted efforts have shed some light on the cellular internalization pathways of CPPs, quantification of CPP uptake has proved problematic. Here we describe an experimental approach that combines two powerful biophysical techniques, fluorescence-activated cell sorting (FACS) and fluorescence correlation spectroscopy (FCS), to directly, accurately and precisely measure the cellular uptake of fluorescently-labeled molecules. This rapid and technically simple approach is highly versatile and can readily be applied to characterize all major CPP properties that normally require multiple assays, including amount taken up by cells (in moles/cell), uptake efficiency, internalization pathways, intracellular distribution, intracellular degradation and toxicity threshold. The FACS-FCS approach provides a means for quantifying any intracellular biochemical entity, whether expressed in the cell or introduced exogenously and transported across the plasma membrane. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. JF - Biochimica et biophysica acta AU - Rezgui, Rachid AU - Blumer, Katy AU - Yeoh-Tan, Gilbert AU - Trexler, Adam J AU - Magzoub, Mazin AD - Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates. ; Physics Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates. ; Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates. ; Laboratory of Molecular Biophysics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. ; Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates. Electronic address: mazin.magzoub@nyu.edu. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 1499 EP - 1506 VL - 1858 IS - 7 Pt A SN - 0006-3002, 0006-3002 KW - Alexa Fluor 488 carboxylic acid succinimidyl ester KW - 0 KW - Cell-Penetrating Peptides KW - Fluorescent Dyes KW - Succinimides KW - beta-Cyclodextrins KW - methyl-beta-cyclodextrin KW - Ammonium Chloride KW - 01Q9PC255D KW - Cytochalasin D KW - 22144-77-0 KW - Biotin KW - 6SO6U10H04 KW - Filipin KW - 87Z59R7D14 KW - Streptavidin KW - 9013-20-1 KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Drug delivery KW - Intracellular degradation KW - Internalization pathways KW - Cellular uptake KW - Intracellular distribution KW - Toxicity threshold KW - HeLa Cells KW - Protein Transport -- drug effects KW - Humans KW - Biotin -- chemistry KW - Fluorescent Dyes -- chemistry KW - Ammonium Chloride -- pharmacology KW - Chlorpromazine -- pharmacology KW - Streptavidin -- chemistry KW - Spectrometry, Fluorescence -- methods KW - Succinimides -- chemistry KW - Cell Membrane Permeability -- drug effects KW - Kinetics KW - Endocytosis -- drug effects KW - beta-Cyclodextrins -- pharmacology KW - Cytochalasin D -- pharmacology KW - Flow Cytometry KW - Filipin -- pharmacology KW - Cell-Penetrating Peptides -- metabolism KW - Cell-Penetrating Peptides -- analysis KW - Cell Membrane -- drug effects KW - Staining and Labeling -- methods KW - Cell Membrane -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789758022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Precise+quantification+of+cellular+uptake+of+cell-penetrating+peptides+using+fluorescence-activated+cell+sorting+and+fluorescence+correlation+spectroscopy.&rft.au=Rezgui%2C+Rachid%3BBlumer%2C+Katy%3BYeoh-Tan%2C+Gilbert%3BTrexler%2C+Adam+J%3BMagzoub%2C+Mazin&rft.aulast=Rezgui&rft.aufirst=Rachid&rft.date=2016-07-01&rft.volume=1858&rft.issue=7+Pt+A&rft.spage=1499&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/10.1016%2Fj.bbamem.2016.03.023 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-18 N1 - Date created - 2016-05-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bbamem.2016.03.023 ER - TY - JOUR T1 - Changes in RANKL and osteoprotegerin expression after chronic exposure to indoor air pollution as a result of cooking with biomass fuel. AN - 1789033891; 26691826 AB - The impact of indoor air pollution as a result of cooking with unprocessed biomass on membrane-bound and serum receptor activator of nuclear factor-kappa ligand 1 (RANKL), its soluble decoy receptor osteoprotegerin (OPG) and osteoclast precursor CD14(+) CD16(+) monocytes was investigated. Seventy-four pre-menopausal women from eastern India using biomass and 65 control women who cooked with cleaner liquefied petroleum gas were enrolled. PM10 and PM2.5 levels in their indoor air were measured with real-time aerosol monitors. The levels of membrane-bound RANKL on leukocytes and percentage CD14(+) CD16(+) monocytes in the subjects' blood were assayed by flow cytometry. Soluble RANKL and OPG in serum were measured by ELISA. The results showed that PM10 and PM2.5 levels were significantly higher in the indoor air of biomass-using households. Compared with the control women, the levels of CD4(+) and CD19(+) lymphocytes and circulating granulocytes with elevated levels of membrane-bound RANKL were higher in biomass users. The serum levels of RANKL were increased by 41% whereas serum OPG was reduced by 22% among biomass users. The absolute number of CD14(+) CD16(+) monocytes was significantly increased in biomass users than the control women. After controlling for potential confounders, PM10 and PM2.5 levels were found to be positively associated with leukocyte and serum RANKL and CD14(+) CD16(+) monocyte levels, but negatively with serum OPG. From these results, we can conclude that chronic exposure to biomass smoke increased membrane-bound and soluble RANKL and circulating osteoclast precursors but decreased OPG, suggesting an increased risk of bone resorption and consequent osteoporosis in biomass-exposed women of a child-bearing age. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. JF - Journal of applied toxicology : JAT AU - Saha, Hirak AU - Mukherjee, Bidisha AU - Bindhani, Banani AU - Ray, Manas Ranjan AD - Department of Experimental Hematology, Chittaranjan National Cancer Institute, Kolkata-, 700 026, India. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 969 EP - 976 VL - 36 IS - 7 KW - Index Medicus KW - biomass smoke KW - RANKL KW - indoor air pollution KW - women KW - osteoprotegerin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789033891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+toxicology+%3A+JAT&rft.atitle=Changes+in+RANKL+and+osteoprotegerin+expression+after+chronic+exposure+to+indoor+air+pollution+as+a+result+of+cooking+with+biomass+fuel.&rft.au=Saha%2C+Hirak%3BMukherjee%2C+Bidisha%3BBindhani%2C+Banani%3BRay%2C+Manas+Ranjan&rft.aulast=Saha&rft.aufirst=Hirak&rft.date=2016-07-01&rft.volume=36&rft.issue=7&rft.spage=969&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=1099-1263&rft_id=info:doi/10.1002%2Fjat.3275 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-14 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1002/jat.3275 ER - TY - JOUR T1 - Drug Recognition Expert (DRE) examination characteristics of cannabis impairment. AN - 1787085746; 27107471 AB - The Drug Evaluation and Classification Program (DECP) is commonly utilized in driving under the influence (DUI) cases to help determine category(ies) of impairing drug(s) present in drivers. Cannabis, one of the categories, is associated with approximately doubled crash risk. Our objective was to determine the most reliable DECP metrics for identifying cannabis-driving impairment. We evaluated 302 toxicologically-confirmed (blood Δ(9)-tetrahydrocannabinol [THC] ≥1μg/L) cannabis-only DECP cases, wherein examiners successfully identified cannabis, compared to normative data (302 non-impaired individuals). Physiological measures, pupil size/light reaction, and performance on psychophysical tests (one leg stand [OLS], walk and turn [WAT], finger to nose [FTN], Modified Romberg Balance [MRB]) were included. Cases significantly differed from controls (p<0.05) in pulse (increased), systolic blood pressure (elevated), and pupil size (dilated). Blood collection time after arrest significantly decreased THC concentrations; no significant differences were detected between cases with blood THC <5μg/L versus ≥5μg/L. The FTN best predicted cannabis impairment (sensitivity, specificity, positive/negative predictive value, and efficiency ≥87.1%) utilizing ≥3 misses as the deciding criterion; MRB eyelid tremors produced ≥86.1% for all diagnostic characteristics. Other strong indicators included OLS sway, ≥2 WAT clues, and pupil rebound dilation. Requiring ≥2/4 of: ≥3 FTN misses, MRB eyelid tremors, ≥2 OLS clues, and/or ≥2 WAT clues produced the best results (all characteristics ≥96.7%). Blood specimens should be collected as early as possible. The frequently-debated 5μg/L blood THC per se cutoff showed limited relevance. Combined observations on psychophysical and eye exams produced the best cannabis-impairment indicators. Published by Elsevier Ltd. JF - Accident; analysis and prevention AU - Hartman, Rebecca L AU - Richman, Jack E AU - Hayes, Charles E AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard Ste 200 Rm 05A721, Baltimore, MD, 21224, USA. Electronic address: rebecca.hartman@umaryland.edu. ; Hingham Police Department, 212 Central Street, Hingham, MA 02043, USA. Electronic address: jack.richman@comcast.net. ; International Association of Chiefs of Police, 44 Canal Center Plaza, Suite 200, Alexandria, VA 22314, USA. Electronic address: hayes@theiacp.org. ; Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard Ste 200 Rm 05A721, Baltimore, MD, 21224, USA. Electronic address: marilyn.huestis@gmail.com. Y1 - 2016/07// PY - 2016 DA - July 2016 SP - 219 EP - 229 VL - 92 KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Driving KW - THC KW - Drug Evaluation and Classification Program KW - Cannabis KW - Impairment KW - Drug Recognition Expert KW - Sensitivity and Specificity KW - Young Adult KW - Heart Rate KW - Humans KW - Dronabinol -- blood KW - Adult KW - Case-Control Studies KW - Walking KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Driving Under the Influence KW - Substance Abuse Detection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787085746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Accident%3B+analysis+and+prevention&rft.atitle=Drug+Recognition+Expert+%28DRE%29+examination+characteristics+of+cannabis+impairment.&rft.au=Hartman%2C+Rebecca+L%3BRichman%2C+Jack+E%3BHayes%2C+Charles+E%3BHuestis%2C+Marilyn+A&rft.aulast=Hartman&rft.aufirst=Rebecca&rft.date=2016-07-01&rft.volume=92&rft.issue=&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Accident%3B+analysis+and+prevention&rft.issn=1879-2057&rft_id=info:doi/10.1016%2Fj.aap.2016.04.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-03 N1 - Date created - 2016-05-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.aap.2016.04.012 ER - TY - JOUR T1 - Mucosal alpha-papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from South Africa, China and Iran and from a world-wide meta-analysis. AN - 1781540053; 26529033 AB - Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol- and formalin-fixed paraffin-embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high-incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha-papillomaviruses by two sensitive, broad-spectrum genotyping methods, and for the markers of HPV-transformed phenotype: (i) HPV16/18 viral loads by quantitative real-time PCR, (ii) type-specific viral mRNA by E6*I/E6 full-length RT-PCR assays and (iii) expression of cellular protein p16(INK4a). Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16(INK4a) negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16(INK4a) upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16(INK4a) upregulation. These results were supported by a meta-analysis of 14 other similar studies regarding HPV-transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis. © 2015 UICC. JF - International journal of cancer AU - Halec, Gordana AU - Schmitt, Markus AU - Egger, Sam AU - Abnet, Christian C AU - Babb, Chantal AU - Dawsey, Sanford M AU - Flechtenmacher, Christa AU - Gheit, Tarik AU - Hale, Martin AU - Holzinger, Dana AU - Malekzadeh, Reza AU - Taylor, Philip R AU - Tommasino, Massimo AU - Urban, Margaret I AU - Waterboer, Tim AU - Pawlita, Michael AU - Sitas, Freddy AU - InterSCOPE Collaboration AD - Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. ; Cancer Council NSW, Cancer Research Division, Sydney, New South Wales, Australia. ; Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD. ; National Health Laboratory Service, NHLS/MRC Cancer Epidemiology Research Group, Johannesburg, South Africa. ; Institute of Pathology, University of Heidelberg, Heidelberg, Germany. ; Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France. ; Department of Anatomical Pathology, National Health Laboratory Service, Johannesburg, South Africa. ; Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. ; InterSCOPE Collaboration Y1 - 2016/07/01/ PY - 2016 DA - 2016 Jul 01 SP - 85 EP - 98 VL - 139 IS - 1 KW - E6 protein, Human papillomavirus type 16 KW - 0 KW - Oncogene Proteins, Viral KW - Repressor Proteins KW - Index Medicus KW - meta-analysis KW - human papillomavirus KW - HPV-transformed phenotype KW - p16INK4 KW - esophageal cancer KW - serology KW - HPV RNA KW - Genotype KW - Iran KW - Humans KW - Oncogene Proteins, Viral -- genetics KW - Aged KW - Middle Aged KW - South Africa KW - Repressor Proteins -- genetics KW - Male KW - Female KW - China KW - Human papillomavirus 18 -- genetics KW - Human papillomavirus 16 -- pathogenicity KW - Carcinogenesis -- genetics KW - Esophageal Neoplasms -- virology KW - Carcinoma, Squamous Cell -- epidemiology KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Human papillomavirus 16 -- genetics KW - Human papillomavirus 18 -- pathogenicity KW - Carcinoma, Squamous Cell -- virology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781540053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Mucosal+alpha-papillomaviruses+are+not+associated+with+esophageal+squamous+cell+carcinomas%3A+Lack+of+mechanistic+evidence+from+South+Africa%2C+China+and+Iran+and+from+a+world-wide+meta-analysis.&rft.au=Halec%2C+Gordana%3BSchmitt%2C+Markus%3BEgger%2C+Sam%3BAbnet%2C+Christian+C%3BBabb%2C+Chantal%3BDawsey%2C+Sanford+M%3BFlechtenmacher%2C+Christa%3BGheit%2C+Tarik%3BHale%2C+Martin%3BHolzinger%2C+Dana%3BMalekzadeh%2C+Reza%3BTaylor%2C+Philip+R%3BTommasino%2C+Massimo%3BUrban%2C+Margaret+I%3BWaterboer%2C+Tim%3BPawlita%2C+Michael%3BSitas%2C+Freddy%3BInterSCOPE+Collaboration&rft.aulast=Halec&rft.aufirst=Gordana&rft.date=2016-07-01&rft.volume=139&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.29911 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-26 N1 - Date created - 2016-04-15 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Comment In: Int J Cancer. 2016 Jul 1;139(1):9-11 [26999772] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.29911 ER - TY - JOUR T1 - Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair. AN - 1762968450; 26848151 AB - BRCA germline mutations are being targeted for development of PARP inhibitors. BRCA genes collaborate with several others in the Fanconi Anemia (FA) pathway. We screened cancer patients' tumors for FA functional defects then aimed to establish the safety/feasibility of administering PARP inhibitors as monotherapy and combined with a DNA-breaking agent. Patients underwent FA functional screening for the presence (or lack) of tumor FancD2 nuclear foci formation on their archival tumor material, utilizing a newly developed method (Fanconi Anemia triple-stain immunofluorescence [FATSI]), performed in a Clinical Laboratory Improvement Amendments-certified laboratory. FATSI-negative patients were selected for enrollment in a two-arm dose escalation trial of veliparib, or veliparib/mitomycin-C (MMC). One hundred eighty-five of 643 (28.7%) screened patients were FATSI-negative. Sixty-one received veliparib or veliparib/MMC through 14 dose levels. Moderate/severe toxicities included fatigue (DLT at veliparib 400mg BID), diarrhea, and thrombocytopenia. Recommended doses are 300mg BID veliparib and veliparib 200mg BID for 21 days following 10mg/m(2) MMC every 28 days. Six antitumor responses occurred, five in the combination arm (3 breast, 1 ovarian, 1 endometrial [uterine], and 1 non-small cell lung cancer). Two patients have received 36 and 60 cycles to date. BRCA germline analysis among 51 patients revealed five deleterious mutations while a targeted FA sequencing gene panel showed missense/nonsense mutations in 29 of 49 FATSI-negative tumor specimens. FATSI screening showed that a substantial number of patients' tumors have FA functional deficiency, which led to germline alterations in several patients' tumors. Veliparib alone or with MMC was safely administered to these patients and produced clinical benefit in some. However, a better understanding of resistance mechanisms in this setting is needed. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. JF - Journal of the National Cancer Institute AU - Villalona-Calero, Miguel A AU - Duan, Wenrui AU - Zhao, Weiqiang AU - Shilo, Konstantin AU - Schaaf, Larry J AU - Thurmond, Jennifer AU - Westman, Judith A AU - Marshall, John AU - Xiaobai, Li AU - Ji, Jiuping AU - Rose, Jeffrey AU - Lustberg, Maryam AU - Bekaii-Saab, Tanios AU - Chen, Alice AU - Timmers, Cynthia AD - Divisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University, Columbus, OH; Lombardi Cancer Center, Georgetown University, Washington, DC (JM); National Cancer Institute, Bethesda, MD (JJ, AC). miguelvil@BaptistHealth.net. ; Divisions of Medical Oncology (MAVC, WD, JR, ML, TBS) and Clinical Cancer Genetics (JAW), Department of Pathology (WZ, KS), Comprehensive Cancer Center (MAVC, WD, LJS, JT, TBS, CT), and Center for Biostatistics (LX), The Ohio State University, Columbus, OH; Lombardi Cancer Center, Georgetown University, Washington, DC (JM); National Cancer Institute, Bethesda, MD (JJ, AC). Y1 - 2016/07// PY - 2016 DA - July 2016 VL - 108 IS - 7 KW - Antineoplastic Agents KW - 0 KW - Benzimidazoles KW - Poly(ADP-ribose) Polymerase Inhibitors KW - veliparib KW - 01O4K0631N KW - Mitomycin KW - 50SG953SK6 KW - Index Medicus KW - Pedigree KW - Drug Administration Schedule KW - Humans KW - Fatigue -- chemically induced KW - Genes, BRCA2 KW - Aged KW - Genes, BRCA1 KW - Diarrhea -- chemically induced KW - Feasibility Studies KW - Adult KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Germ-Line Mutation KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Poly(ADP-ribose) Polymerase Inhibitors -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Benzimidazoles -- administration & dosage KW - Benzimidazoles -- adverse effects KW - Benzimidazoles -- therapeutic use KW - Mitomycin -- administration & dosage KW - Antineoplastic Agents -- adverse effects KW - Poly(ADP-ribose) Polymerase Inhibitors -- therapeutic use KW - Recombinational DNA Repair -- genetics KW - Poly(ADP-ribose) Polymerase Inhibitors -- adverse effects KW - Recombinational DNA Repair -- drug effects KW - Antineoplastic Agents -- therapeutic use KW - Fanconi Anemia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762968450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Veliparib+Alone+or+in+Combination+with+Mitomycin+C+in+Patients+with+Solid+Tumors+With+Functional+Deficiency+in+Homologous+Recombination+Repair.&rft.au=Villalona-Calero%2C+Miguel+A%3BDuan%2C+Wenrui%3BZhao%2C+Weiqiang%3BShilo%2C+Konstantin%3BSchaaf%2C+Larry+J%3BThurmond%2C+Jennifer%3BWestman%2C+Judith+A%3BMarshall%2C+John%3BXiaobai%2C+Li%3BJi%2C+Jiuping%3BRose%2C+Jeffrey%3BLustberg%2C+Maryam%3BBekaii-Saab%2C+Tanios%3BChen%2C+Alice%3BTimmers%2C+Cynthia&rft.aulast=Villalona-Calero&rft.aufirst=Miguel&rft.date=2016-07-01&rft.volume=108&rft.issue=7&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/10.1093%2Fjnci%2Fdjv437 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-12 N1 - Date created - 2016-02-05 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nature. 2005 Apr 14;434(7035):913-7 [15829966] Nat Rev Cancer. 2003 Jan;3(1):23-34 [12509764] Clin Cancer Res. 2005 Oct 15;11(20):7508-15 [16243825] Cancer Lett. 2006 Jan 28;232(1):99-106 [16246487] J Nucl Med. 2006 Jun;47(6):1059-66 [16741317] Cancer Res. 2006 Aug 15;66(16):8109-15 [16912188] Mol Cell. 2006 Aug;23(4):589-96 [16916645] Nat Genet. 2007 Feb;39(2):162-4 [17200671] Nat Genet. 2007 Feb;39(2):159-61 [17200672] Cancer Biol Ther. 2006 Dec;5(12):1632-6 [17106252] Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6788-93 [17420451] Cell. 2007 Apr 20;129(2):289-301 [17412408] Cytogenet Genome Res. 2007;118(2-4):166-76 [18000367] Nat Genet. 2008 Apr;40(4):390-1 [18362882] Cancer Res. 2008 Apr 15;68(8):2581-6 [18413725] Eur J Cancer. 2009 Jan;45(2):228-47 [19097774] Cell. 2009 Mar 6;136(5):823-37 [19269363] J Clin Oncol. 2009 Jun 1;27(16):2705-11 [19364967] N Engl J Med. 2009 Jul 9;361(2):123-34 [19553641] Mutat Res. 2009 Jul 31;668(1-2):54-72 [19622404] Mol Cell. 2009 Aug 28;35(4):534-41 [19716796] Nat Genet. 2010 May;42(5):406-9 [20400963] Nat Genet. 2010 May;42(5):410-4 [20400964] Nat Struct Mol Biol. 2010 Jun;17(6):688-95 [20453858] Lancet. 2010 Jul 24;376(9737):245-51 [20609468] Clin Cancer Res. 2010 Sep 15;16(18):4532-42 [20823146] Nat Genet. 2011 Feb;43(2):138-41 [21240277] Am J Hum Genet. 2011 Apr 8;88(4):440-9 [21457909] J Clin Oncol. 2011 Aug 1;29(22):3008-15 [21709188] Cancer Biol Ther. 2011 Aug 1;12(3):165-8 [21613821] Breast Cancer Res Treat. 2012 Sep;135(2):505-17 [22875744] Cancer Res. 2012 Nov 1;72(21):5588-99 [23118055] J Pathol. 2013 Feb;229(3):422-9 [23165508] Transl Res. 2013 Mar;161(3):156-64 [23063585] Am J Hum Genet. 2013 May 2;92(5):800-6 [23623386] Cancer Discov. 2015 Feb;5(2):135-42 [25472942] J Clin Oncol. 2015 Jun 10;33(17):1966-73 [25918285] Mol Cell. 2001 Feb;7(2):249-62 [11239454] Mol Cancer Ther. 2013 Jun;12(6):1002-15 [23729402] Clin Cancer Res. 2013 Sep 15;19(18):5003-15 [23881923] Curr Opin Hematol. 2003 Jan;10(1):68-76 [12483114] Breast Cancer Res. 2014;16(3):211 [25093514] Blood. 2003 Mar 1;101(5):2072 [12584146] Nat Med. 2003 May;9(5):568-74 [12692539] Cell Cycle. 2004 Feb;3(2):179-81 [14712086] Hum Genet. 1983;64(4):384-7 [6413386] Blood. 1989 Feb;73(2):391-6 [2917181] Nat Med. 2013 Nov;19(11):1381-8 [24202391] Clin Cancer Res. 2014 Feb 1;20(3):764-75 [24240112] Mol Cancer Ther. 2014 Feb;13(2):433-43 [24356813] Med Oncol. 2014 Oct;31(10):199 [25186150] Nature. 2005 Apr 14;434(7035):917-21 [15829967] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/jnci/djv437 ER - TY - JOUR T1 - First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces? AN - 1801437905; 27357210 AB - The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early-stage and advanced HER2-positive breast cancer (BC).HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC. This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti-HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles.There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective. JF - Journal of experimental & clinical cancer research : CR AU - Fabi, Alessandra AU - Malaguti, Paola AU - Vari, Sabrina AU - Cognetti, Francesco AD - Division of Medical Oncology 1, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. alessandra.fabi@virgilio.it. ; Division of Medical Oncology 1, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. Y1 - 2016/06/30/ PY - 2016 DA - 2016 Jun 30 SP - 104 VL - 35 KW - ERBB2 protein, human KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Trastuzumab KW - P188ANX8CK KW - Index Medicus KW - Pertuzumab KW - Metastatic breast cancer KW - HER2 target terapies KW - Humans KW - Signal Transduction -- drug effects KW - Neoplasm Metastasis KW - Trastuzumab -- therapeutic use KW - Female KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- drug therapy KW - Receptor, ErbB-2 -- genetics KW - Receptor, ErbB-2 -- metabolism KW - Breast Neoplasms -- metabolism KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801437905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=First-line+therapy+in+HER2+positive+metastatic+breast+cancer%3A+is+the+mosaic+fully+completed+or+are+we+missing+additional+pieces%3F&rft.au=Fabi%2C+Alessandra%3BMalaguti%2C+Paola%3BVari%2C+Sabrina%3BCognetti%2C+Francesco&rft.aulast=Fabi&rft.aufirst=Alessandra&rft.date=2016-06-30&rft.volume=35&rft.issue=&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=1756-9966&rft_id=info:doi/10.1186%2Fs13046-016-0380-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-06-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13046-016-0380-5 ER - TY - JOUR T1 - Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations. AN - 1801432847; 27357212 AB - Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial. JF - Acta neuropathologica communications AU - Khundakar, Ahmad A AU - Hanson, Peter S AU - Erskine, Daniel AU - Lax, Nichola Z AU - Roscamp, Joseph AU - Karyka, Evangelia AU - Tsefou, Eliona AU - Singh, Preeti AU - Cockell, Simon J AU - Gribben, Andrew AU - Ramsay, Lynne AU - Blain, Peter G AU - Mosimann, Urs P AU - Lett, Deborah J AU - Elstner, Matthias AU - Turnbull, Douglass M AU - Xiang, Charles C AU - Brownstein, Michael J AU - O'Brien, John T AU - Taylor, John-Paul AU - Attems, Johannes AU - Thomas, Alan J AU - McKeith, Ian G AU - Morris, Christopher M AD - Edwardson Building, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Westgate Road, Newcastle upon Tyne, NE4 5PL, UK. ; Medical Toxicology Centre, Newcastle University, Wolfson Building, Claremont Place, Newcastle, NE2 4AA, UK. ; Bioinformatics Support Unit, Newcastle University, Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. ; University Hospital of Old Age Psychiatry, University Bern, CH 3010, Bern, Switzerland. ; Department of Neurology and Clinical Neurophysiology, Academic Hospital Bogenhausen, Technical University of Munich, Munich, Germany. ; Laboratory of Genetics at the National Institute of Mental Health/National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, MD20892, USA. ; Biomedical Research Building, Institute of Neuroscience, Newcastle University, Newcastle University, Westgate Road, Newcastle upon Tyne, NE4 5PL, UK. ; Edwardson Building, Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Westgate Road, Newcastle upon Tyne, NE4 5PL, UK. c.m.morris@ncl.ac.uk. Y1 - 2016/06/30/ PY - 2016 DA - 2016 Jun 30 SP - 66 VL - 4 IS - 1 KW - Index Medicus KW - Alzheimer’s disease KW - Hallucinations KW - Dementia with Lewy bodies KW - Primary visual cortex KW - α-synuclein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801432847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+neuropathologica+communications&rft.atitle=Analysis+of+primary+visual+cortex+in+dementia+with+Lewy+bodies+indicates+GABAergic+involvement+associated+with+recurrent+complex+visual+hallucinations.&rft.au=Khundakar%2C+Ahmad+A%3BHanson%2C+Peter+S%3BErskine%2C+Daniel%3BLax%2C+Nichola+Z%3BRoscamp%2C+Joseph%3BKaryka%2C+Evangelia%3BTsefou%2C+Eliona%3BSingh%2C+Preeti%3BCockell%2C+Simon+J%3BGribben%2C+Andrew%3BRamsay%2C+Lynne%3BBlain%2C+Peter+G%3BMosimann%2C+Urs+P%3BLett%2C+Deborah+J%3BElstner%2C+Matthias%3BTurnbull%2C+Douglass+M%3BXiang%2C+Charles+C%3BBrownstein%2C+Michael+J%3BO%27Brien%2C+John+T%3BTaylor%2C+John-Paul%3BAttems%2C+Johannes%3BThomas%2C+Alan+J%3BMcKeith%2C+Ian+G%3BMorris%2C+Christopher+M&rft.aulast=Khundakar&rft.aufirst=Ahmad&rft.date=2016-06-30&rft.volume=4&rft.issue=1&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Acta+neuropathologica+communications&rft.issn=2051-5960&rft_id=info:doi/10.1186%2Fs40478-016-0334-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s40478-016-0334-3 ER - TY - JOUR T1 - Toxicities of chimeric antigen receptor T cells: recognition and management. AN - 1801431052; 27207799 AB - Chimeric antigen receptor (CAR) T cells can produce durable remissions in hematologic malignancies that are not responsive to standard therapies. Yet the use of CAR T cells is limited by potentially severe toxicities. Early case reports of unexpected organ damage and deaths following CAR T-cell therapy first highlighted the possible dangers of this new treatment. CAR T cells can potentially damage normal tissues by specifically targeting a tumor-associated antigen that is also expressed on those tissues. Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CRS is the most common type of toxicity caused by CAR T cells. Neurologic toxicity due to CAR T cells might in some cases have a different pathophysiology than CRS and requires different management. Aggressive supportive care is necessary for all patients experiencing CAR T-cell toxicities, with early intervention for hypotension and treatment of concurrent infections being essential. Interleukin-6 receptor blockade with tocilizumab remains the mainstay pharmacologic therapy for CRS, though indications for administration vary among centers. Corticosteroids should be reserved for neurologic toxicities and CRS not responsive to tocilizumab. Pharmacologic management is complicated by the risk of immunosuppressive therapy abrogating the antimalignancy activity of the CAR T cells. This review describes the toxicities caused by CAR T cells and reviews the published approaches used to manage toxicities. We present guidelines for treating patients experiencing CRS and other adverse events following CAR T-cell therapy. JF - Blood AU - Brudno, Jennifer N AU - Kochenderfer, James N AD - Office of the Clinical Director, Center for Cancer Research, and. ; Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD. Y1 - 2016/06/30/ PY - 2016 DA - 2016 Jun 30 SP - 3321 EP - 3330 VL - 127 IS - 26 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801431052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Toxicities+of+chimeric+antigen+receptor+T+cells%3A+recognition+and+management.&rft.au=Brudno%2C+Jennifer+N%3BKochenderfer%2C+James+N&rft.aulast=Brudno&rft.aufirst=Jennifer&rft.date=2016-06-30&rft.volume=127&rft.issue=26&rft.spage=3321&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=1528-0020&rft_id=info:doi/10.1182%2Fblood-2016-04-703751 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1182/blood-2016-04-703751 ER - TY - JOUR T1 - Associations of antibiotic use with risk of primary liver cancer in the Clinical Practice Research Datalink AN - 1808653001; PQ0003363435 AB - Background: Use of antibiotics could alter human microbiota composition and decrease bacterial diversity. Such microbial dysbiosis may have implications in hepatocarcinogenesis; however, the association between antibiotic use and liver cancer risk has been minimally examined in humans. Methods: We performed a nested case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink. Antibiotic use was obtained from prescription records. Multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using conditional logistic regression. Results: Ever-use of prescription antibiotics was associated with a slightly increased risk of liver cancer, compared to non-use (OR=1.22, 95% CI=1.03-1.45). However, there was no clear dose-response relationship by the number of prescriptions or cumulative dose of antibiotic use, suggesting a non-causal association. Conclusions: Our results do not support a role of antibiotic use in liver cancer development. JF - British Journal of Cancer AU - Yang, Baiyu AU - Hagberg, Katrina Wilcox AU - Chen, Jie AU - Sahasrabuddhe, Vikrant V AU - Graubard, Barry I AU - Jick, Susan AU - McGlynn, Katherine A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-9774 USA Y1 - 2016/06/28/ PY - 2016 DA - 2016 Jun 28 SP - 85 EP - 89 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 115 IS - 1 SN - 0007-0920, 0007-0920 KW - Microbiology Abstracts B: Bacteriology; Oncogenes & Growth Factors Abstracts KW - Liver cancer KW - Dose-response effects KW - Antibiotics KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808653001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=Associations+of+antibiotic+use+with+risk+of+primary+liver+cancer+in+the+Clinical+Practice+Research+Datalink&rft.au=Yang%2C+Baiyu%3BHagberg%2C+Katrina+Wilcox%3BChen%2C+Jie%3BSahasrabuddhe%2C+Vikrant+V%3BGraubard%2C+Barry+I%3BJick%2C+Susan%3BMcGlynn%2C+Katherine+A&rft.aulast=Yang&rft.aufirst=Baiyu&rft.date=2016-06-28&rft.volume=115&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1038%2Fbjc.2016.148 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-11-09 N1 - SubjectsTermNotLitGenreText - Dose-response effects; Liver cancer; Antibiotics DO - http://dx.doi.org/10.1038/bjc.2016.148 ER - TY - JOUR T1 - Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging. AN - 1800129429; 27346580 AB - Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance. JF - Scientific reports AU - Wang, Rui-Hong AU - Zhao, Tingrui AU - Cui, Kairong AU - Hu, Gangqing AU - Chen, Qiang AU - Chen, Weiping AU - Wang, Xin-Wei AU - Soto-Gutierrez, Alejandro AU - Zhao, Keji AU - Deng, Chu-Xia AD - Faculty of Health Sciences, University of Macau, Macau SAR, China. ; Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Systems Biology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. ; Genomic Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Y1 - 2016/06/27/ PY - 2016 DA - 2016 Jun 27 SP - 28633 VL - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1800129429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Negative+reciprocal+regulation+between+Sirt1+and+Per2+modulates+the+circadian+clock+and+aging.&rft.au=Wang%2C+Rui-Hong%3BZhao%2C+Tingrui%3BCui%2C+Kairong%3BHu%2C+Gangqing%3BChen%2C+Qiang%3BChen%2C+Weiping%3BWang%2C+Xin-Wei%3BSoto-Gutierrez%2C+Alejandro%3BZhao%2C+Keji%3BDeng%2C+Chu-Xia&rft.aulast=Wang&rft.aufirst=Rui-Hong&rft.date=2016-06-27&rft.volume=6&rft.issue=&rft.spage=28633&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep28633 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep28633 ER - TY - JOUR T1 - Urinary Metabolite Risk Biomarkers of Lung Cancer: A Prospective Cohort Study AN - 1808662053; PQ0003460983 AB - Background: Lung cancer is a major health burden causing 160,000 and 1.6 million deaths annually in the United States and worldwide, respectively.Methods: While seeking to identify stable and reproducible biomarkers in noninvasively collected biofluids, we assessed whether previously identified metabolite urinary lung cancer biomarkers, creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate, and indeterminate metabolite 561+, were elevated in the urines of subjects prior to lung cancer diagnosis in a well-characterized prospective Southern Community Cohort Study (SCCS). Urine was examined from 178 patients and 351 nondiseased controls, confirming that one of four metabolites was associated with lung cancer risk in the overall case-control set, whereas two metabolites were associated with lung cancer risk in European-Americans.Results: OR of lung cancer associated with elevated CR levels, and adjusted for smoking and other potential confounders, was 2.0 [95% confidence interval (CI), 1.2-3.4; P= 0.01]. In European-Americans, both CR and NANA were significantly associated with lung cancer risk (OR = 5.3; 95% CI, 1.6-17.6; P= 0.006 and OR=3.5; 95% CI, 1.5-8.4; P= 0.004, respectively). However, race itself did not significantly modify the associations. ROC analysis showed that adding CR and NANA to a model containing previously established lung cancer risk factors led to a significantly improved classifier (P= 0.01). Increasing urinary levels of CR and NANA displayed a positive association with increasing tumor size, strengthening a previously established link to altered tumor metabolism.Conclusion and Impact: These replicated results provide evidence that identified urinary metabolite biomarkers have a potential utility as noninvasive, clinical screening tools for early diagnosis of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 978-86. copyright 2016 AACR. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Haznadar, Majda AU - Cai, Qiuyin AU - Krausz, Kristopher W AU - Bowman, Elise D AU - Margono, Ezra AU - Noro, Rintaro AU - Thompson, Matthew D AU - Mathe, Ewy A AU - Munro, Heather M AU - Steinwandel, Mark D AU - Gonzalez, Frank J AU - Blot, William J AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, Curtis_Harris@nih.gov Y1 - 2016/06/24/ PY - 2016 DA - 2016 Jun 24 SP - 978 EP - 986 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 25 IS - 6 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Hydrocortisone KW - N-Acetylneuraminic acid KW - Creatine KW - Metabolites KW - Tumors KW - biomarkers KW - Models KW - Sulfate KW - Smoking KW - Urine KW - Risk factors KW - Races KW - Lung cancer KW - B 26660:Miscellaneous Oncogenes & Growth Factors KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808662053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Urinary+Metabolite+Risk+Biomarkers+of+Lung+Cancer%3A+A+Prospective+Cohort+Study&rft.au=Haznadar%2C+Majda%3BCai%2C+Qiuyin%3BKrausz%2C+Kristopher+W%3BBowman%2C+Elise+D%3BMargono%2C+Ezra%3BNoro%2C+Rintaro%3BThompson%2C+Matthew+D%3BMathe%2C+Ewy+A%3BMunro%2C+Heather+M%3BSteinwandel%2C+Mark+D%3BGonzalez%2C+Frank+J%3BBlot%2C+William+J%3BHarris%2C+Curtis+C&rft.aulast=Haznadar&rft.aufirst=Majda&rft.date=2016-06-24&rft.volume=25&rft.issue=6&rft.spage=978&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&rft_id=info:doi/10.1158%2F1055-9965.EPI-15-1191 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-11-23 N1 - SubjectsTermNotLitGenreText - Hydrocortisone; N-Acetylneuraminic acid; Creatine; Metabolites; Tumors; biomarkers; Sulfate; Models; Smoking; Urine; Risk factors; Races; Lung cancer DO - http://dx.doi.org/10.1158/1055-9965.EPI-15-1191 ER - TY - JOUR T1 - DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy. AN - 1826701370; 27323799 AB - Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable. To develop a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa). This score reliably predicted smoking status in the training set (N=1,057; accuracy=96%, sensitivity=80%, specificity=98%). Sensitivity (58%) was predictably lower in the much smaller test set (N=221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known impact of maternal smoking, was as strongly related to the score as to cotinine. A three site score had lower, but acceptable, performance (accuracytrain=82%, accuracytest=83%). Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects. JF - Environmental health perspectives AU - Reese, Sarah E AU - Zhao, Shanshan AU - Wu, Michael C AU - Joubert, Bonnie R AU - Parr, Christine L AU - Håberg, Siri E AU - Ueland, Per Magne AU - Nilsen, Roy M AU - Midttun, Øivind AU - Vollset, Stein Emil AU - Peddada, Shyamal D AU - Nystad, Wenche AU - London, Stephanie J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; Population Health Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Department of Management and Staff, Norwegian Institute of Public Health, Oslo, Norway. ; Department of Clinical Science, University of Bergen, Bergen, Norway. ; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. ; Bevital A/S, Bergen, Norway. ; Center for Disease Burden, Norwegian Institute of Public Health, Oslo/Bergen, Norway. ; Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. Y1 - 2016/06/21/ PY - 2016 DA - 2016 Jun 21 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826701370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=DNA+Methylation+Score+as+a+Biomarker+in+Newborns+for+Sustained+Maternal+Smoking+during+Pregnancy.&rft.au=Reese%2C+Sarah+E%3BZhao%2C+Shanshan%3BWu%2C+Michael+C%3BJoubert%2C+Bonnie+R%3BParr%2C+Christine+L%3BH%C3%A5berg%2C+Siri+E%3BUeland%2C+Per+Magne%3BNilsen%2C+Roy+M%3BMidttun%2C+%C3%98ivind%3BVollset%2C+Stein+Emil%3BPeddada%2C+Shyamal+D%3BNystad%2C+Wenche%3BLondon%2C+Stephanie+J&rft.aulast=Reese&rft.aufirst=Sarah&rft.date=2016-06-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Design, Synthesis and in vitro Evaluation of Indolotacrine Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease. AN - 1798994310; 26427608 AB - Novel indolotacrine analogues were designed, synthesized, and evaluated as potential drugs for the treatment of Alzheimer's disease. By using a multitarget-directed ligand approach, compounds were designed to act simultaneously as cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors. The compounds were also evaluated for antioxidant, cytotoxic, hepatotoxic, and blood-brain barrier (BBB) permeability properties. Indolotacrine 9 b (9-methoxy-2,3,4,6-tetrahydro-1H-indolo[2,3-b]quinolin-11-amine) showed the most promising results in the in vitro assessment; it is a potent inhibitor of acetylcholinesterase (AChE IC50 : 1.5 μm), butyrylcholinesterase (BChE IC50 : 2.4 μm) and MAO A (IC50 : 0.49 μm), and it is also a weak inhibitor of MAO B (IC50 : 53.9 μm). Although its cytotoxic (IC50 : 5.5±0.4 μm) and hepatotoxic (IC50 : 1.22±0.11 μm) profiles are not as good as those of the standard 7-methoxytacrine (IC50 : 63±4 and 11.50±0.77 μm, respectively), the overall improvement in the inhibitory activities and potential to cross the BBB make indolotacrine 9 b a promising lead compound for further development and investigation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. JF - ChemMedChem AU - Benek, Ondrej AU - Soukup, Ondrej AU - Pasdiorova, Marketa AU - Hroch, Lukas AU - Sepsova, Vendula AU - Jost, Petr AU - Hrabinova, Martina AU - Jun, Daniel AU - Kuca, Kamil AU - Zala, Dominykas AU - Ramsay, Rona R AU - Marco-Contelles, José AU - Musilek, Kamil AD - Department of Toxicology and Military Pharmacy, Department of Epidemiology, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic. ; National Institute of Mental Health, Topolova 748, 250 67, Klecany, Czech Republic. ; University Hospital, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. ; School of Biology, Biomolecular Sciences Building, University of St. Andrews, North Haugh, St. Andrews, KY16 9ST, UK. ; Laboratory of Medicinal Chemistry, (IQOG, CSIC), Juan de la Cierva 3, 28006, Madrid, Spain. iqoc21@iqog.csic.es. ; University Hospital, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. kamil.musilek@gmail.com. Y1 - 2016/06/20/ PY - 2016 DA - 2016 Jun 20 SP - 1264 EP - 1269 VL - 11 IS - 12 KW - Index Medicus KW - multitarget-directed ligands KW - inhibitors KW - monoamine oxidase KW - Alzheimer's disease KW - cytotoxicity KW - cholinesterases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1798994310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ChemMedChem&rft.atitle=Design%2C+Synthesis+and+in+vitro+Evaluation+of+Indolotacrine+Analogues+as+Multitarget-Directed+Ligands+for+the+Treatment+of+Alzheimer%27s+Disease.&rft.au=Benek%2C+Ondrej%3BSoukup%2C+Ondrej%3BPasdiorova%2C+Marketa%3BHroch%2C+Lukas%3BSepsova%2C+Vendula%3BJost%2C+Petr%3BHrabinova%2C+Martina%3BJun%2C+Daniel%3BKuca%2C+Kamil%3BZala%2C+Dominykas%3BRamsay%2C+Rona+R%3BMarco-Contelles%2C+Jos%C3%A9%3BMusilek%2C+Kamil&rft.aulast=Benek&rft.aufirst=Ondrej&rft.date=2016-06-20&rft.volume=11&rft.issue=12&rft.spage=1264&rft.isbn=&rft.btitle=&rft.title=ChemMedChem&rft.issn=1860-7187&rft_id=info:doi/10.1002%2Fcmdc.201500383 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cmdc.201500383 ER - TY - JOUR T1 - Toxic Dopamine Metabolite DOPAL Forms an Unexpected Dicatechol Pyrrole Adduct with Lysines of α-Synuclein. AN - 1797867701; 27158766 AB - Parkinson's disease has long been known to involve the loss of dopaminergic neurons in the substantia nigra and the coincidental appearance of Lewy bodies containing oligomerized forms of α-synuclein. The "catecholaldehyde hypothesis" posits a causal link between these two central pathologies mediated by 3,4-dihydroxyphenylacetaldehyde (DOPAL), the most toxic dopamine metabolite. Here we determine the structure of the dominant product in reactions between DOPAL and α-synuclein, a dicatechol pyrrole lysine adduct. This novel modification results from the addition of two DOPAL molecules to the Lys sidechain amine through their aldehyde moieties and the formation of a new carbon-carbon bond between their alkyl chains to generate a pyrrole ring. The product is detectable at low concentrations of DOPAL and its discovery should provide a valuable chemical basis for future studies of DOPAL-induced crosslinking of α-synuclein. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. JF - Angewandte Chemie (International ed. in English) AU - Werner-Allen, Jon W AU - DuMond, Jenna F AU - Levine, Rodney L AU - Bax, Ad AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA. ; Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA. ; Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA. rlevine@nih.gov. ; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA. bax@nih.gov. Y1 - 2016/06/20/ PY - 2016 DA - 2016 Jun 20 SP - 7374 EP - 7378 VL - 55 IS - 26 KW - Index Medicus KW - covalent modification KW - amyloid disease KW - Paal-Knorr synthesis KW - Parkinson's disease KW - oxidative stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797867701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Angewandte+Chemie+%28International+ed.+in+English%29&rft.atitle=Toxic+Dopamine+Metabolite+DOPAL+Forms+an+Unexpected+Dicatechol+Pyrrole+Adduct+with+Lysines+of+%CE%B1-Synuclein.&rft.au=Werner-Allen%2C+Jon+W%3BDuMond%2C+Jenna+F%3BLevine%2C+Rodney+L%3BBax%2C+Ad&rft.aulast=Werner-Allen&rft.aufirst=Jon&rft.date=2016-06-20&rft.volume=55&rft.issue=26&rft.spage=7374&rft.isbn=&rft.btitle=&rft.title=Angewandte+Chemie+%28International+ed.+in+English%29&rft.issn=1521-3773&rft_id=info:doi/10.1002%2Fanie.201600277 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/anie.201600277 ER - TY - JOUR T1 - The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth. AN - 1797866273; 26522723 AB - Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis. JF - Oncogene AU - Palazzo, E AU - Kellett, M AU - Cataisson, C AU - Gormley, A AU - Bible, P W AU - Pietroni, V AU - Radoja, N AU - Hwang, J AU - Blumenberg, M AU - Yuspa, S H AU - Morasso, M I AD - Laboratory of Skin Biology, NIAMS, NIH, Bethesda, MD, USA. ; Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda, MD, USA. ; Department of Dermatology, New York University, New York, NY, USA. Y1 - 2016/06/16/ PY - 2016 DA - 2016 Jun 16 SP - 3114 EP - 3124 VL - 35 IS - 24 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797866273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+homeoprotein+DLX3+and+tumor+suppressor+p53+co-regulate+cell+cycle+progression+and+squamous+tumor+growth.&rft.au=Palazzo%2C+E%3BKellett%2C+M%3BCataisson%2C+C%3BGormley%2C+A%3BBible%2C+P+W%3BPietroni%2C+V%3BRadoja%2C+N%3BHwang%2C+J%3BBlumenberg%2C+M%3BYuspa%2C+S+H%3BMorasso%2C+M+I&rft.aulast=Palazzo&rft.aufirst=E&rft.date=2016-06-16&rft.volume=35&rft.issue=24&rft.spage=3114&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2015.380 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2015.380 ER - TY - JOUR T1 - Beyond accuracy: creating interoperable and scalable text-mining web services AN - 1808737555; PQ0003388141 AB - Summary: The biomedical literature is a knowledge-rich resource and an important foundation for future research. With over 24 million articles in PubMed and an increasing growth rate, research in automated text processing is becoming increasingly important. We report here our recently developed web-based text mining services for biomedical concept recognition and normalization. Unlike most text-mining software tools, our web services integrate several state-of-the-art entity tagging systems (DNorm, GNormPlus, SR4GN, tmChem and tmVar) and offer a batch-processing mode able to process arbitrary text input (e.g. scholarly publications, patents and medical records) in multiple formats (e.g. BioC). We support multiple standards to make our service interoperable and allow simpler integration with other text-processing pipelines. To maximize scalability, we have preprocessed all PubMed articles, and use a computer cluster for processing large requests of arbitrary text.Availability and implementation: Our text-mining web service is freely available at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/tmTools/#curl JF - Bioinformatics AU - Wei, Chih-Hsuan AU - Leaman, Robert AU - Lu, Zhiyong AD - *To whom correspondence should be addressed., Zhiyong.Lu@nih.gov Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 1907 EP - 1910 PB - Oxford University Press, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 32 IS - 12 SN - 1367-4803, 1367-4803 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Growth rate KW - Computer programs KW - Integration KW - software KW - medical records KW - Patents KW - Computers KW - Bioinformatics KW - Internet KW - N 14810:Methods KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808737555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics&rft.atitle=Beyond+accuracy%3A+creating+interoperable+and+scalable+text-mining+web+services&rft.au=Wei%2C+Chih-Hsuan%3BLeaman%2C+Robert%3BLu%2C+Zhiyong&rft.aulast=Wei&rft.aufirst=Chih-Hsuan&rft.date=2016-06-15&rft.volume=32&rft.issue=12&rft.spage=1907&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/10.1093%2Fbioinformatics%2Fbtv760 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Growth rate; Integration; Computer programs; software; medical records; Computers; Patents; Bioinformatics; Internet DO - http://dx.doi.org/10.1093/bioinformatics/btv760 ER - TY - JOUR T1 - Exposure to Ambient Air Pollution and Premature Rupture of Membranes AN - 1808718592; PQ0003388115 AB - Premature rupture of membranes (PROM) is a major factor that predisposes women to preterm delivery. Results from previous studies have suggested that there are associations between exposure to air pollution and preterm birth, but evidence of a relationship with PROM is sparse. Modified Community Multiscale Air Quality models were used to estimate mean exposures to particulate matter less than 10 mu m or less than 2.5 mu m in aerodynamic diameter, nitrogen oxides, carbon monoxide, sulfur dioxide, and ozone among 223,375 singleton deliveries in the Air Quality and Reproductive Health Study (2002-2008). We used log-linear models with generalized estimating equations to estimate adjusted relative risks and 95% confidence intervals for PROM per each interquartile-range increase in pollutants across the whole pregnancy, on the day of delivery, and 5 hours before delivery. Whole-pregnancy exposures to carbon monoxide and sulfur dioxide were associated with an increased risk of PROM (for carbon monoxide, relative risk (RR) = 1.09, 95% confidence interval (CI): 1.04, 1.14; for sulfur dioxide, RR = 1.15, 95% CI: 1.06, 1.25) but not preterm PROM. Ozone exposure increased the risk of PROM on the day of delivery (RR = 1.06, 95% CI: 1.02, 1.09) and 1 day prior (RR = 1.04, 95% CI: 1.01, 1.07). In the 5 hours preceding delivery, there were 3%-7% increases in risk associated with exposure to ozone and particulate matter less than 2.5 mu m in aerodynamic diameter and inverse associations with exposure to carbon monoxide and nitrogen oxides. Acute and long-term air pollutant exposures merit further study in relation to PROM. JF - American Journal of Epidemiology AU - Wallace, Maeve E AU - Grantz, Katherine L AU - Liu, Danping AU - Zhu, Yeyi AU - Kim, Sung Soo AU - Mendola, Pauline AD - Correspondence to Dr. Pauline Mendola, Epidemiology Branch, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Boulevard, Rockville, MD 20852. Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 1114 EP - 1121 PB - Oxford University Press, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 183 IS - 12 SN - 0002-9262, 0002-9262 KW - Toxicology Abstracts; Pollution Abstracts; CSA Neurosciences Abstracts; Health & Safety Science Abstracts KW - ambient air pollution KW - premature rupture of membranes KW - preterm birth KW - Risk assessment KW - Particulate matter KW - Pollution effects KW - Air quality KW - Particulates KW - Models KW - Carbon monoxide KW - Sulfur dioxide KW - Pollutants KW - Aerodynamics KW - Risk factors KW - oxides KW - Ozone KW - Membranes KW - Mathematical models KW - Rupture KW - Nitrogen oxides KW - Pregnancy KW - Birth KW - Air pollution KW - Photochemicals KW - Reproduction KW - Nitrogen KW - P 0000:AIR POLLUTION KW - N3 11028:Neuropharmacology & toxicology KW - H 12000:Epidemiology and Public Health KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808718592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Exposure+to+Ambient+Air+Pollution+and+Premature+Rupture+of+Membranes&rft.au=Wallace%2C+Maeve+E%3BGrantz%2C+Katherine+L%3BLiu%2C+Danping%3BZhu%2C+Yeyi%3BKim%2C+Sung+Soo%3BMendola%2C+Pauline&rft.aulast=Wallace&rft.aufirst=Maeve&rft.date=2016-06-15&rft.volume=183&rft.issue=12&rft.spage=1114&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/10.1093%2Faje%2Fkwv284 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Risk assessment; Mathematical models; Particulate matter; Rupture; Pregnancy; Models; Carbon monoxide; Air pollution; Birth; Sulfur dioxide; Pollutants; oxides; Ozone; Nitrogen; Membranes; Pollution effects; Air quality; Particulates; Nitrogen oxides; Photochemicals; Risk factors; Aerodynamics; Reproduction DO - http://dx.doi.org/10.1093/aje/kwv284 ER - TY - JOUR T1 - Maternal Helminth Infection Is Associated With Higher Infant Immunoglobulin A Titers to Antigen in Orally Administered Vaccines AN - 1808677256; PQ0003232940 AB - Background. Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system. Methods. Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection. Results. Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups. Conclusions. Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines. JF - Journal of Infectious Diseases AU - Clark, Carolyn E AU - Fay, Michael P AU - Chico, Martha E AU - Sandoval, Carlos A AU - Vaca, Maritza G AU - Boyd, Alexis AU - Cooper, Philip J AU - Nutman, Thomas B AD - Laboratory of Parasitic Diseases, tnutman@niaid.nih.gov Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 1996 EP - 2004 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 12 SN - 0022-1899, 0022-1899 KW - Immunology Abstracts; Health & Safety Science Abstracts KW - maternal KW - helminth KW - vaccine KW - immunization KW - IgA KW - Rotavirus KW - Poliovirus KW - Haemophilus influenzae KW - Immune system KW - Socioeconomics KW - Helminths KW - Children KW - Infection KW - Pregnancy KW - Infectious diseases KW - ISE, Ecuador KW - Vaccines KW - Immunoassays KW - Infants KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808677256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Maternal+Helminth+Infection+Is+Associated+With+Higher+Infant+Immunoglobulin+A+Titers+to+Antigen+in+Orally+Administered+Vaccines&rft.au=Clark%2C+Carolyn+E%3BFay%2C+Michael+P%3BChico%2C+Martha+E%3BSandoval%2C+Carlos+A%3BVaca%2C+Maritza+G%3BBoyd%2C+Alexis%3BCooper%2C+Philip+J%3BNutman%2C+Thomas+B&rft.aulast=Clark&rft.aufirst=Carolyn&rft.date=2016-06-15&rft.volume=213&rft.issue=12&rft.spage=1996&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw066 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Poliovirus; Infectious diseases; Immune system; Socioeconomics; Helminths; Vaccines; Infection; Children; Immunoassays; Pregnancy; Infants; Rotavirus; Haemophilus influenzae; ISE, Ecuador DO - http://dx.doi.org/10.1093/infdis/jiw066 ER - TY - JOUR T1 - Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures: PREVAIL II, the Ebola MCM Study AN - 1808672518; PQ0003232928 AB - Background. Unique challenges posed by emerging infectious diseases often expose inadequacies in the conventional phased investigational therapeutic development paradigm. The recent Ebola outbreak in West Africa presents a critical case-study highlighting barriers to faster development. During the outbreak, clinical trials were implemented with unprecedented speed. Yet, in most cases, this fast-tracked approach proved too slow for the rapidly evolving epidemic. Controversy abounded as to the most appropriate study designs to yield safety and efficacy data, potentially causing delays in pivotal studies. Preparation for research during future outbreaks may require acceptance of a paradigm that circumvents, accelerates, or reorders traditional phases, without losing sight of the traditional benchmarks by which drug candidates must be assessed for activity, safety and efficacy. Methods. We present the design of an adaptive, parent protocol, ongoing in West Africa until January 2016. The exigent circumstances of the outbreak and limited prior clinical experience with experimental treatments, led to more direct bridging from preclinical studies to human trials than the conventional paradigm would typically have sanctioned, and required considerable design flexibility. Results. Preliminary evaluation of the "barely Bayesian" design was provided through computer simulation studies. The understanding and public discussion of the study design will help its future implementation. JF - Journal of Infectious Diseases AU - Dodd, Lori E AU - Proschan, Michael A AU - Neuhaus, Jacqueline AU - Koopmeiners, Joseph S AU - Neaton, James AU - Beigel, John D AU - Barrett, Kevin AU - Lane, Henry Clifford AU - Davey, Richard T, Jr AD - National Institute of Allergy and Infectious Diseases, Bethesda, doddl@mail.nih.gov Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 1906 EP - 1913 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 12 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - emerging infectious diseases KW - Ebola virus disease KW - clinical trials KW - adaptive design KW - Bayesian design KW - Mathematical models KW - Data processing KW - Epidemics KW - Bayesian analysis KW - Viruses KW - Safety KW - Simulation KW - Ebola virus KW - Drug development KW - Clinical trials KW - Design KW - Safety engineering KW - Infectious diseases KW - Africa KW - Outbreaks KW - Benchmarks KW - Drugs KW - V 22400:Human Diseases KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808672518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Design+of+a+Randomized+Controlled+Trial+for+Ebola+Virus+Disease+Medical+Countermeasures%3A+PREVAIL+II%2C+the+Ebola+MCM+Study&rft.au=Dodd%2C+Lori+E%3BProschan%2C+Michael+A%3BNeuhaus%2C+Jacqueline%3BKoopmeiners%2C+Joseph+S%3BNeaton%2C+James%3BBeigel%2C+John+D%3BBarrett%2C+Kevin%3BLane%2C+Henry+Clifford%3BDavey%2C+Richard+T%2C+Jr&rft.aulast=Dodd&rft.aufirst=Lori&rft.date=2016-06-15&rft.volume=213&rft.issue=12&rft.spage=1906&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw061 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Epidemics; Data processing; Mathematical models; Infectious diseases; Bayesian analysis; Drug development; Clinical trials; Safety engineering; Safety; Viruses; Simulation; Outbreaks; Benchmarks; Drugs; Design; Ebola virus; Africa DO - http://dx.doi.org/10.1093/infdis/jiw061 ER - TY - JOUR T1 - Estimating Potency in High-Throughput Screening Experiments by Maximizing the Rate of Change in Weighted Shannon Entropy. AN - 1797543820; 27302286 AB - High-throughput in vitro screening experiments can be used to generate concentration-response data for large chemical libraries. It is often desirable to estimate the concentration needed to achieve a particular effect, or potency, for each chemical tested in an assay. Potency estimates can be used to directly compare chemical profiles and prioritize compounds for confirmation studies, or employed as input data for prediction modeling and association mapping. The concentration for half-maximal activity derived from the Hill equation model (i.e., AC50) is the most common potency measure applied in pharmacological research and toxicity testing. However, the AC50 parameter is subject to large uncertainty for many concentration-response relationships. In this study we introduce a new measure of potency based on a weighted Shannon entropy measure termed the weighted entropy score (WES). Our potency estimator (Point of Departure, PODWES) is defined as the concentration producing the maximum rate of change in weighted entropy along a concentration-response profile. This approach provides a new tool for potency estimation that does not depend on the assumption of monotonicity or any other pre-specified concentration-response relationship. PODWES estimates potency with greater precision and less bias compared to the conventional AC50 assessed across a range of simulated conditions. JF - Scientific reports AU - Shockley, Keith R AD - Biostatistics and Computational Biology Branch, The National Institute of Environmental Health Sciences, National Institutes of Health, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 27897 VL - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797543820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Estimating+Potency+in+High-Throughput+Screening+Experiments+by+Maximizing+the+Rate+of+Change+in+Weighted+Shannon+Entropy.&rft.au=Shockley%2C+Keith+R&rft.aulast=Shockley&rft.aufirst=Keith&rft.date=2016-06-15&rft.volume=6&rft.issue=&rft.spage=27897&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep27897 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep27897 ER - TY - JOUR T1 - Aryl hydrocarbon receptor influences nitric oxide and arginine production and alters M1/M2 macrophage polarization. AN - 1795875327; 27153778 AB - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of environmental pollutants. It is also implicated in the regulation of the immune system. Ahr-null macrophages overproduce several proinflammatory cytokines following LPS-mediated stimulation, suggesting that AHR affects the balance between the inflammatory M1 and anti-inflammatory M2 phenotypes. Therefore, the present study aimed to examine whether the loss of AHR modifies macrophage polarization. Peritoneal macrophages from wild-type and Ahr-null mice were differentiated into M1 or M2 phenotype by treatment with LPS/IFNγ or IL-4, and several M1 and M2 markers were determined by qPCR and ELISA assays. Macrophage phagocytic capacity was determined through phagocytosis of yeast and Leishmania major infection assays. Nitric oxide (NO) and urea production, and arginase activity were also determined. When macrophages were polarized to the M1 phenotype, Ahr-null cells presented a mixed response; higher levels of IL-1β, IL-6, IL-12, and TNFα were observed after IFNγ- and LPS-mediated activation. However, Ahr-null cells also exhibited decreased NO production and phagocytic capacity. When macrophage was polarized to the M2 phenotype, Ahr-null cells exhibited lower levels of Fizz1, Ym1, and IL-10. In contrast, arginase activity was increased when compared to wild-type macrophages. In addition, macrophages from Ahr-null mice were more susceptible to L. major infection. Disruption of the Ahr gene alters macrophage polarization when compared to WT macrophage. These changes may affect the development and resolution of several diseases such as bacterial or parasitic infections. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Life sciences AU - Climaco-Arvizu, Samantha AU - Domínguez-Acosta, Omar AU - Cabañas-Cortés, María Asunción AU - Rodríguez-Sosa, Miriam AU - Gonzalez, Frank J AU - Vega, Libia AU - Elizondo, Guillermo AD - Departamento de Biología Celular, CINVESTAV-IPN, Zacatenco, Av. IPN 2508, C.P. 07360 México D.F., Mexico. ; Facultad de Estudios Superiores-Iztacala, UNAM, Unidad de Biomedicina, C.P. 54090 Tlalnepantla, Estado de México, Mexico. ; Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, MD 20892, USA. ; Departamento de Toxicología, CINVESTAV-IPN, Zacatenco, Av. IPN 2508, C.P. 07360 México D.F., Mexico. ; Departamento de Biología Celular, CINVESTAV-IPN, Zacatenco, Av. IPN 2508, C.P. 07360 México D.F., Mexico. Electronic address: gazuela@cinvestav.mx. Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 76 EP - 84 VL - 155 KW - Index Medicus KW - Leishmaniasis KW - Arginase KW - Aryl hydrocarbon receptor KW - Macrophage KW - Nitric oxide UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795875327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Aryl+hydrocarbon+receptor+influences+nitric+oxide+and+arginine+production+and+alters+M1%2FM2+macrophage+polarization.&rft.au=Climaco-Arvizu%2C+Samantha%3BDom%C3%ADnguez-Acosta%2C+Omar%3BCaba%C3%B1as-Cort%C3%A9s%2C+Mar%C3%ADa+Asunci%C3%B3n%3BRodr%C3%ADguez-Sosa%2C+Miriam%3BGonzalez%2C+Frank+J%3BVega%2C+Libia%3BElizondo%2C+Guillermo&rft.aulast=Climaco-Arvizu&rft.aufirst=Samantha&rft.date=2016-06-15&rft.volume=155&rft.issue=&rft.spage=76&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=1879-0631&rft_id=info:doi/10.1016%2Fj.lfs.2016.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.lfs.2016.05.001 ER - TY - JOUR T1 - Therapeutic radiation and the potential risk of second malignancies. AN - 1793900397; 26950597 AB - Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society. © 2016 American Cancer Society. JF - Cancer AU - Kamran, Sophia C AU - Berrington de Gonzalez, Amy AU - Ng, Andrea AU - Haas-Kogan, Daphne AU - Viswanathan, Akila N AD - Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts. ; Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. ; Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Y1 - 2016/06/15/ PY - 2016 DA - 2016 Jun 15 SP - 1809 EP - 1821 VL - 122 IS - 12 KW - Abridged Index Medicus KW - Index Medicus KW - risk KW - carcinogenesis KW - second primary KW - neoplasm KW - radiotherapy KW - survivors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793900397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Therapeutic+radiation+and+the+potential+risk+of+second+malignancies.&rft.au=Kamran%2C+Sophia+C%3BBerrington+de+Gonzalez%2C+Amy%3BNg%2C+Andrea%3BHaas-Kogan%2C+Daphne%3BViswanathan%2C+Akila+N&rft.aulast=Kamran&rft.aufirst=Sophia&rft.date=2016-06-15&rft.volume=122&rft.issue=12&rft.spage=1809&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=1097-0142&rft_id=info:doi/10.1002%2Fcncr.29841 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cncr.29841 ER - TY - JOUR T1 - Tau pathology-mediated presynaptic dysfunction. AN - 1784461209; 27012611 AB - Brain tauopathies are characterized by abnormal processing of tau protein. While somatodendritic tau mislocalization has attracted considerable attention in tauopathies, the role of tau pathology in axonal transport, connectivity and related dysfunctions remains obscure. We have previously shown using the squid giant synapse that presynaptic microinjection of recombinant human tau protein (htau42) results in failure of synaptic transmission. Here, we evaluated molecular mechanisms mediating this effect. Thus, the initial event, observed after htau42 presynaptic injection, was an increase in transmitter release. This event was mediated by calcium release from intracellular stores and was followed by a reduction in evoked transmitter release. The effect of htau42 on synaptic transmission was recapitulated by a peptide comprising the phosphatase-activating domain of tau, suggesting activation of phosphotransferases. Accordingly, findings indicated that htau42-mediated toxicity involves the activities of both GSK3 and Cdk5 kinases. Copyright © 2016 IBRO. All rights reserved. JF - Neuroscience AU - Moreno, H AU - Morfini, G AU - Buitrago, L AU - Ujlaki, G AU - Choi, S AU - Yu, E AU - Moreira, J E AU - Avila, J AU - Brady, S T AU - Pant, H AU - Sugimori, M AU - Llinás, R R AD - The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Departments of Neurology and Physiology/Pharmacology, Brooklyn, NY 11203, United States; Marine Biological Laboratory, Woods Hole, MA 02543, United States. Electronic address: Herman.Moreno@downstate.edu. ; Marine Biological Laboratory, Woods Hole, MA 02543, United States; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60607, United States. ; The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Departments of Neurology and Physiology/Pharmacology, Brooklyn, NY 11203, United States; Marine Biological Laboratory, Woods Hole, MA 02543, United States. ; Marine Biological Laboratory, Woods Hole, MA 02543, United States. ; Marine Biological Laboratory, Woods Hole, MA 02543, United States; Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, United States. ; Marine Biological Laboratory, Woods Hole, MA 02543, United States; Pathology and Forensic Medicine, Riberão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP 14000-000, Brazil. ; Centro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid, Madrid 28049, Spain. ; Marine Biological Laboratory, Woods Hole, MA 02543, United States; Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, MD 20824, United States. ; Marine Biological Laboratory, Woods Hole, MA 02543, United States; Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, United States. Electronic address: Rodolfo.Llinas@nyumc.org. Y1 - 2016/06/14/ PY - 2016 DA - 2016 Jun 14 SP - 30 EP - 38 VL - 325 KW - Index Medicus KW - IP3 receptor KW - GSK3 KW - ryanodine receptor KW - tauopathy KW - phosphatase-activating domain of tau KW - Cdk5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1784461209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Tau+pathology-mediated+presynaptic+dysfunction.&rft.au=Moreno%2C+H%3BMorfini%2C+G%3BBuitrago%2C+L%3BUjlaki%2C+G%3BChoi%2C+S%3BYu%2C+E%3BMoreira%2C+J+E%3BAvila%2C+J%3BBrady%2C+S+T%3BPant%2C+H%3BSugimori%2C+M%3BLlin%C3%A1s%2C+R+R&rft.aulast=Moreno&rft.aufirst=H&rft.date=2016-06-14&rft.volume=325&rft.issue=&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=1873-7544&rft_id=info:doi/10.1016%2Fj.neuroscience.2016.03.044 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-25 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cell Calcium. 1999 Jul-Aug;26(1-2):9-13 [10892566] Chem Biol. 2000 Oct;7(10):793-803 [11033082] Cell Calcium. 2001 Feb;29(2):111-6 [11162848] Biochemistry. 2001 May 22;40(20):5983-91 [11352733] J Biol Chem. 2001 Jun 1;276(22):18888-96 [11259416] EMBO J. 2002 Feb 1;21(3):281-93 [11823421] Am J Pathol. 2003 May;162(5):1623-7 [12707046] EMBO J. 2004 Jun 2;23(11):2235-45 [15152189] Proc Natl Acad Sci U S A. 1985 May;82(9):3035-9 [2859595] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8257-61 [1978321] J Biol Chem. 1994 May 20;269(20):14566-74 [7514173] J Neurochem. 1996 Dec;67(6):2390-8 [8931471] Neuron. 1997 Sep;19(3):723-33 [9331361] J Biochem. 1997 Sep;122(3):498-505 [9348075] Fundam Clin Pharmacol. 1997;11(6):576-83 [9444526] Ann Neurol. 1998 Jul;44(1):99-109 [9667597] Curr Opin Neurobiol. 2005 Jun;15(3):275-81 [15919193] Physiol Rev. 2006 Jan;86(1):369-408 [16371601] J Biol Chem. 2006 Dec 15;281(50):38440-7 [17050533] J Biol Chem. 2006 Dec 29;281(52):39907-14 [17085446] J Am Chem Soc. 2007 Jul 4;129(26):8328-32 [17552518] J Neurosci Res. 2007 Sep;85(12):2620-30 [17265463] J Neurosci. 2008 Feb 13;28(7):1682-7 [18272688] Neuron. 2008 Jun 26;58(6):871-83 [18579078] J Neurosci Res. 2009 Feb;87(2):440-51 [18798283] Neurocrit Care. 2009;10(1):103-15 [18696266] J Neuropathol Exp Neurol. 2009 May;68(5):503-14 [19525898] J Biol Chem. 2010 Oct 29;285(44):34202-12 [20720012] J Neurosci. 2011 Jul 6;31(27):9858-68 [21734277] Neuron. 2012 Feb 23;73(4):685-97 [22365544] FASEB J. 2013 Jan;27(1):174-86 [23038754] J Neurosci. 2013 Jan 2;33(1):334-43 [23283346] J Biol Chem. 2013 Jan 18;288(3):1856-70 [23188818] Acta Neuropathol. 2014 Feb;127(2):257-70 [24271788] J Biol Chem. 2014 Apr 18;289(16):11007-19 [24610780] Neuroimage Clin. 2014;4:711-7 [24936422] J Neurosci. 2014 Jul 9;34(28):9222-34 [25009256] Trends Neurosci. 2014 Dec;37(12):721-32 [25223701] Neuropathol Appl Neurobiol. 2015 Feb;41(1):3-23 [25495175] Acta Neuropathol Commun. 2014;2:146 [25330988] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuroscience.2016.03.044 ER - TY - JOUR T1 - Urinary Concentrations of Parabens and Other Antimicrobial Chemicals and Their Association with Couples' Fecundity. AN - 1826699750; 27286252 AB - Human exposure to parabens and other antimicrobial chemicals is continual and pervasive. The hormone disrupting properties of these environmental chemicals may adversely affect human reproduction. To prospectively assess couples' urinary concentrations of antimicrobial chemicals in the context of fecundity, measured as time-to-pregnancy (TTP). In a prospective cohort of 501 couples, we examined preconception urinary chemical concentrations of parabens, triclosan and triclorcarban in relation to TTP; chemical concentrations were modeled both continuously and in quartiles. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs) adjusting for a priori defined confounders. In light of TTP being a couple-dependent outcome, both partner and couple-based exposure models were analyzed. In all models, FOR estimates < 1.0 denote diminished fecundity (longer TTP). Overall, 347 (69%) couples became pregnant. The highest quartile of female urinary methyl paraben (MP) concentrations relative to the lowest reflected a 34% reduction in fecundity [aFOR= 0.66; 95% CI=(0.45, 0.97) and remained so when accounting for couples' concentrations [aFOR= 0.63; 95% CI=(0.41, 0.96)]. Similar associations were observed between ethyl paraben (EP) and couple fecundity for both partner and couple-based-models (p-trend=0.02 and p-trend=0.05, respectively). No associations were observed with couple fecundity when chemicals were modeled continuously. Higher quartiles of preconception urinary concentrations of MP and EP among female partners were associated with reduced couple fecundity in partner-specific and couple-based exposure models. JF - Environmental health perspectives AU - Smarr, Melissa M AU - Sundaram, Rajeshwari AU - Honda, Masato AU - Kannan, Kurunthachalam AU - Buck Louis, Germaine M AD - Office of the Director, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland, USA. ; Biostatics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland, USA. ; Wadsworth Center, New York State Department of Health, and Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Albany, New York, USA. Y1 - 2016/06/10/ PY - 2016 DA - 2016 Jun 10 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826699750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Urinary+Concentrations+of+Parabens+and+Other+Antimicrobial+Chemicals+and+Their+Association+with+Couples%27+Fecundity.&rft.au=Smarr%2C+Melissa+M%3BSundaram%2C+Rajeshwari%3BHonda%2C+Masato%3BKannan%2C+Kurunthachalam%3BBuck+Louis%2C+Germaine+M&rft.aulast=Smarr&rft.aufirst=Melissa&rft.date=2016-06-10&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-10 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Combination of the novel histone deacetylase inhibitor YCW1 and radiation induces autophagic cell death through the downregulation of BNIP3 in triple-negative breast cancer cells in vitro and in an orthotopic mouse model. AN - 1796686578; 27286975 AB - Triple-negative breast cancer (TNBC) is the most aggressive and invasive of the breast cancer subtypes. TNBC is a challenging disease that lacks targets for treatment. Histone deacetylase inhibitors (HDACi) are a group of targeted anticancer agents that enhance radiosensitivity. Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) is a member of the Bcl-2 subfamily. BNIP3 is not found in normal breast tissue but is up-regulated in breast cancer. In the present study, we investigated the anti-cancer effects of a newly developed HDACi, YCW1, combined with ionizing radiation (IR) in TNBC in vitro and in an orthotopic mouse model. Furthermore, we examined the relationship between autophagy and BNIP3. Trypan blue exclusion was used to investigate the viability of 4 T1 (a mouse TNBC cell line) and MDA-MB-231 cells (a human TNBC cell line) following combined YCW1 and IR treatment. Flow cytometry was used to determine apoptosis and autophagy. The expression levels of BNIP3, endoplasmic reticulum (ER) stress- and autophagic-related proteins were measured using western blot analysis. An orthotopic mouse model was used to investigate the in vivo effects of YCW1 and IR alone and in combination. Tumor volumes were monitored using a bioluminescence-based IVIS Imaging System 200. We found that YCW1 significantly enhanced toxicity in 4 T1 cells compared with suberoylanilide hydroxamic acid (SAHA), which was the first HDACi approved by the Food and Drug Administration for clinical use in cancer patients. The combined treatment of YCW1 and IR enhanced cytotoxicity by inducing ER stress and increasing autophagy induction. Additionally, the combined treatment caused autophagic flux and autophagic cell death. Furthermore, the expression level of BNIP3 was significantly decreased in cells following combined treatment. The downregulation of BNIP3 led to a significant increase in autophagy and cytotoxicity. The combined anti-tumor effects of YCW1 and IR were also observed in an orthotopic mouse model; combination therapy resulted in a significant increase in autophagy and decreased tumor tissue expression of BNIP3 in the tumor tissue. These data support the possibility of using a combination of HDACi and IR in the treatment of TNBC. Moreover, BNIP3 may be a potential target protein for TNBC treatment. JF - Molecular cancer AU - Chiu, Hui-Wen AU - Yeh, Ya-Ling AU - Wang, Yi-Ching AU - Huang, Wei-Jan AU - Ho, Sheng-Yow AU - Lin, Pinpin AU - Wang, Ying-Jan AD - Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. ; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan, Taiwan, 704. ; Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan. ; Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan. ; Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan. ; National Institute of Environmental Health Sciences, National Health Research Institutes, No. 35 Keyan Road, Zhunan Town, Miaoli County, 350, Taiwan. pplin@nhri.org.tw. ; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan, Taiwan, 704. yjwang@mail.ncku.edu.tw. Y1 - 2016/06/10/ PY - 2016 DA - 2016 Jun 10 SP - 46 VL - 15 IS - 1 KW - Index Medicus KW - Histone deacetylase inhibitor KW - Radiation KW - Autophagy KW - Triple-negative breast cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1796686578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer&rft.atitle=Combination+of+the+novel+histone+deacetylase+inhibitor+YCW1+and+radiation+induces+autophagic+cell+death+through+the+downregulation+of+BNIP3+in+triple-negative+breast+cancer+cells+in+vitro+and+in+an+orthotopic+mouse+model.&rft.au=Chiu%2C+Hui-Wen%3BYeh%2C+Ya-Ling%3BWang%2C+Yi-Ching%3BHuang%2C+Wei-Jan%3BHo%2C+Sheng-Yow%3BLin%2C+Pinpin%3BWang%2C+Ying-Jan&rft.aulast=Chiu&rft.aufirst=Hui-Wen&rft.date=2016-06-10&rft.volume=15&rft.issue=1&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer&rft.issn=1476-4598&rft_id=info:doi/10.1186%2Fs12943-016-0531-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s12943-016-0531-5 ER - TY - JOUR T1 - Peptides Composed of Alternating L- and D-Amino Acids Inhibit Amyloidogenesis in Three Distinct Amyloid Systems Independent of Sequence. AN - 1792374703; 27012425 AB - There is now substantial evidence that soluble oligomers are primary toxic agents in amyloid diseases. The development of an antibody recognizing the toxic soluble oligomeric forms of different and unrelated amyloid species suggests a common conformational intermediate during amyloidogenesis. We previously observed a common occurrence of a novel secondary structure element, which we call α-sheet, in molecular dynamics (MD) simulations of various amyloidogenic proteins, and we hypothesized that the toxic conformer is composed of α-sheet structure. As such, α-sheet may represent a conformational signature of the misfolded intermediates of amyloidogenesis and a potential unique binding target for peptide inhibitors. Recently, we reported the design and characterization of a novel hairpin peptide (α1 or AP90) that adopts stable α-sheet structure and inhibits the aggregation of the β-Amyloid Peptide Aβ42 and transthyretin. AP90 is a 23-residue hairpin peptide featuring alternating D- and L-amino acids with favorable conformational propensities for α-sheet formation, and a designed turn. For this study, we reverse engineered AP90 to identify which of its design features is most responsible for conferring α-sheet stability and inhibitory activity. We present experimental characterization (CD and FTIR) of seven peptides designed to accomplish this. In addition, we measured their ability to inhibit aggregation in three unrelated amyloid species: Aβ42, transthyretin, and human islet amylin polypeptide. We found that a hairpin peptide featuring alternating L- and D-amino acids, independent of sequence, is sufficient for conferring α-sheet structure and inhibition of aggregation. Additionally, we show a correlation between α-sheet structural stability and inhibitory activity. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Journal of molecular biology AU - Kellock, Jackson AU - Hopping, Gene AU - Caughey, Byron AU - Daggett, Valerie AD - Department of Bioengineering, University of Washington, Seattle, WA 98105-5013, USA. ; Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840-2932, USA. ; Department of Bioengineering, University of Washington, Seattle, WA 98105-5013, USA. Electronic address: daggett@uw.edu. Y1 - 2016/06/05/ PY - 2016 DA - 2016 Jun 05 SP - 2317 EP - 2328 VL - 428 IS - 11 KW - Index Medicus KW - toxic oligomer KW - α-sheet KW - beta amyloid KW - inhibitor KW - amyloid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1792374703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Peptides+Composed+of+Alternating+L-+and+D-Amino+Acids+Inhibit+Amyloidogenesis+in+Three+Distinct+Amyloid+Systems+Independent+of+Sequence.&rft.au=Kellock%2C+Jackson%3BHopping%2C+Gene%3BCaughey%2C+Byron%3BDaggett%2C+Valerie&rft.aulast=Kellock&rft.aufirst=Jackson&rft.date=2016-06-05&rft.volume=428&rft.issue=11&rft.spage=2317&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=1089-8638&rft_id=info:doi/10.1016%2Fj.jmb.2016.03.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-28 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12277-82 [9770477] Nat Struct Biol. 1996 Jul;3(7):604-12 [8673604] Methods Enzymol. 1999;309:274-84 [10507030] J Am Chem Soc. 2005 Jul 13;127(27):9700-1 [15998070] Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13433-8 [16157882] Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17342-7 [16293696] Acc Chem Res. 2006 Sep;39(9):594-602 [16981675] Biochemistry. 2006 Dec 26;45(51):15702-9 [17176092] J Biol Chem. 2007 Apr 6;282(14):10311-24 [17284452] J Phys Chem B. 2008 Jul 24;112(29):8737-43 [18582018] Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12259-64 [18713857] J Biol Chem. 2008 Oct 31;283(44):29639-43 [18723507] Nat Chem Biol. 2009 Jan;5(1):15-22 [19088715] Nature. 2009 Feb 26;457(7233):1128-32 [19242475] Annu Rev Biophys. 2009;38:125-52 [19416063] Biochem J. 2009 Aug 1;421(3):415-23 [19435461] J Mol Biol. 2010 Jan 29;395(4):717-27 [19781557] J Chem Phys. 2010 Apr 28;132(16):165103 [20441311] Nat Struct Mol Biol. 2010 May;17(5):561-7 [20383142] J Biol Chem. 2010 Aug 20;285(34):26377-83 [20576610] Mol Biosyst. 2011 Apr;7(4):1232-40 [21279219] Biochemistry. 2011 Sep 27;50(38):8202-12 [21848289] J Am Chem Soc. 2011 Oct 26;133(42):16958-69 [21916458] Nat Neurosci. 2012 Mar;15(3):349-57 [22286176] Science. 2012 Mar 9;335(6073):1228-31 [22403391] Proc Natl Acad Sci U S A. 2012 May 15;109(20):7717-22 [22547798] Protein Eng Des Sel. 2012 Jul;25(7):337-45 [22670059] J Phys Chem B. 2012 Nov 15;116(45):13368-73 [23101885] Elife. 2014;3:e01681 [25027691] Protein Eng Des Sel. 2014 Nov;27(11):447-55 [25233851] Hum Mutat. 2001 Jun;17(6):493-503 [11385707] J Biol Chem. 2000 Nov 17;275(46):36436-40 [10961999] J Mol Biol. 2001 Oct 5;312(5):1103-19 [11580253] Nature. 2002 Apr 4;416(6880):507-11 [11932737] Science. 2002 Jul 19;297(5580):353-6 [12130773] J Neurosci Res. 2002 Sep 1;69(5):567-77 [12210822] Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11884-9 [12186976] J Mol Biol. 2003 Jan 24;325(4):743-57 [12507477] Science. 2003 Apr 18;300(5618):486-9 [12702875] Annu Rev Neurosci. 2003;26:267-98 [12704221] Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2293-8 [14983003] J Comput Chem. 2004 Oct;25(13):1605-12 [15264254] Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11622-7 [15280548] Structure. 2004 Oct;12(10):1847-63 [15458633] Protein Sci. 2004 Nov;13(11):2888-98 [15459334] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8628-32 [3317417] Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8368-72 [8078889] Biochemistry. 1996 May 21;35(20):6470-82 [8639594] J Mol Biol. 1999 Apr 9;287(4):781-96 [10191146] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jmb.2016.03.013 ER - TY - JOUR T1 - Prediction of non-muscle invasive bladder cancer outcomes assessed by innovative multimarker prognostic models. AN - 1794472732; 27259534 AB - We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients. Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient. Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (ĥ (2)) of both outcomes was <1 % in NMIBC. We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models. JF - BMC cancer AU - López de Maturana, E AU - Picornell, A AU - Masson-Lecomte, A AU - Kogevinas, M AU - Márquez, M AU - Carrato, A AU - Tardón, A AU - Lloreta, J AU - García-Closas, M AU - Silverman, D AU - Rothman, N AU - Chanock, S AU - Real, F X AU - Goddard, M E AU - Malats, N AU - SBC/EPICURO Study Investigators AD - Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández, Almagro, 3, 28029, Madrid, Spain. ; Centre for Research in Environmental Epidemiology (CREAL), Parc de Salut Mar, Barcelona, Spain. ; Servicio de Oncología, Hospital Universitario Ramon y Cajal, Madrid, and Servicio de Oncología, Hospital Universitario de Elche, Elche, Spain. ; Department of Preventive Medicine Universidad de Oviedo, Oviedo, Spain. ; Parc de Salut Mar and Departament of Pathology, Hospital del Mar - IMAS, Barcelona, Spain. ; Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland, USA. ; Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, and Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. ; Biosciences Research Division, Department of Environment and Primary Industries, Agribio, and Department of Food and Agricultural Systems, University of Melbourne, Melbourne, Australia. ; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández, Almagro, 3, 28029, Madrid, Spain. nmalats@cnio.es. ; SBC/EPICURO Study Investigators Y1 - 2016/06/03/ PY - 2016 DA - 2016 Jun 03 SP - 351 VL - 16 KW - Index Medicus KW - Illumina Infinium HumanHap 1 M array KW - Prognosis KW - AUC-ROC KW - Bayesian regression KW - Recurrence KW - Progression KW - Determination coefficient KW - Bladder cancer outcome KW - Genome-wide common SNP KW - Predictive ability KW - Bayesian LASSO KW - heritability KW - Multimarker models KW - Bayesian statistical learning method UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794472732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+cancer&rft.atitle=Prediction+of+non-muscle+invasive+bladder+cancer+outcomes+assessed+by+innovative+multimarker+prognostic+models.&rft.au=L%C3%B3pez+de+Maturana%2C+E%3BPicornell%2C+A%3BMasson-Lecomte%2C+A%3BKogevinas%2C+M%3BM%C3%A1rquez%2C+M%3BCarrato%2C+A%3BTard%C3%B3n%2C+A%3BLloreta%2C+J%3BGarc%C3%ADa-Closas%2C+M%3BSilverman%2C+D%3BRothman%2C+N%3BChanock%2C+S%3BReal%2C+F+X%3BGoddard%2C+M+E%3BMalats%2C+N%3BSBC%2FEPICURO+Study+Investigators&rft.aulast=L%C3%B3pez+de+Maturana&rft.aufirst=E&rft.date=2016-06-03&rft.volume=16&rft.issue=&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=BMC+cancer&rft.issn=1471-2407&rft_id=info:doi/10.1186%2Fs12885-016-2361-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s12885-016-2361-7 ER - TY - JOUR T1 - Wake me when it's over - Bacterial toxin-antitoxin proteins and induced dormancy AN - 1846406870; PQ0003293035 AB - Toxin-antitoxin systems are encoded by bacteria and archaea to enable an immediate response to environmental stresses, including antibiotics and the host immune response. During normal conditions, the antitoxin components prevent toxins from interfering with metabolism and arresting growth; however, toxin activation enables microbes to remain dormant through unfavorable conditions that might continue over millions of years. Intense investigations have revealed a multitude of mechanisms for both regulation and activation of toxin-antitoxin systems, which are abundant in pathogenic microorganisms. This minireview provides an overview of the current knowledge regarding type II toxin-antitoxin systems along with their clinical and environmental implications. JF - Experimental Biology and Medicine AU - Coussens, Nathan P AU - Daines, Dayle A AD - 1 .Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA, ddaines@odu.edu Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1332 EP - 1342 VL - 241 IS - 12 SN - 1535-3702, 1535-3702 KW - Microbiology Abstracts B: Bacteriology KW - Bacteria KW - biomedical KW - microbiology KW - protein-protein interactions KW - proteolysis KW - enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846406870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+Biology+and+Medicine&rft.atitle=Wake+me+when+it%27s+over+-+Bacterial+toxin-antitoxin+proteins+and+induced+dormancy&rft.au=Coussens%2C+Nathan+P%3BDaines%2C+Dayle+A&rft.aulast=Coussens&rft.aufirst=Nathan&rft.date=2016-06-01&rft.volume=241&rft.issue=12&rft.spage=1332&rft.isbn=&rft.btitle=&rft.title=Experimental+Biology+and+Medicine&rft.issn=15353702&rft_id=info:doi/10.1177%2F1535370216651938 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 133 N1 - Last updated - 2016-12-07 DO - http://dx.doi.org/10.1177/1535370216651938 ER - TY - JOUR T1 - Research involving pediatric stem cell donors: A way forward AN - 1811908812; PQ0003079383 AB - The most suitable donor for younger patients who undergo hematopoietic stem cell transplantation in the research setting is frequently a minor sibling. These cases raise the question of whether minors who serve as stem cell donors for research subjects should be regarded as research subjects themselves. Regarding pediatric donors as research subjects ensures that an Institutional Review Boards reviews their involvement and determines whether it is appropriate. Yet, Institutional Review Boards must follow the US regulations for pediatric research, which were designed for patients and healthy volunteers, not for healthy donors. As a result, regarding pediatric donors as research subjects also can pose unnecessary obstacles to appropriate and potentially life-saving research. This article considers a new way to address this dilemma. The federal research regulations allow for waiver of some or all of the included requirements when they are unnecessary for a study or a class of studies. We argue that this option offers a way to ensure that the involvement of pediatric donors receives sufficient review and approval without inadvertently undermining valuable and potentially life-saving research. JF - Clinical Trials AU - Wendler, David AU - Shah, Nirali N AU - Pulsipher, Michael A AU - Fry, Terry AU - Grady, Christine AD - 1 .Department of Bioethics, NIH Clinical Center, Bethesda, MD, USA, dwendler@nih.gov Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 304 EP - 310 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 13 IS - 3 SN - 1740-7745, 1740-7745 KW - Physical Education Index KW - Transplantation KW - donor KW - pediatric KW - regulations KW - Contracts KW - Pediatrics KW - Organ transplants KW - Patients KW - Health KW - Volunteerism KW - PE 140:Business, Marketing & Sports Equipment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811908812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Trials&rft.atitle=Research+involving+pediatric+stem+cell+donors%3A+A+way+forward&rft.au=Wendler%2C+David%3BShah%2C+Nirali+N%3BPulsipher%2C+Michael+A%3BFry%2C+Terry%3BGrady%2C+Christine&rft.aulast=Wendler&rft.aufirst=David&rft.date=2016-06-01&rft.volume=13&rft.issue=3&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Clinical+Trials&rft.issn=17407745&rft_id=info:doi/10.1177%2F1740774515627156 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Number of references - 20 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Contracts; Pediatrics; Organ transplants; Health; Patients; Volunteerism DO - http://dx.doi.org/10.1177/1740774515627156 ER - TY - JOUR T1 - Progression of Nonradiographic Axial Spondyloarthritis to Ankylosing Spondylitis: A Population-Based Cohort Study AN - 1811907505; PQ0003230104 AB - Objective The long-term outcome of patients with nonradiographic axial spondyloarthritis (SpA) is unclear, particularly whether few or most progress to ankylosing spondylitis (AS). Our objective was to examine the progression to AS in a population-based inception cohort of patients with nonradiographic axial SpA. Methods The Rochester Epidemiology Project (REP) is a longstanding population-based study of health in the residents of Olmsted County, Minnesota. We searched the REP from 1985 to 2010 using diagnostic and procedural codes for back pain, HLA-B27, and magnetic resonance imaging of the pelvis, and we performed detailed chart reviews to identify subjects who fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA but did not have AS. We followed these subjects from disease onset to March 15, 2015, and used survival analysis to measure the time to progression to AS. Results After screening 2,151 patients, we identified 83 subjects with new-onset nonradiographic axial SpA. Over a mean follow-up of 10.6 years, progression to AS occurred in 16 patients. The probability that the condition would remain as nonradiographic axial SpA at 5, 10, and 15 years was 93.6%, 82.7%, and 73.6%, respectively. There was more frequent and more rapid progression among subjects in the imaging arm (n=18) than among those in the clinical arm (n=65) (28% versus 17%; hazard ratio 3.50 [95% confidence interval 1.15-10.6], P=0.02). Conclusion Progression to AS occurred in a minority (26%) of patients with nonradiographic axial SpA over as long as 15 years of follow-up. This suggests that the classification criteria for nonradiographic axial SpA identifies many patients in whom the condition is unlikely to progress to AS or that nonradiographic axial SpA represents a prolonged prodromal state that takes longer to evolve to AS and thus requires longer follow-up. JF - Arthritis & Rheumatology AU - Wang, Runsheng AU - Gabriel, Sherine E AU - Ward, Michael M AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1415 EP - 1421 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 68 IS - 6 SN - 2326-5191, 2326-5191 KW - Physical Education Index KW - Evaluation KW - Classification KW - Scanning KW - Epidemiology KW - Objectives KW - Analysis KW - Patients KW - Health KW - Backache KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811907505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+%26+Rheumatology&rft.atitle=Progression+of+Nonradiographic+Axial+Spondyloarthritis+to+Ankylosing+Spondylitis%3A+A+Population-Based+Cohort+Study&rft.au=Wang%2C+Runsheng%3BGabriel%2C+Sherine+E%3BWard%2C+Michael+M&rft.aulast=Wang&rft.aufirst=Runsheng&rft.date=2016-06-01&rft.volume=68&rft.issue=6&rft.spage=1415&rft.isbn=&rft.btitle=&rft.title=Arthritis+%26+Rheumatology&rft.issn=23265191&rft_id=info:doi/10.1002%2Fart.39542 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Evaluation; Epidemiology; Scanning; Classification; Analysis; Objectives; Health; Patients; Backache DO - http://dx.doi.org/10.1002/art.39542 ER - TY - JOUR T1 - Compressive and shear hip joint contact forces are affected by pediatric obesity during walking AN - 1811894746; PQ0003219568 AB - Obese children exhibit altered gait mechanics compared to healthy-weight children and have an increased prevalence of hip pain and pathology. This study sought to determine the relationships between body mass and compressive and shear hip joint contact forces during walking. Kinematic and kinetic data were collected during treadmill walking at 1ms-1 in 10 obese and 10 healthy-weight 8-12 year-olds. We estimated body composition, segment masses, lower-extremity alignment, and femoral neck angle via radiographic images, created personalized musculoskeletal models in OpenSim, and computed muscle forces and hip joint contact forces. Hip extension at mid-stance was 9 degree less, on average, in the obese children (p<0.001). Hip abduction, knee flexion, and body-weight normalized peak hip moments were similar between groups. Normalized to body-weight, peak contact forces were similar at the first peak and slightly lower at the second peak between the obese and healthy-weight participants. Total body mass explained a greater proportion of contact force variance compared to lean body mass in the compressive (r2=0.89) and vertical shear (perpendicular to the physis acting superior-to-inferior) (r2=0.84) directions; lean body mass explained a greater proportion in the posterior shear direction (r2=0.54). Stance-average contact forces in the compressive and vertical shear directions increased by 41N and 48N, respectively, for every kilogram of body mass. Age explained less than 27% of the hip loading variance. No effect of sex was found. The proportionality between hip loads and body-weight may be implicated in an obese child's increased risk of hip pain and pathology. JF - Journal of Biomechanics AU - Lerner, Zachary F AU - Browning, Raymond C AD - Functional and Applied Biomechanics Section, Rehabilitation Medicine Department, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1547 EP - 1553 PB - Elsevier B.V., P.O. Box 800 Kidlington Oxford OX5 1DX United Kingdom VL - 49 IS - 9 SN - 0021-9290, 0021-9290 KW - Physical Education Index KW - Obesity KW - Gait biomechanics KW - Musculoskeletal modeling KW - Personalized KW - Joint loading KW - OpenSim KW - Orthopedics KW - Body mass KW - Walking KW - Pain KW - Work load KW - Children KW - Hips KW - Treadmill ergometry KW - Joints KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811894746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomechanics&rft.atitle=Compressive+and+shear+hip+joint+contact+forces+are+affected+by+pediatric+obesity+during+walking&rft.au=Lerner%2C+Zachary+F%3BBrowning%2C+Raymond+C&rft.aulast=Lerner&rft.aufirst=Zachary&rft.date=2016-06-01&rft.volume=49&rft.issue=9&rft.spage=1547&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomechanics&rft.issn=00219290&rft_id=info:doi/10.1016%2Fj.jbiomech.2016.03.033 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Number of references - 30 N1 - Last updated - 2016-11-23 N1 - SubjectsTermNotLitGenreText - Obesity; Body mass; Walking; Work load; Pain; Children; Treadmill ergometry; Hips; Joints DO - http://dx.doi.org/10.1016/j.jbiomech.2016.03.033 ER - TY - JOUR T1 - Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress AN - 1811889891; PQ0003529963 AB - Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30days as evidenced by upregulation of liver enzymes and increased synthesis of total bile acids, aggravated inflammatory response and enhanced intrahepatic lipid deposition. Global transcriptomic changes confirmed the enrichment of networks involved in steatosis and cholestasis. In addition, signaling pathways related to glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction were significantly affected by the loss of c-Met function. Mechanistically, exacerbation of oxidative stress in MetKO livers was corroborated by increased lipid and protein oxidation. Western blot analysis further revealed suppression of Erk, NF-kB and Nrf2 survival pathways and downstream target genes (e.g. cyclin D1, SOD1, gamma-GCS), as well as up-regulation of proapoptotic signaling (e.g. p53, caspase 3). Consistent with the observed steatotic and cholestatic phenotype, nuclear receptors RAR, RXR showed increased activation while expression levels of CAR, FXR and PPAR-alpha were decreased in MetKO. Collectively, our data provide evidence for the critical involvement of c-Met signaling in cholesterol and bile acids toxicity. JF - Toxicology AU - Gomez-Quiroz, Luis E AU - Seo, Daekwan AU - Lee, Yun-Han AU - Kitade, Mitsuteru AU - Gaiser, Timo AU - Gillen, Matthew AU - Lee, Seung-Bum AU - Gutierrez-Ruiz, Ma Concepcion AU - Conner, Elizabeth A AU - Factor, Valentina M AU - Thorgeirsson, Snorri S AU - Marquardt, Jens U AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 39 EP - 48 PB - Elsevier B.V., P.O. Box 85 Limerick Ireland VL - 361 SN - 0300-483X, 0300-483X KW - Environment Abstracts; Toxicology Abstracts KW - c-Met KW - Oxidative stress KW - Cholestasis KW - Cholesterol KW - Apoptosis KW - Injuries KW - Hepatocytes KW - Glutathione KW - Lipids KW - Histopathology KW - Survival KW - Mitochondria KW - Homeostasis KW - Nutrition KW - DNA microarrays KW - NF- Kappa B protein KW - Gene expression KW - Bile acids KW - Downstream KW - Diets KW - Western blotting KW - steatosis KW - Enzymes KW - Mice KW - Toxicity KW - p53 protein KW - Caspase-3 KW - Liver KW - Proteins KW - Metabolism KW - Signal transduction KW - X 24300:Methods KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811889891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Loss+of+c-Met+signaling+sensitizes+hepatocytes+to+lipotoxicity+and+induces+cholestatic+liver+damage+by+aggravating+oxidative+stress&rft.au=Gomez-Quiroz%2C+Luis+E%3BSeo%2C+Daekwan%3BLee%2C+Yun-Han%3BKitade%2C+Mitsuteru%3BGaiser%2C+Timo%3BGillen%2C+Matthew%3BLee%2C+Seung-Bum%3BGutierrez-Ruiz%2C+Ma+Concepcion%3BConner%2C+Elizabeth+A%3BFactor%2C+Valentina+M%3BThorgeirsson%2C+Snorri+S%3BMarquardt%2C+Jens+U&rft.aulast=Gomez-Quiroz&rft.aufirst=Luis&rft.date=2016-06-01&rft.volume=361&rft.issue=&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2016.07.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-08-01 N1 - Number of references - 44 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Western blotting; Apoptosis; Injuries; Glutathione; Hepatocytes; steatosis; Mitochondria; Enzymes; Homeostasis; Toxicity; DNA microarrays; p53 protein; NF- Kappa B protein; Gene expression; Oxidative stress; Bile acids; Liver; Caspase-3; Signal transduction; Diets; Lipids; Survival; Histopathology; Mice; Nutrition; Proteins; Downstream; Metabolism DO - http://dx.doi.org/10.1016/j.tox.2016.07.004 ER - TY - JOUR T1 - The usefulness of 'age at first drink' as a concept in alcohol research and prevention AN - 1811883853; PQ0003082873 AB - Commentary to: Is 'age at first drink' a useful concept in alcohol research and prevention? We doubt that JF - Addiction AU - Hingson, R AU - Zha, W AU - White, A AD - Division of Epidemiology and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 968 EP - 970 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 111 IS - 6 SN - 0965-2140, 0965-2140 KW - Physical Education Index KW - Alcohol KW - Preventive health KW - Addiction KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811883853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction&rft.atitle=The+usefulness+of+%27age+at+first+drink%27+as+a+concept+in+alcohol+research+and+prevention&rft.au=Hingson%2C+R%3BZha%2C+W%3BWhite%2C+A&rft.aulast=Hingson&rft.aufirst=R&rft.date=2016-06-01&rft.volume=111&rft.issue=6&rft.spage=968&rft.isbn=&rft.btitle=&rft.title=Addiction&rft.issn=09652140&rft_id=info:doi/10.1111%2Fadd.13218 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Alcohol; Preventive health; Addiction DO - http://dx.doi.org/10.1111/add.13218 ER - TY - JOUR T1 - Endocannabinoid regulation of beta -cell functions: implications for glycaemic control and diabetes AN - 1811876715; PQ0002986233 AB - Visceral obesity is a major risk factor for the development of insulin resistance which can progress to overt type 2 diabetes (T2D) with loss of beta -cell function and, ultimately, loss of beta -cells. Insulin secretion by beta -cells of the pancreatic islets is tightly coupled to blood glucose concentration and modulated by a large number of blood-borne or locally released mediators, including endocannabinoids. Obesity and its complications, including T2D, are associated with increased activity of the endocannabinoid/CB sub(1) receptor (CB sub(1)R) system, as indicated by the therapeutic effects of CB sub(1)R antagonists. Similar beneficial effects of CB sub(1)R antagonists with limited brain penetrance indicate the important role of CB sub(1)R in peripheral tissues, including the endocrine pancreas. Pancreatic beta -cells express all of the components of the endocannabinoid system, and endocannabinoids modulate their function via both autocrine and paracrine mechanisms, which influence basal and glucose-induced insulin secretion and also affect beta -cell proliferation and survival. The present brief review will survey available information on the modulation of these processes by endocannabinoids and their receptors, with an attempt to assess the contribution of such effects to glycaemic control in T2D and insulin resistance. JF - Diabetes, Obesity and Metabolism AU - Jourdan, T AU - Godlewski, G AU - Kunos, G AD - Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 549 EP - 557 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 18 IS - 6 SN - 1462-8902, 1462-8902 KW - Physical Education Index KW - Obesity KW - Pancreas KW - Risk factors KW - Brain KW - Blood glucose KW - Surveys KW - Hormones KW - Diabetes KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811876715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes%2C+Obesity+and+Metabolism&rft.atitle=Endocannabinoid+regulation+of+beta+-cell+functions%3A+implications+for+glycaemic+control+and+diabetes&rft.au=Jourdan%2C+T%3BGodlewski%2C+G%3BKunos%2C+G&rft.aulast=Jourdan&rft.aufirst=T&rft.date=2016-06-01&rft.volume=18&rft.issue=6&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Diabetes%2C+Obesity+and+Metabolism&rft.issn=14628902&rft_id=info:doi/10.1111%2Fdom.12646 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Obesity; Risk factors; Pancreas; Brain; Surveys; Blood glucose; Hormones; Diabetes DO - http://dx.doi.org/10.1111/dom.12646 ER - TY - JOUR T1 - A Novel Peptidomic Approach to Strain Typing of Clinical Acinetobacter baumannii Isolates Using Mass Spectrometry AN - 1808735505; PQ0003220648 AB - BACKGROUND:Acinetobacter baumannii is a common nosocomial pathogen and strain-typing methods play an important role in hospital outbreak investigations and epidemiologic surveillance. We describe a method for identifying strain-specific peptide markers based on LC-MS/MS profiling of digested peptides. This method classified a test set of A. baumannii isolates collected from a hospital outbreak with discriminatory performance exceeding that of MALDI-TOF mass spectrometry.METHODS:Following the construction of a species "pan-peptidome" by in silico translation and digestion of whole genome sequences, a hypothetical set of genome-specific peptides for an isolate was constructed from the disjoint set of the pan-peptidome and the isolate's calculated peptidome. The genome-specific peptidome guided selection of highly expressed genome-specific peptides from LC-MS/MS experimental profiles as potential peptide markers. The species specificity of each experimentally identified genome-specific peptide was confirmed through a Unipept lowest common ancestor analysis.RESULTS:Fifteen A. baumannii isolates were analyzed to derive a set of genome- and species-specific peptides that could be used as peptide markers. Identified peptides were cross-checked with protein BLAST against a set of 22 A. baumannii whole genome sequences. A subset of these peptide markers was confirmed to be present in the actual peptide profiles generated by multiple reaction monitoring and targeted LC-MS/MS. The experimentally identified peptides separated these isolates into 6 strains that agreed with multilocus sequence typing analysis performed on the same isolates.CONCLUSIONS:This approach may be generalizable to other bacterial species, and the peptides may be useful for rapid MS strain tracking of isolates with broad application to infectious disease diagnosis. JF - Clinical Chemistry AU - Wang, Honghui AU - Drake, Steven K AU - Yong, Chen AU - Gucek, Marjan AU - Tropea, Margaret AU - Rosenberg, Avi Z AU - Dekker, John P AU - Suffredini, Anthony F AD - Critical Care Medicine Department, Clinical Center,, asuffredini@cc.nih.gov Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 866 EP - 875 PB - American Association for Clinical Chemistry, Inc. VL - 62 IS - 6 SN - 0009-9147, 0009-9147 KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Digestion KW - Translation KW - Acinetobacter baumannii KW - Typing KW - Infectious diseases KW - Pathogens KW - Mass spectroscopy KW - Hospitals KW - multilocus sequence typing KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808735505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Chemistry&rft.atitle=A+Novel+Peptidomic+Approach+to+Strain+Typing+of+Clinical+Acinetobacter+baumannii+Isolates+Using+Mass+Spectrometry&rft.au=Wang%2C+Honghui%3BDrake%2C+Steven+K%3BYong%2C+Chen%3BGucek%2C+Marjan%3BTropea%2C+Margaret%3BRosenberg%2C+Avi+Z%3BDekker%2C+John+P%3BSuffredini%2C+Anthony+F&rft.aulast=Wang&rft.aufirst=Honghui&rft.date=2016-06-01&rft.volume=62&rft.issue=6&rft.spage=866&rft.isbn=&rft.btitle=&rft.title=Clinical+Chemistry&rft.issn=00099147&rft_id=info:doi/10.1373%2Fclinchem.2015.253468 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Digestion; Genomes; Translation; Typing; Infectious diseases; Pathogens; Mass spectroscopy; multilocus sequence typing; Hospitals; Acinetobacter baumannii DO - http://dx.doi.org/10.1373/clinchem.2015.253468 ER - TY - JOUR T1 - Radiological-pathological correlation of diffusion tensor and magnetization transfer imaging in a closed head traumatic brain injury model AN - 1808716317; PQ0003229961 AB - Objective Metrics of diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) can detect diffuse axonal injury in traumatic brain injury (TBI). The relationship between the changes in these imaging measures and the underlying pathologies is still relatively unknown. This study investigated the radiological-pathological correlation between these imaging techniques and immunohistochemistry using a closed head rat model of TBI. Methods TBI was performed on female rats followed longitudinally by magnetic resonance imaging (MRI) out to 30 days postinjury, with a subset of animals selected for histopathological analyses. A MRI-based finite element analysis was generated to characterize the pattern of the mechanical insult and estimate the extent of brain injury to direct the pathological correlation with imaging findings. Results DTI axial diffusivity and fractional anisotropy (FA) were sensitive to axonal integrity, whereas radial diffusivity showed significant correlation to the myelin compactness. FA was correlated with astrogliosis in the gray matter, whereas mean diffusivity was correlated with increased cellularity. Secondary inflammatory responses also partly affected the changes of these DTI metrics. The magnetization transfer ratio (MTR) at 3.5ppm demonstrated a strong correlation with both axon and myelin integrity. Decrease in MTR at 20ppm correlated with the extent of astrogliosis in both gray and white matter. Interpretation Although conventional T2-weighted MRI did not detect abnormalities following TBI, DTI and MTI afforded complementary insight into the underlying pathologies reflecting varying injury states over time, and thus may substitute for histology to reveal diffusive axonal injury pathologies in vivo. This correlation of MRI and histology furthers understanding of the microscopic pathology underlying DTI and MTI changes in TBI. Ann Neurol 2016; 79:907-920 JF - Annals of Neurology AU - Tu, Tsang-Wei AU - Williams, Rashida A AU - Lescher, Jacob D AU - Jikaria, Neekita AU - Turtzo, LChristine AU - Frank, Joseph A AD - Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 907 EP - 920 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 79 IS - 6 SN - 0364-5134, 0364-5134 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Neuroimaging KW - Mathematical models KW - Anisotropy KW - Myelin KW - Head KW - Magnetic resonance imaging KW - Animal models KW - Substantia alba KW - Inflammation KW - Gliosis KW - Axons KW - Traumatic brain injury KW - Immunohistochemistry KW - Substantia grisea KW - X 24390:Radioactive Materials KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808716317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Neurology&rft.atitle=Radiological-pathological+correlation+of+diffusion+tensor+and+magnetization+transfer+imaging+in+a+closed+head+traumatic+brain+injury+model&rft.au=Tu%2C+Tsang-Wei%3BWilliams%2C+Rashida+A%3BLescher%2C+Jacob+D%3BJikaria%2C+Neekita%3BTurtzo%2C+LChristine%3BFrank%2C+Joseph+A&rft.aulast=Tu&rft.aufirst=Tsang-Wei&rft.date=2016-06-01&rft.volume=79&rft.issue=6&rft.spage=907&rft.isbn=&rft.btitle=&rft.title=Annals+of+Neurology&rft.issn=03645134&rft_id=info:doi/10.1002%2Fana.24641 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Anisotropy; Mathematical models; Head; Myelin; Magnetic resonance imaging; Animal models; Substantia alba; Inflammation; Gliosis; Axons; Traumatic brain injury; Immunohistochemistry; Substantia grisea DO - http://dx.doi.org/10.1002/ana.24641 ER - TY - JOUR T1 - beta -Globin-Expressing Definitive Erythroid Progenitor Cells Generated from Embryonic and Induced Pluripotent Stem Cell-Derived Sacs AN - 1808705168; PQ0003238570 AB - Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a potential alternative source for red blood cell transfusion. However, when using traditional methods with embryoid bodies, ES cell-derived erythroid cells predominantly express embryonic type -globin, with lesser fetal type gamma -globin and very little adult type beta -globin. Furthermore, no beta -globin expression is detected in iPS cell-derived erythroid cells. ES cell-derived sacs (ES sacs) have been recently used to generate functional platelets. Due to its unique structure, we hypothesized that ES sacs serve as hemangioblast-like progenitors capable to generate definitive erythroid cells that express beta -globin. With our ES sac-derived erythroid differentiation protocol, we obtained 120 erythroid cells per single ES cell. Both primitive (-globin expressing) and definitive ( gamma - and beta -globin expressing) erythroid cells were generated from not only ES cells but also iPS cells. Primitive erythropoiesis is gradually switched to definitive erythropoiesis during prolonged ES sac maturation, concurrent with the emergence of hematopoietic progenitor cells. Primitive and definitive erythroid progenitor cells were selected on the basis of glycophorin A or CD34 expression from cells within the ES sacs before erythroid differentiation. This selection and differentiation strategy represents an important step toward the development of in vitro erythroid cell production systems from pluripotent stem cells. Further optimization to improve expansion should be required for clinical application. Stem Cells 2016; 34:1541-1552 JF - Stem Cells AU - Fujita, Atsushi AU - Uchida, Naoya AU - Haro-Mora, Juan J AU - Winkler, Thomas AU - Tisdale, John AD - Molecular and Clinical Hematology Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1541 EP - 1552 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 6 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Differentiation KW - Stem cells KW - Erythropoiesis KW - Erythroid cells KW - Erythrocytes KW - Platelets KW - Hemopoiesis KW - Therapeutic applications KW - Embryos KW - CD34 antigen KW - Fetuses KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808705168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=beta+-Globin-Expressing+Definitive+Erythroid+Progenitor+Cells+Generated+from+Embryonic+and+Induced+Pluripotent+Stem+Cell-Derived+Sacs&rft.au=Fujita%2C+Atsushi%3BUchida%2C+Naoya%3BHaro-Mora%2C+Juan+J%3BWinkler%2C+Thomas%3BTisdale%2C+John&rft.aulast=Fujita&rft.aufirst=Atsushi&rft.date=2016-06-01&rft.volume=34&rft.issue=6&rft.spage=1541&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2335 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Differentiation; Stem cells; Erythropoiesis; Erythrocytes; Erythroid cells; Platelets; Therapeutic applications; Hemopoiesis; CD34 antigen; Embryos; Fetuses DO - http://dx.doi.org/10.1002/stem.2335 ER - TY - JOUR T1 - Molecular Analysis of Neutrophil Differentiation from Human Induced Pluripotent Stem Cells Delineates the Kinetics of Key Regulators of Hematopoiesis AN - 1808691925; PQ0003238567 AB - Abstract In vitro generation of mature neutrophils from human induced pluripotent stem cells (iPSCs) requires hematopoietic progenitor development followed by myeloid differentiation. The purpose of our studies was to extensively characterize this process, focusing on the critical window of development between hemogenic endothelium, hematopoietic stem/progenitor cells (HSPCs), and myeloid commitment, to identify associated regulators and markers that might enable the stem cell field to improve the efficiency and efficacy of iPSC hematopoiesis. We utilized a four-stage differentiation protocol involving: embryoid body (EB) formation (stage-1); EB culture with hematopoietic cytokines (stage-2); HSPC expansion (stage-3); and neutrophil maturation (stage-4). CD34 super(+)CD45 super(-) putative hemogenic endothelial cells were observed in stage-3 cultures, and expressed VEGFR-2/Flk-1/KDR and VE-cadherin endothelial markers, GATA-2, AML1/RUNX1, and SCL/TAL1 transcription factors, and endothelial/HSPC-associated microRNAs miR-24, miR-125a-3p, miR-126/126*, and miR-155. Upon further culture, CD34 super(+)CD45 super(-) cells generated CD34 super(+)CD45 super(+) HSPCs that produced hematopoietic CFUs. Mid-stage-3 CD34 super(+)CD45 super(+) HSPCs exhibited increased expression of GATA-2, AML1/RUNX1, SCL/TAL1, C/EBP alpha , and PU.1 transcription factors, but exhibited decreased expression of HSPC-associated microRNAs, and failed to engraft in immune-deficient mice. Mid-stage-3 CD34 super(-)CD45 super(+) cells maintained PU.1 expression and exhibited increased expression of hematopoiesis-associated miR-142-3p/5p and a trend towards increased miR-223 expression, indicating myeloid commitment. By late Stage-4, increased CD15, CD16b, and C/EBP expression were observed, with 25%-65% of cells exhibiting morphology and functions of mature neutrophils. These studies demonstrate that hematopoiesis and neutrophil differentiation from human iPSCs recapitulates many features of embryonic hematopoiesis and neutrophil production in marrow, but reveals unexpected molecular signatures that may serve as a guide for enhancing iPSC hematopoiesis. Stem Cells 2016; 34:1513-1526 JF - Stem Cells AU - Sweeney, Colin L AU - Teng, Ruifeng AU - Wang, Hongmei AU - Merling, Randall K AU - Lee, Janet AU - Choi, Uimook AU - Koontz, Sherry AU - Wright, Daniel G AU - Malech, Harry L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1513 EP - 1526 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 6 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - GATA-2 protein KW - miRNA KW - Inhibitory postsynaptic potentials KW - Leukocytes (neutrophilic) KW - Cell culture KW - Endothelial cells KW - Differentiation KW - Stem cells KW - Transcription factors KW - Colony-forming cells KW - Kinetics KW - Endothelium KW - PU.1 protein KW - AML1 protein KW - Hemopoiesis KW - Cytokines KW - Embryos KW - CCAAT/enhancer-binding protein KW - Runx1 protein KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808691925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Molecular+Analysis+of+Neutrophil+Differentiation+from+Human+Induced+Pluripotent+Stem+Cells+Delineates+the+Kinetics+of+Key+Regulators+of+Hematopoiesis&rft.au=Sweeney%2C+Colin+L%3BTeng%2C+Ruifeng%3BWang%2C+Hongmei%3BMerling%2C+Randall+K%3BLee%2C+Janet%3BChoi%2C+Uimook%3BKoontz%2C+Sherry%3BWright%2C+Daniel+G%3BMalech%2C+Harry+L&rft.aulast=Sweeney&rft.aufirst=Colin&rft.date=2016-06-01&rft.volume=34&rft.issue=6&rft.spage=1513&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2332 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - GATA-2 protein; Inhibitory postsynaptic potentials; miRNA; Leukocytes (neutrophilic); Cell culture; Endothelial cells; Differentiation; Stem cells; Kinetics; Colony-forming cells; Transcription factors; Endothelium; AML1 protein; PU.1 protein; Cytokines; Hemopoiesis; Embryos; CCAAT/enhancer-binding protein; Runx1 protein DO - http://dx.doi.org/10.1002/stem.2332 ER - TY - JOUR T1 - Stable, Nonviral Expression of Mutated Tumor Neoantigen-specific T-cell Receptors Using the Sleeping Beauty Transposon/Transposase System AN - 1808675763; PQ0003363450 AB - Neoantigens unique to each patient's tumor can be recognized by autologous T cells through their T-cell receptor (TCR) but the low frequency and/or terminal differentiation of mutation-specific T cells in tumors can limit their utility as adoptive T-cell therapies. Transfer of TCR genes into younger T cells from peripheral blood with a high proliferative potential could obviate this problem. We generated a rapid, cost-effective strategy to genetically engineer cancer patient T cells with TCRs using the clinical Sleeping Beauty transposon/transposase system. Patient-specific TCRs reactive against HLA-A*0201-restriced neoantigens AHNAK super(S2580F) or ERBB2 super(H473Y) or the HLA-DQB*0601-restricted neoantigen ERBB2IP super(E805G) were assembled with murine constant chains and cloned into Sleeping Beauty transposons. Patient peripheral blood lymphocytes were coelectroporated with SB11 transposase and Sleeping Beauty transposon, and transposed T cells were enriched by sorting on murine TCR beta (mTCR beta ) expression. Rapid expansion of mTCR beta super(+) T cells with irradiated allogeneic peripheral blood lymphocytes feeders, OKT3, interleukin-2 (IL-2), IL-15, and IL-21 resulted in a preponderance of effector (CD27 super(-)CD45RA super(- )) and less-differentiated (CD27 super(+)CD45RA super(+) ) T cells. Transposed T cells specifically mounted a polyfunctional response against cognate mutated neoantigens and tumor cell lines. Thus, Sleeping Beauty transposition of mutation-specific TCRs can facilitate the use of personalized T-cell therapy targeting unique neoantigens. JF - Molecular Therapy AU - Deniger, Drew C AU - Pasetto, Anna AU - Tran, Eric AU - Parkhurst, Maria R AU - Cohen, Cyrille J AU - Robbins, Paul F AU - Cooper, Laurence JN AU - Rosenberg, Steven A AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1078 EP - 1089 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 24 IS - 6 SN - 1525-0016, 1525-0016 KW - Immunology Abstracts; Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Histocompatibility antigen HLA KW - T-cell receptor KW - Interleukin 2 KW - Transposition KW - Peripheral blood KW - Tumors KW - Interleukin 21 KW - Transposons KW - Differentiation KW - transposase KW - Tumor cell lines KW - Interleukin 15 KW - Lymphocytes T KW - W 30925:Genetic Engineering KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808675763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Therapy&rft.atitle=Stable%2C+Nonviral+Expression+of+Mutated+Tumor+Neoantigen-specific+T-cell+Receptors+Using+the+Sleeping+Beauty+Transposon%2FTransposase+System&rft.au=Deniger%2C+Drew+C%3BPasetto%2C+Anna%3BTran%2C+Eric%3BParkhurst%2C+Maria+R%3BCohen%2C+Cyrille+J%3BRobbins%2C+Paul+F%3BCooper%2C+Laurence+JN%3BRosenberg%2C+Steven+A&rft.aulast=Deniger&rft.aufirst=Drew&rft.date=2016-06-01&rft.volume=24&rft.issue=6&rft.spage=1078&rft.isbn=&rft.btitle=&rft.title=Molecular+Therapy&rft.issn=15250016&rft_id=info:doi/10.1038%2Fmt.2016.51 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Histocompatibility antigen HLA; T-cell receptor; Interleukin 2; Transposition; Peripheral blood; Tumors; Interleukin 21; Transposons; transposase; Differentiation; Tumor cell lines; Interleukin 15; Lymphocytes T DO - http://dx.doi.org/10.1038/mt.2016.51 ER - TY - JOUR T1 - Estimating the Mechanical Behavior of the Knee Joint During Crouch Gait: Implications for Real-Time Motor Control of Robotic Knee Orthoses AN - 1808665544; PQ0003325332 AB - Individuals with cerebral palsy frequently exhibit crouch gait, a pathological walking pattern characterized by excessive knee flexion. Knowledge of the knee joint moment during crouch gait is necessary for the design and control of assistive devices used for treatment. Our goal was to 1) develop statistical models to estimate knee joint moment extrema and dynamic stiffness during crouch gait, and 2) use the models to estimate the instantaneous joint moment during weight-acceptance. We retrospectively computed knee moments from 10 children with crouch gait and used stepwise linear regression to develop statistical models describing the knee moment features. The models explained at least 90% of the response value variability: peak moment in early (99%) and late (90%) stance, and dynamic stiffness of weight-acceptance flexion (94%) and extension (98%). We estimated knee extensor moment profiles from the predicted dynamic stiffness and instantaneous knee angle. This approach captured the timing and shape of the computed moment (root-mean-squared error: 2.64 Nm); including the predicted early-stance peak moment as a correction factor improved model performance (root-mean-squared error: 1.37 Nm). Our strategy provides a practical, accurate method to estimate the knee moment during crouch gait, and could be used for real-time, adaptive control of robotic orthoses. JF - IEEE Transactions on Neural Systems and Rehabilitation Engineering AU - Lerner, Zachary F AU - Damiano, Diane L AU - Bulea, Thomas C AD - Functional and Applied Biomechanics Section, Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 621 EP - 629 PB - Institute of Electrical and Electronics Engineers, Inc., 3 Park Avenue, 17th Fl New York NY 10016-5997 United States VL - 24 IS - 6 SN - 1534-4320, 1534-4320 KW - Biotechnology and Bioengineering Abstracts KW - Mathematical models KW - Rehabilitation KW - Motor task performance KW - Statistical analysis KW - Walking KW - Children KW - Knee KW - Joints KW - Models KW - Paralysis KW - Regression analysis KW - robotics KW - gait KW - Mechanical properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808665544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IEEE+Transactions+on+Neural+Systems+and+Rehabilitation+Engineering&rft.atitle=Estimating+the+Mechanical+Behavior+of+the+Knee+Joint+During+Crouch+Gait%3A+Implications+for+Real-Time+Motor+Control+of+Robotic+Knee+Orthoses&rft.au=Lerner%2C+Zachary+F%3BDamiano%2C+Diane+L%3BBulea%2C+Thomas+C&rft.aulast=Lerner&rft.aufirst=Zachary&rft.date=2016-06-01&rft.volume=24&rft.issue=6&rft.spage=621&rft.isbn=&rft.btitle=&rft.title=IEEE+Transactions+on+Neural+Systems+and+Rehabilitation+Engineering&rft.issn=15344320&rft_id=info:doi/10.1109%2FTNSRE.2016.2550860 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Mathematical models; Rehabilitation; Motor task performance; Statistical analysis; Walking; Children; Knee; Models; Joints; Paralysis; Regression analysis; robotics; gait; Mechanical properties DO - http://dx.doi.org/10.1109/TNSRE.2016.2550860 ER - TY - JOUR T1 - Cognitive testing of tobacco use items for administration to patients with cancer and cancer survivors in clinical research AN - 1808664552; PQ0003164266 AB - BACKGROUND To the authors' knowledge, there are currently no standardized measures of tobacco use and secondhand smoke exposure in patients diagnosed with cancer, and this gap hinders the conduct of studies examining the impact of tobacco on cancer treatment outcomes. The objective of the current study was to evaluate and refine questionnaire items proposed by an expert task force to assess tobacco use. METHODS Trained interviewers conducted cognitive testing with cancer patients aged greater than or equal to 21 years with a history of tobacco use and a cancer diagnosis of any stage and organ site who were recruited at the National Institutes of Health Clinical Center in Bethesda, Maryland. Iterative rounds of testing and item modification were conducted to identify and resolve cognitive issues (comprehension, memory retrieval, decision/judgment, and response mapping) and instrument navigation issues until no items warranted further significant modification. RESULTS Thirty participants (6 current cigarette smokers, 1 current cigar smoker, and 23 former cigarette smokers) were enrolled from September 2014 to February 2015. The majority of items functioned well. However, qualitative testing identified wording ambiguities related to cancer diagnosis and treatment trajectory, such as "treatment" and "surgery"; difficulties with lifetime recall; errors in estimating quantities; and difficulties with instrument navigation. Revisions to item wording, format, order, response options, and instructions resulted in a questionnaire that demonstrated navigational ease as well as good question comprehension and response accuracy. CONCLUSIONS The Cancer Patient Tobacco Use Questionnaire (C-TUQ) can be used as a standardized item set to accelerate the investigation of tobacco use in the cancer setting. Cancer 2016; 122:1728-34. copyright 2016 American Cancer Society. Tobacco use by patients with cancer is an understudied area, and research and clinical management have been impeded by a lack of standardized self-report measures for assessment. The current study reports the development and cognitive interviewing study of the newly designed Cancer Patient Tobacco Use Questionnaire (C-TUQ), which is now available to assess tobacco use in patients during and after cancer treatment. JF - Cancer AU - Land, Stephanie R AU - Warren, Graham W AU - Crafts, Jennifer L AU - Hatsukami, Dorothy K AU - Ostroff, Jamie S AU - Willis, Gordon B AU - Chollette, Veronica Y AU - Mitchell, Sandra A AU - Folz, Jasmine NM AU - Gulley, James L AU - Szabo, Eva AU - Brandon, Thomas H AU - Duffy, Sonia A AU - Toll, Benjamin A AD - Tobacco Control Research Branch, Behavioral Research Program, National Cancer Institute, Bethesda, Maryland. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1728 EP - 1734 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 122 IS - 11 SN - 0008-543X, 0008-543X KW - Toxicology Abstracts KW - Smoke KW - Inventories KW - Decision making KW - Memory KW - Cigarettes KW - Cognitive ability KW - Surgery KW - Navigation behavior KW - Tobacco KW - Mapping KW - Cancer KW - X 24380:Social Poisons & Drug Abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808664552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Cognitive+testing+of+tobacco+use+items+for+administration+to+patients+with+cancer+and+cancer+survivors+in+clinical+research&rft.au=Land%2C+Stephanie+R%3BWarren%2C+Graham+W%3BCrafts%2C+Jennifer+L%3BHatsukami%2C+Dorothy+K%3BOstroff%2C+Jamie+S%3BWillis%2C+Gordon+B%3BChollette%2C+Veronica+Y%3BMitchell%2C+Sandra+A%3BFolz%2C+Jasmine+NM%3BGulley%2C+James+L%3BSzabo%2C+Eva%3BBrandon%2C+Thomas+H%3BDuffy%2C+Sonia+A%3BToll%2C+Benjamin+A&rft.aulast=Land&rft.aufirst=Stephanie&rft.date=2016-06-01&rft.volume=122&rft.issue=11&rft.spage=1728&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/10.1002%2Fcncr.29964 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Smoke; Decision making; Inventories; Memory; Cigarettes; Cognitive ability; Surgery; Navigation behavior; Tobacco; Mapping; Cancer DO - http://dx.doi.org/10.1002/cncr.29964 ER - TY - JOUR T1 - The NIH Countermeasures Against Chemical Threats Program: overview and special challenges AN - 1808660760; PQ0003466841 AB - Intentional exposures to toxic chemicals can stem from terrorist attacks, such as the release of sarin in the Tokyo subway system in 1995, as well as from toxic industrial accidents that are much more common. Developing effective medical interventions is a critical component of the overall strategy to overcome the challenges of chemical emergencies. These challenges include the rapid and lethal mode of action of many toxic chemicals that require equally fast-acting therapies, the large number of chemicals that are considered threats, and the diverse demographics and vulnerabilities of those who may be affected. In addition, there may be long-term deleterious effects in survivors of a chemical exposure. Several U.S. federal agencies are invested in efforts to improve preparedness and response capabilities during and after chemical emergencies. For example, the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) Program supports investigators who are developing therapeutics to reduce mortality and morbidity from chemical exposures. The program awards grants to individual laboratories and includes contract resource facilities and interagency agreements with Department of Defense laboratories. The range of high-quality research within the NIH CounterACT Program network is discussed. JF - Annals of the New York Academy of Sciences AU - Jett, David A AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 5 EP - 9 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1374 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts KW - Mortality KW - Terrorism KW - Contracts KW - Grants KW - Intervention KW - Morbidity KW - Demography KW - Accidents KW - Reviews KW - Sarin KW - Awards KW - Vulnerability KW - INW, Japan, Honshu, Tokyo Prefect., Tokyo KW - F 06935:Development, Aging & Organ Systems KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808660760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+NIH+Countermeasures+Against+Chemical+Threats+Program%3A+overview+and+special+challenges&rft.au=Jett%2C+David+A&rft.aulast=Jett&rft.aufirst=David&rft.date=2016-06-01&rft.volume=1374&rft.issue=1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13179 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Demography; Mortality; Accidents; Reviews; Sarin; Morbidity; Terrorism; Contracts; Grants; Intervention; Vulnerability; Awards; INW, Japan, Honshu, Tokyo Prefect., Tokyo DO - http://dx.doi.org/10.1111/nyas.13179 ER - TY - JOUR T1 - Binuclear Cells in the Lactating Mammary Gland: New Insights on an Old Concept? AN - 1808650518; PQ0003405864 AB - In a recent paper (Rios et al. Nat Commun. 7:11400, 2016), it was reported that polyploid cells are frequent in lactating mammary tissues. This phenomenon was observed in mammary tissue sampled from five separate mammalian species. According to that report, these binucleated cells occur late in pregnancy and early in lactation. Unfortunately, this paper did not mention a number of earlier observations and findings that remain pertinent to this day (Banerjee et al. Life sciences Pt 2: Biochemistry, general and molecular biology. 10(15):867-77, 1971; Banerjee MR, Wagner JE. Biochem. Biophys. Res. Commun. 49(2):480-7, 1972). In these classical experiments, the authors demonstrated in vivo that DNA synthesis continued without commensurate cell division during late pregnancy and lactation, and that this DNA synthesis was imperative for functional differentiation of the mammary epithelium. Later studies showed that DNA synthesis was indispensable to the induction of milk protein production in explant cultures of mammary tissue from unprimed, nulliparous mice. This dependence on DNA synthesis in mammary explant cultures stimulated by lactogenic hormones was found to be dispensable following a single pregnancy. The absolute requirement for DNA synthesis in nulliparous mouse mammary explants stimulated to synthesize milk protein in vitro has remained unexplained, as has the need for DNA synthesis prior to the onset of lactation. From a historical perspective, it is more likely that binuclear secretory cells in the lactating mammary gland are a consequence of the DNA synthesis requirement for lactation, rather than an essential element. JF - Journal of Mammary Gland Biology and Neoplasia AU - Smith, Gilbert H AD - Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg. 37, Rm. 1122A, 37 Convent Drive, Bethesda, MD, 20892, USA, gs4d@nih.gov Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 21 EP - 23 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 21 IS - 1-2 SN - 1083-3021, 1083-3021 KW - Biotechnology and Bioengineering Abstracts KW - DNA biosynthesis KW - Milk KW - Polyploidy KW - Mammary gland KW - Cell culture KW - Hormones KW - Lactation KW - Pregnancy KW - Differentiation KW - Cell division KW - Epithelium KW - Explants KW - W 30935:Food Biotechnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808650518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Mammary+Gland+Biology+and+Neoplasia&rft.atitle=Binuclear+Cells+in+the+Lactating+Mammary+Gland%3A+New+Insights+on+an+Old+Concept%3F&rft.au=Smith%2C+Gilbert+H&rft.aulast=Smith&rft.aufirst=Gilbert&rft.date=2016-06-01&rft.volume=21&rft.issue=1-2&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Journal+of+Mammary+Gland+Biology+and+Neoplasia&rft.issn=10833021&rft_id=info:doi/10.1007%2Fs10911-016-9356-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 12 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Differentiation; DNA biosynthesis; Cell division; Polyploidy; Milk; Mammary gland; Epithelium; Cell culture; Hormones; Explants; Pregnancy; Lactation DO - http://dx.doi.org/10.1007/s10911-016-9356-5 ER - TY - JOUR T1 - Changes of serum amino acid profiles by an epidermal growth factor receptor mutation and benzo[a]pyrene in mouse lung tumorigenesis AN - 1808646596; PQ0003358374 AB - Studies suggest that gene mutation and carcinogen exposure contribute to lung tumorigenesis including a mutation of epidermal growth factor receptor (EGFR) and exposure to benzo[a]pyrene (BaP). However, the interaction between EGFR mutation and BaP exposure during lung tumorigenesis is unclear. Metabolomics has become an important tool in clinical research and has been utilized to help our understanding of mechanisms and to identify indicators of cancers. This study's aim was to identify the changes in metabolite profiles in mice associated with an EGFR exon 21 deletion and/or BaP treatment-induced lung tumorigenesis. While the EGFR mutation increased the incidence of lung adenoma in transgenic mice (EGFR mutant mice) at 32 weeks of age, exposure to BaP caused the onset of lung tumorigenesis in these mice as early as 16 weeks after exposure. Using a metabolomics strategy involving liquid chromatography-mass spectrometry in conjunction with principal component analysis and confirmation by liquid chromatography triple quadrupole tandem mass spectrometry, we demonstrated that the serum amino acid profiles of these mice were changed. A total of eight amino acid concentrations were lower in EGFR mutant mice than in wild-type mice at 32 weeks of age. Five amino acids were lower in tumor-bearing mice than in non-tumor-bearing EGFR mutant mice at 10th week post-treatment of BaP, namely phenylalanine, tyrosine, alanine, proline, and threonine. Our results suggest that gene mutation and carcinogen exposure-induced lung adenomas share some common mechanisms. Changes in serum amino acid profiles may be early indicators of lung tumorigenesis. JF - Toxicology Research AU - Lin, Pinpin AU - Chen, Yi-Rong AU - Chen, Chao-Yu AU - Chang, Ya-Ting AU - Chen, Jhih-Sheng AU - Tsai, Ming-Hsien AU - Kuo, Cheng-Chin AU - Lee, Hui-Ling AD - National Institute of Environmental Health Sciences; National Health Research Institutes; Zhunan; Miaoli County 350; Taiwan Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1182 EP - 1192 PB - Royal Society of Chemistry, c/o Springer-Verlag New York Inc. Secaucus New Jersey 07096 2485 United States VL - 5 IS - 4 SN - 2045-452X, 2045-452X KW - Toxicology Abstracts KW - Age KW - Proline KW - Amino acids KW - Alanine KW - Point mutation KW - Tumorigenesis KW - Tyrosine KW - Epidermal growth factor receptors KW - Metabolites KW - Carcinogens KW - Phenylalanine KW - Mass spectroscopy KW - Liquid chromatography KW - Lung KW - Benzo(a)pyrene KW - Threonine KW - Adenoma KW - metabolomics KW - Amino acid sequence KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808646596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Research&rft.atitle=Changes+of+serum+amino+acid+profiles+by+an+epidermal+growth+factor+receptor+mutation+and+benzo%5Ba%5Dpyrene+in+mouse+lung+tumorigenesis&rft.au=Lin%2C+Pinpin%3BChen%2C+Yi-Rong%3BChen%2C+Chao-Yu%3BChang%2C+Ya-Ting%3BChen%2C+Jhih-Sheng%3BTsai%2C+Ming-Hsien%3BKuo%2C+Cheng-Chin%3BLee%2C+Hui-Ling&rft.aulast=Lin&rft.aufirst=Pinpin&rft.date=2016-06-01&rft.volume=5&rft.issue=4&rft.spage=1182&rft.isbn=&rft.btitle=&rft.title=Toxicology+Research&rft.issn=2045452X&rft_id=info:doi/10.1039%2Fc6tx00010j LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 40 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Proline; Age; Amino acids; Alanine; Tumorigenesis; Point mutation; Tyrosine; Metabolites; Epidermal growth factor receptors; Carcinogens; Phenylalanine; Mass spectroscopy; Lung; Liquid chromatography; Benzo(a)pyrene; Adenoma; Threonine; metabolomics; Amino acid sequence DO - http://dx.doi.org/10.1039/c6tx00010j ER - TY - JOUR T1 - Obesity, diabetes, serum glucose, and risk of primary liver cancer by birth cohort, race/ethnicity, and sex: Multiphasic health checkup study AN - 1808643920; PQ0003264700 AB - Objective Obesity and diabetes have been associated with liver cancer. However, recent US-based studies have suggested a lack of association between obesity and liver cancer among blacks and women. Methods We conducted a nested case-control study within the Multiphasic Health Checkup (MHC) cohort of Kaiser Permanente Northern California (KPNC) members. Liver cancer was diagnosed using the KPNC Cancer Registry. Detailed self-administered questionnaires and a standardized examination that included measurement of height and weight and a 1-h glucose tolerance test were completed prior to diagnosis of liver cancer for cases (n=450) and matched controls (4489). Height and weight were utilized to calculate BMI (kg/m2) as a measure of adiposity: underweight (15- less than or equal to 8.5kg/m2), normal weight (18.5- less than or equal to 25kg/m2), overweight (25- less than or equal to 30kg/m2), and obese ( greater than or equal to 30kg/m2). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between BMI, diabetes, and serum glucose with subsequent incidence of liver cancer, in models that were stratified by birth cohort, race/ethnicity, and sex. Results Compared to normal weight individuals, obese individuals had a 2.4-fold increased risk of liver cancer (OR=2.38, 95% CI: 1.68-3.36), and overweight individuals had a 32% increased risk (OR=1.32, 95% CI: 1.03-1.70). This association did not differ when stratified by birth cohort, race/ethnicity, or sex (pint>0.05). Among blacks and women, obesity was associated with at least a 2-fold increased risk of liver cancer (OR=2.29, 95% CI: 1.22-4.28 and OR=2.00, 95% CI: 1.14-3.52, respectively). More moderate increased odds ratios were noted for diabetes (OR=1.28, 95% CI: 0.65-2.54) and serum glucose greater than or equal to 200mg/dL (OR=1.63, 95% CI: 0.48-5.55), although the results did not attain statistical significance. Conclusion In summary, our finding of a positive association between obesity and liver cancer suggests that a higher BMI may increase the risk of liver cancer in the US, for both sexes and all race/ethnicities. JF - Cancer Epidemiology AU - Petrick, Jessica L AU - Freedman, Neal D AU - Demuth, Jane AU - Yang, Baiyu AU - Van Den Eeden, Stephen K AU - Engel, Lawrence S AU - McGlynn, Katherine A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 140 EP - 146 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 42 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - Inventories KW - Obesity KW - Statistics KW - Liver cancer KW - Major histocompatibility complex KW - Underweight KW - Models KW - Diabetes mellitus KW - Body weight KW - Regression analysis KW - Glucose tolerance KW - Adipose tissue KW - Races KW - Ethnic groups KW - Sex KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808643920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Obesity%2C+diabetes%2C+serum+glucose%2C+and+risk+of+primary+liver+cancer+by+birth+cohort%2C+race%2Fethnicity%2C+and+sex%3A+Multiphasic+health+checkup+study&rft.au=Petrick%2C+Jessica+L%3BFreedman%2C+Neal+D%3BDemuth%2C+Jane%3BYang%2C+Baiyu%3BVan+Den+Eeden%2C+Stephen+K%3BEngel%2C+Lawrence+S%3BMcGlynn%2C+Katherine+A&rft.aulast=Petrick&rft.aufirst=Jessica&rft.date=2016-06-01&rft.volume=42&rft.issue=&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.04.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 33 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Obesity; Inventories; Statistics; Liver cancer; Major histocompatibility complex; Underweight; Models; Diabetes mellitus; Body weight; Regression analysis; Adipose tissue; Glucose tolerance; Ethnic groups; Races; Sex DO - http://dx.doi.org/10.1016/j.canep.2016.04.009 ER - TY - JOUR T1 - Patterns and prevalence of medication use across the menstrual cycle among healthy, reproductive aged women AN - 1808641166; PQ0003232008 AB - Purpose The purpose of this study is to characterize the patterns of medication intake in healthy, reproductive-age women not using hormonal contraception. Methods Two hundered fifty-nine healthy, premenopausal women (18-44years of age) enrolled in the BioCycle Study (2005-2007) were followed over two menstrual cycles. Women were excluded if they were currently using oral contraceptives or other chronic medications. Over-the-counter and prescription medication use among participants was evaluated daily throughout the study via a diary assessing type of medication, dosage, units, and frequency. Medications were categorized as allergy, antibiotics, central nervous system (CNS), cold and cough, gastrointestinal, musculoskeletal, and pain medication based on primary active ingredient. Medication use within each category was assessed across standardized 28-day cycles to evaluate differences in use across cycle phases (i.e., early, middle, and late). Results Medication use was reported by 73% of participants. The most and least frequently used medications, respectively, were pain (69%) and musculoskeletal medications (1%). Pain, CNS, and antibiotic medication use varied significantly across the cycle, with pain and CNS medication more frequently reported during menses and antibiotics more frequently during the luteal phase. Allergy, cold and cough, gastrointestinal, and musculoskeletal medication use did not vary across the cycle. Conclusions Patterns of medication use among reproductive age women vary across the menstrual cycle for certain types of medications, particularly in pain (e.g., Ibuprofen), antibiotics (e,g, Amoxicillin), and CNS (e.g., Adderall) medications. Future studies involving use of these types of medication in premenopausal women may need to consider the relationship of their use to the menstrual cycle. JF - Pharmacoepidemiology and Drug Safety AU - Johnson, Kristen A AU - Sjaarda, Lindsey A AU - Mumford, Sunni L AU - Garbose, Rebecca A AU - Schliep, Karen C AU - Mattison, Donald AU - Perkins, Neil J AU - Wactawski-Wende, Jean AU - Schisterman, Enrique F AD - Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 618 EP - 627 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 25 IS - 6 SN - 1053-8569, 1053-8569 KW - Toxicology Abstracts KW - Central nervous system KW - Hypersensitivity KW - Age KW - Ibuprofen KW - Amoxicillin KW - Menstrual cycle KW - Contraception KW - Cough KW - Pain KW - Antibiotics KW - Contraceptives (oral) KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808641166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacoepidemiology+and+Drug+Safety&rft.atitle=Patterns+and+prevalence+of+medication+use+across+the+menstrual+cycle+among+healthy%2C+reproductive+aged+women&rft.au=Johnson%2C+Kristen+A%3BSjaarda%2C+Lindsey+A%3BMumford%2C+Sunni+L%3BGarbose%2C+Rebecca+A%3BSchliep%2C+Karen+C%3BMattison%2C+Donald%3BPerkins%2C+Neil+J%3BWactawski-Wende%2C+Jean%3BSchisterman%2C+Enrique+F&rft.aulast=Johnson&rft.aufirst=Kristen&rft.date=2016-06-01&rft.volume=25&rft.issue=6&rft.spage=618&rft.isbn=&rft.btitle=&rft.title=Pharmacoepidemiology+and+Drug+Safety&rft.issn=10538569&rft_id=info:doi/10.1002%2Fpds.3993 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Central nervous system; Amoxicillin; Ibuprofen; Age; Hypersensitivity; Contraception; Menstrual cycle; Cough; Antibiotics; Pain; Contraceptives (oral) DO - http://dx.doi.org/10.1002/pds.3993 ER - TY - JOUR T1 - Protection against malaria at 1 year and immune correlates following PfSPZ vaccination AN - 1808630192; PQ0003268463 AB - An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 10 super(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21-25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon- gamma -producing CD8 T cells were present at 100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection. JF - Nature Medicine AU - Ishizuka, Andrew S AU - Lyke, Kirsten E AU - DeZure, Adam AU - Berry, Andrea A AU - Richie, Thomas L AU - Mendoza, Floreliz H AU - Enama, Mary E AU - Gordon, Ingelise J AU - Chang, Lee-Jah AU - Sarwar, Uzma N AU - Zephir, Kathryn L AU - Holman, LaSonji A AU - James, Eric R AU - Billingsley, Peter F AU - Gunasekera, Anusha AU - Chakravarty, Sumana AU - Manoj, Anita AU - Li, MingLin AU - Ruben, Adam J AU - Li, Tao AU - Eappen, Abraham G AU - Stafford, Richard E AU - K C, Natasha AU - Murshedkar, Tooba AU - DeCederfelt, Hope AU - Plummer, Sarah H AU - Hendel, Cynthia S AU - Novik, Laura AU - Costner, Pamela J M AU - Saunders, Jamie G AU - Laurens, Matthew B AU - Plowe, Christopher V AU - Flynn, Barbara AU - Whalen, William R AU - Todd, J P AU - Noor, Jay AU - Rao, Srinivas AU - Sierra-Davidson, Kailan AU - Lynn, Geoffrey M AU - Epstein, Judith E AU - Kemp, Margaret A AU - Fahle, Gary A AU - Mikolajczak, Sebastian A AU - Fishbaugher, Matthew AU - Sack, Brandon K AU - Kappe, Stefan H I AU - Davidson, Silas A AU - Garver, Lindsey S AU - Bjorkstrom, Niklas K AU - Nason, Martha C AU - et. al. AD - Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 614 EP - 623 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 22 IS - 6 SN - 1078-8956, 1078-8956 KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology; Immunology Abstracts KW - Parasites KW - Intravenous administration KW - Human diseases KW - Disease control KW - Sporozoites KW - Malaria KW - Plasmodium falciparum KW - CD8 antigen KW - Infection KW - Vaccination KW - Immunization KW - Public health KW - Blood KW - parasitemia KW - Antibodies KW - Lymphocytes T KW - Liver KW - Vaccines KW - F 06905:Vaccines KW - K 03400:Human Diseases KW - Q1 08604:Stock assessment and management KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808630192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Protection+against+malaria+at+1+year+and+immune+correlates+following+PfSPZ+vaccination&rft.au=Ishizuka%2C+Andrew+S%3BLyke%2C+Kirsten+E%3BDeZure%2C+Adam%3BBerry%2C+Andrea+A%3BRichie%2C+Thomas+L%3BMendoza%2C+Floreliz+H%3BEnama%2C+Mary+E%3BGordon%2C+Ingelise+J%3BChang%2C+Lee-Jah%3BSarwar%2C+Uzma+N%3BZephir%2C+Kathryn+L%3BHolman%2C+LaSonji+A%3BJames%2C+Eric+R%3BBillingsley%2C+Peter+F%3BGunasekera%2C+Anusha%3BChakravarty%2C+Sumana%3BManoj%2C+Anita%3BLi%2C+MingLin%3BRuben%2C+Adam+J%3BLi%2C+Tao%3BEappen%2C+Abraham+G%3BStafford%2C+Richard+E%3BK+C%2C+Natasha%3BMurshedkar%2C+Tooba%3BDeCederfelt%2C+Hope%3BPlummer%2C+Sarah+H%3BHendel%2C+Cynthia+S%3BNovik%2C+Laura%3BCostner%2C+Pamela+J+M%3BSaunders%2C+Jamie+G%3BLaurens%2C+Matthew+B%3BPlowe%2C+Christopher+V%3BFlynn%2C+Barbara%3BWhalen%2C+William+R%3BTodd%2C+J+P%3BNoor%2C+Jay%3BRao%2C+Srinivas%3BSierra-Davidson%2C+Kailan%3BLynn%2C+Geoffrey+M%3BEpstein%2C+Judith+E%3BKemp%2C+Margaret+A%3BFahle%2C+Gary+A%3BMikolajczak%2C+Sebastian+A%3BFishbaugher%2C+Matthew%3BSack%2C+Brandon+K%3BKappe%2C+Stefan+H+I%3BDavidson%2C+Silas+A%3BGarver%2C+Lindsey+S%3BBjorkstrom%2C+Niklas+K%3BNason%2C+Martha+C%3Bet.+al.&rft.aulast=Ishizuka&rft.aufirst=Andrew&rft.date=2016-06-01&rft.volume=22&rft.issue=6&rft.spage=614&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2Fnm.4110 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Parasites; Blood; Antibodies; Human diseases; Disease control; Malaria; Vaccines; Immunization; Public health; Intravenous administration; parasitemia; Liver; Lymphocytes T; Sporozoites; CD8 antigen; Infection; Vaccination; Plasmodium falciparum DO - http://dx.doi.org/10.1038/nm.4110 ER - TY - JOUR T1 - Molecular Epidemiology of Blood-Borne Human Parasites in a Loa loa-, Mansonella perstans-, and Plasmodium falciparum-Endemic Region of Cameroon AN - 1808623770; PQ0003290526 AB - The study of the interactions among parasites within their hosts is crucial to the understanding of epidemiology of disease and for the design of effective control strategies. We have conducted an assessment of infections with Loa loa, Mansonella perstans, Wuchereria bancrofti, and Plasmodium falciparum in eastern Cameroon using a highly sensitive and specific quantitative polymerase chain reaction assay using archived dried whole blood spots. The resident population (N= 1,085) was parasitized with M. perstans(76%), L. loa(39%), and P. falciparum(33%), but not with W. bancrofti. Compared with single infections (40.1%), coinfection was more common (48.8%): 21.0% had L. loa-M. perstans(Ll super(+)/Mp super(+) /Pf super(-)), 2.7% had L. loa-P. falciparum(Ll super(+)/Pf super(+ )/Mp super(-)), 15.1% had M. perstans-P. falciparum(Mp super(+)/Pf super(+ )/Ll super(-)), and 10.0% had L. loa-M. perstans-P. falciparum(Ll super(+)/Mp super(+ )/Pf super(+)). Interestingly, those with all three infections (Ll super(+)/Mp super(+)/Pf super(+)) had significantly higher L. loa microfilaria (mf) counts than either single Ll super(+)(P= 0.004) or double Ll super(+)/Mp super(+)(P= 0.024) infected individuals. Of those infected with L. loa, the mean estimated counts of L. loa mf varied based on location and were positively correlated with estimated intensities of M. perstans mf. Finally, at a community level, heavy L. loa infections were concentrated in a few individuals whereby they were likely the major reservoir for infection. JF - American Journal of Tropical Medicine and Hygiene AU - Drame, Papa M AU - Montavon, Celine AU - Pion, Sebastien D AU - Kubofcik, Joseph AU - Fay, Michael P AU - Nutman, Thomas B AD - Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, dramepm@niaid.nih.gov Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1301 EP - 1308 PB - American Society of Tropical Medicine and Hygiene, 60 Revere Drive, Suite 500 Northbrook IL 60062 United States VL - 94 IS - 6 SN - 0002-9637, 0002-9637 KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Health & Safety Science Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Parasites KW - Reservoir KW - Nucleotide sequence KW - Disease control KW - Plasmodium falciparum KW - Hosts KW - Infection KW - Blood KW - Wuchereria bancrofti KW - Epidemiology KW - Filarioidea KW - Polymerase chain reaction KW - Archives KW - Hygiene KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - Q1 08604:Stock assessment and management KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808623770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Molecular+Epidemiology+of+Blood-Borne+Human+Parasites+in+a+Loa+loa-%2C+Mansonella+perstans-%2C+and+Plasmodium+falciparum-Endemic+Region+of+Cameroon&rft.au=Drame%2C+Papa+M%3BMontavon%2C+Celine%3BPion%2C+Sebastien+D%3BKubofcik%2C+Joseph%3BFay%2C+Michael+P%3BNutman%2C+Thomas+B&rft.aulast=Drame&rft.aufirst=Papa&rft.date=2016-06-01&rft.volume=94&rft.issue=6&rft.spage=1301&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/10.4269%2Fajtmh.15-0746 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Reservoir; Blood; Parasites; Epidemiology; Nucleotide sequence; Disease control; Archives; Hosts; Hygiene; Polymerase chain reaction; Infection; Wuchereria bancrofti; Filarioidea; Plasmodium falciparum DO - http://dx.doi.org/10.4269/ajtmh.15-0746 ER - TY - JOUR T1 - Seasonal Distribution and Climatic Correlates of Dengue Disease in Dhaka, Bangladesh AN - 1808623566; PQ0003290535 AB - Dengue has been regularly reported in Dhaka, Bangladesh, since a large outbreak in 2000. However, to date, we have limited information on the seasonal distribution of dengue disease and how case distribution correlates with climate. Here, we analyzed dengue cases detected at a private diagnostic facility in Dhaka during 2010-2014. We calculated Pearson cross-correlation coefficients to examine the relationship between the timing of cases and both rainfall and temperature. There were 2,334 cases diagnosed during the study period with 76% over the age of 15 years. Cases were reported in every month of the study; however, 90% of cases occurred between June and November. Increases in rainfall were correlated with increases in cases 2 months later (correlation of 0.7). The large proportion of adult cases is consistent with substantial population susceptibility and suggests Dhaka remains at risk for outbreaks. Although cases occurred year-round, public health preparedness should be focused during peak months. JF - American Journal of Tropical Medicine and Hygiene AU - Morales, Ivonne AU - Salje, Henrik AU - Saha, Samir AU - Gurley, Emily S AD - Section on Membrane and Cellular Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, egurley@icddrb.org Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1359 EP - 1361 PB - American Society of Tropical Medicine and Hygiene, 60 Revere Drive, Suite 500 Northbrook IL 60062 United States VL - 94 IS - 6 SN - 0002-9637, 0002-9637 KW - Virology & AIDS Abstracts; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Health & Safety Science Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Temperature effects KW - ISW, Bangladesh KW - Age KW - Human diseases KW - Rainfall KW - Climate KW - Temperature KW - Seasonal distribution KW - Public health KW - Dengue KW - Outbreaks KW - Hygiene KW - K 03400:Human Diseases KW - H 12000:Epidemiology and Public Health KW - Q1 08481:Productivity KW - Q5 08524:Public health, medicines, dangerous organisms KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808623566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Seasonal+Distribution+and+Climatic+Correlates+of+Dengue+Disease+in+Dhaka%2C+Bangladesh&rft.au=Morales%2C+Ivonne%3BSalje%2C+Henrik%3BSaha%2C+Samir%3BGurley%2C+Emily+S&rft.aulast=Morales&rft.aufirst=Ivonne&rft.date=2016-06-01&rft.volume=94&rft.issue=6&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/10.4269%2Fajtmh.15-0846 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Temperature effects; Human diseases; Seasonal distribution; Hygiene; Public health; Age; Dengue; Rainfall; Climate; Temperature; Outbreaks; ISW, Bangladesh DO - http://dx.doi.org/10.4269/ajtmh.15-0846 ER - TY - JOUR T1 - Herpes Simplex Virus Type 2 Seroprevalence and Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young African-American Women AN - 1808616949; PQ0003280188 AB - For decades reproductive tract infections (RTIs) have been hypothesized to play a role in uterine fibroid development. The few previous studies conducted used self-reported history of RTIs and had inconsistent findings. We investigated this hypothesis further using serological analysis, an immunological measure of past exposure. We focused on herpes simplex virus type 2 (HSV-2) because prior published data have suggested a possible association with fibroids, and serology for HSV-2 is much more sensitive than self-report. We used cross-sectional enrollment data from African-American women enrolled in a prospective study of fibroid incidence and growth (recruited 2010-2012) in the Detroit, Michigan, area. The women were aged 23-34 years and were screened for fibroids using a standardized ultrasound examination at their enrollment. Age- and multivariable-adjusted logistic regression models were used to estimate odds ratios. Of 1,696 participants, 1,658 had blood samples and HSV-2 serology results; 22% of participants with serology results had fibroids. There was no significant association between HSV-2 seropositivity and the presence of fibroids (multivariable-adjusted odds ratio = 0.94, 95% confidence interval: 0.73, 1.20), nor were there any associations with size of the largest fibroid, number of fibroids, or total fibroid volume. Our data provide no evidence for an influence of HSV-2 exposure on fibroid risk in young African-American women. Further study of other serologically measured RTIs is warranted. JF - American Journal of Epidemiology AU - Moore, Kristen R AU - Smith, Jennifer S AU - Cole, Stephen R AU - Schoenbach, Victor J AU - Schlusser, Katherine AU - Gaydos, Charlotte A AU - Baird, Donna D AD - Correspondence to Dr. Donna D. Baird, Epidemiology Branch A3-05, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 961 EP - 968 PB - Oxford University Press, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 183 IS - 11 SN - 0002-9262, 0002-9262 KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - herpes simplex virus type 2 KW - seroprevalence KW - uterine fibroids KW - Historical account KW - Uterus KW - Data processing KW - Viruses KW - Herpes simplex virus 2 KW - Infection KW - Serology KW - Reproductive system KW - Models KW - Blood KW - USA, Michigan, Detroit KW - Regression analysis KW - Standards KW - Females KW - Ultrasound KW - Ethnic groups KW - H 12000:Epidemiology and Public Health KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808616949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Herpes+Simplex+Virus+Type+2+Seroprevalence+and+Ultrasound-Diagnosed+Uterine+Fibroids+in+a+Large+Population+of+Young+African-American+Women&rft.au=Moore%2C+Kristen+R%3BSmith%2C+Jennifer+S%3BCole%2C+Stephen+R%3BSchoenbach%2C+Victor+J%3BSchlusser%2C+Katherine%3BGaydos%2C+Charlotte+A%3BBaird%2C+Donna+D&rft.aulast=Moore&rft.aufirst=Kristen&rft.date=2016-06-01&rft.volume=183&rft.issue=11&rft.spage=961&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/10.1093%2Faje%2Fkwv313 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Uterus; Data processing; Regression analysis; Infection; Ultrasound; Serology; Reproductive system; Models; Historical account; Blood; Viruses; Standards; Females; Ethnic groups; Herpes simplex virus 2; USA, Michigan, Detroit DO - http://dx.doi.org/10.1093/aje/kwv313 ER - TY - JOUR T1 - Subtype-specific incidence rates of lymphoid malignancies in Hong Kong compared to the United States, 2001-2010 AN - 1808614775; PQ0003264703 AB - Clinical studies of lymphoid malignancies (LMs) have suggested that the descriptive patterns of LMs differ in East Asia compared to Western populations. However, there are very limited available data on population-based, subtype-specific incidence rates of LMs in the East Asian population, particularly in Chinese. Using data from the Hong Kong (HK) Cancer Registry and United States (U.S.) SEER Program, we calculated and compared age-adjusted incidence rates of LM subtypes in HK to those in Whites and Asians living in the U.S. Overall and sex-specific rates were calculated for the period 2001-2010. The incidence of most subtypes was low in the HK population, with rates <1 case per 100,000 for all subtypes except for diffuse large B-cell lymphoma (3.26/100,000) and plasma cell neoplasms (1.99/100,000). Age-adjusted incidence rates of all evaluated B-cell subtypes were significantly higher in U.S. Whites compared to HK, with standardized rate ratios (SRRs) ranging from 1.6 (Burkitt lymphoma) to 9.1 (chronic lymphocytic leukemia/small lymphocytic lymphoma). Rates in U.S. Asians were generally intermediate to those in U.S. Whites and HK. Conversely, rates of extranodal NK/T-cell lymphoma were significantly lower in both U.S. Whites (SRR=0.2) and U.S. Asians (SRR=0.5) compared to HK. Our data provide new insight into the subtype-specific patterns of LMs in the Chinese population, and suggest the need for etiological studies of LMs in the East Asian population to elucidate the factors responsible for these differences in the geographic incidence patterns. JF - Cancer Epidemiology AU - Bassig, Bryan A AU - Au, Wing-Yan AU - Mang, Oscar AU - Ngan, Roger AU - Morton, Lindsay M AU - Ip, Dennis KM AU - Hu, Wei AU - Zheng, Tongzhang AU - Seow, Wei Jie AU - Xu, Jun AU - Lan, Qing AU - Rothman, Nathaniel AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 15 EP - 23 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 42 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - Lymphoid malignancies KW - Hong Kong KW - Incidence rates KW - Non-Hodgkin lymphoma KW - Descriptive epidemiology KW - Burkitt's lymphoma KW - Malignancy KW - B-cell lymphoma KW - Data processing KW - Lymphocytes B KW - T-cell lymphoma KW - Chronic lymphatic leukemia KW - Plasma cells KW - Cancer KW - X 24500:Reviews, Legislation, Book & Conference Notices UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808614775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Subtype-specific+incidence+rates+of+lymphoid+malignancies+in+Hong+Kong+compared+to+the+United+States%2C+2001-2010&rft.au=Bassig%2C+Bryan+A%3BAu%2C+Wing-Yan%3BMang%2C+Oscar%3BNgan%2C+Roger%3BMorton%2C+Lindsay+M%3BIp%2C+Dennis+KM%3BHu%2C+Wei%3BZheng%2C+Tongzhang%3BSeow%2C+Wei+Jie%3BXu%2C+Jun%3BLan%2C+Qing%3BRothman%2C+Nathaniel&rft.aulast=Bassig&rft.aufirst=Bryan&rft.date=2016-06-01&rft.volume=42&rft.issue=&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.02.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 25 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Burkitt's lymphoma; B-cell lymphoma; Malignancy; Data processing; Lymphocytes B; T-cell lymphoma; Plasma cells; Chronic lymphatic leukemia; Cancer DO - http://dx.doi.org/10.1016/j.canep.2016.02.007 ER - TY - JOUR T1 - Metabolic syndrome in relation to Barrett's esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink AN - 1808614469; PQ0003264685 AB - Gastroesophageal reflux disease (GERD) causes local chronic inflammation that increases risks of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA), yet symptomatic GERD is absent in approximately half of all such patients. Obesity exacerbates GERD and is also a component of metabolic syndrome (MetS). We evaluated the hypothesis that MetS is a GERD-independent mechanism by which obesity is associated with increased risks of BE and EA using data from the UK Clinical Practice Research Datalink. BE cases (n=10,215) and EA cases (n=592) were each individually matched to five population controls based on age, sex, and general practice. MetS was defined as occurrence of at least three of the following: obesity, type 2 diabetes, hypertension, and high cholesterol. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. MetS was marginally associated with BE (OR=1.12, 95%CI 1.00-1.25). Similar effects were found for the individual component factors of obesity, hypertension, and high cholesterol. History of GERD modified the association (P-effect modification <1E-5), with the MetS-BE association confined to patients without a history of GERD (OR=1.33, 95%CI 1.12-1.58). No association between MetS and risk of EA was detected in the main or stratified analyses. In this large population-based case-control study, individuals with MetS had a marginally increased risk of BE in the absence of GERD. The systemic inflammatory state (MetS) may represent a reflux-independent inflammatory pathway that increases the risk of BE. MetS did not increase risk of EA in this study population. JF - Cancer Epidemiology AU - Drahos, Jennifer AU - Li, Lin AU - Jick, Susan S AU - Cook, Michael B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 9 EP - 14 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 42 SN - 1877-7821, 1877-7821 KW - Toxicology Abstracts KW - BE Barrett's esophagus KW - CPRD Clinical Practice Research Datalink KW - EA esophageal adenocarcinoma KW - GERD gastroesophageal reflux disease KW - MetS metabolic syndrome KW - (MeSH): Barrett esophagus KW - Esophageal Cancer KW - Metabolic syndrome X KW - Obesity KW - Gastroesophageal reflux KW - Esophagus KW - Data processing KW - Metabolic disorders KW - Barrett's esophagus KW - Population studies KW - Cholesterol KW - Inflammation KW - Diabetes mellitus KW - Adenocarcinoma KW - Sex KW - Hypertension KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808614469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Metabolic+syndrome+in+relation+to+Barrett%27s+esophagus+and+esophageal+adenocarcinoma%3A+Results+from+a+large+population-based+case-control+study+in+the+Clinical+Practice+Research+Datalink&rft.au=Drahos%2C+Jennifer%3BLi%2C+Lin%3BJick%2C+Susan+S%3BCook%2C+Michael+B&rft.aulast=Drahos&rft.aufirst=Jennifer&rft.date=2016-06-01&rft.volume=42&rft.issue=&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.02.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 36 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Esophagus; Obesity; Data processing; Metabolic disorders; Barrett's esophagus; Population studies; Cholesterol; Inflammation; Diabetes mellitus; Gastroesophageal reflux; Adenocarcinoma; Hypertension; Sex DO - http://dx.doi.org/10.1016/j.canep.2016.02.008 ER - TY - JOUR T1 - Characterization of human papillomavirus antibodies in individuals with head and neck cancer AN - 1808614022; PQ0003264692 AB - Background Human papillomavirus type 16 (HPV16) E6 antibodies are a promising biomarker of oropharyngeal cancer (OPC); however, seropositivity among non-OPC cases is not well characterized. Methods Pre-treatment sera from 260 (38 OPC, 222 non-OPC) incident head and neck cancers diagnosed at the University of Pittsburgh between 2003 and 2006 were tested for HPV16 (L1,E1,E2,E4,E6,E7) and non-HPV16 E6 (HPV6,11,18,33) antibodies. Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven tumors was evaluated among tumors with known HPV status (n=25). Results 63.2% of OPC versus 27.5% of non-OPC cases were HPV16 seropositive; HPV16 E6 seroprevalence was 60.5% and 6.3% respectively, odds ratio 22.8 (95% confidence interval [CI] 9.8-53.1). Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven OPC was 100% [95% CI: 50-100%; n=6] and 100% [95% CI: 60-100%, n=4] compared to 0% (n=2) and 0% (n=13) for non-OPC cases. Conclusions HPV16 antibodies were significantly more common in OPC versus non-OPC cases, particularly HPV16 E6 antibodies. JF - Cancer Epidemiology AU - Lang Kuhs, Krystle A AU - Pawlita, Michael AU - Gibson, Sandra P AU - Schmitt, Nicole C AU - Trivedi, Sumita AU - Argiris, Athanassios AU - Kreimer, Aimee R AU - Ferris, Robert L AU - Waterboer, Tim AD - National Cancer Institute, NIH, 9609 Medical Center Drive, Bethesda, MD 20892, USA Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 46 EP - 52 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 42 SN - 1877-7821, 1877-7821 KW - Virology & AIDS Abstracts; Toxicology Abstracts KW - Human papillomavirus 16 KW - HPV16 KW - HPV16 E6 KW - HPV antibodies KW - HPV seropositivity KW - Oropharyngeal cancer KW - OPC KW - Non-oropharyngeal cancer KW - Non-OPC KW - Antibodies KW - Head and neck cancer KW - Tumors KW - biomarkers KW - oropharyngeal cancer KW - X 24490:Other KW - V 22370:Oncology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808614022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Epidemiology&rft.atitle=Characterization+of+human+papillomavirus+antibodies+in+individuals+with+head+and+neck+cancer&rft.au=Lang+Kuhs%2C+Krystle+A%3BPawlita%2C+Michael%3BGibson%2C+Sandra+P%3BSchmitt%2C+Nicole+C%3BTrivedi%2C+Sumita%3BArgiris%2C+Athanassios%3BKreimer%2C+Aimee+R%3BFerris%2C+Robert+L%3BWaterboer%2C+Tim&rft.aulast=Lang+Kuhs&rft.aufirst=Krystle&rft.date=2016-06-01&rft.volume=42&rft.issue=&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology&rft.issn=18777821&rft_id=info:doi/10.1016%2Fj.canep.2016.03.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 23 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Antibodies; Head and neck cancer; Tumors; biomarkers; oropharyngeal cancer; Human papillomavirus 16 DO - http://dx.doi.org/10.1016/j.canep.2016.03.003 ER - TY - JOUR T1 - Transcriptome Analysis of Escherichia coli during dGTP Starvation AN - 1808612726; PQ0003246922 AB - Our laboratory recently discovered that Escherichia coli cells starved for the DNA precursor dGTP are killed efficiently (dGTP starvation) in a manner similar to that described for thymineless death (TLD). Conditions for specific dGTP starvation can be achieved by depriving an E. coli optA1 gpt strain of the purine nucleotide precursor hypoxanthine (Hx). To gain insight into the mechanisms underlying dGTP starvation, we conducted genome-wide gene expression analyses of actively growing optA1 gpt cells subjected to hypoxanthine deprivation for increasing periods. The data show that upon Hx withdrawal, the optA1 gpt strain displays a diminished ability to derepress the de novo purine biosynthesis genes, likely due to internal guanine accumulation. The impairment in fully inducing the purR regulon may be a contributing factor to the lethality of dGTP starvation. At later time points, and coinciding with cell lethality, strong induction of the SOS response was observed, supporting the concept of replication stress as a final cause of death. No evidence was observed in the starved cells for the participation of other stress responses, including the rpoS-mediated global stress response, reinforcing the lack of feedback of replication stress to the global metabolism of the cell. The genome-wide expression data also provide direct evidence for increased genome complexity during dGTP starvation, as a markedly increased gradient was observed for expression of genes located near the replication origin relative to those located toward the replication terminus. IMPORTANCE Control of the supply of the building blocks (deoxynucleoside triphosphates [dNTPs]) for DNA replication is important for ensuring genome integrity and cell viability. When cells are starved specifically for one of the four dNTPs, dGTP, the process of DNA replication is disturbed in a manner that can lead to eventual death. In the present study, we investigated the transcriptional changes in the bacterium E. coli during dGTP starvation. The results show increasing DNA replication stress with an increased time of starvation, as evidenced by induction of the bacterial SOS system, as well as a notable lack of induction of other stress responses that could have saved the cells from cell death by slowing down cell growth. JF - Journal of Bacteriology AU - Itsko, Mark AU - Schaaper, Roel M Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1631 EP - 1644 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 198 IS - 11 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Starvation KW - DNA biosynthesis KW - Data processing KW - Replication KW - Stress KW - Transcription KW - purines KW - Nucleotides KW - Gene expression KW - Cell death KW - Guanine KW - Lethality KW - SOS response KW - Escherichia coli KW - Replication origins KW - Hypoxanthine KW - Feedback KW - Metabolism KW - J 02320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808612726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Transcriptome+Analysis+of+Escherichia+coli+during+dGTP+Starvation&rft.au=Itsko%2C+Mark%3BSchaaper%2C+Roel+M&rft.aulast=Itsko&rft.aufirst=Mark&rft.date=2016-06-01&rft.volume=198&rft.issue=11&rft.spage=1631&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.00218-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 71 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Starvation; Genomes; DNA biosynthesis; Data processing; Replication; Transcription; Stress; Nucleotides; purines; Gene expression; Guanine; Cell death; Lethality; SOS response; Hypoxanthine; Replication origins; Feedback; Metabolism; Escherichia coli DO - http://dx.doi.org/10.1128/JB.00218-16 ER - TY - JOUR T1 - Computational study of the inhibitory mechanism of the kinase CDK5 hyperactivity by peptide p5 and derivation of a pharmacophore. AN - 1804860460; 27387995 AB - The hyperactivity of the cyclic dependent kinase 5 (CDK5) induced by the activator protein p25 has been linked to a number of pathologies of the brain. The CDK5-p25 complex has thus emerged as a major therapeutic target for Alzheimer's disease (AD) and other neurodegenerative conditions. Experiments have shown that the peptide p5 reduces the CDK5-p25 activity without affecting the endogenous CDK5-p35 activity, whereas the peptide TFP5, obtained from p5, elicits similar inhibition, crosses the blood-brain barrier, and exhibits behavioral rescue of AD mice models with no toxic side effects. The molecular basis of the kinase inhibition is not currently known, and is here investigated by computer simulations. It is shown that p5 binds the kinase at the same CDK5/p25 and CDK5/p35 interfaces, and is thus a non-selective competitor of both activators, in agreement with available experimental data in vitro. Binding of p5 is enthalpically driven with an affinity estimated in the low µM range. A quantitative description of the binding site and pharmacophore is presented, and options are discussed to increase the binding affinity and selectivity in the design of drug-like compounds against AD. JF - Journal of computer-aided molecular design AU - Cardone, A AU - Brady, M AU - Sriram, R AU - Pant, H C AU - Hassan, S A AD - Software and System Division, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA. antonio.cardone@nist.gov. ; Software and System Division, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA. ; Laboratory of Neurochemistry, NINDS, National Institutes of Health, Bethesda, MD, 20892, USA. ; Center for Molecular Modeling, Division of Computational Bioscience, CIT, National Institutes of Health, Bethesda, MD, 20892, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 513 EP - 521 VL - 30 IS - 6 KW - Index Medicus KW - p35 KW - Beta amyloid KW - p5 KW - Protein–protein association KW - Alzheimer’s disease KW - Hyperphosphorylation KW - Computer simulation KW - p25 KW - TFP5 KW - Molecular dynamics KW - CDK5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1804860460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+computer-aided+molecular+design&rft.atitle=Computational+study+of+the+inhibitory+mechanism+of%C2%A0the+kinase+CDK5+hyperactivity+by+peptide+p5+and+derivation+of+a+pharmacophore.&rft.au=Cardone%2C+A%3BBrady%2C+M%3BSriram%2C+R%3BPant%2C+H+C%3BHassan%2C+S+A&rft.aulast=Cardone&rft.aufirst=A&rft.date=2016-06-01&rft.volume=30&rft.issue=6&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Journal+of+computer-aided+molecular+design&rft.issn=1573-4951&rft_id=info:doi/10.1007%2Fs10822-016-9922-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10822-016-9922-3 ER - TY - JOUR T1 - Comparison of Patient- and Practitioner-Reported Toxic Effects Associated With Chemoradiotherapy for Head and Neck Cancer. AN - 1797871852; 27149571 AB - Agreement between patient- and practitioner-reported toxic effects during chemoradiotherapy for head and neck cancer is unknown. To compare patient-reported symptom severity and practitioner-reported toxic effects among patients receiving chemoradiotherapy for head and neck cancer. Forty-four patients participating in a phase 2 trial of deintensified chemoradiotherapy for oropharyngeal carcinoma were included in the present study (conducted from February 8, 2012, to March 2, 2015). Most treatment (radiotherapy, 60 Gy, with concurrent weekly administration of cisplatin, 30 mg/m2) was administered at academic medical centers. Included patients had no prior head and neck cancers, were 18 years or older, and had a smoking history of 10 pack-years or less or more than 10 pack-years but 30 pack-years or less and abstinent for the past 5 years. Cancer status was untreated human papillomavirus or p16-positive squamous cell carcinoma of the oropharynx or unknown head and neck primary site; and cancer staging was category T0 to T3, category N0 to N2c, M0, and Eastern Cooperative Oncology Group performance status 0 to 1. Baseline, weekly, and posttreatment toxic effects were assessed by physicians or nurse practitioners using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Patient-reported symptom severity was measured using the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE). Descriptive statistics were used to characterize raw agreement between CTCAE grades and PRO-CTCAE severity ratings. Baseline, weekly, and posttreatment toxic effects assessed using CTCAE, version 4.0, and PRO-CTCAE. Raw agreement indices between patient-reported toxic effects, including symptom frequency, severity, and interference with daily activities (score range, 0 [none] to 4 [very severe]), and practitioner-measured toxic effects, including swallowing, oral pain, and hoarseness (score range, 1 [mild] to 5 [death]). Of the 44 patients included in the analysis (39 men, 5 women; mean [SD] age, 61 [8.4] years), there were 327 analyzable pairs of CTCAE and PRO-CTCAE symptom surveys and no treatment delays due to toxic effects. Patient-reported and practitioner-reported symptom severity agreement was high at baseline when most symptoms were absent but declined throughout treatment as toxic effects increased. Most disagreement was due to lower severity of toxic effects reported by practitioners (eg, from 45% agreement at baseline to 27% at the final week of treatment for pain). This was particularly noted for domains that are not easily evaluated by physical examination, such as anxiety and fatigue (eg, severity of fatigue decreased from 43% at baseline to 12% in the final week of treatment). Practitioner-reported toxic effects are lower than patient self-reports during head and neck chemoradiotherapy. The inclusion of patient-reported symptomatic toxic effects provides information that can potentially enhance clinical management and improve data quality in clinical trials. JF - JAMA otolaryngology-- head & neck surgery AU - Falchook, Aaron D AU - Green, Rebecca AU - Knowles, Mary E AU - Amdur, Robert J AU - Mendenhall, William AU - Hayes, David N AU - Grilley-Olson, Juneko E AU - Weiss, Jared AU - Reeve, Bryce B AU - Mitchell, Sandra A AU - Basch, Ethan M AU - Chera, Bhishamjit S AD - Department of Radiation Oncology, University of North Carolina, Chapel Hill. ; Department of Radiation Oncology, University of Florida Hospitals, Gainesville3Shands Cancer Center, University of Florida Hospitals, Gainesville. ; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill5Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill. ; Gillings School of Global Public Health, University of North Carolina, Chapel Hill. ; Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland. ; Department of Radiation Oncology, University of North Carolina, Chapel Hill4Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 517 EP - 523 VL - 142 IS - 6 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1797871852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA+otolaryngology--+head+%26+neck+surgery&rft.atitle=Comparison+of+Patient-+and+Practitioner-Reported+Toxic+Effects+Associated+With+Chemoradiotherapy+for+Head+and+Neck+Cancer.&rft.au=Falchook%2C+Aaron+D%3BGreen%2C+Rebecca%3BKnowles%2C+Mary+E%3BAmdur%2C+Robert+J%3BMendenhall%2C+William%3BHayes%2C+David+N%3BGrilley-Olson%2C+Juneko+E%3BWeiss%2C+Jared%3BReeve%2C+Bryce+B%3BMitchell%2C+Sandra+A%3BBasch%2C+Ethan+M%3BChera%2C+Bhishamjit+S&rft.aulast=Falchook&rft.aufirst=Aaron&rft.date=2016-06-01&rft.volume=142&rft.issue=6&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=JAMA+otolaryngology--+head+%26+neck+surgery&rft.issn=2168-619X&rft_id=info:doi/10.1001%2Fjamaoto.2016.0656 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1001/jamaoto.2016.0656 ER - TY - JOUR T1 - Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia. AN - 1795863387; 26982511 AB - Ibrutinib, a Bruton tyrosine kinase inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well tolerated but long-term treatment is required until disease progression or intolerable toxic effects occur. Little is known regarding its cutaneous adverse effects. To describe the hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL. Prospective study of 66 patients with CLL enrolled in a single-arm phase 2 clinical trial of ibrutinib for CLL between March 2014 and October 2015 at the National Institutes of Health. The primary outcome, nail and hair changes associated with ibrutinib therapy, was assessed by an 11-question survey. In addition, the severity of nail changes was determined from a 0 to 3 rating scale for both onychoschizia and onychorrhexis. Among 66 patients (43 men and 23 women with ages ranging from 55 to 85 years), 44 (67%) reported brittle fingernails at a median of 6.5 (95% CI, 6-12) months after starting ibrutinib therapy. Fifteen patients (23%) developed brittle toenails after a median of 9 (95% CI, 6-15) months of ibrutinib therapy. Textural hair changes were reported in 17 patients (26%), at a median of 9 (95% CI, 6-12) months of ibrutinib treatment. Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiating therapy. Ibrutinib inhibits Bruton tyrosine kinase by covalently binding to cysteine 481. Whether ibrutinib affects the hair and nails by binding and altering cysteine-rich proteins of hair and nails or by means of another mechanism remains unknown. clinicaltrials.gov Identifier: NCT01500733. JF - JAMA dermatology AU - Bitar, Carole AU - Farooqui, Mohammed Z H AU - Valdez, Janet AU - Saba, Nakhle S AU - Soto, Susan AU - Bray, Amanda AU - Marti, Gerald AU - Wiestner, Adrian AU - Cowen, Edward W AD - Department of Medicine, Tulane University, New Orleans, Louisiana2Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. ; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. ; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland3Section of Hematology and Medical Oncology, Department of Medicine, Tulane University, New Orleans, Louisiana. ; Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 698 EP - 701 VL - 152 IS - 6 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795863387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA+dermatology&rft.atitle=Hair+and+Nail+Changes+During+Long-term+Therapy+With+Ibrutinib+for+Chronic+Lymphocytic+Leukemia.&rft.au=Bitar%2C+Carole%3BFarooqui%2C+Mohammed+Z+H%3BValdez%2C+Janet%3BSaba%2C+Nakhle+S%3BSoto%2C+Susan%3BBray%2C+Amanda%3BMarti%2C+Gerald%3BWiestner%2C+Adrian%3BCowen%2C+Edward+W&rft.aulast=Bitar&rft.aufirst=Carole&rft.date=2016-06-01&rft.volume=152&rft.issue=6&rft.spage=698&rft.isbn=&rft.btitle=&rft.title=JAMA+dermatology&rft.issn=2168-6084&rft_id=info:doi/10.1001%2Fjamadermatol.2016.0225 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1001/jamadermatol.2016.0225 ER - TY - JOUR T1 - Psycho-Oncology, Third Edition Edited by Jimmie C. Holland, William S. Breitbart, Paul B. Jacobsen, Matthew J. Loscalzo, Ruth McCorkle, and Phyllis N. Butow. Oxford University Press ( 808 pages) ISBN-13: 978-0199363315. $175.00 AN - 1795827138 JF - Psycho-Oncology AU - Rowland, Julia H AD - Division of Cancer Control and Population Sciences, National Cancer Institute, NIH/DHHS, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 745 EP - 746 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 25 IS - 6 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Oncology KW - Holland, William UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795827138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Psycho-Oncology&rft.atitle=Psycho-Oncology%2C+Third+Edition+Edited+by+Jimmie+C.+Holland%2C+William+S.+Breitbart%2C+Paul+B.+Jacobsen%2C+Matthew+J.+Loscalzo%2C+Ruth+McCorkle%2C+and+Phyllis+N.+Butow.+Oxford+University+Press+%28+808+pages%29+ISBN-13%3A+978-0199363315.+%24175.00&rft.au=Rowland%2C+Julia+H&rft.aulast=Rowland&rft.aufirst=Julia&rft.date=2016-06-01&rft.volume=25&rft.issue=6&rft.spage=745&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.4151 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 John Wiley & Sons, Ltd. N1 - People - Holland, William N1 - Last updated - 2016-09-20 N1 - SubjectsTermNotLitGenreText - Holland, William DO - http://dx.doi.org/10.1002/pon.4151 ER - TY - JOUR T1 - Soy-Based Infant Formula Feeding and Ultrasound-Detected Uterine Fibroids among Young African-American Women with No Prior Clinical Diagnosis of Fibroids. AN - 1793909568; 26565393 AB - Early-life soy phytoestrogen exposure has been shown in Eker rats to increase uterine fibroid incidence in adulthood. Two large epidemiologic cohorts have provided some support for increased fibroid risk with infant soy formula feeding in women, but both cohorts relied on self-report of clinically diagnosed fibroids. We evaluated the relationship between infant soy formula feeding and ultrasound-detected fibroids. The Study of Environment, Lifestyle & Fibroids (SELF) is an ongoing cohort study of 1,696 African-American women ages 23-34 years with baseline ultrasound screening to detect and measure fibroids ≥ 0.5 cm in diameter. Questionnaire data on soy formula feeding during infancy was ascertained for 1,553 participants (89% based on mother's report), of whom 345 were found to have fibroids. We estimated the association between soy formula feeding and fibroid prevalence and tumor number using log-binomial regression. Among those with fibroids, we compared fibroid size between soy formula-exposed and unexposed women using multivariable linear regression. We did not observe an association between soy formula feeding and fibroid prevalence [adjusted prevalence ratio (aPR) 0.9, 95% CI: 0.7, 1.3]. Nor were exposed women with fibroids more likely to have ≥ 2 tumors than unexposed women with fibroids (aPR 1.0, 95% CI: 0.7, 1.6). However, exposed women with fibroids had significantly larger fibroids than unexposed women with fibroids. On average, soy formula feeding was associated with a 32% increase in the diameter of the largest fibroid (95% CI: 6%, 65%) and a 127% increase in total tumor volume (95% CI: 12%, 358%). Our observation that women fed soy formula as infants have larger fibroids than unexposed women provides further support for persistent effects of early life phytoestrogen exposure on the uterus. Upson K, Harmon QE, Baird DD. 2016. Soy-based infant formula feeding and ultrasound-detected uterine fibroids among young African-American women with no prior clinical diagnosis of fibroids. Environ Health Perspect 124:769-775; http://dx.doi.org/10.1289/ehp.1510082. JF - Environmental health perspectives AU - Upson, Kristen AU - Harmon, Quaker E AU - Baird, Donna D AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 769 EP - 775 VL - 124 IS - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793909568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Soy-Based+Infant+Formula+Feeding+and+Ultrasound-Detected+Uterine+Fibroids+among+Young+African-American+Women+with+No+Prior+Clinical+Diagnosis+of+Fibroids.&rft.au=Upson%2C+Kristen%3BHarmon%2C+Quaker+E%3BBaird%2C+Donna+D&rft.aulast=Upson&rft.aufirst=Kristen&rft.date=2016-06-01&rft.volume=124&rft.issue=6&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1510082 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1510082 ER - TY - JOUR T1 - A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer. AN - 1793908577; 26783290 AB - PI3K/AKT pathway activation is an important endocrine resistance mechanism in estrogen receptor-positive (ER(+)) breast cancer. After promising preclinical modeling of MK-2206, an allosteric pan-AKT inhibitor, with either estrogen deprivation or fulvestrant, we conducted a phase I trial in patients with metastatic ER(+)HER2(-) breast cancer to determine the recommended phase II treatment dose (RPTD) of MK-2206 when combined with either anastrozole, fulvestrant, or anastrozole/fulvestrant. ER(+) breast cancer cell lines were exposed in vitro to MK-2206 plus estrogen deprivation with or without fulvestrant and monitored for apoptosis. A standard 3+3 design was employed to first determine the maximum tolerated dose (MTD) of MK-2206 plus anastrozole based on cycle 1 toxicity. Each cycle was 28 days. The RPTD was determined on the basis of toxicities observed at MTD level during the first 3 cycles. Subsequent patients received MK-2206, at the RPTD determined above, plus fulvestrant or anastrozole/fulvestrant to define RPTD for these additional regimens. MK-2206 induced apoptosis in parental ER(+) but not in long-term estrogen-deprived cell lines, for which fulvestrant was required for apoptosis induction. Thirty-one patients enrolled. The RPTD was defined as MK-2206 150 mg orally weekly with prednisone prophylaxis for each combination. Grade 3 rash was dose limiting. 42% (95% CI, 23%-63%) patients derived clinical benefit without progression within 6 months. Response was not associated with tumor PIK3CA mutation. MK-2206 plus endocrine treatments were tolerable. MK-2206 in combination with anastrozole is being further evaluated in a phase II neoadjuvant trial for newly diagnosed ER(+)HER2(-) breast cancer. Clin Cancer Res; 22(11); 2650-8. ©2016 AACRSee related commentary by Jansen et al., p. 2599. ©2016 American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Ma, Cynthia X AU - Sanchez, Cesar AU - Gao, Feng AU - Crowder, Robert AU - Naughton, Michael AU - Pluard, Timothy AU - Creekmore, Allison AU - Guo, Zhanfang AU - Hoog, Jeremy AU - Lockhart, A Craig AU - Doyle, Austin AU - Erlichman, Charles AU - Ellis, Matthew J AD - Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. cma@dom.wustl.edu mjellis@bcm.edu. ; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. ; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. ; Cancer Therapy Evaluation Program, NCI, Bethesda, MD. ; Mayo Clinic, Rochester, Minnesota. ; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. cma@dom.wustl.edu mjellis@bcm.edu. Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 2650 EP - 2658 VL - 22 IS - 11 SN - 1078-0432, 1078-0432 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793908577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+Phase+I+Study+of+the+AKT+Inhibitor+MK-2206+in+Combination+with+Hormonal+Therapy+in+Postmenopausal+Women+with+Estrogen+Receptor-Positive+Metastatic+Breast+Cancer.&rft.au=Ma%2C+Cynthia+X%3BSanchez%2C+Cesar%3BGao%2C+Feng%3BCrowder%2C+Robert%3BNaughton%2C+Michael%3BPluard%2C+Timothy%3BCreekmore%2C+Allison%3BGuo%2C+Zhanfang%3BHoog%2C+Jeremy%3BLockhart%2C+A+Craig%3BDoyle%2C+Austin%3BErlichman%2C+Charles%3BEllis%2C+Matthew+J&rft.aulast=Ma&rft.aufirst=Cynthia&rft.date=2016-06-01&rft.volume=22&rft.issue=11&rft.spage=2650&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2160 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2160 ER - TY - JOUR T1 - High-affinity FRβ-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity. AN - 1793568360; 26898190 AB - Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) folate receptor beta (FRβ)-specific single-chain variable fragment (2.48 nm KD) for optimization of FRβ-redirected CAR T-cell therapy for AML. T cells stably expressing the HA-FRβ CAR exhibited greatly enhanced antitumor activity against FRβ(+) AML in vitro and in vivo compared with a low-affinity FRβ CAR (54.3 nm KD). Using the HA-FRβ immunoglobulin G, FRβ expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34(+) hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRβ CAR T cells lysed mature CD14(+) monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA-electroporated HA-FRβ CAR T cells retained effective antitumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRβ CAR T cells is highly effective against AML and reduces the risk for long-term myeloid toxicity. JF - Leukemia AU - Lynn, R C AU - Feng, Y AU - Schutsky, K AU - Poussin, M AU - Kalota, A AU - Dimitrov, D S AU - Powell, D J AD - Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ; Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA. ; Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1355 EP - 1364 VL - 30 IS - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793568360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=High-affinity+FR%CE%B2-specific+CAR+T+cells+eradicate+AML+and+normal+myeloid+lineage+without+HSC+toxicity.&rft.au=Lynn%2C+R+C%3BFeng%2C+Y%3BSchutsky%2C+K%3BPoussin%2C+M%3BKalota%2C+A%3BDimitrov%2C+D+S%3BPowell%2C+D+J&rft.aulast=Lynn&rft.aufirst=R&rft.date=2016-06-01&rft.volume=30&rft.issue=6&rft.spage=1355&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=1476-5551&rft_id=info:doi/10.1038%2Fleu.2016.35 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-01 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Blood. 2002 Jul 15;100(2):594-602 [12091353] J Immunol Methods. 2003 Oct 1;281(1-2):65-78 [14580882] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3070-4 [1348364] Biochemistry. 1994 Feb 8;33(5):1209-15 [8110752] Cancer. 1999 Jan 15;85(2):348-57 [10023702] Blood. 1999 Jun 1;93(11):3940-8 [10339503] Arthritis Rheum. 1999 Aug;42(8):1609-16 [10446858] J Immunol. 2004 Dec 15;173(12):7647-53 [15585893] Mol Cancer Ther. 2006 Jan;5(1):114-20 [16432169] J Clin Oncol. 2006 May 1;24(13):e20-2 [16648493] Cancer Res. 2006 Nov 15;66(22):10995-1004 [17108138] J Immunol. 2007 Apr 1;178(7):4650-7 [17372024] Orphanet J Rare Dis. 2007;2:35 [17784964] J Immunol. 2008 May 15;180(10):7028-38 [18453625] J Clin Oncol. 2008 Dec 10;26(35):5728-34 [18981462] Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3360-5 [19211796] Mol Ther. 2009 Aug;17(8):1453-64 [19384291] Clin Ther. 2009;31 Pt 2:2349-70 [20110045] Mol Ther. 2010 Apr;18(4):843-51 [20179677] J Clin Invest. 2011 May;121(5):1822-6 [21540550] Cancer Res. 2011 Jul 1;71(13):4617-27 [21546571] Arthritis Res Ther. 2011;13(2):R59 [21477314] Blood. 2012 Jan 19;119(3):696-706 [22117050] Mol Ther. 2012 Mar;20(3):633-43 [22127019] Sci Transl Med. 2013 Mar 20;5(177):177ra38 [23515080] Br J Haematol. 2013 May;161(3):389-401 [23432359] N Engl J Med. 2013 Apr 18;368(16):1509-18 [23527958] Clin Cancer Res. 2013 Jun 15;19(12):3153-64 [23620405] Blood. 2013 Oct 31;122(18):3138-48 [24030378] Nat Biotechnol. 2013 Nov;31(11):999-1008 [24142051] Blood. 2014 Apr 10;123(15):2343-54 [24596416] Cancer Immunol Res. 2013 Jul;1(1):26-31 [24777247] J Leukoc Biol. 2014 Oct;96(4):563-70 [25015955] Lancet. 2015 Feb 7;385(9967):517-28 [25319501] Blood. 2015 May 28;125(22):3466-76 [25887778] Leukemia. 2015 Aug;29(8):1637-47 [25721896] Oncotarget. 2015 Aug 28;6(25):21533-46 [26101914] Oncotarget. 2015 Oct 6;6(30):28911-28 [26359629] Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024-8 [2513569] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/leu.2016.35 ER - TY - JOUR T1 - A Mechanistic Review of Cell Death in Alcohol-Induced Liver Injury. AN - 1793566643; 27130888 AB - Alcoholic liver disease (ALD) is a major health problem in the United States and worldwide without successful treatments. Chronic alcohol consumption can lead to ALD, which is characterized by steatosis, inflammation, fibrosis, cirrhosis, and even liver cancer. Recent studies suggest that alcohol induces both cell death and adaptive cell survival pathways in the liver, and the balance of cell death and cell survival ultimately decides the pathogenesis of ALD. This review summarizes the recent progress on the role and mechanisms of apoptosis, necroptosis, and autophagy in the pathogenesis of ALD. Understanding the complex regulation of apoptosis, necrosis, and autophagy may help to develop novel therapeutic strategies by targeting all 3 pathways simultaneously. Copyright © 2016 by the Research Society on Alcoholism. JF - Alcoholism, clinical and experimental research AU - Wang, Shaogui AU - Pacher, Pal AU - De Lisle, Robert C AU - Huang, Heqing AU - Ding, Wen-Xing AD - Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas. ; Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland. ; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas. ; Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1215 EP - 1223 VL - 40 IS - 6 KW - Index Medicus KW - Alcohol KW - Apoptosis KW - Autophagy KW - Liver Injury KW - Necroptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793566643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=A+Mechanistic+Review+of+Cell+Death+in+Alcohol-Induced+Liver+Injury.&rft.au=Wang%2C+Shaogui%3BPacher%2C+Pal%3BDe+Lisle%2C+Robert+C%3BHuang%2C+Heqing%3BDing%2C+Wen-Xing&rft.aulast=Wang&rft.aufirst=Shaogui&rft.date=2016-06-01&rft.volume=40&rft.issue=6&rft.spage=1215&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=1530-0277&rft_id=info:doi/10.1111%2Facer.13078 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-06-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/acer.13078 ER - TY - JOUR T1 - Raltegravir in second-line antiretroviral therapy in resource-limited settings (SELECT): a randomised, phase 3, non-inferiority study. AN - 1793214314; 27240787 AB - For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings. A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe). Adults with plasma HIV-1 RNA concentrations of at least 1000 copies per mL after at least 24 weeks on a regimen based on a non-NRTI inhibitor were randomly assigned (1:1) to receive oral ritonavir-boosted lopinavir (100 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plus two or three NRTIs selected from an algorithm (eg, zidovudine after failure with tenofovir and vice versa; NRTI group). Randomised group assignment was done with a computer algorithm concealed to site personnel, and stratified by HIV-1 RNA viral load, CD4 cell count, and intention to use zidovudine, with the groups balanced by each site. The primary endpoint was time to confirmed virological failure (two measurements of HIV-1 RNA viral load >400 copies per mL) at or after week 24 in the intention-to-treat population. Non-inferiority (10% margin) was assessed by comparing the cumulative probability of virological failure by 48 weeks. This trial was registered with ClinicalTrials.gov, NCT01352715. Between March 13, 2012, and Oct 2, 2013, we randomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were excluded from analyses because of ineligibility. By the end of follow-up (October, 2014), 96 participants had virological failure (46 in the raltegravir group and 50 in the NRTI group). By 48 weeks, the cumulative probability of virological failure was 10·3% (95% CI 6·5-14·0) in the raltegravir group and 12·4% (8·3-16·5) in the NRTI group, with a weighted difference of -3·4% (-8·4 to 1·5), indicating that raltegravir was non-inferior, but not superior, to NRTIs. 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had grade 3 or higher adverse events; 19 (7%) and 29 (11%), respectively, had serious adverse events. Three participants in each group died, all from HIV-related causes. In settings with extensive NRTI resistance but no available resistance testing, our data support WHO's recommendation for ritonavir-boosted lopinavir plus NRTI for second-line antiretroviral therapy. Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if NRTI use is limited by toxicity. National Institutes of Health. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - The lancet. HIV AU - La Rosa, Alberto M AU - Harrison, Linda J AU - Taiwo, Babafemi AU - Wallis, Carole L AU - Zheng, Lu AU - Kim, Peter AU - Kumarasamy, Nagalingeswaran AU - Hosseinipour, Mina C AU - Jarocki, Bernadette AU - Mellors, John W AU - Collier, Ann C AU - ACTG A5273 Study Group AD - Asociacion Civil Impacta Salud y Educacion, Lima, Peru. ; Harvard T H Chan School of Public Health, Boston, MA, USA. ; Northwestern University, Chicago, IL, USA. ; BARC-SA and Lancet Laboratories, Johannesburg, South Africa. ; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. ; YRG CARE, Chennai, India. ; University of North Carolina, Chapel Hill, NC, USA; UNC Project, Lilongwe, Malawi. ; Frontier Science and Technology Research Foundation, Buffalo, NY, USA. ; University of Pittsburgh, Pittsburgh, PA, USA. ; University of Washington, Seattle, WA, USA. Electronic address: acollier@u.washington.edu. ; ACTG A5273 Study Group Y1 - 2016/06// PY - 2016 DA - June 2016 SP - e247 EP - e258 VL - 3 IS - 6 KW - Index Medicus KW - AIDS/HIV UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793214314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+lancet.+HIV&rft.atitle=Raltegravir+in+second-line+antiretroviral+therapy+in+resource-limited+settings+%28SELECT%29%3A+a+randomised%2C+phase+3%2C+non-inferiority+study.&rft.au=La+Rosa%2C+Alberto+M%3BHarrison%2C+Linda+J%3BTaiwo%2C+Babafemi%3BWallis%2C+Carole+L%3BZheng%2C+Lu%3BKim%2C+Peter%3BKumarasamy%2C+Nagalingeswaran%3BHosseinipour%2C+Mina+C%3BJarocki%2C+Bernadette%3BMellors%2C+John+W%3BCollier%2C+Ann+C%3BACTG+A5273+Study+Group&rft.aulast=La+Rosa&rft.aufirst=Alberto&rft.date=2016-06-01&rft.volume=3&rft.issue=6&rft.spage=e247&rft.isbn=&rft.btitle=&rft.title=The+lancet.+HIV&rft.issn=2352-3018&rft_id=info:doi/10.1016%2FS2352-3018%2816%2930011-X LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/S2352-3018(16)30011-X ER - TY - JOUR T1 - Granulosa cell and oocyte mitochondrial abnormalities in a mouse model of fragile X primary ovarian insufficiency. AN - 1793214152; 26965313 AB - We hypothesized that the mitochondria of granulosa cells (GC) and/or oocytes might be abnormal in a mouse model of fragile X premutation (FXPM). Mice heterozygous and homozygous for the FXPM have increased death (atresia) of large ovarian follicles, fewer corpora lutea with a gene dosage effect manifesting in decreased litter size(s). Furthermore, granulosa cells (GC) and oocytes of FXPM mice have decreased mitochondrial content, structurally abnormal mitochondria, and reduced expression of critical mitochondrial genes. Because this mouse allele produces the mutant Fragile X mental retardation 1 (Fmr1) transcript and reduced levels of wild-type (WT) Fmr1 protein (FMRP), but does not produce a Repeat Associated Non-ATG Translation (RAN)-translation product, our data lend support to the idea that Fmr1 mRNA with large numbers of CGG-repeats is intrinsically deleterious in the ovary. Mitochondrial dysfunction has been detected in somatic cells of human and mouse FX PM carriers and mitochondria are essential for oogenesis and ovarian follicle development, FX-associated primary ovarian insufficiency (FXPOI) is seen in women with FXPM alleles. These alleles have 55-200 CGG repeats in the 5' UTR of an X-linked gene known as FMR1. The molecular basis of the pathology seen in this disorder is unclear but is thought to involve either some deleterious consequence of overexpression of RNA with long CGG-repeat tracts or of the generation of a repeat-associated non-AUG translation (RAN translation) product that is toxic. Analysis of ovarian function in a knock-in FXPM mouse model carrying 130 CGG repeats was performed as follows on WT, PM/+, and PM/PM genotypes. Histomorphometric assessment of follicle and corpora lutea numbers in ovaries from 8-month-old mice was executed, along with litter size analysis. Mitochondrial DNA copy number was quantified in oocytes and GC using quantitative PCR, and cumulus granulosa mitochondrial content was measured by flow cytometric analysis after staining of cells with Mitotracker dye. Transmission electron micrographs were prepared of GC within small growing follicles and mitochondrial architecture was compared. Quantitative RT-PCR analysis of key genes involved in mitochondrial structure and recycling was performed. A defect was found in follicle survival at the large antral stage in PM/+ and PM/PM mice. Litter size was significantly decreased in PM/PM mice, and corpora lutea were significantly reduced in mice of both mutant genotypes. Mitochondrial DNA copy number was significantly decreased in GC and metaphase II eggs in mutants. Flow cytometric analysis revealed that PM/+ and PM/PM animals lack the cumulus GC that harbor the greatest mitochondrial content as found in wild-type animals. Electron microscopic evaluation of GC of small growing follicles revealed mitochondrial structural abnormalities, including disorganized and vacuolar cristae. Finally, aberrant mitochondrial gene expression was detected. Mitofusin 2 (Mfn2) and Optic atrophy 1 (Opa1), genes involved in mitochondrial fusion and structure, respectively, were significantly decreased in whole ovaries of both mutant genotypes. Mitochondrial fission factor 1 (Mff1) was significantly decreased in PM/+ and PM/PM GC and eggs compared with wild-type controls. Data from the mouse model used for these studies should be viewed with some caution when considering parallels to the human FXPOI condition. Our data lend support to the idea that Fmr1 mRNA with large numbers of CGG-repeats is intrinsically deleterious in the ovary. FXPM disease states, including FXPOI, may share mitochondrial dysfunction as a common underlying mechanism. Not applicable. Studies were supported by NIH R21 071873 (J.J./G.H), The Albert McKern Fund for Perinatal Research (J.J.), NIH Intramural Funds (K.U.), and a TUBITAK Research Fellowship Award (B.U.). No conflict(s) of interest or competing interest(s) are noted. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com. JF - Molecular human reproduction AU - Conca Dioguardi, Carola AU - Uslu, Bahar AU - Haynes, Monique AU - Kurus, Meltem AU - Gul, Mehmet AU - Miao, De-Qiang AU - De Santis, Lucia AU - Ferrari, Maurizio AU - Bellone, Stefania AU - Santin, Alessandro AU - Giulivi, Cecilia AU - Hoffman, Gloria AU - Usdin, Karen AU - Johnson, Joshua AD - Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Division of Reproductive Endocrinology and Infertility, Yale School of Medicine, New Haven, CT, USA Vita-Salute San Raffaele University/IRCCS San Raffaele Hospital, Milan, Italy. ; Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Division of Reproductive Endocrinology and Infertility, Yale School of Medicine, New Haven, CT, USA. ; Department of Histology & Embryology, Izmir Katip Celebi University School of Medicine, Izmir, Turkey. ; Department of Histology & Embryology, Inonu University School of Medicine, Malatya, Turkey. ; Department of Obstetrics & Gynecology, IVF Unit, Vita-Salute San Raffaele University/IRCCS San Raffaele Hospital, Milan, Italy. ; Laboratory of Clinical Molecular Biology and Cytogenetics, Vita-Salute San Raffaele University/IRCCS San Raffaele Hospital, Milan, Italy. ; Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Division of Gynecologic Oncology, Yale School of Medicine, New Haven, CT, USA. ; Department of Molecular Biosciences, M.I.N.D. Institute, University of California-Davis, Davis, CA, USA. ; Department of Biology, Morgan State University, Baltimore, MD, USA. ; Laboratory of Cellular and Molecular Biology, NIH/NIDDK, Bethesda, MD, USA. ; Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA Division of Reproductive Endocrinology and Infertility, Yale School of Medicine, New Haven, CT, USA josh.johnson@yale.edu. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 384 EP - 396 VL - 22 IS - 6 KW - Index Medicus KW - mitochondria KW - ovary KW - fragile X primary ovarian insufficiency KW - oocyte KW - follicle KW - fertility KW - atresia KW - fragile X premutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793214152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+human+reproduction&rft.atitle=Granulosa+cell+and+oocyte+mitochondrial+abnormalities+in+a+mouse+model+of+fragile+X+primary+ovarian+insufficiency.&rft.au=Conca+Dioguardi%2C+Carola%3BUslu%2C+Bahar%3BHaynes%2C+Monique%3BKurus%2C+Meltem%3BGul%2C+Mehmet%3BMiao%2C+De-Qiang%3BDe+Santis%2C+Lucia%3BFerrari%2C+Maurizio%3BBellone%2C+Stefania%3BSantin%2C+Alessandro%3BGiulivi%2C+Cecilia%3BHoffman%2C+Gloria%3BUsdin%2C+Karen%3BJohnson%2C+Joshua&rft.aulast=Conca+Dioguardi&rft.aufirst=Carola&rft.date=2016-06-01&rft.volume=22&rft.issue=6&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=Molecular+human+reproduction&rft.issn=1460-2407&rft_id=info:doi/10.1093%2Fmolehr%2Fgaw023 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-31 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Anat Rec. 1980 Feb;196(2):183-90 [7416511] J Histochem Cytochem. 2012 Jun;60(6):439-56 [22470123] Free Radic Biol Med. 1993 Jan;14(1):79-84 [8454226] Hum Mol Genet. 1992 Sep;1(6):397-400 [1301913] Adv Exp Med Biol. 1994;366:185-97 [7771253] J Med Genet. 1998 Aug;35(8):637-40 [9719368] J Clin Invest. 1962 Sep;41:1776-804 [14467237] J Cell Sci. 2004 Dec 15;117(Pt 26):6535-46 [15572413] Hum Mol Genet. 2005 Apr 15;14(8):1041-8 [15757976] J Neurochem. 2012 Nov;123(4):613-21 [22924671] Hum Mol Genet. 2012 Dec 1;21(23):5039-47 [22914733] Nature. 2012 Dec 20;492(7429):382-6 [23235829] Syst Biol Reprod Med. 2013 Apr;59(2):91-8 [23278116] Cell Rep. 2013 Mar 28;3(3):869-80 [23478018] Neuron. 2013 May 8;78(3):440-55 [23602499] Lancet Neurol. 2013 Aug;12(8):786-98 [23867198] Autophagy. 2013 Aug;9(8):1131-58 [23774882] Vitam Horm. 2014;94:99-127 [24388188] Ultrastruct Pathol. 2014 May;38(3):204-10 [24579828] Cell Cycle. 2014;13(16):2600-8 [25486200] Biol Reprod. 2015 Jan;92(1):23 [25376232] Hum Reprod. 2015 Jul;30(7):1653-64 [25994667] Hum Mol Genet. 2015 Aug 1;24(15):4317-26 [25954027] Rev Bras Ginecol Obstet. 2015 Sep;37(9):411-6 [26352944] Hum Reprod. 2016 Jan;31(1):158-68 [26537920] FASEB J. 2016 Jan;30(1):466-76 [26432782] Am J Med Genet. 2000 Sep 18;94(3):232-6 [10995510] J Soc Gynecol Investig. 2001 Jan-Feb;8(1 Suppl Proceedings):S40-2 [11223371] Hum Mol Genet. 2001 Aug 1;10(16):1693-9 [11487573] Dev Cell. 2001 Oct;1(4):515-25 [11703942] Fertil Steril. 2002 Jun;77(6):1184-90 [12057726] J Cell Biol. 2003 Jan 20;160(2):189-200 [12527753] Hum Mol Genet. 2003 May 1;12(9):949-59 [12700164] Reprod Suppl. 2003;61:49-54 [14635926] Nature. 2004 Mar 11;428(6979):145-50 [15014492] Reproduction. 2004 May;127(5):569-80 [15129012] Reprod Biol Endocrinol. 2003 Feb 6;1:11 [12646064] Reproduction. 2004 Sep;128(3):269-80 [15333778] J Clin Endocrinol Metab. 2004 Sep;89(9):4569-74 [15356064] EMBO J. 2010 Apr 7;29(7):1248-61 [20186122] Cell. 2010 Apr 16;141(2):280-9 [20403324] Biochem J. 2010 Aug 1;429(3):545-52 [20513237] Nature. 2011 Feb 17;470(7334):359-65 [21307849] Hum Mol Genet. 2011 Aug 1;20(15):3079-92 [21558427] Mitochondrion. 2011 Sep;11(5):797-813 [20933103] FEBS Lett. 2005 May 9;579(12):2702-8 [15862312] Mech Ageing Dev. 2006 Dec;127(12):917-21 [17101170] Exp Cell Res. 2007 Jan 15;313(2):244-53 [17150213] RNA. 2007 Apr;13(4):555-62 [17283214] Hum Reprod. 2007 Aug;22(8):2142-52 [17588953] Am J Med Genet A. 2008 Apr 15;146A(8):1009-16 [18348275] Am J Pathol. 2009 Jan;174(1):34-43 [19095954] Hum Mol Genet. 2011 Oct 1;20(19):3811-21 [21729883] Cell. 1991 Aug 23;66(4):817-22 [1878973] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/molehr/gaw023 ER - TY - JOUR T1 - The anti-dementia drug candidate, (-)-clausenamide, improves memory impairment through its multi-target effect. AN - 1793213763; 26812265 AB - Multi-target drugs, such as the cocktail therapy used for treating AIDS, often show stronger efficacy than single-target drugs in treating complicated diseases. This review will focus on clausenamide (clau), a small molecule compound originally isolated from the traditional Chinese herbal medicine, Clausenalansium. The finding of four chiral centers in clau molecules predicted the presence of 16 clau enantiomers, including (-)-clau and (+)-clau. All of the predicted enantiomers have been successfully synthesized via innovative chemical approaches, and pharmacological studies have demonstrated (-)-clau as a eutomer and (+)-clau as a distomer in improving cognitive function in both normal physiological and pathological conditions. Mechanistically, the nootropic effect of (-)-clau is mediated by its multi-target actions, which include mild elevation of intracellular Ca(2+) concentrations, modulation of the cholinergic system, regulation of synaptic plasticity, and activation of cellular and molecular signaling pathways involved in learning and memory. Furthermore, (-)-clau suppresses the pathogenesis of Alzheimer's disease by inhibiting multiple etiological processes: (1) beta amyloid protein-induced intracellular Ca(2+) overload and apoptosis and (2) tau hyperphosphorylation and neurodegeneration. In conclusion, the nature of the multi-target actions of (-)-clau substantiates it as a promising chiral drug candidate for enhancing human cognition in normal conditions and treating memory impairment in neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Pharmacology & therapeutics AU - Chu, Shifeng AU - Liu, Shaolin AU - Duan, Wenzhen AU - Cheng, Yong AU - Jiang, Xueying AU - Zhu, Chuanjiang AU - Tang, Kang AU - Wang, Runsheng AU - Xu, Lin AU - Wang, Xiaoying AU - Yu, Xiaoming AU - Wu, Kemei AU - Wang, Yan AU - Wang, Muzou AU - Huang, Huiyong AU - Zhang, Juntian AD - Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Key Laboratory of Diagnostics of Traditional Chinese Medicine, Collaborative Innovation Center of Digital Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China. ; Department of Anatomy & Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ; Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. ; Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. ; National Institute of Mental Health, Bethesda, MD 20892, USA. ; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA. ; MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA. ; Franciscan Hospital for Children, Brighton, MA 02135, USA. ; Research Center for Pharmacology and Toxicity, Chinese Academy of Medical Science & Peking Union Medical College, Institute of Medicinal Plant Development, Beijing 100193, China. ; Key Laboratory of Diagnostics of Traditional Chinese Medicine, Collaborative Innovation Center of Digital Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China. ; Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: zhangjt@imm.ac.cn. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 179 EP - 187 VL - 162 KW - Index Medicus KW - Signaling pathway KW - Calcium KW - Clausenamide KW - Long-term potentiation KW - Dementia KW - Chirality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793213763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+therapeutics&rft.atitle=The+anti-dementia+drug+candidate%2C+%28-%29-clausenamide%2C+improves+memory+impairment+through+its+multi-target+effect.&rft.au=Chu%2C+Shifeng%3BLiu%2C+Shaolin%3BDuan%2C+Wenzhen%3BCheng%2C+Yong%3BJiang%2C+Xueying%3BZhu%2C+Chuanjiang%3BTang%2C+Kang%3BWang%2C+Runsheng%3BXu%2C+Lin%3BWang%2C+Xiaoying%3BYu%2C+Xiaoming%3BWu%2C+Kemei%3BWang%2C+Yan%3BWang%2C+Muzou%3BHuang%2C+Huiyong%3BZhang%2C+Juntian&rft.aulast=Chu&rft.aufirst=Shifeng&rft.date=2016-06-01&rft.volume=162&rft.issue=&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+therapeutics&rft.issn=1879-016X&rft_id=info:doi/10.1016%2Fj.pharmthera.2016.01.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.pharmthera.2016.01.002 ER - TY - JOUR T1 - Adapting Cancer Immunotherapy Models for the Real World. AN - 1792772226; 27105824 AB - Early experiments in mice predicted the success of checkpoint blockade immunotherapy in cancer patients. However, these same animal studies failed to accurately predict many of the limitations and toxicities of treatment. One of the likely reasons for this discrepancy is the nearly universal use of young healthy mice, which stand in stark contrast to diverse patient populations varying in age, weight, diet, and hygiene. Because these variables impact immunity and metabolism, they also influence outcomes during immunotherapy and should be incorporated into the study design of preclinical experiments. Here, we discuss recent findings that highlight how efficacy and toxicity of cancer immunotherapy are affected by patient variation, and how distinct host environments can be better modeled in animal studies. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Trends in immunology AU - Klevorn, Lauryn E AU - Teague, Ryan M AD - Saint Louis University School of Medicine, Molecular Microbiology and Immunology Department, 1100 South Grand Boulevard, St Louis, MO 63104, USA. ; Saint Louis University School of Medicine, Molecular Microbiology and Immunology Department, 1100 South Grand Boulevard, St Louis, MO 63104, USA; Alvin J. Siteman NCI Comprehensive Cancer Center, St Louis, MO, USA. Electronic address: rteague@slu.edu. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 354 EP - 363 VL - 37 IS - 6 KW - Index Medicus KW - checkpoint blockade KW - age KW - obesity KW - immunotherapy KW - microbiota KW - cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1792772226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+immunology&rft.atitle=Adapting+Cancer+Immunotherapy+Models+for+the+Real+World.&rft.au=Klevorn%2C+Lauryn+E%3BTeague%2C+Ryan+M&rft.aulast=Klevorn&rft.aufirst=Lauryn&rft.date=2016-06-01&rft.volume=37&rft.issue=6&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Trends+in+immunology&rft.issn=1471-4981&rft_id=info:doi/10.1016%2Fj.it.2016.03.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-30 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: N Engl J 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Jun 5;109(23):9065-70 [22615388] N Engl J Med. 2012 Jun 28;366(26):2443-54 [22658127] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.it.2016.03.010 ER - TY - JOUR T1 - Subchronic exposures to fungal bioaerosols promotes allergic pulmonary inflammation in naïve mice. AN - 1792375085; 26892490 AB - Epidemiological surveys indicate that occupants of mold contaminated environments are at increased risk of respiratory symptoms. The immunological mechanisms associated with these responses require further characterization. The aim of this study was to characterize the immunotoxicological outcomes following repeated inhalation of dry Aspergillus fumigatus spores aerosolized at concentrations potentially encountered in contaminated indoor environments. Aspergillus fumigatus spores were delivered to the lungs of naïve BALB/cJ mice housed in a multi-animal nose-only chamber twice a week for a period of 13 weeks. Mice were evaluated at 24 and 48 h post-exposure for histopathological changes in lung architecture, recruitment of specific immune cells to the airways, and serum antibody responses. Germinating A. fumigatus spores were observed in lungs along with persistent fungal debris in the perivascular regions of the lungs. Repeated exposures promoted pleocellular infiltration with concomitant epithelial mucus hypersecretion, goblet cell metaplasia, subepithelial fibrosis and enhanced airway hyperreactivity. Cellular infiltration in airways was predominated by CD4(+) T cells expressing the pro-allergic cytokine IL-13. Furthermore, our studies show that antifungal T cell responses (IFN-γ(+) or IL-17A(+) ) co-expressed IL-13, revealing a novel mechanism for the dysregulated immune response to inhaled fungi. Total IgE production was augmented in animals repeatedly exposed to A. fumigatus. Repeated inhalation of fungal aerosols resulted in significant pulmonary pathology mediated by dynamic shifts in specific immune populations and their cytokines. These studies provide novel insights into the immunological mechanisms and targets that govern the health outcomes that result from repeated inhalation of fungal bioaerosols in contaminated environments. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology AU - Nayak, A P AU - Green, B J AU - Lemons, A R AU - Marshall, N B AU - Goldsmith, W T AU - Kashon, M L AU - Anderson, S E AU - Germolec, D R AU - Beezhold, D H AD - Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 861 EP - 870 VL - 46 IS - 6 KW - Index Medicus KW - fungi KW - subchronic KW - Aspergillus fumigatus KW - asthma KW - immunotoxicity KW - allergy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1792375085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+experimental+allergy+%3A+journal+of+the+British+Society+for+Allergy+and+Clinical+Immunology&rft.atitle=Subchronic+exposures+to+fungal+bioaerosols+promotes+allergic+pulmonary+inflammation+in+na%C3%AFve+mice.&rft.au=Nayak%2C+A+P%3BGreen%2C+B+J%3BLemons%2C+A+R%3BMarshall%2C+N+B%3BGoldsmith%2C+W+T%3BKashon%2C+M+L%3BAnderson%2C+S+E%3BGermolec%2C+D+R%3BBeezhold%2C+D+H&rft.aulast=Nayak&rft.aufirst=A&rft.date=2016-06-01&rft.volume=46&rft.issue=6&rft.spage=861&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+allergy+%3A+journal+of+the+British+Society+for+Allergy+and+Clinical+Immunology&rft.issn=1365-2222&rft_id=info:doi/10.1111%2Fcea.12724 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-27 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Immunol. 2012 Oct 1;189(7):3653-60 [22933634] Eur J Immunol. 2012 Sep;42(9):2322-8 [22684943] J Proteome Res. 2013 Jun 7;12(6):2552-70 [23656496] Pediatr Allergy Immunol. 2013 Nov;24(7):697-703 [24112429] J Allergy Clin Immunol. 2013 Nov;132(5):1194-1204.e2 [24060272] Nat Commun. 2014;5:3753 [24796415] PLoS One. 2014;9(10):e109855 [25340353] Environ Health Perspect. 2015 Jan;123(1):6-20 [25303775] Nat Immunol. 2015 Feb;16(2):161-9 [25531830] Indoor Air. 2015 Apr;25(2):125-56 [25601374] J Allergy Clin Immunol. 2002 Aug;110(2):285-92 [12170270] J Allergy Clin Immunol. 2003 Feb;111(2):285-9 [12589346] Annu Rev Immunol. 2003;21:425-56 [12615888] J Occup Environ Med. 2003 May;45(5):470-8 [12762072] Cytometry A. 2004 Oct;61(2):170-77 [15382026] J Allergy Clin Immunol. 2006 Feb;117(2):473; author reply 474 [16461157] J Allergy Clin Immunol. 2006 Feb;117(2):326-33 [16514772] PLoS Pathog. 2005 Nov;1(3):e30 [16304610] J Allergy Clin Immunol. 2006 Oct;118(4):892-8 [17030243] J Clin Invest. 2007 Mar;117(3):530-8 [17332880] J Immunol Methods. 2007 Oct 31;327(1-2):63-74 [17716680] Nat Med. 2008 Mar;14(3):282-9 [18264109] Am J Physiol Lung Cell Mol Physiol. 2008 Oct;295(4):L552-65 [18658273] Crit Rev Toxicol. 2009;39(10):799-864 [19863384] J Exp Med. 2010 Oct 25;207(11):2479-91 [20921287] Med Mycol. 2010 Dec;48(8):1056-65 [20482452] Infect Immun. 2011 Jan;79(1):125-35 [21041495] Fungal Biol. 2011 Jan;115(1):21-9 [21215951] J Allergy Clin Immunol. 2011 Jul;128(1):192-201.e6 [21601259] Clin Vaccine Immunol. 2011 Sep;18(9):1568-76 [21734068] J Immunol. 2012 Feb 1;188(3):1503-13 [22198948] J Allergy Clin Immunol. 2012 Feb;129(2):280-91; quiz 292-3 [22284927] Clin Exp Allergy. 2012 May;42(5):782-91 [22515394] Toxicol Sci. 2012 Jun;127(2):371-81 [22403157] J Allergy Clin Immunol. 2012 Jun;129(6):1438-49; quiz1450-1 [22657405] Nat Rev Immunol. 2013 Feb;13(2):145-9 [23348417] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/cea.12724 ER - TY - JOUR T1 - Proceedings of the 2015 National Toxicology Program Satellite Symposium. AN - 1791741241; 27075180 AB - The 2015 Annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Veterinary Clinical Pathology/Society of Toxicologic Pathology combined meeting. The goal of this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. Because of the combined meeting, both laboratory and domestic animal cases were presented. This article presents summaries of the speakers' talks, including challenging diagnostic cases or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included hepatocellular lesions, a proposed harmonized diagnostic approach to rat cardiomyopathy, crop milk in a bird, avian feeding accoutrement, heat exchanger in a tuna, metastasis of a tobacco carcinogen-induced pulmonary carcinoma, neurocytoma in a rat, pituicytoma in a rat, rodent mammary gland whole mounts, dog and rat alveolar macrophage ultrastructure, dog and rat pulmonary phospholipidosis, alveolar macrophage aggregation in a dog, degenerating yeast in a cat liver aspirate, myeloid leukemia in lymph node aspirates from a dog, Trypanosoma cruzi in a dog, solanum toxicity in a cow, bovine astrovirus, malignant microglial tumor, and nomenclature challenges from the Special Senses International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Group. © The Author(s) 2016. JF - Toxicologic pathology AU - Elmore, Susan A AU - Farman, Cindy A AU - Hailey, James R AU - Kovi, Ramesh C AU - Malarkey, David E AU - Morrison, James P AU - Neel, Jennifer AU - Pesavento, Patricia A AU - Porter, Brian F AU - Szabo, Kathleen A AU - Teixeira, Leandro B C AU - Quist, Erin M AD - National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA elmore@niehs.nih.gov. ; Genentech, Inc., South San Francisco, California, USA. ; Covance Laboratories, Inc., Chantilly, Virginia, USA. ; Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina, USA. ; National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. ; Charles River Laboratories, Inc., Durham, North Carolina, USA. ; College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA. ; School of Veterinary Medicine, University of California at Davis, Davis, California, USA. ; Texas A&M University, College Station, Texas, USA. ; University of Wisconsin-Madison, Madison, Wisconsin, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 502 EP - 535 VL - 44 IS - 4 KW - Index Medicus KW - oral ornamentation KW - persistent fetal vasculature KW - cardiomyopathy KW - crop milk KW - neurocytoma KW - histoplasmosis KW - tuna heat exchanger KW - persistent hyperplastic tunica vasculosa lentis KW - pulmonary metastatic tumor KW - diagnostic neuropathology KW - pulmonary ultrastructure KW - focal nodular hyperplasia KW - leukemia +/− cytology KW - NTP Satellite Symposium KW - persistent hyperplastic primary vitreous KW - ocular inflammation KW - mammary gland whole mounts KW - INHAND UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791741241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Proceedings+of+the+2015+National+Toxicology+Program+Satellite+Symposium.&rft.au=Elmore%2C+Susan+A%3BFarman%2C+Cindy+A%3BHailey%2C+James+R%3BKovi%2C+Ramesh+C%3BMalarkey%2C+David+E%3BMorrison%2C+James+P%3BNeel%2C+Jennifer%3BPesavento%2C+Patricia+A%3BPorter%2C+Brian+F%3BSzabo%2C+Kathleen+A%3BTeixeira%2C+Leandro+B+C%3BQuist%2C+Erin+M&rft.aulast=Elmore&rft.aufirst=Susan&rft.date=2016-06-01&rft.volume=44&rft.issue=4&rft.spage=502&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=1533-1601&rft_id=info:doi/10.1177%2F0192623316631844 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0192623316631844 ER - TY - JOUR T1 - Pharmacodynamic effects and relationships to plasma and oral fluid pharmacokinetics after intravenous cocaine administration. AN - 1791734835; 27114201 AB - No controlled cocaine administration data describe cocaine and metabolite disposition in oral fluid (OF) collected with commercially-available collection devices, OF-plasma ratios, and pharmacodynamic relationships with plasma and OF cocaine and metabolite concentrations. Eleven healthy, cocaine-using adults received 25mg intravenous cocaine. Physiological and subjective effects (visual analogue scales), and plasma were collected one hour prior, and up to 21h post-dose. OF was collected with the Quantisal™ device up to 69h post-dose. Cocaine, benzoylecgonine (BE) and ecgonine methyl ester were quantified in plasma by liquid chromatography-tandem mass spectrometry; cocaine and BE were quantified in OF by two dimensional-gas chromatography-mass spectrometry. Increases in heart rate, blood pressure and positive subjective effects occurred within the first 15min, persisting up to 1h ("Rush"), with clockwise hysteresis observed for plasma and OF concentrations and some subjective measures. Peak subjective effects ("Rush," "Good drug effect" and "Bad drug effect") occurred prior to peak OF cocaine concentration, whereas observed peak plasma concentrations and subjective measures occurred simultaneously, most likely due to significantly earlier plasma Tmax compared to OF Tmax.Tlast was generally longer in OF (12.5h cocaine; 33.0h BE) than plasma (9.5h cocaine; >21h BE, cutoffs 1μg/L); 8 and 10μg/L OF cocaine confirmatory cutoffs yielded detection times similar to cocaine's impairing effects, suggesting usefulness for DUID testing. OF offers advantages as an alternative matrix to blood and plasma for identifying cocaine intake, defining pharmacokinetic parameters at different confirmation cutoffs, and aiding different drug testing programs to best achieve their monitoring goals. Copyright © 2016. Published by Elsevier Ireland Ltd. JF - Drug and alcohol dependence AU - Ellefsen, Kayla N AU - Concheiro, Marta AU - Pirard, Sandrine AU - Gorelick, David A AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, United States. ; Currently Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY, United States. ; University of Maryland Health Center, College Park, MD, United States. ; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States. ; Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States. Electronic address: marilyn.huestis@gmail.com. Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 116 EP - 125 VL - 163 KW - Index Medicus KW - Plasma KW - Benzoylecgonine KW - Oral fluid KW - Cocaine KW - Pharmacokinetics KW - Pharmacodynamics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791734835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Pharmacodynamic+effects+and+relationships+to+plasma+and+oral+fluid+pharmacokinetics+after+intravenous+cocaine+administration.&rft.au=Ellefsen%2C+Kayla+N%3BConcheiro%2C+Marta%3BPirard%2C+Sandrine%3BGorelick%2C+David+A%3BHuestis%2C+Marilyn+A&rft.aulast=Ellefsen&rft.aufirst=Kayla&rft.date=2016-06-01&rft.volume=163&rft.issue=&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=1879-0046&rft_id=info:doi/10.1016%2Fj.drugalcdep.2016.04.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.drugalcdep.2016.04.004 ER - TY - JOUR T1 - Sensitivity Enhancement of an Inductively Coupled Local Detector Using a HEMT-Based Current Amplifier AN - 1790970499; PQ0003114905 AB - Purpose To improve the signal transmission efficiency and sensitivity of a local detection coil that is weakly inductively coupled to a larger receive coil. Methods The resonant detection coil is connected in parallel with the gate of a high electron mobility transistor (HEMT) transistor without impedance matching. When the drain of the transistor is capacitively shunted to ground, current amplification occurs in the resonator by feedback that transforms a capacitive impedance on the transistor's source to a negative resistance on its gate. Results High resolution images were obtained from a mouse brain using a small, 11 mm diameter surface coil that was inductively coupled to a commercial, phased array chest coil. Although the power consumption of the amplifier was only 88 mu W, 14 dB gain was obtained with excellent noise performance. Conclusion An integrated current amplifier based on a HEMT can enhance the sensitivity of inductively coupled local detectors when weakly coupled. This amplifier enables efficient signal transmission between customized user coils and commercial clinical coils, without the need for a specialized signal interface. Magn Reson Med 75:2573-2578, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. JF - Magnetic Resonance in Medicine AU - Qian, Chunqi AU - Duan, Qi AU - Dodd, Steve AU - Koretsky, Alan AU - Murphy-Boesch, Joe AD - Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 2573 EP - 2578 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 75 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Neurotransmission KW - Mobility KW - Brain KW - N.M.R. KW - Feedback KW - Drains KW - Chest KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790970499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Sensitivity+Enhancement+of+an+Inductively+Coupled+Local+Detector+Using+a+HEMT-Based+Current+Amplifier&rft.au=Qian%2C+Chunqi%3BDuan%2C+Qi%3BDodd%2C+Steve%3BKoretsky%2C+Alan%3BMurphy-Boesch%2C+Joe&rft.aulast=Qian&rft.aufirst=Chunqi&rft.date=2016-06-01&rft.volume=75&rft.issue=6&rft.spage=2573&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25850 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Mobility; Neurotransmission; Brain; Drains; Feedback; N.M.R.; Chest DO - http://dx.doi.org/10.1002/mrm.25850 ER - TY - JOUR T1 - Analysis of mcDESPOT- and CPMG-derived parameter estimates for two-component nonexchanging systems AN - 1790968892; PQ0003114907 AB - Purpose To compare the reliability and stability of the multicomponent-driven equilibrium single pulse observation of T sub(1) and T sub(2) (mcDESPOT) and Carl-Purcell-Meiboom-Gill (CPMG) approaches to parameter estimation. Methods The stability and reliability of mcDESPOT and CPMG-derived parameter estimates were compared through examination of energy surfaces, evaluation of model sloppiness, and Monte Carlo simulations. Comparisons were performed on an equal time basis and assuming a two-component system. Parameter estimation bias, reflecting accuracy, and dispersion, reflecting precision, were derived for a range of signal-to-noise ratios (SNRs) and relaxation parameters. Results The energy surfaces for parameters incorporated into the mcDESPOT signal model exhibit flatness, a complex structure of local minima, and instability to noise to a much greater extent than the corresponding surfaces for CPMG. Although both mcDESPOT and CPMG performed well at high SNR, the CPMG approach yielded parameter estimates of considerably greater accuracy and precision at lower SNR. Conclusion mcDESPOT and CPMG both permit high-quality parameter estimates under SNR that are clinically achievable under many circumstances, depending upon available hardware and resolution and acquisition time constraints. At moderate to high SNR, the mcDESPOT approach incorporating two-step phase increments can yield accurate parameter estimates while providing values for longitudinal relaxation times that are not available through CPMG. However, at low SNR, the CPMG approach is more stable and provides superior parameter estimates. Magn Reson Med 75:2406-2420, 2016. JF - Magnetic Resonance in Medicine AU - Bouhrara, Mustapha AU - Reiter, David A AU - Celik, Hasan AU - Fishbein, Kenneth W AU - Kijowski, Richard AU - Spencer, Richard G AD - Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 2406 EP - 2420 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 75 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Monte Carlo simulation KW - Energy KW - N.M.R. KW - Models KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790968892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Analysis+of+mcDESPOT-+and+CPMG-derived+parameter+estimates+for+two-component+nonexchanging+systems&rft.au=Bouhrara%2C+Mustapha%3BReiter%2C+David+A%3BCelik%2C+Hasan%3BFishbein%2C+Kenneth+W%3BKijowski%2C+Richard%3BSpencer%2C+Richard+G&rft.aulast=Bouhrara&rft.aufirst=Mustapha&rft.date=2016-06-01&rft.volume=75&rft.issue=6&rft.spage=2406&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25801 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Monte Carlo simulation; Energy; N.M.R.; Models DO - http://dx.doi.org/10.1002/mrm.25801 ER - TY - JOUR T1 - Real-time distortion correction of spiral and echo planar images using the gradient system impulse response function AN - 1790967382; PQ0003114904 AB - Purpose MRI-guided interventions demand high frame rate imaging, making fast imaging techniques such as spiral imaging and echo planar imaging (EPI) appealing. In this study, we implemented a real-time distortion correction framework to enable the use of these fast acquisitions for interventional MRI. Methods Distortions caused by gradient waveform inaccuracies were corrected using the gradient impulse response function (GIRF), which was measured by standard equipment and saved as a calibration file on the host computer. This file was used at runtime to calculate the predicted k-space trajectories for image reconstruction. Additionally, the off-resonance reconstruction frequency was modified in real time to interactively deblur spiral images. Results Real-time distortion correction for arbitrary image orientations was achieved in phantoms and healthy human volunteers. The GIRF-predicted k-space trajectories matched measured k-space trajectories closely for spiral imaging. Spiral and EPI image distortion was visibly improved using the GIRF-predicted trajectories. The GIRF calibration file showed no systematic drift in 4 months and was demonstrated to correct distortions after 30 min of continuous scanning despite gradient heating. Interactive off-resonance reconstruction was used to sharpen anatomical boundaries during continuous imaging. Conclusions This real-time distortion correction framework will enable the use of these high frame rate imaging methods for MRI-guided interventions. Magn Reson Med 75:2278-2285, 2016. JF - Magnetic Resonance in Medicine AU - Campbell-Washburn, Adrienne E AU - Xue, Hui AU - Lederman, Robert J AU - Faranesh, Anthony Z AU - Hansen, Michael S AD - Pulmonary and Cardiovascular Branch, Division of Intramural Research National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 2278 EP - 2285 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 75 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Scanning KW - Drift KW - Computers KW - Magnetic resonance imaging KW - Boundaries KW - Image processing KW - N.M.R. KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790967382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Real-time+distortion+correction+of+spiral+and+echo+planar+images+using+the+gradient+system+impulse+response+function&rft.au=Campbell-Washburn%2C+Adrienne+E%3BXue%2C+Hui%3BLederman%2C+Robert+J%3BFaranesh%2C+Anthony+Z%3BHansen%2C+Michael+S&rft.aulast=Campbell-Washburn&rft.aufirst=Adrienne&rft.date=2016-06-01&rft.volume=75&rft.issue=6&rft.spage=2278&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25788 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Scanning; Drift; Computers; Magnetic resonance imaging; Boundaries; Image processing; N.M.R. DO - http://dx.doi.org/10.1002/mrm.25788 ER - TY - JOUR T1 - Improvement of temporal signal-to-noise ratio of GRAPPA accelerated echo planar imaging using a FLASH based calibration scan AN - 1790955356; PQ0003114884 AB - Purpose To demonstrate that the temporal signal-to-noise ratio (SNR) of generalized autocalibrating partially parallel acquisitions (GRAPPA) accelerated echo planar imaging (EPI) can be enhanced and made more spatially uniform by using a fast low angle shot (FLASH) based calibration scan. Methods EPI of a phantom and human brains were acquired at 3 Tesla without and with GRAPPA acceleration factor of 2. The GRAPPA accelerated data were reconstructed using calibration scans acquired with EPI and FLASH acquisition schemes. The increase in temporal signal fluctuation due to GRAPPA reconstruction was quantified and compared. Simulated g-factor maps were also created for different calibration scans. Results GRAPPA accelerated phantom data exhibited areas with high g values when using the EPI based calibration for reconstruction. The g-factor maps were uniform when using the FLASH calibration scan. g was greater than 1.1 in 74% of pixels in 64 64 data reconstructed with the EPI calibration compared with only 15% when using the FLASH calibration scan. Human data also showed abnormally high g regions when using the EPI calibration but not when using the FLASH calibration scan. Use of the FLASH calibration scan increased the whole brain temporal SNR by 12% without affecting the image quality. Experimental observations were confirmed by simulations. Conclusion A calibration scan based on a FLASH acquisition scheme can be used to improve the temporal SNR of GRAPPA accelerated EPI time series. Magn Reson Med 75:2362-2371, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. JF - Magnetic Resonance in Medicine AU - Talagala, SLalith AU - Sarlls, Joelle E AU - Liu, Siyuan AU - Inati, Souheil J AD - NIH MRI Research Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 2362 EP - 2371 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 75 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - Data processing KW - Brain KW - N.M.R. KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790955356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Improvement+of+temporal+signal-to-noise+ratio+of+GRAPPA+accelerated+echo+planar+imaging+using+a+FLASH+based+calibration+scan&rft.au=Talagala%2C+SLalith%3BSarlls%2C+Joelle+E%3BLiu%2C+Siyuan%3BInati%2C+Souheil+J&rft.aulast=Talagala&rft.aufirst=SLalith&rft.date=2016-06-01&rft.volume=75&rft.issue=6&rft.spage=2362&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25846 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Data processing; Brain; N.M.R. DO - http://dx.doi.org/10.1002/mrm.25846 ER - TY - JOUR T1 - New Insights Into the Transmissibility of Leishmania infantum From Dogs to Sand Flies: Experimental Vector-Transmission Reveals Persistent Parasite Depots at Bite Sites AN - 1790950477; PQ0003120238 AB - Canine leishmaniasis (CanL) is a chronic fatal disease of dogs and a major source of human infection through propagation of parasites in vectors. Here, we infected 8 beagles through multiple experimental vector transmissions with Leishmania infantum-infected Lutzomyia longipalpis. CanL clinical signs varied, although live parasites were recovered from all dog spleens. Splenic parasite burdens correlated positively with Leishmania-specific interleukin 10 levels, negatively with Leishmania-specific interferon [gamma] and interleukin 2 levels, and negatively with Leishmania skin test reactivity. A key finding was parasite persistence for 6 months in lesions observed at the bite sites in all dogs. These recrudesced following a second transmission performed at a distal site. Notably, sand flies efficiently acquired parasites after feeding on lesions at the primary bite site. In this study, controlled vector transmissions identify a potentially unappreciated role for skin at infectious bite sites in dogs with CanL, providing a new perspective regarding the mechanism of Leishmania transmissibility to vector sand flies. JF - Journal of Infectious Diseases AU - Aslan, Hamide AU - Oliveira, Fabiano AU - Meneses, Claudio AU - Castrovinci, Philip AU - Gomes, Regis AU - Teixeira, Clarissa AU - Derenge, Candace A AU - Orandle, Marlene AU - Gradoni, Luigi AU - Oliva, Gaetano AU - Fischer, Laurent AU - Valenzuela, Jesus G AU - Kamhawi, Shaden AD - Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, skamhawi@niaid.nih.gov Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 1752 EP - 1761 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 11 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Health & Safety Science Abstracts KW - canine leishmaniasis KW - Leishmania infantum KW - Lutzomyia longipalpis KW - dogs KW - reservoir KW - vector transmission KW - skin KW - bite site KW - infectivity parasite-pickup KW - Leishmaniasis KW - Parasites KW - gamma -Interferon KW - Feeding KW - Skin KW - Interleukin 2 KW - Bites KW - Vectors KW - Spleen KW - Infection KW - Interleukin 10 KW - Disease transmission KW - Skin tests KW - Infectious diseases KW - Sand KW - Chronic infection KW - Lesions KW - K 03410:Animal Diseases KW - H 6000:Natural Disasters/Civil Defense/Emergency Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790950477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=New+Insights+Into+the+Transmissibility+of+Leishmania+infantum+From+Dogs+to+Sand+Flies%3A+Experimental+Vector-Transmission+Reveals+Persistent+Parasite+Depots+at+Bite+Sites&rft.au=Aslan%2C+Hamide%3BOliveira%2C+Fabiano%3BMeneses%2C+Claudio%3BCastrovinci%2C+Philip%3BGomes%2C+Regis%3BTeixeira%2C+Clarissa%3BDerenge%2C+Candace+A%3BOrandle%2C+Marlene%3BGradoni%2C+Luigi%3BOliva%2C+Gaetano%3BFischer%2C+Laurent%3BValenzuela%2C+Jesus+G%3BKamhawi%2C+Shaden&rft.aulast=Aslan&rft.aufirst=Hamide&rft.date=2016-06-01&rft.volume=213&rft.issue=11&rft.spage=1752&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw022 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Leishmaniasis; Feeding; gamma -Interferon; Parasites; Interleukin 2; Bites; Chronic infection; Spleen; Vectors; Interleukin 10; Skin tests; Disease transmission; Skin; Infectious diseases; Sand; Lesions; Infection; Leishmania infantum; Lutzomyia longipalpis DO - http://dx.doi.org/10.1093/infdis/jiw022 ER - TY - JOUR T1 - Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype. AN - 1790461052; 26844528 AB - The majority of hepatocellular carcinoma develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or nonalcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and β-catenin (CAT), followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride. Also, the impact of DDC-induced chronic liver inflammation was compared between two liver tumor models using a combination of AKT-CAT or AKT-NRAS(G12V) . Treatment with DDC and carbon tetrachloride significantly facilitated the adenoma-to-carcinoma conversion and accelerated the growth of AKT-CAT tumors. Furthermore, DDC treatment altered the morphology of AKT-CAT tumors and caused loss of lipid droplets. Transcriptome analysis of AKT-CAT tumors revealed that cellular growth and proliferation were mainly affected by chronic inflammation and caused up-regulation of Cxcl16, Galectin-3, and Nedd9, among others. Integration with transcriptome profiles from human hepatocellular carcinomas further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRAS(G12V) tumors and primarily enhanced already existent tumor characteristics as supported by transcriptome analysis. However, it also reduced lipid droplets in AKT-NRAS(G12V) tumors. Our study suggests that liver tumor phenotype is defined by a combination of driving oncogenes but also the nature of chronic liver inflammation. (Hepatology 2016;63:1888-1899). © 2016 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. JF - Hepatology (Baltimore, Md.) AU - Matter, Matthias S AU - Marquardt, Jens U AU - Andersen, Jesper B AU - Quintavalle, Cristina AU - Korokhov, Nikolay AU - Stauffer, Jim K AU - Kaji, Kosuke AU - Decaens, Thomas AU - Quagliata, Luca AU - Elloumi, Fathi AU - Hoang, Tanya AU - Molinolo, Alfredo AU - Conner, Elizabeth A AU - Weber, Achim AU - Heikenwalder, Mathias AU - Factor, Valentina M AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. ; Institute of Pathology, University Hospital of Basel, Basel, Switzerland. ; Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD. ; National Cancer Institute, CCR at Leidos Inc., National Institutes of Health, Bethesda, MD. ; Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD. ; Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. ; Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1888 EP - 1899 VL - 63 IS - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790461052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Oncogenic+driver+genes+and+the+inflammatory+microenvironment+dictate+liver+tumor+phenotype.&rft.au=Matter%2C+Matthias+S%3BMarquardt%2C+Jens+U%3BAndersen%2C+Jesper+B%3BQuintavalle%2C+Cristina%3BKorokhov%2C+Nikolay%3BStauffer%2C+Jim+K%3BKaji%2C+Kosuke%3BDecaens%2C+Thomas%3BQuagliata%2C+Luca%3BElloumi%2C+Fathi%3BHoang%2C+Tanya%3BMolinolo%2C+Alfredo%3BConner%2C+Elizabeth+A%3BWeber%2C+Achim%3BHeikenwalder%2C+Mathias%3BFactor%2C+Valentina+M%3BThorgeirsson%2C+Snorri+S&rft.aulast=Matter&rft.aufirst=Matthias&rft.date=2016-06-01&rft.volume=63&rft.issue=6&rft.spage=1888&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28487 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-21 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Hepatology. 2004 Sep;40(3):667-76 [15349906] Gastroenterology. 2015 Oct;149(5):1226-1239.e4 [26099527] Pharmacol Ther. 1989;43(1):139-54 [2675128] Lab Invest. 1999 Feb;79(2):103-9 [10068199] Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 [16199517] Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5060-5 [16549783] Cancer Cell. 2006 Aug;10(2):99-111 [16904609] PLoS One. 2008;3(6):e2493 [18560566] N Engl J Med. 2008 Nov 6;359(19):1995-2004 [18923165] Cell. 2010 Mar 19;140(6):883-99 [20303878] Mol Cancer. 2010;9:74 [20380719] Toxicol Pathol. 2010 Dec;38(7 Suppl):5S-81S [21191096] Science. 2011 Mar 25;331(6024):1565-70 [21436444] Cancer Res. 2011 Apr 1;71(7):2718-27 [21324921] J Clin Invest. 2011 Jun;121(6):2102-10 [21633178] N Engl J Med. 2011 Sep 22;365(12):1118-27 [21992124] Nat Rev Clin Oncol. 2011 Dec;8(12):711-9 [21826083] J Clin Invest. 2012 Feb;122(2):586-99 [22251704] Hepatology. 2012 Mar;55(3):833-45 [21993994] Cancer Res. 2012 Jul 15;72(14):3546-56 [22710437] J Clin Invest. 2012 Aug;122(8):2911-5 [22797301] Hepatology. 2013 Feb;57(2):610-24 [22911555] Toxicol Sci. 2013 Mar;132(1):53-63 [23288052] PLoS One. 2013;8(9):e73054 [24039859] Clin Cancer Res. 2014 Jan 1;20(1):28-34 [24158702] Oncol Rep. 2015 May;33(5):2375-83 [25812772] Lab Invest. 2015 Oct;95(10):1145-56 [26146960] Cancer Lett. 1980 Jun;9(4):319-25 [7397685] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28487 ER - TY - JOUR T1 - Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits. AN - 1790452420; 26930443 AB - Excessive stimulation of NMDA receptors with glutamate or other potent agonists such as NMDA leads to excitotoxicity and neural injury. In this study, we aimed to provide insight into an animal model of brain excitotoxic damage; single unilateral infusion of NMDA at mild dose into the hippocampal formation. NMDA infusion induced chronic, focal neurodegeneration in the proximity of the injection site. The lesion was accompanied by severe and progressive neuroinflammation and affected preferentially principal neurons while sparing GABAergic interneurons. Furthermore, the unilateral lesion did not cause significant impairment of spatial learning abilities. Finally, GluN1 and GluN2B subunits of NMDA receptor were significantly upregulated up to 3 days after the NMDA infusion, while GABAA α5 subunit was downregulated at 30 days after the lesion. Taken together, a single infusion of NMDA into the hippocampal formation represents an animal model of excitotoxicity-induced chronic neurodegeneration of principal neurons accompanied by severe neuroinflammation and subunit specific changes in NMDA and GABAA receptors. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Neuropharmacology AU - Rambousek, Lukas AU - Kleteckova, Lenka AU - Kubesova, Anna AU - Jirak, Daniel AU - Vales, Karel AU - Fritschy, Jean-Marc AD - Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Physiology, Academy of Sciences, Prague, Czech Republic. Electronic address: rambousek@immunology.uzh.ch. ; 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Institute of Physiology, Academy of Sciences, Prague, Czech Republic. ; National Institute of Mental Health, Klecany, Czech Republic. ; Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Biophysics and Informatics, 1st Medicine Faculty, Charles University, Prague, Czech Republic. ; Institute of Physiology, Academy of Sciences, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic. ; Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 594 EP - 606 VL - 105 KW - Index Medicus KW - Interneurons KW - Hippocampus KW - Spatial learning KW - GABA A receptor KW - Neuroinflammation KW - Carousel maze KW - Neurodegeneration KW - NMDA receptor KW - Excitotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790452420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Rat+intra-hippocampal+NMDA+infusion+induces+cell-specific+damage+and+changes+in+expression+of+NMDA+and+GABAA+receptor+subunits.&rft.au=Rambousek%2C+Lukas%3BKleteckova%2C+Lenka%3BKubesova%2C+Anna%3BJirak%2C+Daniel%3BVales%2C+Karel%3BFritschy%2C+Jean-Marc&rft.aulast=Rambousek&rft.aufirst=Lukas&rft.date=2016-06-01&rft.volume=105&rft.issue=&rft.spage=594&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2016.02.035 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.neuropharm.2016.02.035 ER - TY - JOUR T1 - Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors. AN - 1790020306; 27125830 AB - Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data. Endometrial tissue mRNA and protein levels were measured using quantitative real-time PCR and immunohistochemistry, respectively. In postmenopausal women, we observed higher levels of phosphorylated IGF-I/insulin receptor (pIGF1R/pIR) in diabetic versus non-diabetic women (p value =0.02), while women who reported regular nonsteroidal anti-inflammatory drug use versus no use had higher levels of insulin and progesterone receptors (both p values ≤0.03). We also noted differences in pIGF1R/pIR staining with OC use (postmenopausal women only), and the proportion of estrogen receptor-positive tissues varied by the number of live births and PTEN status (premenopausal only) (p values ≤0.04). Compared to premenopausal proliferative phase women, postmenopausal women exhibited lower mRNA levels of IGF1, but higher IGFBP1 and IGFBP3 expression (all p values ≤0.004), and higher protein levels of the receptors for estrogen, insulin, and IGF-I (all p values ≤0.02). Conversely, pIGF1R/pIR levels were higher in premenopausal proliferative phase versus postmenopausal endometrium (p value =0.01). These results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis. JF - Cancer causes & control : CCC AU - Merritt, Melissa A AU - Strickler, Howard D AU - Einstein, Mark H AU - Yang, Hannah P AU - Sherman, Mark E AU - Wentzensen, Nicolas AU - Brouwer-Visser, Jurriaan AU - Cossio, Maria Jose AU - Whitney, Kathleen D AU - Yu, Herbert AU - Gunter, Marc J AU - Huang, Gloria S AD - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK. m.merritt@imperial.ac.uk. ; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA. ; Division of Gynecologic Oncology, Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. ; Department of Pathology, Jack D. Weiler Hospital, The University Hospital for Albert Einstein College of Medicine, Montefiore Medical Center, 1825 Eastchester Road, Room 338, Bronx, NY, 10461, USA. ; Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA. ; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 737 EP - 748 VL - 27 IS - 6 KW - Index Medicus KW - Endometrium KW - Insulin-like growth factor KW - Estrogen receptor KW - Endometrial cancer KW - Insulin UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790020306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Insulin%2FIGF+and+sex+hormone+axes+in+human+endometrium+and+associations+with+endometrial+cancer+risk+factors.&rft.au=Merritt%2C+Melissa+A%3BStrickler%2C+Howard+D%3BEinstein%2C+Mark+H%3BYang%2C+Hannah+P%3BSherman%2C+Mark+E%3BWentzensen%2C+Nicolas%3BBrouwer-Visser%2C+Jurriaan%3BCossio%2C+Maria+Jose%3BWhitney%2C+Kathleen+D%3BYu%2C+Herbert%3BGunter%2C+Marc+J%3BHuang%2C+Gloria+S&rft.aulast=Merritt&rft.aufirst=Melissa&rft.date=2016-06-01&rft.volume=27&rft.issue=6&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=1573-7225&rft_id=info:doi/10.1007%2Fs10552-016-0751-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-18 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1007/s10552-016-0751-4 ER - TY - JOUR T1 - R2d2 Drives Selfish Sweeps in the House Mouse. AN - 1790019357; 26882987 AB - A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. JF - Molecular biology and evolution AU - Didion, John P AU - Morgan, Andrew P AU - Yadgary, Liran AU - Bell, Timothy A AU - McMullan, Rachel C AU - Ortiz de Solorzano, Lydia AU - Britton-Davidian, Janice AU - Bult, Carol J AU - Campbell, Karl J AU - Castiglia, Riccardo AU - Ching, Yung-Hao AU - Chunco, Amanda J AU - Crowley, James J AU - Chesler, Elissa J AU - Förster, Daniel W AU - French, John E AU - Gabriel, Sofia I AU - Gatti, Daniel M AU - Garland, Theodore AU - Giagia-Athanasopoulou, Eva B AU - Giménez, Mabel D AU - Grize, Sofia A AU - Gündüz, İslam AU - Holmes, Andrew AU - Hauffe, Heidi C AU - Herman, Jeremy S AU - Holt, James M AU - Hua, Kunjie AU - Jolley, Wesley J AU - Lindholm, Anna K AU - López-Fuster, María J AU - Mitsainas, George AU - da Luz Mathias, Maria AU - McMillan, Leonard AU - Ramalhinho, Maria da Graça Morgado AU - Rehermann, Barbara AU - Rosshart, Stephan P AU - Searle, Jeremy B AU - Shiao, Meng-Shin AU - Solano, Emanuela AU - Svenson, Karen L AU - Thomas-Laemont, Patricia AU - Threadgill, David W AU - Ventura, Jacint AU - Weinstock, George M AU - Pomp, Daniel AU - Churchill, Gary A AU - Pardo-Manuel de Villena, Fernando AD - Department of Genetics, The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill fernando@med.unc.edu. ; Department of Genetics, The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill. ; Institut des Sciences de l'Evolution, Université De Montpellier, CNRS, IRD, EPHE, Montpellier, France. ; The Jackson Laboratory, Bar Harbor, ME. ; Island Conservation, Puerto Ayora, Galápagos Island, Ecuador School of Geography, Planning & Environmental Management, The University of Queensland, St Lucia, QLD, Australia. ; Department of Biology and Biotechnologies "Charles Darwin", University of Rome "La Sapienza", Rome, Italy. ; Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien City, Taiwan. ; Department of Environmental Studies, Elon University. ; Department of Genetics, The University of North Carolina at Chapel Hill. ; Department of Evolutionary Genetics, Leibniz-Institute for Zoo and Wildlife Research, Berlin, Germany. ; National Toxicology Program, National Institute of Environmental Sciences, NIH, Research Triangle Park, NC. ; Department of Animal Biology & CESAM - Centre for Environmental and Marine Studies, Faculty of Sciences, University of Lisbon, Lisboa, Portugal. ; Department of Biology, University of California Riverside. ; Section of Animal Biology, Department of Biology, University of Patras, Patras, Greece. ; Instituto de Biología Subtropical, CONICET - Universidad Nacional de Misiones, Posadas, Misiones, Argentina. ; Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland. ; Department of Biology, Faculty of Arts and Sciences, University of Ondokuz Mayis, Samsun, Turkey. ; Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD. ; Department of Biodiversity and Molecular Ecology, Research and Innovation Centre, Fondazione Edmund Mach, San Michele All'adige, TN, Italy. ; Department of Natural Sciences, National Museums Scotland, Edinburgh, United Kingdom. ; Department of Computer Science, The University of North Carolina at Chapel Hill. ; Island Conservation, Santa Cruz, CA. ; Faculty of Biology, Universitat de Barcelona, Barcelona, Spain. ; Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD. ; Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY. ; Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. ; Department of Veterinary Pathobiology, Texas A&M University, College Station Department of Molecular and Cellular Medicine, Texas A&M University, College Station. ; Departament de Biologia Animal, de Biologia Vegetal y de Ecologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain. ; Jackson Laboratory for Genomic Medicine, Farmington, CT. ; Department of Genetics, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1381 EP - 1395 VL - 33 IS - 6 KW - Index Medicus KW - Selective Sweep KW - Selfish Genes KW - House Mouse. KW - R2d2 KW - Meiotic Drive UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790019357?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+and+evolution&rft.atitle=R2d2+Drives+Selfish+Sweeps+in+the+House+Mouse.&rft.au=Didion%2C+John+P%3BMorgan%2C+Andrew+P%3BYadgary%2C+Liran%3BBell%2C+Timothy+A%3BMcMullan%2C+Rachel+C%3BOrtiz+de+Solorzano%2C+Lydia%3BBritton-Davidian%2C+Janice%3BBult%2C+Carol+J%3BCampbell%2C+Karl+J%3BCastiglia%2C+Riccardo%3BChing%2C+Yung-Hao%3BChunco%2C+Amanda+J%3BCrowley%2C+James+J%3BChesler%2C+Elissa+J%3BF%C3%B6rster%2C+Daniel+W%3BFrench%2C+John+E%3BGabriel%2C+Sofia+I%3BGatti%2C+Daniel+M%3BGarland%2C+Theodore%3BGiagia-Athanasopoulou%2C+Eva+B%3BGim%C3%A9nez%2C+Mabel+D%3BGrize%2C+Sofia+A%3BG%C3%BCnd%C3%BCz%2C+%C4%B0slam%3BHolmes%2C+Andrew%3BHauffe%2C+Heidi+C%3BHerman%2C+Jeremy+S%3BHolt%2C+James+M%3BHua%2C+Kunjie%3BJolley%2C+Wesley+J%3BLindholm%2C+Anna+K%3BL%C3%B3pez-Fuster%2C+Mar%C3%ADa+J%3BMitsainas%2C+George%3Bda+Luz+Mathias%2C+Maria%3BMcMillan%2C+Leonard%3BRamalhinho%2C+Maria+da+Gra%C3%A7a+Morgado%3BRehermann%2C+Barbara%3BRosshart%2C+Stephan+P%3BSearle%2C+Jeremy+B%3BShiao%2C+Meng-Shin%3BSolano%2C+Emanuela%3BSvenson%2C+Karen+L%3BThomas-Laemont%2C+Patricia%3BThreadgill%2C+David+W%3BVentura%2C+Jacint%3BWeinstock%2C+George+M%3BPomp%2C+Daniel%3BChurchill%2C+Gary+A%3BPardo-Manuel+de+Villena%2C+Fernando&rft.aulast=Didion&rft.aufirst=John&rft.date=2016-06-01&rft.volume=33&rft.issue=6&rft.spage=1381&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+and+evolution&rft.issn=1537-1719&rft_id=info:doi/10.1093%2Fmolbev%2Fmsw036 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-18 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Genetics. 2001 Nov;159(3):1179-89 [11729161] Nature. 2002 May 16;417(6886):227 [12015578] Nature. 2002 Oct 24;419(6909):832-7 [12397357] Genetics. 2004 Mar;166(3):1357-66 [15082554] Am J Hum Genet. 2004 Jun;74(6):1111-20 [15114531] Genetics. 1973 Apr;73(4):613-29 [4197166] Genet Res. 1974 Feb;23(1):23-35 [4407212] Genetics. 1989 Dec;123(4):887-99 [2612899] Genetics. 1991 Aug;128(4):813-21 [1916246] Mol Biol Evol. 1996 Feb;13(2):297-308 [8587496] Genetics. 1996 Aug;143(4):1739-52 [8844160] Am J Hum Genet. 1998 Jun;62(6):1507-15 [9585595] Behav Genet. 1998 May;28(3):227-37 [9670598] Genetics. 2005 Aug;170(4):1839-47 [15879509] PLoS Biol. 2006 Mar;4(3):e72 [16494531] Am J Hum Genet. 2006 Apr;78(4):629-44 [16532393] Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1587-92 [17242362] Am J Hum Genet. 2007 Sep;81(3):559-75 [17701901] PLoS Genet. 2007 Jun;3(6):e90 [17542651] PLoS Genet. 2007 Aug;3(8):e144 [17722986] Mol Biol Evol. 2008 Feb;25(2):409-16 [18071199] Science. 2008 Dec 5;322(5907):1559-62 [19056989] PLoS Genet. 2009 May;5(5):e1000463 [19412335] Genetics. 2010 Jan;184(1):253-65 [19897749] Physiol Genomics. 2010 Jan 8;40(2):111-20 [19903762] Bioinformatics. 2010 Jun 15;26(12):i199-207 [20529906] Physiol Genomics. 2010 Jul 7;42(2):190-200 [20388837] Genetics. 2010 Sep;186(1):295-308 [20592267] BMC Genet. 2010;11:98 [21044349] Science. 2011 Feb 18;331(6019):920-4 [21330547] Nat Genet. 2011 Jul;43(7):648-55 [21623374] Curr Biol. 2011 Aug 9;21(15):1296-301 [21782438] PLoS Genet. 2011 Sep;7(9):e1002287 [21966277] Mol Ecol. 2011 Nov;20(22):4722-36 [22004102] Genetics. 2012 Feb;190(2):709-23 [22143919] Genetics. 2012 Feb;190(2):389-401 [22345608] Genetics. 2012 Feb;190(2):437-47 [22345611] PLoS Genet. 2012;8(8):e1002891 [22956910] PLoS Genet. 2012;8(11):e1002967 [23166502] Physiol Genomics. 2012 Dec 1;44(23):1141-53 [23048196] Genome Res. 2013 Jan;23(1):99-110 [23051690] Mamm Genome. 2013 Feb;24(1-2):1-20 [23223940] Cell. 2013 Feb 14;152(4):703-13 [23415221] Genetics. 2013 Mar;193(3):929-41 [23307896] Genetics. 2013 Jun;194(2):459-71 [23535385] Annu Rev Genomics Hum Genet. 2013;14:467-89 [23834317] Mamm Genome. 2014 Apr;25(3-4):95-108 [24487921] Genetics. 2014 May;197(1):91-106 [24578350] Genome Biol. 2014;15(6):R88 [24980144] Mol Biol Evol. 2014 Oct;31(10):2824-7 [25015648] PLoS Genet. 2015 Feb;11(2):e1004850 [25679959] Science. 2015 Apr 24;348(6233):442-4 [25908821] Genome Res. 2015 Aug;25(8):1114-24 [26149421] Mamm Genome. 2015 Oct;26(9-10):521-39 [26135136] Nat Biotechnol. 2016 Jan;34(1):78-83 [26641531] G3 (Bethesda). 2016 Feb;6(2):263-79 [26684931] Bioinformatics. 2009 Aug 15;25(16):2078-9 [19505943] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/molbev/msw036 ER - TY - JOUR T1 - Childhood peer network characteristics: genetic influences and links with early mental health trajectories AN - 1789951503 AB - Background Peer relationships are important for children's mental health, yet little is known of their etiological underpinnings. Here, we explore the genetic influences on childhood peer network characteristics in three different networks defined by rejection, acceptance, and prosocial behavior. We further examine the impact of early externalizing and internalizing trajectories on these same peer network characteristics. Methods Participants were 1,288 children from the Dutch 'Generation R' birth cohort. At age 7, we mapped out children's classroom peer networks for peer rejection, acceptance, and prosocial behavior using mutual peer nominations. In each network, genetic influences were estimated for children's degree centrality, closeness centrality and link reciprocity from DNA using Genome-wide Complex Trait Analysis. Preschool externalizing and internalizing trajectories were computed using parental ratings at ages 1.5, 3, and 5 years. Results Of the three network properties examined, closeness centrality emerged as significantly heritable across all networks. Preschool externalizing problems predicted unfavorable positions within peer rejection networks and having fewer mutual friendships. In contrast, children with preschool-internalizing problems were not actively rejected by their peers, but were less well-connected within their social support network. Conclusions Our finding of significant heritability for closeness centrality should be taken as preliminary evidence that requires replication. Nevertheless, it can orient us to the role of genes in shaping a child's position within peer networks. Additionally, social network perspectives offer rich insights into how early life mental health trajectories impact a child's later functioning within peer networks. Read the Commentary on this article at doi: 10.1111/jcpp.12536 JF - Journal of Child Psychology and Psychiatry AU - Szekely, Eszter AU - Pappa, Irene AU - Wilson, James D AU - Bhamidi, Shankar AU - Jaddoe, Vincent W AU - Verhulst, Frank C AU - Tiemeier, Henning AU - Shaw, Philip AD - Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD, USA ; School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands ; Department of Mathematics and Statistics, University of San Francisco, San Francisco, CA, USA ; Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA ; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands ; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands ; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 687 EP - 694 CY - Malden PB - Wiley Subscription Services, Inc. VL - 57 IS - 6 KW - Psychology KW - Acceptance KW - Childhood KW - Genetic factors KW - Mental health KW - Prosocial behaviour KW - Social networks KW - Rejection KW - Peers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789951503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Psychology+and+Psychiatry&rft.atitle=Childhood+peer+network+characteristics%3A+genetic+influences+and+links+with+early+mental+health+trajectories&rft.au=Szekely%2C+Eszter%3BPappa%2C+Irene%3BWilson%2C+James+D%3BBhamidi%2C+Shankar%3BJaddoe%2C+Vincent+W%3BVerhulst%2C+Frank+C%3BTiemeier%2C+Henning%3BShaw%2C+Philip&rft.aulast=Szekely&rft.aufirst=Eszter&rft.date=2016-06-01&rft.volume=57&rft.issue=6&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=&rft_id=info:doi/10.1111%2Fjcpp.12493 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Association for Child and Adolescent Mental Health. N1 - Last updated - 2016-05-23 DO - http://dx.doi.org/10.1111/jcpp.12493 ER - TY - JOUR T1 - Efficacy and mucosal toxicity of concomitant chemo-radiotherapy in patients with locally-advanced squamous cell carcinoma of the head-and-neck in the light of a novel mathematical model. AN - 1789496420; 27157527 AB - In the last several decades, combined radiotherapy (RT) and chemotherapy (CT) have been recognized as feasible in locally-advanced-squamous-cell-carcinoma of the head-and-neck (LA-HNSCC). Several meta-analyses identified concurrent RT+CT (CRT) most likely effective approach respect to RT-alone. However, radiobiological models comparing different chemotherapeutic schedules against delivered RT fractionation schedule for overall survival and toxicity are still needed. Based on 9 randomized trials (2785 patients), radiobiological models and multivariate logistic regression model were used to derive dose-response curves and estimate the 5-year-overall survival (OS) and ≥G3 acute mucositis rate of CRT or RT-alone. Equivalent dose at 2 Gy/fraction (EQD2) was calculated using the linear quadratic model. The effect of CRT schedules, considering the CT type and its administration schedule and the HPV status of tumors were estimated using the univariate/multivariate logistic regression. The multivariate logistic regression model for 5y-OS indicated EQD2 and the type of CT, the chemo-sensitization fraction and the HPV status significant prognostic factors, while for toxicity both EQD2 and the concomitant administration of 5-fluorouracil (5Fu) resulted as significant prognostic factors. Combined schedules cisplatin (DDP)+/-5Fu+RT produced the higher OS compared with combined carboplatin+/-5Fu+RT or RT-alone. The concomitant administration of Fu and schedule with high EQD2 increase the rate of observed ≥G3 acute mucositis. Multivariate logistic regression models can be used to predict CRT effect in terms of OS and ≥G3-mucositis, contributing to the identification of novel treatment schedules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Critical reviews in oncology/hematology AU - Strigari, Lidia AU - Pinnarò, Paola AU - Carlini, Paolo AU - Torino, Francesco AU - Strolin, Silvia AU - Minosse, Silvia AU - Sanguineti, Giuseppe AU - Benassi, Marcello AD - Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy. Electronic address: strigari@ifo.it. ; Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Systems Medicine, Chair of Medical Oncology, University of Rome Tor Vergata, Rome, Italy. ; Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy. ; Medical Physics Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, FC, Italy. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 101 EP - 110 VL - 102 KW - Index Medicus KW - Advanced KW - Efficacy KW - Tumors KW - Toxicity KW - Radiobiology KW - Head and neck KW - Randomized Controlled Trials as Topic KW - Humans KW - Models, Biological KW - Head and Neck Neoplasms -- therapy KW - Chemoradiotherapy -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Mucous Membrane -- drug effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Radiation Injuries KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789496420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oncology%2Fhematology&rft.atitle=Efficacy+and+mucosal+toxicity+of+concomitant+chemo-radiotherapy+in+patients+with+locally-advanced+squamous+cell+carcinoma+of+the+head-and-neck+in+the+light+of+a+novel+mathematical+model.&rft.au=Strigari%2C+Lidia%3BPinnar%C3%B2%2C+Paola%3BCarlini%2C+Paolo%3BTorino%2C+Francesco%3BStrolin%2C+Silvia%3BMinosse%2C+Silvia%3BSanguineti%2C+Giuseppe%3BBenassi%2C+Marcello&rft.aulast=Strigari&rft.aufirst=Lidia&rft.date=2016-06-01&rft.volume=102&rft.issue=&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncology%2Fhematology&rft.issn=1879-0461&rft_id=info:doi/10.1016%2Fj.critrevonc.2016.04.004 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-26 N1 - Date created - 2016-05-16 N1 - Date revised - 2017-01-30 N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1016/j.critrevonc.2016.04.004 ER - TY - JOUR T1 - Hypofractionated Volumetric Modulated Arc Radiotherapy with simultaneous Elective Nodal Irradiation is feasible in prostate cancer patients: A single institution experience. AN - 1789495965; 27133975 AB - To assess feasibility, toxicity and biochemical relapse-free survival (b-RFS) for a group of organ confined (OC) Saudi prostate cancer patients treated by hypo-fractionated Volumetric Modulated Arc Radiation Therapy (VMAT) Simultaneous Integrated Boost (SIB) Elective Nodal Irradiation (ENI) whole pelvic radiotherapy (WPRT). Between March 2009 and January 2014, 29 OC prostate cancer patients; median age 64years, PS 0-1 were treated in King Faisal Specialist Hospital - Riyadh, Kingdom of Saudi Arabia using VMAT-SIB-ENI-WPRT, to a total dose of 70Gy in 28 fractions. Twenty Four patients (83%) were treated with neo-adjuvant; concurrent androgen deprivation therapy (ADT). Median follow-up (FU) was 42months (range: 18-72months). The 3-year actuarial b-RFS for low/intermediate and high risk groups were 100%, and 48%, respectively (p=0.09) with a median FU period of 34months (range: 14-53months). Gleason Score (p=0.02), and pretreatment PSA (p=0.01) were predictive for biochemical failure on univariate analysis; with no observed prostate cancer-related deaths. Grade 2 acute/late GI and GU toxicities were 28%/0% and 17%/10% respectively with no reported grade 3/4 toxicities. Four (50%) out of the 8 patients with baseline partial potency, retained sexual function on long term follow-up. Hypo-fractionation dose escalation VMAT-SIB-ENI-WPRT using 2 arcs is a feasible technique for intermediate/high risk OC prostate cancer patients, with acceptable rates of acute/late toxicities, much favorable planning target volume (PTV) coverage, and shorter overall treatment time. Prospective randomized controlled trials are encouraged to confirm its equivalence to other fractionation schemes. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved. JF - Journal of the Egyptian National Cancer Institute AU - Hegazy, Mohamed W AU - Mahmood, Rana I AU - Al Otaibi, Mohammed F AU - Khalil, Ehab M AD - Department of Radiation Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Department of Clinical Oncology & Nuclear Medicine, Zagazig Faculty of Medicine, Egypt. Electronic address: mhegazy@kfshrc.edu.sa. ; Department of Radiation Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. Electronic address: rmahmood99@kfshrc.edu.sa. ; Department of Urology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. Electronic address: otaibim@kfshrc.edu.sa. ; Department of Radiation Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Radiation Oncology & Nuclear Medicine Department, NCI, Cairo University, Egypt. Electronic address: ehab.khalil@nci.cu.edu.eg. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 101 EP - 110 VL - 28 IS - 2 SN - 1110-0362, 1110-0362 KW - Index Medicus KW - Hypo-fractionation KW - Prostate cancer KW - Radiotherapy KW - VMAT-intensity modulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789495965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+Egyptian+National+Cancer+Institute&rft.atitle=Hypofractionated+Volumetric+Modulated+Arc+Radiotherapy+with+simultaneous+Elective+Nodal+Irradiation+is+feasible+in+prostate+cancer+patients%3A+A+single+institution+experience.&rft.au=Hegazy%2C+Mohamed+W%3BMahmood%2C+Rana+I%3BAl+Otaibi%2C+Mohammed+F%3BKhalil%2C+Ehab+M&rft.aulast=Hegazy&rft.aufirst=Mohamed&rft.date=2016-06-01&rft.volume=28&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Egyptian+National+Cancer+Institute&rft.issn=11100362&rft_id=info:doi/10.1016%2Fj.jnci.2016.04.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jnci.2016.04.001 ER - TY - JOUR T1 - Patient Perceptions of Telephone vs. In-Person BRCA1/BRCA2 Genetic Counseling AN - 1789450993 AB - Telephone genetic counseling (TC) for hereditary breast/ovarian cancer risk has been associated with positive outcomes in high risk women. However, little is known about how patients perceive TC. As part of a randomized trial of TC versus usual care (UC; in-person genetic counseling), we compared high risk women's perceptions of: (1) overall satisfaction with genetic counseling; (2) convenience; (3) attentiveness during the session; (4) counselor effectiveness in providing support; and (5) counselor ability to recognize emotional responses during the session. Among the 554 participants (TC, N=272; UC, N=282), delivery mode was not associated with self-reported satisfaction. However, TC participants found counseling significantly more convenient than UC participants (OR=4.78, 95 % CI=3.32, 6.89) while also perceiving lower levels of support (OR=0.56, 95 % CI=0.40-0.80) and emotional recognition (OR=0.53, 95 % CI=0.37-0.76). In exploratory analyses, we found that non-Hispanic white participants reported higher counselor support in UC than in TC (69.4 % vs. 52.8 %; OR=3.06, 95 % CI=1.39-6.74), while minority women perceived less support in UC vs. TC (58.3 % vs. 38.7 %; OR=0.80, 95 % CI=0.39-1.65). We discuss potential research and practice implications of these findings which may further improve the effectiveness and utilization of TC. JF - Journal of Genetic Counseling AU - Peshkin, Beth N AU - Kelly, Scott AU - Nusbaum, Rachel H AU - Similuk, Morgan AU - Demarco, Tiffani A AU - Hooker, Gillian W AU - Valdimarsdottir, Heiddis B AU - Forman, Andrea D AU - Joines, Jessica Rispoli AU - Davis, Claire AU - Mccormick, Shelley R AU - Mckinnon, Wendy AU - Graves, Kristi D AU - Isaacs, Claudine AU - Garber, Judy AU - Wood, Marie AU - Jandorf, Lina AU - Schwartz, Marc D AD - Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research, Georgetown University, Washington, DC, USA ; Department of Epidemiology and Biostatistics, George Washington University, Washington, DC, USA ; GeneDx, Gaithersburg, MD, USA ; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA ; Cancer Genetic Counseling Program, Inova Translational Medicine Institute, Inova Health System, Falls Church, VA, USA ; NextGxDx, Inc, Franklin, TN, USA ; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychology, Reyjavik University, Reyjavik, Iceland ; Department of Clinical Genetics, Risk Assessment Program, Fox Chase Cancer Center, Philadelphia, PA, USA ; Department of Medicine, Division of Hematology/Oncology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center, Baltimore, MD, USA ; Joan H. Marks Graduate Program in Human Genetics, Sarah Lawrence College, Yonkers, NY, USA ; Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA ; Familial Cancer Program, University of Vermont Cancer Center, Burlington, VT, USA ; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 472 EP - 482 CY - New York PB - Springer Science & Business Media VL - 25 IS - 3 SN - 1059-7700 KW - Psychology KW - BRCA1/BRCA2 KW - Genetic counseling KW - Patient satisfaction KW - Telephone counseling KW - Breast cancer KW - Emotional responses KW - Genetic counselling KW - Ovarian cancer KW - Risk perception KW - Women UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789450993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Genetic+Counseling&rft.atitle=Patient+Perceptions+of+Telephone+vs.+In-Person+BRCA1%2FBRCA2+Genetic+Counseling&rft.au=Peshkin%2C+Beth+N%3BKelly%2C+Scott%3BNusbaum%2C+Rachel+H%3BSimiluk%2C+Morgan%3BDemarco%2C+Tiffani+A%3BHooker%2C+Gillian+W%3BValdimarsdottir%2C+Heiddis+B%3BForman%2C+Andrea+D%3BJoines%2C+Jessica+Rispoli%3BDavis%2C+Claire%3BMccormick%2C+Shelley+R%3BMckinnon%2C+Wendy%3BGraves%2C+Kristi+D%3BIsaacs%2C+Claudine%3BGarber%2C+Judy%3BWood%2C+Marie%3BJandorf%2C+Lina%3BSchwartz%2C+Marc+D&rft.aulast=Peshkin&rft.aufirst=Beth&rft.date=2016-06-01&rft.volume=25&rft.issue=3&rft.spage=472&rft.isbn=&rft.btitle=&rft.title=Journal+of+Genetic+Counseling&rft.issn=10597700&rft_id=info:doi/10.1007%2Fs10897-015-9897-6 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - National Society of Genetic Counselors, Inc. 2016 N1 - Last updated - 2016-05-19 DO - http://dx.doi.org/10.1007/s10897-015-9897-6 ER - TY - JOUR T1 - Easing the Burden: Describing the Role of Social, Emotional and Spiritual Support in Research Families with Li-Fraumeni Syndrome AN - 1789449869 AB - This study presents findings of a mixed-method descriptive exploration of the role of friends and spirituality/religiosity in easing the burden of families with the rare inherited disorder, Li-Fraumeni Syndrome (LFS). LFS is caused by germline mutations in the TP53 gene and is associated with very high lifetime risk of developing one or more malignancies. During the first clinical visit we assessed several types of social support among a subset of study participants (N = 66) using an established interactive research tool called the Colored Eco-Genetic Relationship Map (CEGRM). We performed both quantitative and qualitative analyses of social relationships with LFS family members and close non-kin. Distress scores (N = 59) were mostly low normal, with some outliers. We found that reported friendships varied widely, that the friendships were often deep and enduring, and were important sources of informational, tangible, emotional and spiritual support. Confidantes tended to be best friends and/or spouses. Organized religion was important in selected families, typically from mainstream traditions. However, a number of people identified themselves as "spiritual" and reported spiritual and humanist explorations. Our results shed preliminary light on how some people in families with LFS cope in the face of tremendous medical, social and emotional challenges. JF - Journal of Genetic Counseling AU - Peters, June A AU - Kenen, Regina AU - Bremer, Renee AU - Givens, Shannon AU - Savage, Sharon A AU - Mai, Phuong L AD - Clinical Genetics Branch (CGB), Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), NIH, DHHS, Rockville, MD, USA ; Department of Sociology and Anthropology, The College of New Jersey, Ewing, NJ, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 529 EP - 542 CY - New York PB - Springer Science & Business Media VL - 25 IS - 3 SN - 1059-7700 KW - Psychology KW - Li-fraumeni syndrome (LFS) KW - TP53 germline mutation KW - Hereditary cancer susceptibility KW - Genetic counseling KW - Genetic testing KW - Social support KW - Psychosocial KW - Psychosocial adaptation KW - Resilience KW - Qualitative research KW - Cegrm KW - Religious KW - Spiritual KW - Burden KW - Friendships KW - Psychological distress KW - Relatives KW - Religiosity KW - Social relationships KW - Spirituality KW - Spouses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789449869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Genetic+Counseling&rft.atitle=Easing+the+Burden%3A+Describing+the+Role+of+Social%2C+Emotional+and+Spiritual+Support+in+Research+Families+with+Li-Fraumeni+Syndrome&rft.au=Peters%2C+June+A%3BKenen%2C+Regina%3BBremer%2C+Renee%3BGivens%2C+Shannon%3BSavage%2C+Sharon+A%3BMai%2C+Phuong+L&rft.aulast=Peters&rft.aufirst=June&rft.date=2016-06-01&rft.volume=25&rft.issue=3&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=Journal+of+Genetic+Counseling&rft.issn=10597700&rft_id=info:doi/10.1007%2Fs10897-015-9905-x LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - National Society of Genetic Counselors, Inc. 2016 N1 - Last updated - 2016-05-19 DO - http://dx.doi.org/10.1007/s10897-015-9905-x ER - TY - JOUR T1 - Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion. AN - 1789048998; 26269650 AB - An imbalance of neuroactive kynurenine pathway metabolites has been proposed as one mechanism behind the neuropsychiatric sequelae of certain neurological disorders. We hypothesized that concussed football players would have elevated plasma levels of neurotoxic kynurenine metabolites and reduced levels of neuroprotective metabolites relative to healthy football players and that altered kynurenine levels would correlate with post-concussion mood symptoms. Mood scales and plasma concentrations of kynurenine metabolites were assessed in concussed (N=18; 1.61 days post-injury) and healthy football players (N=18). A subset of football players returned at 1-week (N=14; 9.29 days) and 1-month post-concussion (N=14, 30.93 days). Concussed athletes had significantly elevated levels of quinolinic acid (QUIN) and significantly lower ratios of kynurenic acid (KYNA) to QUIN at all time points compared with healthy athletes (p's<0.05), with no longitudinal evidence of normalization of KYNA or KYNA/QUIN. At 1-day post-injury, concussed athletes with lower levels of the putatively neuroprotective KYNA/QUIN ratio reported significantly worse depressive symptoms (p=0.04), and a trend toward worse anxiety symptoms (p=0.06), while at 1-month higher QUIN levels were associated with worse mood symptoms (p's<0.01). Finally, concussed athletes with worse concussion outcome, defined as number of days until return-to-play, had higher QUIN and lower KYNA/QUIN at 1-month post-injury (p's<0.05). These results converge with existing kynurenine literature on psychiatric patients and provide the first evidence of altered peripheral levels of kynurenine metabolites following sports-related concussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ JF - Journal of neurology, neurosurgery, and psychiatry AU - Singh, Rashmi AU - Savitz, Jonathan AU - Teague, T Kent AU - Polanski, David W AU - Mayer, Andrew R AU - Bellgowan, Patrick S F AU - Meier, Timothy B AD - Laureate Institute for Brain Research, Tulsa, Oklahoma, USA. ; Laureate Institute for Brain Research, Tulsa, Oklahoma, USA Faculty of Community Medicine, The University of Tulsa, Tulsa, Oklahoma, USA. ; Departments of Surgery and Psychiatry, University of Oklahoma College of Medicine, Tulsa, Oklahoma, USA Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, Oklahoma, USA Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, USA. ; Department of Athletics, The University of Tulsa, Tulsa, Oklahoma, USA. ; The Mind Research Network/Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA Neurology Department, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA. ; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. ; Laureate Institute for Brain Research, Tulsa, Oklahoma, USA The Mind Research Network/Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 670 EP - 675 VL - 87 IS - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789048998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurology%2C+neurosurgery%2C+and+psychiatry&rft.atitle=Mood+symptoms+correlate+with+kynurenine+pathway+metabolites+following+sports-related+concussion.&rft.au=Singh%2C+Rashmi%3BSavitz%2C+Jonathan%3BTeague%2C+T+Kent%3BPolanski%2C+David+W%3BMayer%2C+Andrew+R%3BBellgowan%2C+Patrick+S+F%3BMeier%2C+Timothy+B&rft.aulast=Singh&rft.aufirst=Rashmi&rft.date=2016-06-01&rft.volume=87&rft.issue=6&rft.spage=670&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurology%2C+neurosurgery%2C+and+psychiatry&rft.issn=1468-330X&rft_id=info:doi/10.1136%2Fjnnp-2015-311369 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/jnnp-2015-311369 ER - TY - JOUR T1 - Rice endosperm is cost-effective for the production of recombinant griffithsin with potent activity against HIV. AN - 1789038848; 26800650 AB - Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV-endemic regions such as sub-Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS) GRFT in the best-performing plants was 223 μg/g dry seed weight. We also established a one-step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger-scale process to facilitate inexpensive downstream processing. (OS) GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole-cell assays using purified (OS) GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS) GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom-to-operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. JF - Plant biotechnology journal AU - Vamvaka, Evangelia AU - Arcalis, Elsa AU - Ramessar, Koreen AU - Evans, Abbey AU - O'Keefe, Barry R AU - Shattock, Robin J AU - Medina, Vicente AU - Stöger, Eva AU - Christou, Paul AU - Capell, Teresa AD - Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida-Agrotecnio Center, Lleida, Spain. ; Department for Applied Genetics and Cell Biology, Molecular Plant Physiology and Crop Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria. ; Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD, USA. ; Department of Medicine, Imperial College London, Norfolk Place, London, UK. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1427 EP - 1437 VL - 14 IS - 6 KW - Index Medicus KW - griffithsin KW - rice KW - endosperm KW - lectin KW - HIV KW - microbicides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789038848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Plant+biotechnology+journal&rft.atitle=Rice+endosperm+is+cost-effective+for+the+production+of+recombinant+griffithsin+with+potent+activity+against+HIV.&rft.au=Vamvaka%2C+Evangelia%3BArcalis%2C+Elsa%3BRamessar%2C+Koreen%3BEvans%2C+Abbey%3BO%27Keefe%2C+Barry+R%3BShattock%2C+Robin+J%3BMedina%2C+Vicente%3BSt%C3%B6ger%2C+Eva%3BChristou%2C+Paul%3BCapell%2C+Teresa&rft.aulast=Vamvaka&rft.aufirst=Evangelia&rft.date=2016-06-01&rft.volume=14&rft.issue=6&rft.spage=1427&rft.isbn=&rft.btitle=&rft.title=Plant+biotechnology+journal&rft.issn=1467-7652&rft_id=info:doi/10.1111%2Fpbi.12507 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-12 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - CAA39776; GENBANK N1 - SuppNotes - Cited By: Best Pract Res Clin Obstet Gynaecol. 2012 Aug;26(4):427-39 [22386823] Science. 2012 Jul 20;337(6092):298-300 [22798404] Biotechnol Adv. 2012 Nov-Dec;30(6):1614-26 [22750509] Arch Virol. 2013 Feb;158(2):349-58 [23053519] J Biotechnol. 2012 Dec 15;164(2):300-8 [23376844] J Virol. 2013 Jun;87(11):6257-69 [23536670] PLoS One. 2013;8(5):e64449 [23700478] Antimicrob Agents Chemother. 2013 Aug;57(8):3976-89 [23752505] Curr Pharm Des. 2013;19(31):5543-52 [23394568] Biotechnol J. 2013 Oct;8(10):1203-12 [23960004] Plant Biotechnol J. 2014 Feb;12(2):117-34 [24460888] Plant Cell Rep. 2014 Apr;33(4):585-94 [24413763] BMC Biotechnol. 2015;15:12 [25887919] Plant Biotechnol J. 2015 Sep;13(7):884-92 [25572960] Plant Biotechnol J. 2016 Jan;14(1):97-108 [25845722] Biotechnol J. 2016 Mar;11(4):507-18 [26632519] Proteins. 2007 May 15;67(3):661-70 [17340634] Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905 [12019106] AIDS. 2002 Jul 5;16(10):1351-6 [12131211] Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8401-6 [12815099] J Virol Methods. 1991 Jun;33(1-2):87-100 [1719015] J Virol. 1995 Jun;69(6):3712-20 [7745720] Biochim Biophys Acta. 1963 Nov 8;77:383-93 [14089413] Plant Physiol. 2004 Nov;136(3):3457-66 [15489278] J Biol Chem. 2005 Mar 11;280(10):9345-53 [15613479] Lancet Infect Dis. 2005 Nov;5(11):726-31 [16253890] Sex Transm Dis. 2005 Dec;32(12):765-70 [16314774] AIDS Res Hum Retroviruses. 2006 Mar;22(3):294-6 [16545017] Protein Expr Purif. 2006 May;47(1):194-202 [16300962] Antimicrob Agents Chemother. 2006 May;50(5):1696-700 [16641437] AIDS. 2006 May 12;20(8):1109-16 [16691061] Plant Physiol. 2006 Jun;141(2):578-86 [16632592] Structure. 2006 Jul;14(7):1127-35 [16843894] Biologicals. 2006 Dec;34(4):241-55 [17097303] Protein Sci. 2007 Jul;16(7):1485-9 [17567736] J Virol. 2007 Jul;81(14):7636-46 [17494078] J Med Primatol. 2007 Aug;36(4-5):244-53 [17669213] Plant Biotechnol J. 2008 Feb;6(2):189-201 [17979949] Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3727-32 [18316741] J Virol. 2008 Jul;82(13):6576-84 [18434407] Biotechnol Lett. 2008 Sep;30(9):1679-86 [18425430] Peptides. 2008 Nov;29(11):1862-70 [18708105] Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6099-104 [19332801] Proc Natl Acad Sci U S A. 2009 May 12;106(19):7762-7 [19416835] J Virol. 2009 Aug;83(16):8289-92 [19474095] J Virol. 2010 Mar;84(5):2511-21 [20032190] Curr Pharm Des. 2010;16(4):468-85 [19900164] Virology. 2010 Jun 20;402(1):187-96 [20392471] Structure. 2010 Sep 8;18(9):1104-15 [20826337] J Immunol. 2010 Dec 1;185(11):6876-82 [21041724] Annu Rev Med. 2011;62:127-39 [21054171] Biotechnol Adv. 2011 Mar-Apr;29(2):210-22 [21115109] Hum Vaccin. 2011 Mar;7(3):367-74 [21346415] PLoS One. 2011;6(8):e22635 [21829638] Antimicrob Agents Chemother. 2011 Nov;55(11):5159-67 [21896910] Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19078-83 [22042856] Plant Biotechnol J. 2012 Jan;10(1):20-30 [21627759] Cold Spring Harb Perspect Med. 2012 Feb;2(2):a007385 [22355798] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/pbi.12507 ER - TY - JOUR T1 - Cyanovirin-N produced in rice endosperm offers effective pre-exposure prophylaxis against HIV-1BaL infection in vitro. AN - 1789037423; 27007716 AB - Cyanovirin-N produced in rice endosperm provides efficient pre-exposure prophylaxis against HIV-1 BaL infection in vitro. Cyanovirin-N (CV-N) is a lectin with potent antiviral activity that has been proposed as a component of microbicides for the prevention of infection with Human immunodeficiency virus (HIV). The production of protein-based microbicide components requires a platform that is sufficiently economical and scalable to meet the demands of the large at-risk population, particularly in resource poor developing countries. We, therefore, expressed CV-N in rice endosperm, because the dried seed is ideal for storage and transport and crude extracts could be prepared locally and used as a microbicide component without further purification. We found that crude extracts from rice seeds expressing up to 10 µg CV-N per gram dry seed weight showed dose-dependent gp120 binding activity, confirming that the protein was soluble, correctly folded and active. The recombinant lectin ((OS)CV-N) reduced the infectivity of HIV-1BaL (an R5 virus strain representing the majority of transmitted infections) by ~90 % but showed only weak neutralization activity against HIV-1RF (representative of X4 virus, rarely associated with transmission), suggesting it would be highly effective for pre-exposure prophylaxis against the vast majority of transmitted strains. Crude extracts expressing (OS)CV-N showed no toxicity towards human cells at working dilutions indicating that microbicide components produced in rice endosperm are safe for direct application as topical microbicides in humans. JF - Plant cell reports AU - Vamvaka, E AU - Evans, A AU - Ramessar, K AU - Krumpe, L R H AU - Shattock, R J AU - O'Keefe, B R AU - Christou, P AU - Capell, T AD - Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida-Agrotecnio Center, Lleida, Spain. ; Department of Medicine, Imperial College London, Norfolk Place, London, UK. ; Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD, USA. ; Department of Plant Production and Forestry Science, School of Agrifood and Forestry Science and Engineering (ETSEA), University of Lleida-Agrotecnio Center, Lleida, Spain. teresa.capell@pvcf.udl.cat. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1309 EP - 1319 VL - 35 IS - 6 KW - Index Medicus KW - Endosperm KW - Cyanovirin-N KW - Microbicide KW - Anti-HIV KW - Rice crude extract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789037423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Plant+cell+reports&rft.atitle=Cyanovirin-N+produced+in+rice+endosperm+offers+effective+pre-exposure+prophylaxis+against+HIV-1BaL+infection+in+vitro.&rft.au=Vamvaka%2C+E%3BEvans%2C+A%3BRamessar%2C+K%3BKrumpe%2C+L+R+H%3BShattock%2C+R+J%3BO%27Keefe%2C+B+R%3BChristou%2C+P%3BCapell%2C+T&rft.aulast=Vamvaka&rft.aufirst=E&rft.date=2016-06-01&rft.volume=35&rft.issue=6&rft.spage=1309&rft.isbn=&rft.btitle=&rft.title=Plant+cell+reports&rft.issn=1432-203X&rft_id=info:doi/10.1007%2Fs00299-016-1963-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-12 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00299-016-1963-5 ER - TY - JOUR T1 - Mitochondrial permeabilization without caspase activation mediates the increase of basal apoptosis in cells lacking Nrf2. AN - 1789036311; 27016073 AB - Nuclear factor E2-related factor-2 (Nrf2) is a cap'n'collar/basic leucine zipper (b-ZIP) transcription factor which acts as sensor of oxidative and electrophilic stress. Low levels of Nrf2 predispose cells to chemical carcinogenesis but a dark side of Nrf2 function also exists because its unrestrained activation may allow the survival of potentially dangerous damaged cells. Since Nrf2 inhibition may be of therapeutic interest in cancer, and a decrease of Nrf2 activity may be related with degenerative changes associated with aging, it is important to investigate how the lack of Nrf2 function activates molecular mechanisms mediating cell death. Murine Embryonic Fibroblasts (MEFs) bearing a Nrf2 deletion (Nrf2KO) displayed diminished cellular growth rate and shortened lifespan compared with wild-type MEFs. Basal rates of DNA fragmentation and histone H2A.X phosphorylation were higher in Nrf2KO MEFs, although steady-state levels of reactive oxygen species were not significantly increased. Enhanced rates of apoptotic DNA fragmentation were confirmed in liver and lung tissues from Nrf2KO mice. Apoptosis in Nrf2KO MEFs was associated with a decrease of Bcl-2 but not Bax levels, and with the release of the mitochondrial pro-apoptotic factors cytochrome c and AIF. Procaspase-9 and Apaf-1 were also increased in Nrf2KO MEFs but caspase-3 was not activated. Inhibition of XIAP increased death in Nrf2KO but not in wild-type MEFs. Mitochondrial ultrastructure was also altered in Nrf2KO MEFs. Our results support that Nrf2 deletion produces mitochondrial dysfunction associated with mitochondrial permeabilization, increasing basal apoptosis through a caspase-independent and AIF-dependent pathway. Published by Elsevier Inc. JF - Free radical biology & medicine AU - Ariza, Julia AU - González-Reyes, José A AU - Jódar, Laura AU - Díaz-Ruiz, Alberto AU - de Cabo, Rafael AU - Villalba, José Manuel AD - Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Spain. ; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 82 EP - 95 VL - 95 KW - Index Medicus KW - Apoptosis KW - Caspase KW - NRF2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789036311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Mitochondrial+permeabilization+without+caspase+activation+mediates+the+increase+of+basal+apoptosis+in+cells+lacking+Nrf2.&rft.au=Ariza%2C+Julia%3BGonz%C3%A1lez-Reyes%2C+Jos%C3%A9+A%3BJ%C3%B3dar%2C+Laura%3BD%C3%ADaz-Ruiz%2C+Alberto%3Bde+Cabo%2C+Rafael%3BVillalba%2C+Jos%C3%A9+Manuel&rft.aulast=Ariza&rft.aufirst=Julia&rft.date=2016-06-01&rft.volume=95&rft.issue=&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=1873-4596&rft_id=info:doi/10.1016%2Fj.freeradbiomed.2016.03.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.015 ER - TY - JOUR T1 - N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice. AN - 1789032543; 26821200 AB - Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute overexposures. The risk of hepatotoxicity from nonacute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for nonacute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and subacute paracetamol overexposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33 g/kg food) or control diet for 6 weeks. Mice were then dosed orally eight times over 3 days with additional paracetamol (250 mg/kg) or saline, followed by either one or two doses of oral NAC (1200 mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Subacute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from subacute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for subacute paracetamol toxicity. © 2016 Société Française de Pharmacologie et de Thérapeutique. JF - Fundamental & clinical pharmacology AU - Kane, Alice Elizabeth AU - Huizer-Pajkos, Aniko AU - Mach, John AU - McKenzie, Catriona AU - Mitchell, Sarah Jayne AU - de Cabo, Rafael AU - Jones, Brett AU - Cogger, Victoria AU - Le Couteur, David G AU - Hilmer, Sarah Nicole AD - Kolling Institute of Medical Research, Reserve Rd, St Leonards, NSW, Australia. ; Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia. ; National Institute on Aging, National Institutes of Health, Nathan Shock Dr, Baltimore, MD, USA. ; Sydney Medical School, University of Sydney, Camperdown, NSW, Australia. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 263 EP - 275 VL - 30 IS - 3 KW - Index Medicus KW - paracetamol KW - supratherapeutic KW - chronic KW - N-acetyl cysteine KW - ageing KW - hepatotoxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789032543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+%26+clinical+pharmacology&rft.atitle=N-Acetyl+cysteine+does+not+prevent+liver+toxicity+from+chronic+low-dose+plus+subacute+high-dose+paracetamol+exposure+in+young+or+old+mice.&rft.au=Kane%2C+Alice+Elizabeth%3BHuizer-Pajkos%2C+Aniko%3BMach%2C+John%3BMcKenzie%2C+Catriona%3BMitchell%2C+Sarah+Jayne%3Bde+Cabo%2C+Rafael%3BJones%2C+Brett%3BCogger%2C+Victoria%3BLe+Couteur%2C+David+G%3BHilmer%2C+Sarah+Nicole&rft.aulast=Kane&rft.aufirst=Alice&rft.date=2016-06-01&rft.volume=30&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Fundamental+%26+clinical+pharmacology&rft.issn=1472-8206&rft_id=info:doi/10.1111%2Ffcp.12184 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-12 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Australas J Ageing. 2012 Sep;31(3):190-3 [22950592] Clin Toxicol (Phila). 2012 Feb;50(2):91-8 [22320209] Toxicol Appl Pharmacol. 2012 Nov 1;264(3):387-94 [22980195] JPEN J Parenter Enteral Nutr. 2013 Mar;37(2):268-73 [22714592] Hepatology. 2013 Aug;58(2):777-87 [23390034] J Gerontol A Biol Sci Med Sci. 2014 Apr;69(4):387-97 [23863315] Microvasc Res. 2014 Jul;94:36-46 [24819686] Hepatology. 2014 Sep;60(3):1023-34 [24923719] Exp Gerontol. 2015 Jul;67:54-61 [25910621] Br J Clin Pharmacol. 2015 Jul;80(1):45-50 [26099917] AAPS J. 2006;8(1):E48-54 [16584133] Hepatology. 1999 Feb;29(2):451-63 [9918922] Fundam Clin Pharmacol. 2016 Feb;30(1):23-34 [26454000] JAMA. 2006 Jul 5;296(1):87-93 [16820551] Clin Liver Dis. 2007 Aug;11(3):525-48, vi [17723918] Med J Aust. 2008 Mar 3;188(5):296-301 [18312195] JAMA. 2008 Dec 24;300(24):2867-78 [19109115] Biochem Pharmacol. 2009 May 15;77(10):1621-8 [19426699] J Pharmacol Sci. 2009 Oct;111(2):175-81 [19834287] Br J Clin Pharmacol. 2011 Feb;71(2):273-82 [21219409] Fundam Clin Pharmacol. 2011 Jun;25(3):405-10 [20584210] BMJ. 2011;342:d2218 [21508044] Hum Exp Toxicol. 2000 May;19(5):277-83 [10918522] J Emerg Med. 2002 Oct;23(3):253-6 [12426016] Toxicol Sci. 2003 Oct;75(2):458-67 [12883092] J Pharmacol Exp Ther. 1973 Oct;187(1):211-7 [4746329] J Pharmacol Exp Ther. 1985 Mar;232(3):864-72 [3973835] Drug Chem Toxicol. 1988;11(3):237-47 [3181038] Biochem Biophys Res Commun. 1994 Aug 30;203(1):532-9 [8074700] Biochem Pharmacol. 1995 May 26;49(11):1665-73 [7786308] Fundam Appl Toxicol. 1996 Mar;30(1):13-22 [8812206] J Toxicol Sci. 2012;37(5):911-29 [23038001] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/fcp.12184 ER - TY - JOUR T1 - Venues for Meeting Sex Partners and Partner HIV Risk Characteristics: HIV Prevention Trials Network (HPTN064) Women's HIV Seroincidence Study (ISIS) AN - 1788992163 AB - Identifying venues where women meet sexual partners, particular partners who increase women's risk of acquiring HIV, could inform prevention efforts. We categorized venues where women enrolled in HPTN 064 reported meeting their last three sex partners as: (1) Formal, (2) Public, (3) Private, and (4) Virtual spaces. We used multinomial logistic regression to assess the association between these venues and women's individual characteristics and reports of their partners' HIV risk characteristics. The 2099 women reported meeting 3991 partners, 51 % at Public, 30 % Private, 17 % Formal and 3 % at Virtual venues. Women meeting partners at Formal venues reported more education and condom use than women meeting partners at other venues. Fewer partners met through Formal venues had "high" risk characteristics for HIV than through other venues and hence may pose less risk of HIV transmission. HIV prevention interventions can help women choose partners with fewer risk characteristics across all venue types. JF - AIDS and Behavior AU - Roman Isler, M AU - Golin, C AU - Wang, J AU - Hughes, J AU - Justman, J AU - Haley, D AU - Kuo, I AU - Adimora, A AU - Chege, W AU - Hodder, S AD - Department of Social Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA ; Department of Health Behavior, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA ; Fred Hutchinson Cancer Research Center, Statistical Center for HIV/AIDS Research & Prevention (SCHARP), Seattle, WA, USA ; Department of Biostatistics, University of Washington, Seattle, WA, USA ; Department of Epidemiology and Medicine, Columbia University, New York, NY, USA ; FHI360, Durham, NC, USA; Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University, Atlanta, GA, USA ; Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health, Washington, DC, USA ; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA ; Prevention Sciences Program, DAIDS, NIAID, National Institutes of Health, Bethesda, MD, USA ; New Jersey Medical School, Rutgers University, Newark, NJ, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 1208 EP - 1218 CY - New York PB - Springer Science & Business Media VL - 20 IS - 6 SN - 1090-7165 KW - Psychology KW - HIV KW - Women KW - Venue KW - Sexual risk behavior KW - Sexual partners KW - Acquired Immune Deficiency Syndrome KW - Females KW - Sexual Behavior KW - Prevention KW - Risk KW - Trials KW - 6126:acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1788992163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=Venues+for+Meeting+Sex+Partners+and+Partner+HIV+Risk+Characteristics%3A+HIV+Prevention+Trials+Network+%28HPTN064%29+Women%27s+HIV+Seroincidence+Study+%28ISIS%29&rft.au=Roman+Isler%2C+M%3BGolin%2C+C%3BWang%2C+J%3BHughes%2C+J%3BJustman%2C+J%3BHaley%2C+D%3BKuo%2C+I%3BAdimora%2C+A%3BChege%2C+W%3BHodder%2C+S&rft.aulast=Roman+Isler&rft.aufirst=M&rft.date=2016-06-01&rft.volume=20&rft.issue=6&rft.spage=1208&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-015-1057-3 LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-16 DO - http://dx.doi.org/10.1007/s10461-015-1057-3 ER - TY - JOUR T1 - Mediation Analysis of the Efficacy of the Eban HIV/STD Risk-Reduction Intervention for African American HIV Serodiscordant Couples AN - 1788992146 AB - Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled trial conducted in four US cities, 535 African American HIV-serodiscordant couples were randomized to the Eban HIV risk-reduction intervention or attention-matched control intervention. Outcomes were proportion condom-protected sex, consistent condom use, and frequency of unprotected sex measured pre-, immediately post-, and 6 and 12 months post-intervention. Potential mediators included Social-Cognitive-Theory variables: outcome expectancies and self-efficacy. Mediation analyses using the product-of-coefficients approach in a generalized-estimating-equations framework revealed that condom-use outcome expectancy, partner-reaction outcome expectancy, intention, self-efficacy, and safer-sex communication improved post-intervention and mediated intervention-induced improvements in condom-use outcomes. These findings underscore the importance of targeting outcome expectancies, self-efficacy, and safer-sex communication in couples-level HIV risk-reduction interventions. JF - AIDS and Behavior AU - El-bassel, Nabila AU - Jemmott, John B, III AU - Bellamy, Scarlett L AU - Pequegnat, Willo AU - Wingood, Gina M AU - Wyatt, Gail E AU - Richard Landis, J AU - Remien, Robert H AD - Social Intervention Group, School of Social Work, Columbia University, New York, NY, USA ; Annenberg School for Communication and Department of Psychiatry, Perelman School of Medicine, Center for Health Behavior and Communication Research, University of Pennsylvania, Philadelphia, PA, USA ; Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA ; National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA ; Department of Behavioral Sciences and Health Education, Rollins School of Public Health, Emory University, Atlanta, GA, USA ; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA, USA ; Center for Clinical and Behavioral Studies, Department of Psychiatry, Columbia University, New York, NY, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 1197 EP - 1207 CY - New York PB - Springer Science & Business Media VL - 20 IS - 6 SN - 1090-7165 KW - Psychology KW - HIV serodiscordant couples KW - Intervention KW - Social Cognitive Theory KW - Mediation analysis KW - Condom use KW - Cognition KW - Acquired Immune Deficiency Syndrome KW - Black Americans KW - Cities KW - Communication KW - Couples KW - Empowerment KW - Venereal Diseases KW - Risk KW - United States--US KW - 6126:acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1788992146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+and+Behavior&rft.atitle=Mediation+Analysis+of+the+Efficacy+of+the+Eban+HIV%2FSTD+Risk-Reduction+Intervention+for+African+American+HIV+Serodiscordant+Couples&rft.au=El-bassel%2C+Nabila%3BJemmott%2C+John+B%2C+III%3BBellamy%2C+Scarlett+L%3BPequegnat%2C+Willo%3BWingood%2C+Gina+M%3BWyatt%2C+Gail+E%3BRichard+Landis%2C+J%3BRemien%2C+Robert+H&rft.aulast=El-bassel&rft.aufirst=Nabila&rft.date=2016-06-01&rft.volume=20&rft.issue=6&rft.spage=1197&rft.isbn=&rft.btitle=&rft.title=AIDS+and+Behavior&rft.issn=10907165&rft_id=info:doi/10.1007%2Fs10461-015-1249-x LA - English DB - Social Services Abstracts N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-08-16 N1 - SubjectsTermNotLitGenreText - United States--US DO - http://dx.doi.org/10.1007/s10461-015-1249-x ER - TY - JOUR T1 - Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice. AN - 1785738986; 27058323 AB - The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30thweeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30thweek. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Toxicology and applied pharmacology AU - Sur, Subhayan AU - Pal, Debolina AU - Roy, Rituparna AU - Barua, Atish AU - Roy, Anup AU - Saha, Prosenjit AU - Panda, Chinmay Kumar AD - Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India. Electronic address: subhayansur18@gmail.com. ; Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India. ; North Bengal Medical College and Hospital, West Bengal, India. ; Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India. Electronic address: ckpanda.cnci@gmail.com. Y1 - 2016/06/01/ PY - 2016 DA - 2016 Jun 01 SP - 34 EP - 46 VL - 300 KW - Index Medicus KW - β-catenin KW - TF KW - Tongue carcinogenesis KW - Liver carcinogenesis KW - EGCG KW - Gli1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785738986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Tea+polyphenols+EGCG+and+TF+restrict+tongue+and+liver+carcinogenesis+simultaneously+induced+by+N-nitrosodiethylamine+in+mice.&rft.au=Sur%2C+Subhayan%3BPal%2C+Debolina%3BRoy%2C+Rituparna%3BBarua%2C+Atish%3BRoy%2C+Anup%3BSaha%2C+Prosenjit%3BPanda%2C+Chinmay+Kumar&rft.aulast=Sur&rft.aufirst=Subhayan&rft.date=2016-06-01&rft.volume=300&rft.issue=&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.03.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.03.016 ER - TY - JOUR T1 - Depressed Adolescents' Pupillary Response to Peer Acceptance and Rejection: The Role of Rumination AN - 1785729489 AB - Heightened emotional reactivity to peer feedback is predictive of adolescents' depression risk. Examining variation in emotional reactivity within currently depressed adolescents may identify subgroups that struggle the most with these daily interactions. We tested whether trait rumination, which amplifies emotional reactions, explained variance in depressed adolescents' physiological reactivity to peer feedback, hypothesizing that rumination would be associated with greater pupillary response to peer rejection and diminished response to peer acceptance. Twenty currently depressed adolescents (12-17) completed a virtual peer interaction paradigm where they received fictitious rejection and acceptance feedback. Pupillary response provided a time-sensitive index of physiological arousal. Rumination was associated with greater initial pupil dilation to both peer rejection and acceptance, and diminished late pupillary response to peer acceptance trials only. Results indicate that depressed adolescents high on trait rumination are more reactive to social feedback regardless of valence, but fail to sustain cognitive-affective load on positive feedback. JF - Child Psychiatry and Human Development AU - Stone, Lindsey B AU - Silk, Jennifer S AU - Siegle, Greg J AU - Lee, Kyung Hwa AU - Stroud, Laura R AU - Nelson, Eric E AU - Dahl, Ronald E AU - Jones, Neil P AD - Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA ; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA ; Department of Psychiatry and Human Behavior, Brown Medical School, Providence, RI, USA ; Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD, USA ; School of Public Health, University of California, Berkeley, Berkeley, CA, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 397 EP - 406 CY - New York PB - Springer Science & Business Media VL - 47 IS - 3 SN - 0009-398X KW - Medical Sciences--Pediatrics KW - Peer relationships KW - Depression KW - Adolescence KW - Emotional reactivity KW - Pupil KW - Acceptance KW - Adolescents KW - Emotional responses KW - Feedback KW - Fictitious KW - Peer acceptance KW - Peer rejection KW - Peer reviews KW - Physiological arousal KW - Physiological reactivity KW - Positive feedback KW - Reactivity KW - Rumination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785729489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Psychiatry+and+Human+Development&rft.atitle=Depressed+Adolescents%27+Pupillary+Response+to+Peer+Acceptance+and+Rejection%3A+The+Role+of+Rumination&rft.au=Stone%2C+Lindsey+B%3BSilk%2C+Jennifer+S%3BSiegle%2C+Greg+J%3BLee%2C+Kyung+Hwa%3BStroud%2C+Laura+R%3BNelson%2C+Eric+E%3BDahl%2C+Ronald+E%3BJones%2C+Neil+P&rft.aulast=Stone&rft.aufirst=Lindsey&rft.date=2016-06-01&rft.volume=47&rft.issue=3&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Child+Psychiatry+and+Human+Development&rft.issn=0009398X&rft_id=info:doi/10.1007%2Fs10578-015-0574-7 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer Science+Business Media New York 2016 N1 - Last updated - 2016-05-19 DO - http://dx.doi.org/10.1007/s10578-015-0574-7 ER - TY - JOUR T1 - Human βA3/A1-crystallin splicing mutation causes cataracts by activating the unfolded protein response and inducing apoptosis in differentiating lens fiber cells. AN - 1784748843; 26851658 AB - βγ-Crystallins, having a uniquely stable two domain four Greek key structure, are crucial for transparency of the eye lens,. Mutations in lens crystallins have been proposed to cause cataract formation by a variety of mechanisms most of which involve destabilization of the protein fold. The underlying molecular mechanism for autosomal dominant zonular cataracts with sutural opacities in an Indian family caused by a c.215+1G>A splice mutation in the βA3/A1-crystallin gene CRYBA1 was elucidated using three transgenic mice models. This mutation causes a splice defect in which the mutant mRNA escapes nonsense mediated decay by skipping both exons 3 and 4. Skipping these exons results in an in-frame deletion of the mRNA and synthesis of an unstable p.Ile33_Ala119del mutant βA3/A1-crystallin protein. Transgenic expression of mutant βA3/A1-crystallin but not the wild type protein results in toxicity and abnormalities in the maturation and orientation of differentiating lens fibers in c.97_357del CRYBA1 transgenic mice, leading to a small spherical lens, cataract, and often lens capsule rupture. On a cellular level, the lenses accumulated p.Ile33_Ala119del βA3/A1-crystallin with resultant activation of the stress signaling pathway - unfolded protein response (UPR) and inhibition of normal protein synthesis, culminating in apoptosis. This highlights the mechanistic contrast between mild mutations that destabilize crystallins and other proteins, resulting in their being bound by the α-crystallins that buffer lens cells against damage by denatured proteins, and severely misfolded proteins that are not bound by α-crystallin but accumulate and have a direct toxic effect on lens cells, resulting in early onset cataracts. Published by Elsevier B.V. JF - Biochimica et biophysica acta AU - Ma, Zhiwei AU - Yao, Wenliang AU - Chan, Chi-Chao AU - Kannabiran, Chitra AU - Wawrousek, Eric AU - Hejtmancik, J Fielding AD - Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. ; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA; Medimmune, Gaithersburg, MD, USA. ; Histology Core, National Eye Institute, NIH, USA. ; Laboratory of Molecular and Developmental Biology, National Eye Institute, NIH, USA. ; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: f3h@helix.nih.gov. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1214 EP - 1227 VL - 1862 IS - 6 SN - 0006-3002, 0006-3002 KW - Index Medicus KW - Apoptosis KW - Crystallin gene KW - Cataract KW - Unfolded protein response KW - Splice mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1784748843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Human+%CE%B2A3%2FA1-crystallin+splicing+mutation+causes+cataracts+by+activating+the+unfolded+protein+response+and+inducing+apoptosis+in+differentiating+lens+fiber+cells.&rft.au=Ma%2C+Zhiwei%3BYao%2C+Wenliang%3BChan%2C+Chi-Chao%3BKannabiran%2C+Chitra%3BWawrousek%2C+Eric%3BHejtmancik%2C+J+Fielding&rft.aulast=Ma&rft.aufirst=Zhiwei&rft.date=2016-06-01&rft.volume=1862&rft.issue=6&rft.spage=1214&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/10.1016%2Fj.bbadis.2016.02.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-26 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Arch Ophthalmol. 2007 Feb;125(2):165-73 [17296892] Exp Eye Res. 2007 Mar;84(3):513-28 [17217947] Physiology (Bethesda). 2007 Jun;22:193-201 [17557940] Annu Rev Biochem. 2007;76:51-74 [17352659] FEBS J. 2007 Aug;274(16):4135-47 [17651443] Am J Ophthalmol. 2007 Dec;144(6):949-952 [17937925] Mol Cell Neurosci. 2008 Jan;37(1):85-95 [17931883] Mol Vis. 2008;14:1157-70 [18587492] Arch Ophthalmol. 2008 Dec;126(12):1687-93 [19064850] J Cell Mol Med. 2008 Dec;12(6A):2482-96 [18266951] Mol Vis. 2009;15:1014-9 [19461930] Mol Vis. 2009;15:980-4 [19461931] Apoptosis. 2009 Aug;14(8):996-1007 [19360473] J Biol Chem. 2009 Dec 18;284(51):35872-84 [19858219] Mol Vis. 2010;16:154-60 [20142846] Mol Biol Cell. 2010 Jul 15;21(14):2453-68 [20484573] Mol Vis. 2010;16:2007-15 [21042563] Mol Vis. 2010;16:2347-53 [21139983] Invest Ophthalmol Vis Sci. 2011 Jul;52(8):5369-75 [21436266] Mol Vis. 2011;17:2065-71 [21850182] Mol Vis. 2011;17:2197-206 [21866213] Pharmacol Ther. 2012 Jun;134(3):306-16 [22387231] Mol Vis. 2012;18:1283-8 [22665976] Cell Death Dis. 2012;3:e333 [22739985] Mol Vis. 2012;18:2213-20 [22919269] Exp Eye Res. 2012 Sep;102:28-37 [22713599] Hum Mutat. 2013 Mar;34(3):473-80 [23281106] Biol Chem. 2014 Jan;395(1):1-13 [24002662] Biochim Biophys Acta. 2014 Sep;1842(9):1794-805 [24997453] Biochim Biophys Acta. 2016 Jan;1860(1 Pt B):234-9 [26071686] Eye (Lond). 1999 Jun;13 ( Pt 3b):395-402 [10627816] Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3278-85 [11006214] Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3511-5 [11006246] Biophys Chem. 2000 Aug 30;86(2-3):95-108 [11026675] Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4216-22 [11095618] Biochim Biophys Acta. 2001 May 28;1519(1-2):30-8 [11406268] Am J Hum Genet. 2002 Sep;71(3):451-65 [12145749] Annu Rev Biochem. 2003;72:291-336 [12626338] Br J Ophthalmol. 2004 Jan;88(1):79-83 [14693780] Nature. 1981 Feb 26;289(5800):771-7 [7464942] Biochim Biophys Acta. 1983 Sep 9;740(4):441-8 [6309238] Proc Natl Acad Sci U S A. 1985 Apr;82(8):2334-8 [3857584] J Cell Biol. 1989 Oct;109(4 Pt 1):1653-64 [2793935] Dev Biol. 1990 Jan;137(1):68-76 [2295367] Eur J Cell Biol. 1990 Oct;53(1):59-74 [2076709] Protein Eng. 1994 Mar;7(3):445-51 [8177894] Development. 1993 Oct;119(2):363-75 [8287793] Mol Cell Biol. 1993 Oct;13(10):6211-22 [8413221] Ophthalmology. 1994 May;101(5):866-71 [8190472] Am J Ophthalmol. 1996 Feb;121(2):162-8 [8623885] J Mol Biol. 1997 Jun 6;269(2):260-9 [9191069] Exp Eye Res. 1998 Mar;66(3):371-83 [9533864] Mol Vis. 1998 Oct 23;4:21 [9788845] Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1727-37 [10393042] Am J Hum Genet. 1999 Aug;65(2):336-44 [10417276] Mol Vis. 2005;11:274-83 [15851978] Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2100-6 [15914629] Thromb Haemost. 2005 Jun;93(6):1077-81 [15968391] Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3951-9 [16936110] Invest Ophthalmol Vis Sci. 2007 May;48(5):2208-13 [17460281] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bbadis.2016.02.003 ER - TY - JOUR T1 - Effect of attention control on sustained attention during induced anxiety AN - 1784150924 AB - Anxiety has wide-reaching and complex effects on cognitive performance. Although it can intrude on cognition and interfere with performance, it can also facilitate information processing and behavioural responses. In a previous study, we showed that anxiety induced by threat of shock facilitates performance on the Sustained Attention to Response Task, a vigilance test, which probes response inhibition to infrequent nogo stimuli. The present study sought to identify factors that may have contributed to such improved performance, including on- and off-task thinking (assessed with thought probes) and individual differences in attention control, as measured with the Attention Control Scale. Replicating our prior finding, we showed that shock threat significantly reduced errors of commission on the nogo trials. However, we extended this finding in demonstrating that this effect was driven by subjects with low attention control. We therefore confirm that anxiety increases inhibitory control of prepotent responses-a mechanism which is adaptive under threat-and show that this effect is greater in those who rely more upon such prepotent responding, i.e., those with low attentional control. JF - Cognition & Emotion AU - Grillon, Christian AU - Robinson, Oliver J AU - Mathur, Ambika AU - Ernst, Monique AD - Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 700 EP - 712 CY - Hove PB - Taylor & Francis Ltd. VL - 30 IS - 4 SN - 0269-9931 KW - Psychology KW - Anxiety KW - Vigilance KW - Stress KW - SART KW - Threat of shock KW - Attentional processes KW - Behavioural responses KW - Cognition KW - Cognitive performance KW - Individual differences KW - Information processing KW - Inhibition KW - Inhibitory processes KW - Response inhibition KW - Sustained attention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1784150924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cognition+%26+Emotion&rft.atitle=Effect+of+attention+control+on+sustained+attention+during+induced+anxiety&rft.au=Grillon%2C+Christian%3BRobinson%2C+Oliver+J%3BMathur%2C+Ambika%3BErnst%2C+Monique&rft.aulast=Grillon&rft.aufirst=Christian&rft.date=2016-06-01&rft.volume=30&rft.issue=4&rft.spage=700&rft.isbn=&rft.btitle=&rft.title=Cognition+%26+Emotion&rft.issn=02699931&rft_id=info:doi/10.1080%2F02699931.2015.1024614 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law. N1 - Last updated - 2016-05-18 DO - http://dx.doi.org/10.1080/02699931.2015.1024614 ER - TY - JOUR T1 - Experiences with Parents and Youth Physical Health Symptoms and Cortisol: A Daily Diary Investigation AN - 1783854891 AB - Using daily diary data, this study examined the associations between positive and negative parent-youth experiences and youth cortisol and physical health symptoms among a sample of adolescents (N = 132, mean age = 13.39). On days when girls reported more negative experiences than usual, they exhibited more physical health symptoms and flatter evening cortisol slopes than usual. Negative experiences with mothers were associated with higher dinner and bedtime youth cortisol levels (between-person). Daily positive experiences with fathers were linked with lower dinner cortisol levels. Youth with high levels of negative experiences, on average, were less sensitive to daily variation in negative experiences than youth who experienced lower parental negativity. We discuss the benefits of a daily diary approach. JF - Journal of Research on Adolescence AU - Lippold, Melissa A AU - McHale, Susan M AU - Davis, Kelly D AU - Almeida, David M AU - King, Rosalind B AD - The University of North Carolina at Chapel Hill ; The Pennsylvania State University ; National Institute of Child Health and Human Development (NICHD Y1 - 2016/06// PY - 2016 DA - Jun 2016 SP - 226 EP - 240 CY - Hoboken PB - Wiley Subscription Services, Inc. VL - 26 IS - 2 SN - 1050-8392 KW - Psychology KW - Parents KW - Adolescents KW - Autobiographical Materials KW - Females KW - Fathers KW - Health KW - Mothers KW - Symptoms KW - Youth KW - Cortisol KW - Health status KW - Negative experiences KW - Physical symptoms KW - Children KW - 1939:the family and socialization; adolescence & youth KW - 1941:the family and socialization; sociology of the family, marriage, & divorce UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1783854891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Research+on+Adolescence&rft.atitle=Experiences+with+Parents+and+Youth+Physical+Health+Symptoms+and+Cortisol%3A+A+Daily+Diary+Investigation&rft.au=Lippold%2C+Melissa+A%3BMcHale%2C+Susan+M%3BDavis%2C+Kelly+D%3BAlmeida%2C+David+M%3BKing%2C+Rosalind+B&rft.aulast=Lippold&rft.aufirst=Melissa&rft.date=2016-06-01&rft.volume=26&rft.issue=2&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Journal+of+Research+on+Adolescence&rft.issn=10508392&rft_id=info:doi/10.1111%2Fjora.12186 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA); Sociological Abstracts N1 - Copyright - Journal of Research on Adolescence © 2016 Society for Research on Adolescence N1 - Last updated - 2016-06-14 DO - http://dx.doi.org/10.1111/jora.12186 ER - TY - JOUR T1 - Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®): Results From a Phase I Study in Children, Adolescents, and Young Adults With Refractory Solid Tumors or Leukemias. AN - 1781536205; 26891067 AB - Vincristine sulfate liposome injection (VSLI; Marqibo®) is an encapsulated preparation of standard vincristine in sphingomyelin/cholesterol liposomes. Clinical trials in adults have demonstrated safety, tolerability, and activity, leading to Food and Drug Administration (FDA) approval for adults with relapsed acute lymphoblastic leukemia (ALL). Pediatric experience with VSLI is limited. This single center, phase I dose escalation study examined the safety, toxicity, maximum tolerated dose, and pharmacokinetics of VSLI administered weekly to pediatric patients age <21 years with relapsed or chemotherapy-refractory solid tumors or leukemia. Twenty-one subjects were treated in total. Median age was 13.3 years (range 2-19). Fourteen subjects completed one 28-day cycle of therapy and five subjects completed more than one cycle. No subject experienced dose-limiting toxicity (DLT) at the first dose level (1.75 mg/m(2) /dose, dose range: 2-3.7 mg). At the second dose level (2.25 mg/m(2) /dose, dose range: 1.3-4.5 mg), one subject had transient dose-limiting grade 4 transaminase elevation, and this dose level was expanded with no additional DLT observed. The second dose level then opened to an expansion phase to evaluate activity in ALL. Clinical activity included minimal residual disease negative complete remission in one subject with ALL and stable disease in nine subjects. Clearance of total vincristine was found to be approximately 100-fold lower in comparison to published data using standard vincristine. Children tolerate 2.25 mg/m(2) /dose of weekly VSLI (the adult FDA-approved dose) with evidence for clinical activity without dose-limiting neurotoxicity. Future plans include studying VSLI as substitution for standard vincristine with combination chemotherapy in children with ALL. © 2016 Wiley Periodicals, Inc. JF - Pediatric blood & cancer AU - Shah, Nirali N AU - Merchant, Melinda S AU - Cole, Diane E AU - Jayaprakash, Nalini AU - Bernstein, Donna AU - Delbrook, Cindy AU - Richards, Kelly AU - Widemann, Brigitte C AU - Wayne, Alan S AD - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland; Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 997 EP - 1005 VL - 63 IS - 6 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Liposomes KW - Vincristine KW - 5J49Q6B70F KW - Index Medicus KW - Marqibo® KW - phase I KW - acute lymphoblastic leukemia KW - pediatric KW - Registries KW - Young Adult KW - Humans KW - Child KW - Maximum Tolerated Dose KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Vincristine -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Vincristine -- administration & dosage KW - Vincristine -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781536205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+blood+%26+cancer&rft.atitle=Vincristine+Sulfate+Liposomes+Injection+%28VSLI%2C+Marqibo%C2%AE%29%3A+Results+From+a+Phase+I+Study+in+Children%2C+Adolescents%2C+and+Young+Adults+With+Refractory+Solid+Tumors+or+Leukemias.&rft.au=Shah%2C+Nirali+N%3BMerchant%2C+Melinda+S%3BCole%2C+Diane+E%3BJayaprakash%2C+Nalini%3BBernstein%2C+Donna%3BDelbrook%2C+Cindy%3BRichards%2C+Kelly%3BWidemann%2C+Brigitte+C%3BWayne%2C+Alan+S&rft.aulast=Shah&rft.aufirst=Nirali&rft.date=2016-06-01&rft.volume=63&rft.issue=6&rft.spage=997&rft.isbn=&rft.btitle=&rft.title=Pediatric+blood+%26+cancer&rft.issn=1545-5017&rft_id=info:doi/10.1002%2Fpbc.25937 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-19 N1 - Date created - 2016-04-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/pbc.25937 ER - TY - JOUR T1 - Circulating Metabolites and Survival Among Patients With Pancreatic Cancer. AN - 1760878972; 26755275 AB - Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. JF - Journal of the National Cancer Institute AU - Yuan, Chen AU - Clish, Clary B AU - Wu, Chen AU - Mayers, Jared R AU - Kraft, Peter AU - Townsend, Mary K AU - Zhang, Mingfeng AU - Tworoger, Shelley S AU - Bao, Ying AU - Qian, Zhi Rong AU - Rubinson, Douglas A AU - Ng, Kimmie AU - Giovannucci, Edward L AU - Ogino, Shuji AU - Stampfer, Meir J AU - Gaziano, John Michael AU - Ma, Jing AU - Sesso, Howard D AU - Anderson, Garnet L AU - Cochrane, Barbara B AU - Manson, JoAnn E AU - Torrence, Margaret E AU - Kimmelman, Alec C AU - Amundadottir, Laufey T AU - Vander Heiden, Matthew G AU - Fuchs, Charles S AU - Wolpin, Brian M AD - Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (CY, ZRQ, DAR, KN, SO, MGVH, CSF, BMW); Broad Institute of MIT and Harvard University, Cambridge, MA (CBC, MGVH); Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China (CW); Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA (JRM, MET, MGVH); Department of Epidemiology (PK, SST, ELG, SO, MJS, JM, HDS, JEM), Department of Biostatistics (PK), and Department of Nutrition (ELG, MJS), Harvard School of Public Health, Boston, MA; Department of Pathology (SO), and Channing Division of Network Medicine (MKT, SST, YB, ELG, MJS, JM, JEM, CSF) and Division of Preventive Medicine (JMG, HDS, JEM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (MZ, LTA); Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (JMG); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA); University of Washington School of Nursing, Seattle, WA (BBC); Division of Genomic Stability and DNA repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (ACK). ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (CY, ZRQ, DAR, KN, SO, MGVH, CSF, BMW); Broad Institute of MIT and Harvard University, Cambridge, MA (CBC, MGVH); Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China (CW); Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA (JRM, MET, MGVH); Department of Epidemiology (PK, SST, ELG, SO, MJS, JM, HDS, JEM), Department of Biostatistics (PK), and Department of Nutrition (ELG, MJS), Harvard School of Public Health, Boston, MA; Department of Pathology (SO), and Channing Division of Network Medicine (MKT, SST, YB, ELG, MJS, JM, JEM, CSF) and Division of Preventive Medicine (JMG, HDS, JEM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (MZ, LTA); Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (JMG); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA); University of Washington School of Nursing, Seattle, WA (BBC); Division of Genomic Stability and DNA repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (ACK). bwolpin@partners.org. Y1 - 2016/06// PY - 2016 DA - June 2016 SP - 1 VL - 108 IS - 6 KW - Biomarkers, Tumor KW - 0 KW - Isocitrates KW - Tricarboxylic Acids KW - isocitric acid KW - 320-77-4 KW - Aconitic Acid KW - 499-12-7 KW - Iron Regulatory Protein 1 KW - EC 4.2.1.3 KW - Index Medicus KW - Odds Ratio KW - Women's Health KW - Humans KW - Nurses KW - Isocitrates -- blood KW - Aged KW - Genotype KW - Kaplan-Meier Estimate KW - Prospective Studies KW - Aged, 80 and over KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - United States -- epidemiology KW - Aconitic Acid -- blood KW - Female KW - Male KW - Proportional Hazards Models KW - Pancreatic Neoplasms -- diagnosis KW - Tricarboxylic Acids -- blood KW - Polymorphism, Single Nucleotide KW - Iron Regulatory Protein 1 -- blood KW - Pancreatic Neoplasms -- mortality KW - Pancreatic Neoplasms -- blood KW - Iron Regulatory Protein 1 -- genetics KW - Biomarkers, Tumor -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760878972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Circulating+Metabolites+and+Survival+Among+Patients+With+Pancreatic+Cancer.&rft.au=Yuan%2C+Chen%3BClish%2C+Clary+B%3BWu%2C+Chen%3BMayers%2C+Jared+R%3BKraft%2C+Peter%3BTownsend%2C+Mary+K%3BZhang%2C+Mingfeng%3BTworoger%2C+Shelley+S%3BBao%2C+Ying%3BQian%2C+Zhi+Rong%3BRubinson%2C+Douglas+A%3BNg%2C+Kimmie%3BGiovannucci%2C+Edward+L%3BOgino%2C+Shuji%3BStampfer%2C+Meir+J%3BGaziano%2C+John+Michael%3BMa%2C+Jing%3BSesso%2C+Howard+D%3BAnderson%2C+Garnet+L%3BCochrane%2C+Barbara+B%3BManson%2C+JoAnn+E%3BTorrence%2C+Margaret+E%3BKimmelman%2C+Alec+C%3BAmundadottir%2C+Laufey+T%3BVander+Heiden%2C+Matthew+G%3BFuchs%2C+Charles+S%3BWolpin%2C+Brian+M&rft.aulast=Yuan&rft.aufirst=Chen&rft.date=2016-06-01&rft.volume=108&rft.issue=6&rft.spage=djv409&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/10.1093%2Fjnci%2Fdjv409 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-12 N1 - Date created - 2016-01-12 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: BMC Cancer. 2014;14:728 [25266049] Cancer Lett. 2015 Jan 28;356(2 Pt A):217-23 [24614286] Cell Rep. 2014 Dec 24;9(6):2233-49 [25497091] J Clin Oncol. 2015 Jan 1;33(1):29-35 [25403204] Clin Cancer Res. 2015 Jan 1;21(1):10-7 [25564569] Cancer Res. 2015 Feb 1;75(3):544-53 [25644265] JAMA. 2001 Sep 26;286(12):1494-7 [11572743] Ann Epidemiol. 2003 Oct;13(9 Suppl):S107-21 [14575943] J Chronic Dis. 1982;35(6):437-43 [7042727] N Engl J Med. 1989 Jul 20;321(3):129-35 [2664509] Am J Epidemiol. 1994 Dec 1;140(11):1016-9 [7985649] BMJ. 1995 Jan 21;310(6973):170 [7833759] Ann Intern Med. 1995 Mar 1;122(5):327-34 [7847643] Nat Rev Cancer. 2005 May;5(5):388-96 [15864280] N Engl J Med. 2009 Feb 19;360(8):765-73 [19228619] Science. 2009 May 22;324(5930):1029-33 [19460998] Bioinformatics. 2010 Oct 1;26(19):2474-6 [20702402] Nature. 2010 Oct 28;467(7319):1114-7 [20981102] Fam Cancer. 2010 Dec;9(4):625-33 [20574843] N Engl J Med. 2011 May 12;364(19):1817-25 [21561347] Lancet. 2011 Aug 13;378(9791):607-20 [21620466] Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4 [22064851] Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):82-91 [22086883] Science. 2012 May 25;336(6084):1040-4 [22628656] Nat Genet. 2012 Oct;44(10):1084-9 [22941192] Nature. 2013 Apr 4;496(7443):101-5 [23535601] Nat Rev Cancer. 2013 May;13(5):342-55 [23594855] Nat Genet. 2013 Oct;45(10):1238-43 [24013639] Clin Chem. 2013 Nov;59(11):1657-67 [23897902] N Engl J Med. 2013 Oct 31;369(18):1691-703 [24131140] Nat Rev Drug Discov. 2013 Nov;12(11):829-46 [24113830] J Clin Oncol. 2013 Nov 20;31(33):4229-34 [24145341] CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 [24399786] J Clin Oncol. 2014 Feb 1;32(4):297-305 [24344214] Arch Biochem Biophys. 2014 Mar 1;545:69-73 [24393743] Ann Surg Oncol. 2014 Apr;21(4):1082-9 [24322532] Clin Cancer Res. 2014 Apr 1;20(7):1884-90 [24478380] Carcinogenesis. 2014 Jul;35(7):1441-50 [24743516] Br J Cancer. 2014 Jul 8;111(1):181-5 [24786605] Nat Genet. 2014 Sep;46(9):994-1000 [25086665] Int J Cancer. 2014 Nov 15;135(10):2237-48 [25124653] J Clin Endocrinol Metab. 2014 Oct;99(10):3903-11 [25014000] Nat Med. 2014 Oct;20(10):1193-8 [25261994] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/jnci/djv409 ER - TY - JOUR T1 - Nondisclosure of Financial Interest in Clinical Practice Guideline Development: An Intractable Problem? AN - 1808729496; PQ0003329649 AB - In a Perspective linked to Stelfox and colleagues, Hilda Bastian discusses the challenges of improving transparency and management of financial conflicts of interest among committees that develop guidelines for medical practice. JF - PLOS Medicine AU - Bastian, Hilda AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America Y1 - 2016/05/31/ PY - 2016 DA - 2016 May 31 PB - Public Library of Science, 185 Berry Street San Francisco CA 94107 United States VL - 13 IS - 5 SN - 1549-1277, 1549-1277 KW - Health & Safety Science Abstracts; CSA Neurosciences Abstracts KW - Transparency KW - Committees KW - Reviews KW - Guidelines KW - Conflict of interests KW - N3 11003:Developmental neuroscience KW - H 0500:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808729496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLOS+Medicine&rft.atitle=Nondisclosure+of+Financial+Interest+in+Clinical+Practice+Guideline+Development%3A+An+Intractable+Problem%3F&rft.au=Bastian%2C+Hilda&rft.aulast=Bastian&rft.aufirst=Hilda&rft.date=2016-05-31&rft.volume=13&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=PLOS+Medicine&rft.issn=15491277&rft_id=info:doi/10.1371%2Fjournal.pmed.1002030 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Reviews; Transparency; Committees; Conflict of interests; Guidelines DO - http://dx.doi.org/10.1371/journal.pmed.1002030 ER - TY - JOUR T1 - Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the Apc(Min/+) model of colon cancer. AN - 1793216089; 27239962 AB - Thrombospondin 1 is a glycoprotein that regulates cellular phenotype through interactions with its cellular receptors and extracellular matrix-binding partners. Thrombospondin 1 locally regulates angiogenesis and inflammatory responses that contribute to colorectal carcinogenesis in Apc(Min/+) mice. The ability of thrombospondin 1 to regulate responses of cells and tissues to a variety of stresses suggested that loss of thrombospondin 1 may also have broader systemic effects on metabolism to modulate carcinogenesis. Apc(Min/+):Thbs1(-/-) mice exhibited decreased survival and higher tumor multiplicities in the small and large intestine relative to Apc(Min/+) mice when fed a low (5%) fat western diet. However, the protective effect of endogenous thrombospondin 1 was lost when the mice were fed a western diet containing 21% fat. Biochemical profiles of liver tissue identified systemic metabolic changes accompanying the effects of thrombospondin 1 and dietary lipid intake on tumorigenesis. A high-fat western diet differentially regulated elements of amino acid, energy and lipid metabolism in Apc(Min/+):Thbs1(-/-) mice relative to Apc(Min/+):Thbs1(+/+)mice. Metabolic changes in ketone body and tricarboxylic acid cycle intermediates indicate functional interactions between Apc and thrombospondin 1 signaling that control mitochondrial function. The cumulative diet-dependent differential changes observed in Apc(Min/+):Thbs1(-/-) versus Apc(Min/+) mice include altered amino acid and lipid metabolism, mitochondrial dysfunction, eicosanoids and ketone body formation. This metabolic profile suggests that the protective role of thrombospondin 1 to decrease adenoma formation in Apc(Min/+) mice results in part from improved mitochondrial function. JF - Oncogenesis AU - Soto-Pantoja, D R AU - Sipes, J M AU - Martin-Manso, G AU - Westwood, B AU - Morris, N L AU - Ghosh, A AU - Emenaker, N J AU - Roberts, D D AD - Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA. ; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. ; Department of Surgery, Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA. ; Chemical Biology Laboratory, National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA. ; Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, MD, USA. Y1 - 2016/05/30/ PY - 2016 DA - 2016 May 30 SP - 1 VL - 5 IS - 5 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1793216089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogenesis&rft.atitle=Dietary+fat+overcomes+the+protective+activity+of+thrombospondin-1+signaling+in+the+Apc%28Min%2F%2B%29+model+of+colon+cancer.&rft.au=Soto-Pantoja%2C+D+R%3BSipes%2C+J+M%3BMartin-Manso%2C+G%3BWestwood%2C+B%3BMorris%2C+N+L%3BGhosh%2C+A%3BEmenaker%2C+N+J%3BRoberts%2C+D+D&rft.aulast=Soto-Pantoja&rft.aufirst=D&rft.date=2016-05-30&rft.volume=5&rft.issue=5&rft.spage=e230&rft.isbn=&rft.btitle=&rft.title=Oncogenesis&rft.issn=&rft_id=info:doi/10.1038%2Foncsis.2016.37 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-31 N1 - Date created - 2016-05-31 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/oncsis.2016.37 ER - TY - JOUR T1 - General and specific cancer risk perceptions: how are they related? AN - 1808657895; PQ0003401483 AB - Understanding how people construe and act upon cancer risk is important for efforts to target risk-increasing health behaviors. Importantly, research participants are often asked to estimate their risk for cancer (in general), which could mask the fact that cancer represents a range of diseases, and that different cancer types can have distinct risk factors. It is unclear whether individuals perceive general cancer risk as being comprised of an aggregation of risk for specific cancer sites, or whether general cancer risk perceptions reflect the specific type of cancer most salient to them. In this study, general cancer risk perceptions were regressed on specific risk perceptions for colon, lung, prostate (men only), and breast (women only), using data from a nationally representative sample. We found that among men and women, all forms of cancer predicted independent variance in estimates of general cancer risk. There were also stronger relationships between general risk perceptions and each specific risk perception than between any two specific risk perceptions, suggesting that individuals differentiate between specific cancers and general cancer risk. These findings offer some confidence that people's estimates of general cancer risk take multiple cancer types into account. JF - Journal of Risk Research AU - Grenen, Emily G AU - Ferrer, Rebecca A AU - Klein, William MP AU - Han, Paul KJ AD - National Cancer Institute, Behavioral Research Program, Division of Cancer Control and Population Sciences, Rockville, MD, USA Y1 - 2016/05/27/ PY - 2016 DA - 2016 May 27 SP - 602 EP - 613 PB - Taylor & Francis Group Ltd., 2 Park Square Oxford OX14 4RN United Kingdom VL - 19 IS - 5 SN - 1366-9877, 1366-9877 KW - Environment Abstracts KW - cancer KW - risk perception KW - cognition KW - Health risks KW - Perception KW - Lung KW - Risk factors KW - Risk taking KW - Cancer KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808657895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Risk+Research&rft.atitle=General+and+specific+cancer+risk+perceptions%3A+how+are+they+related%3F&rft.au=Grenen%2C+Emily+G%3BFerrer%2C+Rebecca+A%3BKlein%2C+William+MP%3BHan%2C+Paul+KJ&rft.aulast=Grenen&rft.aufirst=Emily&rft.date=2016-05-27&rft.volume=19&rft.issue=5&rft.spage=602&rft.isbn=&rft.btitle=&rft.title=Journal+of+Risk+Research&rft.issn=13669877&rft_id=info:doi/10.1080%2F13669877.2014.1003321 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Health risks; Lung; Perception; Risk factors; Risk taking; Cancer DO - http://dx.doi.org/10.1080/13669877.2014.1003321 ER - TY - JOUR T1 - Screening and Biological Effects of Marine Pyrroloiminoquinone Alkaloids: Potential Inhibitors of the HIF-1α/p300 Interaction. AN - 1792373480; 27140429 AB - Inhibition of the hypoxia-inducible factor 1α (HIF-1α) pathway by disrupting its association with the transcriptional coactivator p300 inhibits angiogenesis and tumor development. Development of HIF-1α/p300 inhibitors has been hampered by preclinical toxicity; therefore, we aimed to identify novel HIF-1α/p300 inhibitors. Using a cell-free assay designed to test compounds that block HIF-1α/p300 binding, 170 298 crude natural product extracts and prefractionated samples were screened, identifying 25 active extracts. One of these extracts, originating from the marine sponge Latrunculia sp., afforded six pyrroloiminoquinone alkaloids that were identified as positive hits (IC50 values: 1-35 μM). Luciferase assays confirmed inhibition of HIF-1α transcriptional activity by discorhabdin B (1) and its dimer (2), 3-dihydrodiscorhabdin C (3), makaluvamine F (5), discorhabdin H (8), discorhabdin L (9), and discorhabdin W (11) in HCT 116 colon cancer cells (0.1-10 μM, p < 0.05). Except for 11, all of these compounds also reduced HIF-1α transcriptional activity in LNCaP prostate cancer cells (0.1-10 μM, p < 0.05). These effects occurred at noncytotoxic concentrations (<50% cell death) under hypoxic conditions. At the downstream HIF-1α target level, compound 8 (0.5 μM) significantly decreased VEGF secretion in LNCaP cells (p < 0.05). In COLO 205 colon cancer cells no activity was shown in the luciferase or cytotoxicity assays. Pyrroloiminoquinone alkaloids are a novel class of HIF-1α inhibitors, which interrupt the protein-protein interaction between HIF-1α and p300 and consequently reduce HIF-related transcription. JF - Journal of natural products AU - Goey, Andrew K L AU - Chau, Cindy H AU - Sissung, Tristan M AU - Cook, Kristina M AU - Venzon, David J AU - Castro, Amaya AU - Ransom, Tanya R AU - Henrich, Curtis J AU - McKee, Tawnya C AU - McMahon, James B AU - Grkovic, Tanja AU - Cadelis, Melissa M AU - Copp, Brent R AU - Gustafson, Kirk R AU - Figg, William D AD - Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702-1201, United States. ; School of Chemical Sciences, University of Auckland , Auckland 1142, New Zealand. Y1 - 2016/05/27/ PY - 2016 DA - 2016 May 27 SP - 1267 EP - 1275 VL - 79 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1792373480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=Screening+and+Biological+Effects+of+Marine+Pyrroloiminoquinone+Alkaloids%3A+Potential+Inhibitors+of+the+HIF-1%CE%B1%2Fp300+Interaction.&rft.au=Goey%2C+Andrew+K+L%3BChau%2C+Cindy+H%3BSissung%2C+Tristan+M%3BCook%2C+Kristina+M%3BVenzon%2C+David+J%3BCastro%2C+Amaya%3BRansom%2C+Tanya+R%3BHenrich%2C+Curtis+J%3BMcKee%2C+Tawnya+C%3BMcMahon%2C+James+B%3BGrkovic%2C+Tanja%3BCadelis%2C+Melissa+M%3BCopp%2C+Brent+R%3BGustafson%2C+Kirk+R%3BFigg%2C+William+D&rft.aulast=Goey&rft.aufirst=Andrew+K&rft.date=2016-05-27&rft.volume=79&rft.issue=5&rft.spage=1267&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=1520-6025&rft_id=info:doi/10.1021%2Facs.jnatprod.5b00846 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jnatprod.5b00846 ER - TY - JOUR T1 - NMDAR inhibition-independent antidepressant actions of ketamine metabolites. AN - 1792373913; 27144355 AB - Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-d-aspartate receptor) antagonist (R,S)-ketamine exerts rapid and sustained antidepressant effects after a single dose in patients with depression, but its use is associated with undesirable side effects. Here we show that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice. These antidepressant actions are independent of NMDAR inhibition but involve early and sustained activation of AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors). We also establish that (2R,6R)-HNK lacks ketamine-related side effects. Our data implicate a novel mechanism underlying the antidepressant properties of (R,S)-ketamine and have relevance for the development of next-generation, rapid-acting antidepressants. JF - Nature AU - Zanos, Panos AU - Moaddel, Ruin AU - Morris, Patrick J AU - Georgiou, Polymnia AU - Fischell, Jonathan AU - Elmer, Greg I AU - Alkondon, Manickavasagom AU - Yuan, Peixiong AU - Pribut, Heather J AU - Singh, Nagendra S AU - Dossou, Katina S S AU - Fang, Yuhong AU - Huang, Xi-Ping AU - Mayo, Cheryl L AU - Wainer, Irving W AU - Albuquerque, Edson X AU - Thompson, Scott M AU - Thomas, Craig J AU - Zarate, Carlos A AU - Gould, Todd D AD - Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. ; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, USA. ; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; Department of Epidemiology and Public Health, Division of Translational Toxicology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ; Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. ; NIMH Psychoactive Drug Screening Program, Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina 27516, USA. ; Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA. ; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. Y1 - 2016/05/26/ PY - 2016 DA - 2016 May 26 SP - 481 EP - 486 VL - 533 IS - 7604 KW - Antidepressive Agents KW - 0 KW - Receptors, AMPA KW - Receptors, N-Methyl-D-Aspartate KW - Ketamine KW - 690G0D6V8H KW - 6-hydroxynorketamine KW - 81395-70-2 KW - Index Medicus KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Mice KW - Receptors, AMPA -- metabolism KW - Receptors, AMPA -- agonists KW - Time Factors KW - Male KW - Female KW - Ketamine -- adverse effects KW - Antidepressive Agents -- pharmacology KW - Ketamine -- metabolism KW - Ketamine -- analogs & derivatives KW - Antidepressive Agents -- adverse effects KW - Antidepressive Agents -- metabolism KW - Ketamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1792373913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=NMDAR+inhibition-independent+antidepressant+actions+of+ketamine+metabolites.&rft.au=Zanos%2C+Panos%3BMoaddel%2C+Ruin%3BMorris%2C+Patrick+J%3BGeorgiou%2C+Polymnia%3BFischell%2C+Jonathan%3BElmer%2C+Greg+I%3BAlkondon%2C+Manickavasagom%3BYuan%2C+Peixiong%3BPribut%2C+Heather+J%3BSingh%2C+Nagendra+S%3BDossou%2C+Katina+S+S%3BFang%2C+Yuhong%3BHuang%2C+Xi-Ping%3BMayo%2C+Cheryl+L%3BWainer%2C+Irving+W%3BAlbuquerque%2C+Edson+X%3BThompson%2C+Scott+M%3BThomas%2C+Craig+J%3BZarate%2C+Carlos+A%3BGould%2C+Todd+D&rft.aulast=Zanos&rft.aufirst=Panos&rft.date=2016-05-26&rft.volume=533&rft.issue=7604&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=1476-4687&rft_id=info:doi/10.1038%2Fnature17998 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-21 N1 - Date created - 2016-05-26 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Comment In: Nature. 2016 May 26;533(7604):477-8 [27144350] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nature17998 ER - TY - JOUR T1 - PBDE flame retardants, thyroid disease, and menopausal status in U.S. women. AN - 1791326855; 27215290 AB - Women have elevated rates of thyroid disease compared to men. Environmental toxicants have been implicated as contributors to this dimorphism, including polybrominated diphenyl ethers (PBDEs), flame retardant chemicals that disrupt thyroid hormone action. PBDEs have also been implicated in the disruption of estrogenic activity, and estrogen levels regulate thyroid hormones. Post-menopausal women may therefore be particularly vulnerable to PBDE induced thyroid effects, given low estrogen reserves. The objective of this study was to test for an association between serum PBDE concentrations and thyroid disease in women from the United States (U.S.), stratified by menopause status. Serum PBDE concentrations (BDEs 47, 99, 100 and 153) from the National Health and Examination Survey (NHANES) and reports on thyroid problems were available in the NHANES 2003-2004 cycle. Odds ratios (ORs) were calculated using multivariate logistic regression models accounting for population-weighted survey techniques and controlling for age, body mass index (BMI), education, smoking, alcohol consumption and thyroid medication. Menopause status was obtained by self-reported absence of menstruation in the previous 12 months and declared menopause. Women in the highest quartile of serum concentrations for BDEs 47, 99, and 100 had increased odds of currently having thyroid disease (ORs: 1.5, 1.8, 1.5, respectively) compared to the reference group (1st and 2nd quartiles combined); stronger associations were observed when the analysis was restricted to postmenopausal women (ORs: 2.2, 3.6, 2.0, respectively). Exposure to BDEs 47, 99, and 100 is associated with thyroid disease in a national sample of U.S. women, with greater effects observed post-menopause, suggesting that the disruption of thyroid signaling by PBDEs may be enhanced by the altered estrogen levels during menopause. JF - Environmental health : a global access science source AU - Allen, Joseph G AU - Gale, Sara AU - Zoeller, R Thomas AU - Spengler, John D AU - Birnbaum, Linda AU - McNeely, Eileen AD - Department of Environmental Health, Harvard T. H. Chan School of Public Health, 401 Park Drive, Boston, MA, 02215, USA. jgallen@hsph.harvard.edu. ; Department of Environmental Health, Harvard T. H. Chan School of Public Health, 401 Park Drive, Boston, MA, 02215, USA. ; University of Massachusetts Amherst, Amherst, MA, USA. ; National Cancer Institute/NIEHS, Research Triangle Park, NC, USA. Y1 - 2016/05/24/ PY - 2016 DA - 2016 May 24 SP - 60 VL - 15 IS - 1 KW - Index Medicus KW - Polybrominated diphenyl ethers KW - PBDE KW - Endocrine disruptors KW - Thyroid KW - Menopause UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791326855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+%3A+a+global+access+science+source&rft.atitle=PBDE+flame+retardants%2C+thyroid+disease%2C+and+menopausal+status+in+U.S.+women.&rft.au=Allen%2C+Joseph+G%3BGale%2C+Sara%3BZoeller%2C+R+Thomas%3BSpengler%2C+John+D%3BBirnbaum%2C+Linda%3BMcNeely%2C+Eileen&rft.aulast=Allen&rft.aufirst=Joseph&rft.date=2016-05-24&rft.volume=15&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Environmental+health+%3A+a+global+access+science+source&rft.issn=1476-069X&rft_id=info:doi/10.1186%2Fs12940-016-0141-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-24 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Environ Sci Technol. 2006 Aug 1;40(15):4548-53 [16913105] Thyroid. 1999 Jul;9(7):661-5 [10447011] Environ Pollut. 2007 Jan;145(1):138-45 [16713050] Environ Sci Technol. 2007 Jul 1;41(13):4574-9 [17695899] Chemosphere. 2008 Jan;70(4):640-7 [17698168] Toxicol Appl Pharmacol. 2008 Feb 1;226(3):244-50 [17964624] Mol Nutr Food Res. 2008 Feb;52(2):284-98 [18161906] Environ Sci Technol. 2008 Feb 15;42(4):1377-84 [18351120] Environ Sci Technol. 2008 Jun 1;42(11):4222-8 [18589991] Diabetes Care. 2008 Sep;31(9):1802-7 [18559655] Environ Int. 2008 Nov;34(8):1085-91 [18456330] J Am Coll Cardiol. 2008 Sep 30;52(14):1152-9 [18804743] Environ Health Perspect. 2008 Oct;116(10):1376-82 [18941581] Environ Health Perspect. 2008 Dec;116(12):1635-41 [19079713] Environ Health Perspect. 2008 Dec;116(12):1694-9 [19079722] Toxicol Sci. 2009 Jan;107(1):27-39 [18978342] Environ Int. 2009 Apr;35(3):539-44 [19019437] Sci Total Environ. 2009 May 1;407(10):3425-9 [19211133] Eur J Endocrinol. 2009 Apr;160(4):503-15 [19095779] Environ Sci Technol. 2009 May 1;43(9):3067-72 [19534115] Environ Health Perspect. 2009 Sep;117(9):1380-6 [19750101] Environ Int. 2009 Nov;35(8):1118-24 [19683343] Environ Health Perspect. 2009 Oct;117(10):1520-5 [20019900] Environ Health Perspect. 2010 May;118(5):686-92 [20089479] Environ Health Perspect. 2010 Oct;118(10):1444-9 [20562054] Toxicology. 2010 Nov 9;277(1-3):20-8 [20804816] Environ Int. 2011 Feb;37(2):365-74 [21131049] Environ Int. 2011 May;37(4):694-708 [21345491] Toxicol Sci. 2011 Aug;122(2):265-74 [21546348] Environ Health Perspect. 2011 Sep;119(9):1247-52 [21715243] Environ Sci Technol. 2011 Sep 15;45(18):7896-905 [21830753] Environ Health Perspect. 2011 Oct;119(10):1454-9 [21715241] Environ Health Perspect. 2012 Apr;120(4):A143-4 [22470049] Endocr Rev. 2012 Jun;33(3):378-455 [22419778] Environ Sci Technol. 2012 Dec 18;46(24):13056-66 [23185960] Environ Health. 2013;12:17 [23413926] Environ Health Perspect. 2013 Apr;121(4):440-6 [23249762] J Expo Sci Environ Epidemiol. 2013 Jul;23(4):337-42 [22739680] Am J Epidemiol. 2013 Sep 1;178(5):701-13 [23924579] Environ Health Perspect. 2013 Oct;121(10):1194-9 [23959441] Environ Sci Technol. 2013 Oct 15;47(20):11776-84 [24066858] Environ Sci Technol. 2013;47(21):12238-47 [24059974] Chem Res Toxicol. 2013 Nov 18;26(11):1692-702 [24089703] Environ Sci Technol. 2014;48(1):753-60 [24298999] Chemosphere. 2016 May;150:505-13 [26693645] Environ Health. 2014;13:118 [25533907] Arch Intern Med. 2000 Feb 28;160(4):526-34 [10695693] Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S109-12 [10997623] Arch Environ Health. 2001 Mar-Apr;56(2):138-43 [11339677] Arch Toxicol. 2001 Jun;75(4):200-8 [11482517] Toxicology. 2002 Aug 15;177(2-3):227-43 [12135626] Chem Biol Interact. 1993 Jul;88(1):7-21 [8330325] J Gastroenterol Hepatol. 1995 May-Jun;10(3):344-50 [7548816] N Engl J Med. 1999 Aug 19;341(8):549-55 [10451459] Environ Health Perspect. 2006 Oct;114(10):1515-20 [17035135] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s12940-016-0141-0 ER - TY - JOUR T1 - Epigenetic Upregulation of Metallothionein 2A by Diallyl Trisulfide Enhances Chemosensitivity of Human Gastric Cancer Cells to Docetaxel Through Attenuating NF-κB Activation. AN - 1790458199; 26801633 AB - Metallothionein 2A (MT2A) and nuclear factor-kappaB (NF-κB) are both involved in carcinogenesis and cancer chemosensitivity. We previously showed decreased expression of MT2A and IκB-α in human gastric cancer (GC) associated with poor prognosis of GC patients. The present study investigated the effect of diallyl trisulfide (DATS), a garlic-derived compound, and docetaxel (DOC) on regulation of MT2A in relation to NF-κB in GC cells. DATS attenuated NF-κB signaling in GC cells, resulting in G2/M cell cycle arrest and apoptosis, culminating in the inhibition of cell proliferation and tumorigenesis in nude mice. The anti-GC effect of DATS was attributable to its capacity to epigenetically upregulate MT2A, which in turn enhanced transcription of IκB-α to suppress NF-κB activation in GC cells. The combination of DATS with DOC exhibited a synergistic anti-GC activity accompanied by MT2A upregulation and NF-κB inactivation. Histopathologic analysis of GC specimens from patients showed a significant increase in MT2A expression following DOC treatment. GC patients with high MT2A expression in tumor specimens showed significantly improved response to chemotherapy and prolonged survival compared with those with low MT2A expression in tumors. We conclude that DATS exerts its anti-GC activity and enhances chemosensitivity of GC to DOC by epigenetic upregulation of MT2A to attenuate NF-κB signaling. Our findings delineate a mechanistic basis of MT2A/NF-κB signaling for DATS- and DOC-mediated anti-GC effects, suggesting that MT2A may be a chemosensitivity indicator in GC patients receiving DOC-based treatment and a promising target for more effective treatment of GC by combination of DATS and DOC. Antioxid. Redox Signal. 24, 839-854. JF - Antioxidants & redox signaling AU - Pan, Yuanming AU - Lin, Shuye AU - Xing, Rui AU - Zhu, Min AU - Lin, Bonan AU - Cui, Jiantao AU - Li, Wenmei AU - Gao, Jing AU - Shen, Lin AU - Zhao, Yuanyuan AU - Guo, Mingzhou AU - Wang, Ji Ming AU - Huang, Jiaqiang AU - Lu, Youyong AD - 1 Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute , Beijing, P.R. China . ; 2 College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuancun, Haidian District, Beijing, P.R. China . ; 4 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University School of Oncology , Peking Cancer Hospital, Beijing, P.R. China . ; 5 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China , Beijing, P.R. China . ; 6 Department of Gastroenterology and Hepatology, Chinese PLA General Hospital , Beijing, P.R. China . ; 3 Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland. Y1 - 2016/05/20/ PY - 2016 DA - 2016 May 20 SP - 839 EP - 854 VL - 24 IS - 15 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790458199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antioxidants+%26+redox+signaling&rft.atitle=Epigenetic+Upregulation+of+Metallothionein+2A+by+Diallyl+Trisulfide+Enhances+Chemosensitivity+of+Human+Gastric+Cancer+Cells+to+Docetaxel+Through+Attenuating+NF-%CE%BAB+Activation.&rft.au=Pan%2C+Yuanming%3BLin%2C+Shuye%3BXing%2C+Rui%3BZhu%2C+Min%3BLin%2C+Bonan%3BCui%2C+Jiantao%3BLi%2C+Wenmei%3BGao%2C+Jing%3BShen%2C+Lin%3BZhao%2C+Yuanyuan%3BGuo%2C+Mingzhou%3BWang%2C+Ji+Ming%3BHuang%2C+Jiaqiang%3BLu%2C+Youyong&rft.aulast=Pan&rft.aufirst=Yuanming&rft.date=2016-05-20&rft.volume=24&rft.issue=15&rft.spage=839&rft.isbn=&rft.btitle=&rft.title=Antioxidants+%26+redox+signaling&rft.issn=1557-7716&rft_id=info:doi/10.1089%2Fars.2014.6128 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1089/ars.2014.6128 ER - TY - JOUR T1 - Danazol Treatment for Telomere Diseases. AN - 1790465170; 27192671 AB - Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.). JF - The New England journal of medicine AU - Townsley, Danielle M AU - Dumitriu, Bogdan AU - Liu, Delong AU - Biancotto, Angélique AU - Weinstein, Barbara AU - Chen, Christina AU - Hardy, Nathan AU - Mihalek, Andrew D AU - Lingala, Shilpa AU - Kim, Yun Ju AU - Yao, Jianhua AU - Jones, Elizabeth AU - Gochuico, Bernadette R AU - Heller, Theo AU - Wu, Colin O AU - Calado, Rodrigo T AU - Scheinberg, Phillip AU - Young, Neal S AD - From the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo. Y1 - 2016/05/19/ PY - 2016 DA - 2016 May 19 SP - 1922 EP - 1931 VL - 374 IS - 20 KW - Estrogen Antagonists KW - 0 KW - Telomerase KW - EC 2.7.7.49 KW - Danazol KW - N29QWW3BUO KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Young Adult KW - Humans KW - Aged KW - Telomerase -- genetics KW - Hair Color -- genetics KW - Prospective Studies KW - Adult KW - Middle Aged KW - Up-Regulation KW - Adolescent KW - Telomerase -- metabolism KW - Mutation KW - Female KW - Male KW - Telomere -- drug effects KW - Liver Cirrhosis -- drug therapy KW - Pulmonary Fibrosis -- drug therapy KW - Telomere -- ultrastructure KW - Danazol -- therapeutic use KW - Bone Marrow Diseases -- drug therapy KW - Estrogen Antagonists -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790465170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Danazol+Treatment+for+Telomere+Diseases.&rft.au=Townsley%2C+Danielle+M%3BDumitriu%2C+Bogdan%3BLiu%2C+Delong%3BBiancotto%2C+Ang%C3%A9lique%3BWeinstein%2C+Barbara%3BChen%2C+Christina%3BHardy%2C+Nathan%3BMihalek%2C+Andrew+D%3BLingala%2C+Shilpa%3BKim%2C+Yun+Ju%3BYao%2C+Jianhua%3BJones%2C+Elizabeth%3BGochuico%2C+Bernadette+R%3BHeller%2C+Theo%3BWu%2C+Colin+O%3BCalado%2C+Rodrigo+T%3BScheinberg%2C+Phillip%3BYoung%2C+Neal+S&rft.aulast=Townsley&rft.aufirst=Danielle&rft.date=2016-05-19&rft.volume=374&rft.issue=20&rft.spage=1922&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/10.1056%2FNEJMoa1515319 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-03 N1 - Date created - 2016-05-19 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT01441037; ClinicalTrials.gov N1 - SuppNotes - Comment In: N Engl J Med. 2016 May 19;374(20):1978-80 [27192677] N Engl J Med. 2016 Sep 15;375(11):1095 [27626529] N Engl J Med. 2016 Sep 15;375(11):1095-6 [27626528] N Engl J Med. 2016 Sep 15;375(11):1095 [27626530] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1056/NEJMoa1515319 ER - TY - JOUR T1 - Copy number variations of HLA-I and activation of NKp30 pathway determine the sensitivity of gastric cancer cells to the cytotoxicity of natural killer cells. AN - 1790454006; 26364607 AB - Nude mice are important in vivo model for characterization of cell malignancy behavior; however, many cancer cells fail to form tumors in it. Understanding this defective mechanism may provide novel insights into tumorigenesis and how tumor cells escape innate immunity. Whole-genome sequencing was conducted on two gastric cancer (GC) cells, BGC823 and AGS, which do and do not form tumors in nude mice, to identify their genomic differences relevant to natural killer (NK) cells. We found that the tumorigenic capacity of human GC cell lines was dependent on the recruitment and activation of NK cells in xenograft tumors. We used whole-genome sequence (WGS) on GC cell lines to identify potential genes controlling susceptibility to NK-mediated killing. The tumorigenic cell line BGC823 expressed high levels of HLA-I because of copy gain and was resistant to NK cell killing. In contrast, another cell line AGS expressing low levels of HLA-I with activated NKp30/MAPK/IL-12 (interleukin-12) or IL-2 (interleukin-2) pathway was susceptible to NK lysis. Treatment of tumor bearing mice with systemic administration of IL-12 in combination with intratumor injection of anti-HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression. In human GC specimens, decreased HLA-I expression and increased NK cells surrounding tumor cells were correlated with decreased metastasis potential and better prognosis of patients. Our results provide a mechanistic basis for GC cells to escape NK lysis and a promising prospect of NK immunotherapy for GC cells. JF - Oncogene AU - Xing, R AU - Li, L AU - Chen, L AU - Gao, Z AU - Wang, H AU - Li, W AU - Cui, J AU - Tian, G AU - Liang, Q AU - Yu, J AU - Sung, J J AU - Luo, G AU - Gao, H AU - Xu, X AU - Yang, H AU - Wang, J AU - Zhang, X AU - Wang, J M AU - Huang, J AU - Yu, Y AU - Lu, Y AD - Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China. ; Beijing Genomics Institute at Shenzhen, Shenzhen, China. ; Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China. ; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA. ; Shanghai Engineering Center for Molecular Medicine, Shanghai, China. ; Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA. ; Department of Surgery, Ruijin Hospital and Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Y1 - 2016/05/19/ PY - 2016 DA - 2016 May 19 SP - 2584 EP - 2591 VL - 35 IS - 20 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790454006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Copy+number+variations+of+HLA-I+and+activation+of+NKp30+pathway+determine+the+sensitivity+of+gastric+cancer+cells+to+the+cytotoxicity+of+natural+killer+cells.&rft.au=Xing%2C+R%3BLi%2C+L%3BChen%2C+L%3BGao%2C+Z%3BWang%2C+H%3BLi%2C+W%3BCui%2C+J%3BTian%2C+G%3BLiang%2C+Q%3BYu%2C+J%3BSung%2C+J+J%3BLuo%2C+G%3BGao%2C+H%3BXu%2C+X%3BYang%2C+H%3BWang%2C+J%3BZhang%2C+X%3BWang%2C+J+M%3BHuang%2C+J%3BYu%2C+Y%3BLu%2C+Y&rft.aulast=Xing&rft.aufirst=R&rft.date=2016-05-19&rft.volume=35&rft.issue=20&rft.spage=2584&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2015.324 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2015.324 ER - TY - JOUR T1 - The Potential Use of Forensic DNA Methods Applied to Sand Fly Blood Meal Analysis to Identify the Infection Reservoirs of Anthroponotic Visceral Leishmaniasis AN - 1808632187; PQ0003280859 AB - Visceral leishmaniasis, also known as kala-azar, is a fatal form of leishmaniasis that is caused by the protozoan parasite Leishmania donovani. In the Indian sub-continent, the parasite is transmitted between people by the sand fly Phlebotomus argentipes. There are four different groups of infected people that can carry the parasite: active cases, cured cases, cases of post-kala azar dermal leishmanisis, and people with asymptomatic infections. The relative contribution of these different groups to sustaining the transmission cycle is not known. In the current work, we explore the feasibility of forensic DNA methods that could be applied to directly trace the human source of an infected blood meal in flies collected from high transmission areas. We report that a readable human DNA profile can be generated from the majority of sand flies so long as the flies are sampled within 24 hours after blood feeding. We developed a highly sensitive nested-PCR method that was able to detect parasites present in a fresh, 24 hour blood meal after feeding on an infected host. JF - PLoS Neglected Tropical Diseases AU - Inbar, Ehud AU - Lawyer, Philip AU - Sacks, David AU - Podini, Daniele AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America Y1 - 2016/05/18/ PY - 2016 DA - 2016 May 18 PB - Public Library of Science, 185 Berry Street San Francisco CA 94107 United States VL - 10 IS - 5 SN - 1935-2727, 1935-2727 KW - Biochemistry Abstracts 2: Nucleic Acids; Entomology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Health & Safety Science Abstracts KW - Feasibility studies KW - Parasites KW - Asymptomatic infection KW - Blood meals KW - Hosts KW - Infection KW - Public health KW - Disease transmission KW - Leishmania donovani KW - Phlebotomus argentipes KW - Sand KW - Forensic science KW - Feeding KW - Skin KW - Visceral leishmaniasis KW - Endoparasites KW - Methodology KW - Blood KW - DNA KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - K 03400:Human Diseases KW - Q1 08484:Species interactions: parasites and diseases KW - Z 05350:Medical, Veterinary, and Agricultural Entomology KW - N 14810:Methods KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808632187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+Neglected+Tropical+Diseases&rft.atitle=The+Potential+Use+of+Forensic+DNA+Methods+Applied+to+Sand+Fly+Blood+Meal+Analysis+to+Identify+the+Infection+Reservoirs+of+Anthroponotic+Visceral+Leishmaniasis&rft.au=Inbar%2C+Ehud%3BLawyer%2C+Philip%3BSacks%2C+David%3BPodini%2C+Daniele&rft.aulast=Inbar&rft.aufirst=Ehud&rft.date=2016-05-18&rft.volume=10&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=PLoS+Neglected+Tropical+Diseases&rft.issn=19352727&rft_id=info:doi/10.1371%2Fjournal.pntd.0004706 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Blood; Parasites; DNA; Hosts; Endoparasites; Disease transmission; Public health; Methodology; Feeding; Skin; Visceral leishmaniasis; Forensic science; Asymptomatic infection; Blood meals; Feasibility studies; Sand; Infection; Leishmania donovani; Phlebotomus argentipes DO - http://dx.doi.org/10.1371/journal.pntd.0004706 ER - TY - JOUR T1 - Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells AN - 1808632125; PQ0003280877 AB - Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN- gamma and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease. Yellow fever virus (YFV) is a mosquito-borne flavivirus that can cause lethal hemorrhagic fever in infected humans. An effective live-attenuated vaccine, 17D, was developed in 1937 and continues to be used today. Over the past several years, a number of cases of vaccine-associated disease have been identified and linked to a compromised immune status. In the studies presented here we evaluated the susceptibility of macrophages and dendritic cells (DCs) to YFV infection, their cytokine response to infection and their ability to interact with and stimulate CD4+ T cells. These studies found that macrophages and DCs derived from both humans and non-human primates were susceptible to infection with either a wild-type Asibi YFV or the 17D vaccine virus, that the two viruses stimulated different cytokine responses in these cells and that human DCs infected with the 17D virus were able to stimulate CD4+ T cells while those infected with Asibi virus did not. These data demonstrate clear differences between the wild-type and vaccine viruses that may be related to the success of the 17D vaccine. These data also suggest that wild-type YFV may be able to inhibit critical components of the immune response to allow virus propagation and dissemination. JF - PLoS Neglected Tropical Diseases AU - Cong, Yu AU - McArthur, Monica A AU - Cohen, Melanie AU - Jahrling, Peter B AU - Janosko, Krisztina B AU - Josleyn, Nicole AU - Kang, Kai AU - Zhang, Tengfei AU - Holbrook, Michael R AD - National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America Y1 - 2016/05/18/ PY - 2016 DA - 2016 May 18 PB - Public Library of Science, 185 Berry Street San Francisco CA 94107 United States VL - 10 IS - 5 SN - 1935-2727, 1935-2727 KW - Virology & AIDS Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Health & Safety Science Abstracts KW - Immune status KW - Macrophages KW - gamma -Interferon KW - Chemokines KW - Interleukin 2 KW - Viruses KW - Disease control KW - Hosts KW - Infection KW - Flavivirus KW - Cell activation KW - Dendritic cells KW - CD4 antigen KW - Antigens KW - Yellow fever KW - Lymphocytes T KW - Cytokines KW - Macaca mulatta KW - Antigen-presenting cells KW - Monocytes KW - Biological surveys KW - Mortality KW - Data processing KW - Replication KW - Immunity KW - Primates KW - Vaccination KW - Yellow fever virus KW - Hemorrhagic fever KW - Immune response KW - Vaccines KW - Q1 08423:Behaviour KW - V 22320:Replication KW - Q5 08524:Public health, medicines, dangerous organisms KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808632125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+Neglected+Tropical+Diseases&rft.atitle=Characterization+of+Yellow+Fever+Virus+Infection+of+Human+and+Non-human+Primate+Antigen+Presenting+Cells+and+Their+Interaction+with+CD4%2B+T+Cells&rft.au=Cong%2C+Yu%3BMcArthur%2C+Monica+A%3BCohen%2C+Melanie%3BJahrling%2C+Peter+B%3BJanosko%2C+Krisztina+B%3BJosleyn%2C+Nicole%3BKang%2C+Kai%3BZhang%2C+Tengfei%3BHolbrook%2C+Michael+R&rft.aulast=Cong&rft.aufirst=Yu&rft.date=2016-05-18&rft.volume=10&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=PLoS+Neglected+Tropical+Diseases&rft.issn=19352727&rft_id=info:doi/10.1371%2Fjournal.pntd.0004709 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Biological surveys; Macrophages; Antigens; Viruses; Disease control; Immunity; Hosts; Vaccines; Vaccination; Immune status; gamma -Interferon; Chemokines; Data processing; Interleukin 2; Replication; Infection; Cell activation; Dendritic cells; CD4 antigen; Lymphocytes T; Cytokines; Hemorrhagic fever; Monocytes; Antigen-presenting cells; Mortality; Yellow fever; Immune response; Primates; Yellow fever virus; Macaca mulatta; Flavivirus DO - http://dx.doi.org/10.1371/journal.pntd.0004709 ER - TY - JOUR T1 - Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection AN - 1794505254; PQ0002976172 AB - With >1600 documented human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) and a case fatality rate of approximately 36%, medical countermeasures are needed to prevent and limit the disease. We examined the in vivo efficacy of the human monoclonal antibody m336, which has high neutralizing activity against MERS-CoV in vitro. m336 was administered to rabbits intravenously or intranasally before infection with MERS-CoV. Prophylaxis with m336 resulted in a reduction of pulmonary viral RNA titers by 40-9000-fold, compared with an irrelevant control antibody with little to no inflammation or viral antigen detected. This protection in rabbits supports further clinical development of m336. JF - Journal of Infectious Diseases AU - Houser, Katherine V AU - Gretebeck, Lisa AU - Ying, Tianlei AU - Wang, Yanping AU - Vogel, Leatrice AU - Lamirande, Elaine W AU - Bock, Kevin W AU - Moore, Ian N AU - Dimitrov, Dimiter S AU - Subbarao, Kanta AD - Laboratory of Infectious Diseases, ksubbarao@niaid.nih.gov Y1 - 2016/05/15/ PY - 2016 DA - 2016 May 15 SP - 1557 EP - 1561 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 10 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - MERS-CoV KW - prophylaxis KW - m336 KW - rabbits KW - human mAb KW - Mortality KW - Coronavirus KW - Monoclonal antibodies KW - Infection KW - Inflammation KW - Infectious diseases KW - RNA KW - Lung KW - Prophylaxis KW - Middle East KW - V 22410:Animal Diseases KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794505254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Prophylaxis+With+a+Middle+East+Respiratory+Syndrome+Coronavirus+%28MERS-CoV%29-Specific+Human+Monoclonal+Antibody+Protects+Rabbits+From+MERS-CoV+Infection&rft.au=Houser%2C+Katherine+V%3BGretebeck%2C+Lisa%3BYing%2C+Tianlei%3BWang%2C+Yanping%3BVogel%2C+Leatrice%3BLamirande%2C+Elaine+W%3BBock%2C+Kevin+W%3BMoore%2C+Ian+N%3BDimitrov%2C+Dimiter+S%3BSubbarao%2C+Kanta&rft.aulast=Houser&rft.aufirst=Katherine&rft.date=2016-05-15&rft.volume=213&rft.issue=10&rft.spage=1557&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw080 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - RNA; Lung; Monoclonal antibodies; Prophylaxis; Infection; Inflammation; Mortality; Infectious diseases; Coronavirus; Middle East DO - http://dx.doi.org/10.1093/infdis/jiw080 ER - TY - JOUR T1 - Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils AN - 1787978272; PQ0002976179 AB - Carbapenem-resistant Klebsiella pneumoniae strains classified as multilocus sequence type 258 (ST258) are among the most widespread multidrug-resistant hospital-acquired pathogens. Treatment of infections caused by these organisms is difficult, and mortality is high. The basis for the success of ST258, outside of antibiotic resistance, remains incompletely determined. Here we tested the hypothesis that ST258 K. pneumoniae has enhanced capacity to circumvent killing by human neutrophils, the primary cellular defense against bacterial infections. There was limited binding and uptake of ST258 by human neutrophils, and correspondingly, there was limited killing of bacteria. On the other hand, transmission electron microscopy revealed that any ingested organisms were degraded readily within neutrophil phagosomes, thus indicating that survival in the neutrophil assays is due to limited phagocytosis, rather than to microbicide resistance after uptake. Our findings suggest that enhancing neutrophil phagocytosis is a potential therapeutic approach for treatment of infection caused by carbapenem-resistant ST258 K. pneumoniae. JF - Journal of Infectious Diseases AU - Kobayashi, Scott D AU - Porter, Adeline R AU - Dorward, David W AU - Brinkworth, Amanda J AU - Chen, Liang AU - Kreiswirth, Barry N AU - Deleo, Frank R AD - Laboratory of Bacteriology, fdeleo@niaid.nih.gov Y1 - 2016/05/15/ PY - 2016 DA - 2016 May 15 SP - 1615 EP - 1622 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 10 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; Health & Safety Science Abstracts KW - Klebsiella pneumoniae KW - neutrophil KW - phagocytosis KW - Cell survival KW - Mortality KW - Transmission electron microscopy KW - Drug resistance KW - Phagosomes KW - Leukocytes (neutrophilic) KW - Survival KW - Pathogens KW - Ingestion KW - Infection KW - Infectious diseases KW - Microscopy KW - Uptake KW - Phagocytosis KW - Antibiotic resistance KW - microbicides KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - J 02400:Human Diseases KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787978272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Phagocytosis+and+Killing+of+Carbapenem-Resistant+ST258+Klebsiella+pneumoniae+by+Human+Neutrophils&rft.au=Kobayashi%2C+Scott+D%3BPorter%2C+Adeline+R%3BDorward%2C+David+W%3BBrinkworth%2C+Amanda+J%3BChen%2C+Liang%3BKreiswirth%2C+Barry+N%3BDeleo%2C+Frank+R&rft.aulast=Kobayashi&rft.aufirst=Scott&rft.date=2016-05-15&rft.volume=213&rft.issue=10&rft.spage=1615&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiw001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Cell survival; Mortality; Drug resistance; Transmission electron microscopy; Phagosomes; Leukocytes (neutrophilic); Pathogens; Infection; Phagocytosis; Antibiotic resistance; microbicides; Infectious diseases; Microscopy; Survival; Uptake; Ingestion; Klebsiella pneumoniae DO - http://dx.doi.org/10.1093/infdis/jiw001 ER - TY - JOUR T1 - Atazanavir exposure in utero and neurodevelopment in infants: a comparative safety study. AN - 1785752446; 26867136 AB - To evaluate the safety of in-utero exposure to atazanavir and neurodevelopment in perinatally HIV-exposed but uninfected (PHEU) infants. Prospective cohort study of mother-PHEU infant pairs in the Surveillance Monitoring for ART Toxicities protocol of the Pediatric HIV/AIDS Cohort Study. Pregnant women living with HIV who initiated an antiretroviral regimen during pregnancy were followed from the date of antiretroviral initiation. Women were classified according to whether the antiretroviral regimen contained atazanavir and the trimester of antiretroviral initiation. Neurodevelopment at 9-15 months was evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). We estimated mean differences for the five Bayley-III domains for atazanavir-containing regimens versus all other regimens. Models included baseline covariates and adjustment for failure to complete the Bayley-III using inverse probability weighting. PHEU infants were exposed in utero to atazanavir-containing (n = 167) and nonatazanavir-containing (n = 750) antiretroviral regimens. The adjusted mean differences (95% confidence interval) in Bayley-III domain scores for initiating an atazanavir-containing regimen in the first trimester were: cognitive, -1.5 (-6.2, 3.2); language, -3.3 (-7.6, 1.0); motor, -2.9 (-7.7, 1.9); social-emotional, 0.1 (-6.2, 6.4); and adaptive behavior, -0.1 (-4.3, 4.0). The mean differences for the second or third trimester were: cognitive, 0.4 (-3.2, 4.0); language, -3.4 (-6.2, -0.5); motor, 0.3 (-2.9, 3.4); social-emotional, -5.9 (-9.4, -2.3); and adaptive behavior, -2.5 (-5.9, 0.8). In-utero exposure to atazanavir-containing regimens compared with non-atazanavir-containing regimens may adversely affect language and social-emotional development in PHEU infants during the first year of life, but the absolute difference is small. JF - AIDS (London, England) AU - Caniglia, Ellen C AU - Patel, Kunjal AU - Huo, Yanling AU - Williams, Paige L AU - Kapetanovic, Suad AU - Rich, Kenneth C AU - Sirois, Patricia A AU - Jacobson, Denise L AU - Hernandez-Diaz, Sonia AU - Hernán, Miguel A AU - Seage, George R AU - Pediatric HIVAIDS Cohort Study AD - aHarvard T.H. Chan School of Public Health, Boston, Massachusetts bDepartment of Psychiatry and Behavioral Sciences, University of Southern California Keck School of Medicine, Los Angeles, California cNational Institutes of Health, National Institute of Mental Health, Bethesda, Maryland dUniversity of Illinois at Chicago College of Medicine, Chicago, Illinois eTulane University School of Medicine, New Orleans, Louisiana fHarvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts, USA. ; Pediatric HIVAIDS Cohort Study Y1 - 2016/05/15/ PY - 2016 DA - 2016 May 15 SP - 1267 EP - 1278 VL - 30 IS - 8 KW - Index Medicus KW - AIDS/HIV UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785752446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Atazanavir+exposure+in+utero+and+neurodevelopment+in+infants%3A+a+comparative+safety+study.&rft.au=Caniglia%2C+Ellen+C%3BPatel%2C+Kunjal%3BHuo%2C+Yanling%3BWilliams%2C+Paige+L%3BKapetanovic%2C+Suad%3BRich%2C+Kenneth+C%3BSirois%2C+Patricia+A%3BJacobson%2C+Denise+L%3BHernandez-Diaz%2C+Sonia%3BHern%C3%A1n%2C+Miguel+A%3BSeage%2C+George+R%3BPediatric+HIVAIDS+Cohort+Study&rft.aulast=Caniglia&rft.aufirst=Ellen&rft.date=2016-05-15&rft.volume=30&rft.issue=8&rft.spage=1267&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=1473-5571&rft_id=info:doi/10.1097%2FQAD.0000000000001052 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-30 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Acquir Immune Defic Syndr. 2011 Aug 1;57(4):290-6 [21602695] HIV Med. 2011 Oct;12(9):570-9 [21569187] HIV Med. 2012 Jan;13(1):1-44 [22171742] J Dev Behav Pediatr. 2012 Feb;33(2):112-23 [22179050] AIDS. 2012 Jun 1;26(9):1151-9 [22382151] Pediatrics. 2012 Nov;130(5):e1326-44 [23118140] Epidemiology. 2000 Sep;11(5):561-70 [10955409] AIDS. 2000 Dec 22;14(18):2913-20 [11398741] Vital Health Stat 11. 2002 May;(246):1-190 [12043359] Cell Tissue Res. 2003 Oct;314(1):119-29 [12955493] Pediatrics. 2004 Jul;114(1):e130-53 [15231986] J Pediatr. 1977 Aug;91(2):292-7 [874689] Early Hum Dev. 1987 Sep;15(5):269-77 [3678119] N Engl J Med. 1994 Nov 3;331(18):1173-80 [7935654] Pediatrics. 1994 Oct;94(4 Pt 1):558-65 [7755691] J Pediatr. 1997 Dec;131(6):851-6 [9427889] Am J Epidemiol. 2005 Aug 1;162(3):199-200 [15987728] Lancet. 2005 Jul 30-Aug 5;366(9483):378-84 [16054937] N Engl J Med. 2006 May 4;354(18):1889-900 [16672700] Pediatrics. 2006 Oct;118(4):e1139-45 [16940166] Neuromolecular Med. 2006;8(4):513-29 [17028373] Drug Saf. 2007;30(3):203-13 [17343429] Pediatrics. 2007 Apr;119(4):e900-6 [17353299] Eur J Clin Nutr. 2007 Dec;61(12):1380-5 [17299469] Pediatrics. 2008 Jul;122(1):119-24 [18595994] Curr HIV Res. 2009 Nov;7(6):620-5 [19929798] Neuropsychol Rev. 2010 Dec;20(4):327-48 [21042938] Eur J Obstet Gynecol Reprod Biol. 2011 Jul;157(1):18-21 [21492993] Int J Dev Biol. 2011;55(4-5):467-76 [21769778] J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):218-22 [21372725] Int J Pediatr Otorhinolaryngol. 2013 Jun;77(6):898-905 [23642487] Pediatr Infect Dis J. 2013 Jun;32(6):648-55 [23340561] Pediatr Infect Dis J. 2013 Oct;32(10):e406-13 [24067563] J Antimicrob Chemother. 2014 May;69(5):1377-84 [24370933] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1097/QAD.0000000000001052 ER - TY - JOUR T1 - Current understanding of interactions between nanoparticles and the immune system. AN - 1777075735; 26739622 AB - The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure-activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle-immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15years of research on the immunotoxicity of engineered nanomaterials. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Toxicology and applied pharmacology AU - Dobrovolskaia, Marina A AU - Shurin, Michael AU - Shvedova, Anna A AD - Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI at Frederick, Frederick, MD 21702, USA. Electronic address: marina@mail.nih.gov. ; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA; Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. ; Health Effects Laboratory Division, National Institute of Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA; Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506, USA. Electronic address: ats1@cdc.gov. Y1 - 2016/05/15/ PY - 2016 DA - 2016 May 15 SP - 78 EP - 89 VL - 299 KW - Index Medicus KW - Drug delivery KW - Immunotoxicity KW - Immunology KW - Preclinical KW - Nanoparticles KW - Animals KW - Particle Size KW - Humans KW - Drug Delivery Systems -- methods KW - Drug Delivery Systems -- adverse effects KW - Immune System -- drug effects KW - Nanoparticles -- metabolism KW - Nanotechnology -- methods KW - Comprehension KW - Immune System -- immunology KW - Nanoparticles -- toxicity KW - Nanotechnology -- trends KW - Nanoparticles -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777075735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Current+understanding+of+interactions+between+nanoparticles+and+the+immune+system.&rft.au=Dobrovolskaia%2C+Marina+A%3BShurin%2C+Michael%3BShvedova%2C+Anna+A&rft.aulast=Dobrovolskaia&rft.aufirst=Marina&rft.date=2016-05-15&rft.volume=299&rft.issue=&rft.spage=78&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2015.12.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-18 N1 - Date created - 2016-03-29 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Clin Cancer Res. 2010 Dec 15;16(24):6139-49 [20876255] Nat Nanotechnol. 2011 Jan;6(1):39-44 [21170037] J Immunotoxicol. 2011 Jan-Mar;8(1):56-67 [21288165] Int J Immunopathol Pharmacol. 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AN - 1777075683; 26773813 AB - Nanoparticle immunogenicity and antigenicity have been under investigation for many years. During the past decade, significant progress has been made in understanding what makes a nanoparticle immunogenic, how immune cells respond to nanoparticles, what consequences of nanoparticle-specific antibody formation exist and how they challenge the application of nanoparticles for drug delivery. Moreover, it has been recognized that accidental contamination of therapeutic protein formulations with nanosized particulate materials may contribute to the immunogenicity of this type of biotechnology products. While the immunological properties of engineered nanomaterials and their application as vaccine carriers and adjuvants have been given substantial consideration in the current literature, little attention has been paid to nanoparticle immuno- and antigenicity. To fill in this gap, we herein provide an overview of this subject to highlight the current state of the field, review past and present research, and discuss future research directions. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Toxicology and applied pharmacology AU - Ilinskaya, Anna N AU - Dobrovolskaia, Marina A AD - Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI at Frederick, Frederick, MD 21702, USA. ; Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI at Frederick, Frederick, MD 21702, USA. Electronic address: marina@mail.nih.gov. Y1 - 2016/05/15/ PY - 2016 DA - 2016 May 15 SP - 70 EP - 77 VL - 299 KW - Adjuvants, Immunologic KW - 0 KW - Drug Carriers KW - Index Medicus KW - Antibody KW - Immunogenicity KW - Antigenicity KW - Anaphylaxis KW - Preclinical KW - Cytokines KW - Phagocytosis KW - Nanoparticles KW - Animals KW - Adjuvants, Immunologic -- toxicity KW - Adjuvants, Immunologic -- administration & dosage KW - Humans KW - Drug Carriers -- administration & dosage KW - Drug Delivery Systems -- methods KW - Drug Carriers -- toxicity KW - Forecasting KW - Drug Delivery Systems -- adverse effects KW - Nanostructures -- administration & dosage KW - Antigenic Modulation -- immunology KW - Immunity, Cellular -- drug effects KW - Antigenic Modulation -- drug effects KW - Comprehension KW - Immunity, Cellular -- immunology KW - Immunogenetic Phenomena -- immunology KW - Nanostructures -- toxicity KW - Immunogenetic Phenomena -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777075683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Understanding+the+immunogenicity+and+antigenicity+of+nanomaterials%3A+Past%2C+present+and+future.&rft.au=Ilinskaya%2C+Anna+N%3BDobrovolskaia%2C+Marina+A&rft.aulast=Ilinskaya&rft.aufirst=Anna&rft.date=2016-05-15&rft.volume=299&rft.issue=&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.01.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-18 N1 - Date created - 2016-03-29 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 May-Jun;2(3):205-18 [20391461] Proc Natl Acad Sci U S A. 2010 May 11;107(19):8760-5 [20410458] Int J Pharm. 2010 Jun 15;392(1-2):218-23 [20227473] Biologicals. 2010 Sep;38(5):602-11 [20702108] Biomacromolecules. 2010 Oct 11;11(10):2700-6 [20795699] Clin Cancer Res. 2010 Dec 15;16(24):6139-49 [20876255] J Am Chem Soc. 2011 Mar 2;133(8):2525-34 [21288025] Biologicals. 2011 Mar;39(2):100-9 [21353596] PDA J Pharm Sci Technol. 2010 Jan-Feb;64(1):11-9 [21501999] J Pharm Sci. 2011 Nov;100(11):5069-77 [21721002] J Pharm Sci. 2011 Nov;100(11):4953-64 [21721003] J Pharm Sci. 2012 Jan;101(1):187-99 [21918983] Analyst. 2012 Jan 7;137(1):98-105 [22053319] J Pharm Sci. 2012 Mar;101(3):946-54 [22170395] Bioconjug Chem. 2012 Mar 21;23(3):485-99 [22332808] Pharm Res. 2012 Jun;29(6):1454-67 [22094831] J Pharm Sci. 2012 Aug;101(8):2952-9 [22674153] J Pharm Sci. 2005 Feb;94(2):256-74 [15570600] J Pharmacol Exp Ther. 2005 Mar;312(3):1020-6 [15525796] J Control Release. 2005 Jul 20;105(3):305-17 [15908032] Int J Pharm. 2006 Jan 3;307(1):93-102 [16303268] Mol Ther. 2006 Feb;13(2):328-37 [16275098] J Control Release. 2006 May 1;112(1):15-25 [16515818] Nano Lett. 2006 Sep;6(9):1870-4 [16967993] J Control Release. 2006 Oct 27;115(3):243-50 [17011060] J Control Release. 2006 Oct 27;115(3):251-8 [17045355] J Pharm Pharmacol. 2006 Nov;58(11):1491-8 [17132212] J Thromb Thrombolysis. 2007 Feb;23(1):9-23 [17111203] J Control Release. 2007 Jun 4;119(2):236-44 [17399838] Cancer. 2007 Jul 1;110(1):103-11 [17516438] J Control Release. 2007 Oct 8;122(3):349-55 [17610982] Am Fam Physician. 2007 Sep 15;76(6):801-8 [17910294] Nat Biotechnol. 2007 Oct;25(10):1159-64 [17873867] Trends Immunol. 2007 Nov;28(11):482-90 [17964218] Biomaterials. 2008 Feb;29(5):551-60 [17981322] N Engl J Med. 2013 Jan 24;368(4):320-32 [23343062] Pharm Res. 2013 Apr;30(4):985-95 [23184228] N Engl J Med. 2002 May 16;346(20):1584-6; 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AN - 1787478563; 26976425 AB - Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs. Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers. Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell-derived factor 1α (P = .037 and .025, respectively). Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies. © 2016 by American Society of Clinical Oncology. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Blakeley, Jaishri O AU - Ye, Xiaobu AU - Duda, Dan G AU - Halpin, Chris F AU - Bergner, Amanda L AU - Muzikansky, Alona AU - Merker, Vanessa L AU - Gerstner, Elizabeth R AU - Fayad, Laura M AU - Ahlawat, Shivani AU - Jacobs, Michael A AU - Jain, Rakesh K AU - Zalewski, Christopher AU - Dombi, Eva AU - Widemann, Brigitte C AU - Plotkin, Scott R AD - Jaishri O. Blakeley, Xiaobu Ye, Amanda L. Bergner, Laura M. Fayad, Shivani Ahlawat, and Michael A. Jacobs, Johns Hopkins University, Baltimore; Christopher Zalewski, National Institute on Deafness and Other Communication Disorders; Eva Dombi and Brigitte C. Widemann, National Cancer Institute, Bethesda, MD; Dan G. Duda, Alona Muzikansky, Vanessa L. Merker, Elizabeth R. Gerstner, Rakesh K. Jain, and Scott R. Plotkin, Massachusetts General Hospital; and Chris F. Halpin, Massachusetts Eye and Ear Infirmary, Boston, MA. jblakel3@jhmi.edu. ; Jaishri O. Blakeley, Xiaobu Ye, Amanda L. Bergner, Laura M. Fayad, Shivani Ahlawat, and Michael A. Jacobs, Johns Hopkins University, Baltimore; Christopher Zalewski, National Institute on Deafness and Other Communication Disorders; Eva Dombi and Brigitte C. Widemann, National Cancer Institute, Bethesda, MD; Dan G. Duda, Alona Muzikansky, Vanessa L. Merker, Elizabeth R. Gerstner, Rakesh K. Jain, and Scott R. Plotkin, Massachusetts General Hospital; and Chris F. Halpin, Massachusetts Eye and Ear Infirmary, Boston, MA. Y1 - 2016/05/10/ PY - 2016 DA - 2016 May 10 SP - 1669 EP - 1675 VL - 34 IS - 14 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787478563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Efficacy+and+Biomarker+Study+of+Bevacizumab+for+Hearing+Loss+Resulting+From+Neurofibromatosis+Type+2-Associated+Vestibular+Schwannomas.&rft.au=Blakeley%2C+Jaishri+O%3BYe%2C+Xiaobu%3BDuda%2C+Dan+G%3BHalpin%2C+Chris+F%3BBergner%2C+Amanda+L%3BMuzikansky%2C+Alona%3BMerker%2C+Vanessa+L%3BGerstner%2C+Elizabeth+R%3BFayad%2C+Laura+M%3BAhlawat%2C+Shivani%3BJacobs%2C+Michael+A%3BJain%2C+Rakesh+K%3BZalewski%2C+Christopher%3BDombi%2C+Eva%3BWidemann%2C+Brigitte+C%3BPlotkin%2C+Scott+R&rft.aulast=Blakeley&rft.aufirst=Jaishri&rft.date=2016-05-10&rft.volume=34&rft.issue=14&rft.spage=1669&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/10.1200%2FJCO.2015.64.3817 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-05 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19059-64 [24190997] Neurosurgery. 1997 Apr;40(4):696-705; discussion 705-6 [9092842] Cancer Chemother Pharmacol. 2014 Jun;73(6):1197-204 [24710627] J Neurosurg. 2013 Dec;119 Suppl:1-6 [25077303] J Neurosurg. 2013 Dec;119 Suppl:195-9 [25077305] Neuro Oncol. 2014 Sep;16(9):1196-209 [24558021] J Neurosurg. 2014 Dec;121 Suppl:143-9 [25434947] Cancer Cell. 2014 Nov 10;26(5):605-22 [25517747] Neuro Oncol. 2015 Apr;17(4):566-73 [25452392] Otolaryngol Clin North Am. 2015 Jun;48(3):407-22 [25886814] J Med Genet. 2015 Aug;52(8):557-62 [26104281] Neurology. 2013 Nov 19;81(21 Suppl 1):S25-32 [24249803] Am J Med Genet A. 2012 Jan;158A(1):24-41 [22140088] Otolaryngol Head Neck Surg. 2012 Nov;147(5):803-7 [22931898] Otol Neurotol. 2012 Aug;33(6):1046-52 [22805104] Neurosurgery. 2010 Nov;67(5):1335-40; discussion 1340 [20871439] J Clin Oncol. 2010 Jun 10;28(17):2817-23 [20458050] Cancer Res. 2010 May 1;70(9):3483-93 [20406973] Otol Neurotol. 2009 Sep;30(6):835-41 [19704365] N Engl J Med. 2009 Jul 23;361(4):358-67 [19587327] Orphanet J Rare Dis. 2009;4:16 [19545378] Lancet. 2009 Jun 6;373(9679):1974-86 [19476995] Nat Rev Clin Oncol. 2009 Jun;6(6):327-38 [19483739] J Neurooncol. 2009 May;93(1):61-77 [19430883] Neurosurgery. 2008 Jun;62(6):1314-9; discussion 1319-20 [18824998] Otol Neurotol. 2007 Dec;28(8):1094-9 [17721409] Nat Rev Neurosci. 2007 Aug;8(8):610-22 [17643088] Lancet Neurol. 2007 Apr;6(4):340-51 [17362838] Otol Neurotol. 2006 Jan;27(1):110-6 [16371857] Neuro Oncol. 2016 Feb;18(2):275-82 [26311690] Arch Neurol. 1994 Feb;51(2):201-7 [8304846] Q J Med. 1992 Aug;84(304):603-18 [1484939] J Speech Hear Res. 1978 Sep;21(3):507-18 [713519] J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1288-93 [12933938] Neurology. 2002 Dec 10;59(11):1759-65 [12473765] Otol Neurotol. 2014 Jan;35(1):e50-6 [24335938] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1200/JCO.2015.64.3817 ER - TY - JOUR T1 - Structural characterization of the virulence factor Sda1 nuclease from Streptococcus pyogenes. AN - 1787478341; 26969731 AB - Infection by Group A Streptococcus pyogenes (GAS) is a leading cause of severe invasive disease in humans, including streptococcal toxic shock syndrome and necrotizing fasciitis. GAS infections lead to nearly 163,000 annual deaths worldwide. Hypervirulent strains of S. pyogenes have evolved a plethora of virulence factors that aid in disease-by promoting bacterial adhesion to host cells, subsequent invasion of deeper tissues and blocking the immune system's attempts to eradicate the infection. Expression and secretion of the extracellular nuclease Sda1 is advantageous for promoting bacterial dissemination throughout the host organism, and evasion of the host's innate immune response. Here we present two crystal structures of Sda1, as well as biochemical studies to address key structural features and surface residues involved in DNA binding and catalysis. In the active site, Asn211 is observed to directly chelate a hydrated divalent metal ion and Arg124, on the putative substrate binding loop, likely stabilizes the transition state during phosphodiester bond cleavage. These structures provide a foundation for rational drug design of small molecule inhibitors to be used in prevention of invasive streptococcal disease. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. JF - Nucleic acids research AU - Moon, Andrea F AU - Krahn, Juno M AU - Lu, Xun AU - Cuneo, Matthew J AU - Pedersen, Lars C AD - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA moon@niehs.nih.gov. ; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. ; Spallation Neutron Source, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. Y1 - 2016/05/05/ PY - 2016 DA - 2016 May 05 SP - 3946 EP - 3957 VL - 44 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787478341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Structural+characterization+of+the+virulence+factor+Sda1+nuclease+from+Streptococcus+pyogenes.&rft.au=Moon%2C+Andrea+F%3BKrahn%2C+Juno+M%3BLu%2C+Xun%3BCuneo%2C+Matthew+J%3BPedersen%2C+Lars+C&rft.aulast=Moon&rft.aufirst=Andrea&rft.date=2016-05-05&rft.volume=44&rft.issue=8&rft.spage=3946&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/10.1093%2Fnar%2Fgkw143 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-06 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Clin Microbiol Rev. 2000 Jul;13(3):470-511 [10885988] Sci Rep. 2015;5:15877 [26522788] Nat Med. 2002 Dec;8(12):1398-404 [12436116] EMBO J. 2003 Aug 1;22(15):4014-25 [12881435] Mol Microbiol. 2004 Jan;51(1):123-34 [14651616] Mol Microbiol. 2004 Oct;54(1):184-97 [15458415] J Mol Biol. 1990 Jun 20;213(4):727-38 [2359120] Lancet. 1992 Feb 29;339(8792):518-21 [1346879] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Biochemistry. 1999 Aug 3;38(31):9948-55 [10433701] J Mol Biol. 1999 Sep 17;292(2):195-202 [10493868] J Bacteriol. 2005 May;187(10):3311-8 [15866915] J Biol Chem. 2005 Jul 29;280(30):27990-7 [15897201] Lancet Infect Dis. 2005 Nov;5(11):685-94 [16253886] Curr Biol. 2006 Feb 21;16(4):396-400 [16488874] Nucleic Acids Res. 2007;35(2):584-94 [17175542] Semin Immunol. 2007 Aug;19(4):262-71 [17560120] Nat Med. 2007 Aug;13(8):981-5 [17632528] Emerg Infect Dis. 2008 Oct;14(10):1511-7 [18826812] Protein Sci. 2010 May;19(5):901-13 [20196072] Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9 [20457744] Nucleic Acids Res. 2011 Apr;39(7):2943-53 [21113026] Nat Rev Microbiol. 2011 Oct;9(10):724-36 [21921933] Nat Methods. 2011;8(10):785-6 [21959131] Nucleic Acids Res. 2012 Jan;40(2):928-38 [21948797] Chembiochem. 2012 Mar 19;13(5):713-21 [22344704] PLoS Pathog. 2012;8(6):e1002736 [22719247] Nucleic Acids Res. 2013 Jul;41(Web Server issue):W349-57 [23748958] Mol Microbiol. 2013 Aug;89(3):518-31 [23772975] J Allergy Clin Immunol. 2013 Dec;132(6):1420-6 [23915714] Nat Struct Mol Biol. 2014 Mar;21(3):253-60 [24487959] Acta Crystallogr D Biol Crystallogr. 2014 Nov;70(Pt 11):2937-49 [25372684] Nat Genet. 2015 Jan;47(1):84-7 [25401300] Eur J Immunol. 2000 Nov;30(11):3247-55 [11093140] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/nar/gkw143 ER - TY - JOUR T1 - Combinatorial targeting of TSLP, IL-25, and IL-33 in type 2 cytokine-driven inflammation and fibrosis AN - 1808729261; PQ0003314788 AB - Thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33 are important initiators of type 2-associated mucosal inflammation and immunity. However, their role in the maintenance of progressive type 2 inflammation and fibrosis is much less clear. Using chronic models of helminth infection and allergic lung inflammation, we show that collective disruption of TSLP, IL-25, and IL-33 signaling suppresses chronic and progressive type 2 cytokine-driven inflammation and fibrosis. In a schistosome lung granuloma model or during chronic Schistosoma mansoni infection in the liver, individual ablation of TSLP, IL-25, or IL-33/ST2 had no impact on the development of IL-4/IL-13-dependent inflammation or fibrosis. However, significant reductions in granuloma-associated eosinophils, hepatic fibrosis, and IL-13-producing type 2 innate lymphoid cells (ILC2s) were observed when signaling of all three mediators was simultaneously disrupted. Combined blockade through monoclonal antibody (mAb) treatment also reduced IL-5 and IL-13 expression during primary and secondary granuloma formation in the lungs. In a model of chronic house dust mite-induced allergic lung inflammation, combined mAb treatment did not decrease established inflammation or fibrosis. TSLP/IL-33 double-knockout mice treated with anti-IL-25 mAb during priming, however, displayed decreased inflammation, mucus production, and lung remodeling in the chronic phase. Together, these studies reveal partially redundant roles for TSLP, IL-25, and IL-33 in the maintenance of type 2 pathology and suggest that in some settings, early combined targeting of these mediators is necessary to ameliorate progressive type 2-driven disease. JF - Science Translational Medicine AU - Vannella, Kevin M AU - Ramalingam, Thirumalai R AU - Borthwick, Lee A AU - Barron, Luke AU - Hart, Kevin M AU - Thompson, Robert W AU - Kindrachuk, Kristen N AU - Cheever, Allen W AU - White, Sandra AU - Budelsky, Alison L AU - Comeau, Michael R AU - Smith, Dirk E AU - Wynn, Thomas A AD - Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2016/05/04/ PY - 2016 DA - 2016 May 04 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 United States VL - 8 IS - 337 SN - 1946-6234, 1946-6234 KW - Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Schistosoma mansoni KW - Lymphoid cells KW - Translation KW - Interleukin 4 KW - Interleukin 5 KW - Mucosal immunity KW - Monoclonal antibodies KW - Fibrosis KW - Animal models KW - Mucus KW - Leukocytes (eosinophilic) KW - Immunity KW - Granuloma KW - Inflammation KW - Interleukin 13 KW - Lung KW - Chronic infection KW - Liver KW - Thymic stromal lymphopoietin KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808729261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+Translational+Medicine&rft.atitle=Combinatorial+targeting+of+TSLP%2C+IL-25%2C+and+IL-33+in+type+2+cytokine-driven+inflammation+and+fibrosis&rft.au=Vannella%2C+Kevin+M%3BRamalingam%2C+Thirumalai+R%3BBorthwick%2C+Lee+A%3BBarron%2C+Luke%3BHart%2C+Kevin+M%3BThompson%2C+Robert+W%3BKindrachuk%2C+Kristen+N%3BCheever%2C+Allen+W%3BWhite%2C+Sandra%3BBudelsky%2C+Alison+L%3BComeau%2C+Michael+R%3BSmith%2C+Dirk+E%3BWynn%2C+Thomas+A&rft.aulast=Vannella&rft.aufirst=Kevin&rft.date=2016-05-04&rft.volume=8&rft.issue=337&rft.spage=337ra65&rft.isbn=&rft.btitle=&rft.title=Science+Translational+Medicine&rft.issn=19466234&rft_id=info:doi/10.1126%2Fscitranslmed.aaf1938 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Lymphoid cells; Translation; Interleukin 4; Interleukin 5; Mucosal immunity; Fibrosis; Monoclonal antibodies; Animal models; Mucus; Immunity; Leukocytes (eosinophilic); Granuloma; Inflammation; Interleukin 13; Lung; Chronic infection; Liver; Thymic stromal lymphopoietin; Schistosoma mansoni DO - http://dx.doi.org/10.1126/scitranslmed.aaf1938 ER - TY - JOUR T1 - Strain Analysis in the Assessment of a Mouse Model of Cardiotoxicity due to Chemotherapy: Sample for Preclinical Research. AN - 1814669965; 27107087 AB - In recent years, the development of more effective anticancer drugs has provided great benefits in patients' quality of life by improving both prognosis and disease-free survival. Nevertheless, the frequency and severity of side-effects, with particular reference to cardiac toxicity, have gained particular attention. The purpose of this study was to create a precise and sensitive preclinical model, able to identify early contractile dysfunction in mice treated with chemotherapy, through use of speckle-tracking echocardiography. We generated a mouse model of cardiotoxicity induced by doxorubicin. C57BL 6 mice were divided into two groups, treated for 7 days by intraperitoneal injections of placebo (vehicle) or doxorubicin (2.17 mg/kg), in order to characterize the cardiac phenotype in vivo. We demonstrated that doxorubicin caused ealy remodeling of the left ventricle: after two days of therapy, the radial, circumferential and strain rates were reduced respectively by 35%, 34%, and 39% (p-value ≤0.001). Moreover, histological analysis revealed that doxorubicin treatment increased fibrosis, cardiomyocyte diameter and apoptosis. In a murine model of doxorubicin-induced cardiac injury, we detected left ventricular dysfunction followed by alterations in conventional echocardiographic indices. Our study suggests that a change in strain could be an effective early marker of myocardial dysfunction for new anticancer treatments and, in preclinical studies, it might also be a valuable indicator for the assessment of activity of cardioprotective agents. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. JF - In vivo (Athens, Greece) AU - Rea, Domenica AU - Coppola, Carmela AU - Barbieri, Antonio AU - Monti, Maria Gaia AU - Misso, Gabriella AU - Palma, Giuseppe AU - Bimonte, Sabrina AU - Zarone, Mayra Rachele AU - Luciano, Antonio AU - Liccardo, Davide AU - Maiolino, Piera AU - Cittadini, Antonio AU - Ciliberto, Gennaro AU - Arra, Claudio AU - Maurea, Nicola AD - Animal Facility Unit, Department of Experimental Oncology, "G. Pascale Foundation", IRCCS, Naples, Italy d.rea@istitutotumori.na.it. ; Cardiology Unit, "G. Pascale Foundation", IRCCS, Naples, Italy. ; Department of Translational Medical Sciences, Federico II University, Naples, Italy. ; Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. ; Division of Abdominal Surgical Oncology, Hepatobiliary Unit, "G. Pascale Foundation", IRCCS, Naples, Italy. ; Department of Health Management, Pharmacy and Quality of Life, "G. Pascale Foundation", IRCCS, Naples, Italy. ; Scientific Direction, National Cancer Institute, "G. Pascale Foundation", IRCCS, Naples, Italy. PY - 2016 SP - 279 EP - 290 VL - 30 IS - 3 KW - Index Medicus KW - cardiotoxicity KW - speckle-tracking echocardiography KW - mouse model KW - Strain KW - chemotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1814669965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Strain+Analysis+in+the+Assessment+of+a+Mouse+Model+of+Cardiotoxicity+due+to+Chemotherapy%3A+Sample+for+Preclinical+Research.&rft.au=Rea%2C+Domenica%3BCoppola%2C+Carmela%3BBarbieri%2C+Antonio%3BMonti%2C+Maria+Gaia%3BMisso%2C+Gabriella%3BPalma%2C+Giuseppe%3BBimonte%2C+Sabrina%3BZarone%2C+Mayra+Rachele%3BLuciano%2C+Antonio%3BLiccardo%2C+Davide%3BMaiolino%2C+Piera%3BCittadini%2C+Antonio%3BCiliberto%2C+Gennaro%3BArra%2C+Claudio%3BMaurea%2C+Nicola&rft.aulast=Rea&rft.aufirst=Domenica&rft.date=2016-05-01&rft.volume=30&rft.issue=3&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=1791-7549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-23 N1 - Date revised - 2017-01-25 N1 - Last updated - 2017-01-25 ER - TY - JOUR T1 - Strategies for Investigating G-Protein Modulation of Voltage-Gated Ca super(2+) Channels AN - 1808739608; PQ0003355142 AB - G-protein-coupled receptor modulation of voltage-gated ion channels is a common means of fine-tuning the response of channels to changes in membrane potential. Such modulation impacts physiological processes such as synaptic transmission, and hence therapeutic strategies often directly or indirectly target these pathways. As an exemplar of channel modulation, we examine strategies for investigating G-protein modulation of Ca sub(V) 2.2 or N-type voltage-gated Ca super(2+) channels. We focus on biochemical and genetic tools for defining the molecular mechanisms underlying the various forms of Ca sub(V) 2.2 channel modulation initiated following ligand binding to G-protein-coupled receptors. JF - Cold Spring Harbor Protocols AU - Lu, Van B AU - Ikeda, Stephen R AD - Section on Transmitter Signaling, Laboratory of Molecular Physiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-9411, sikeda@mail.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States IS - 5 SN - 1940-3402, 1940-3402 KW - Biotechnology and Bioengineering Abstracts KW - Molecular modelling KW - G protein-coupled receptors KW - Ion channels KW - Guanine nucleotide-binding protein KW - Calcium channels (voltage-gated) KW - Synaptic transmission KW - Membrane potential KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808739608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Protocols&rft.atitle=Strategies+for+Investigating+G-Protein+Modulation+of+Voltage-Gated+Ca+super%282%2B%29+Channels&rft.au=Lu%2C+Van+B%3BIkeda%2C+Stephen+R&rft.aulast=Lu&rft.aufirst=Van&rft.date=2016-05-01&rft.volume=&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Protocols&rft.issn=19403402&rft_id=info:doi/10.1101%2Fpdb.top087072 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Molecular modelling; G protein-coupled receptors; Ion channels; Guanine nucleotide-binding protein; Synaptic transmission; Calcium channels (voltage-gated); Membrane potential DO - http://dx.doi.org/10.1101/pdb.top087072 ER - TY - JOUR T1 - G-Protein Modulation of Voltage-Gated Ca super(2+) Channels from Isolated Adult Rat Superior Cervical Ganglion Neurons AN - 1808739592; PQ0003355144 AB - Sympathetic neurons isolated from adult rat superior cervical ganglia (SCG) are a well-established model to study G-protein modulation of voltage-gated Ca super(2+) channels (VGCCs). SCG neurons can be easily dissociated and are amendable to heterologous expression of genes, including genetic tools to study G-protein signaling pathways, within a time frame to maintain good spatial voltage-clamp control of membrane potential during electrophysiological recordings (8-36 h postdissociation). This protocol focuses on examining G-protein modulation of VGCCs; however, the procedures and experimental setup for acute application of agonists can be applied to study modulation of other ion channels (e.g., M-current, G-protein-coupled inwardly rectifying K+ channels). We also discuss some common sources of artifacts that can arise during acute drug application onto dissociated neurons, which can mislead interpretation of results. JF - Cold Spring Harbor Protocols AU - Lu, Van B AU - Ikeda, Stephen R AD - Section on Transmitter Signaling, Laboratory of Molecular Physiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-9411, sikeda@mail.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States IS - 5 SN - 1940-3402, 1940-3402 KW - Biotechnology and Bioengineering Abstracts KW - superior cervical ganglion KW - Animal models KW - Guanine nucleotide-binding protein KW - Calcium channels (voltage-gated) KW - Electrophysiological recording KW - sympathetic nerves KW - Potassium channels (inwardly-rectifying) KW - Neurons KW - Ion channels KW - Drugs KW - Ganglia KW - Membrane potential KW - Signal transduction KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808739592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Protocols&rft.atitle=G-Protein+Modulation+of+Voltage-Gated+Ca+super%282%2B%29+Channels+from+Isolated+Adult+Rat+Superior+Cervical+Ganglion+Neurons&rft.au=Lu%2C+Van+B%3BIkeda%2C+Stephen+R&rft.aulast=Lu&rft.aufirst=Van&rft.date=2016-05-01&rft.volume=&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Protocols&rft.issn=19403402&rft_id=info:doi/10.1101%2Fpdb.prot091223 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - superior cervical ganglion; Animal models; Guanine nucleotide-binding protein; Calcium channels (voltage-gated); Electrophysiological recording; sympathetic nerves; Potassium channels (inwardly-rectifying); Neurons; Ion channels; Ganglia; Drugs; Signal transduction; Membrane potential DO - http://dx.doi.org/10.1101/pdb.prot091223 ER - TY - JOUR T1 - Identification of an Immunogenic Subset of Metastatic Uveal Melanoma AN - 1808674312; PQ0003440111 AB - Purpose: Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma.Experimental Design: We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing.Results: Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8+ T cells, whereas uveal melanoma TIL were CD4+ dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL.Conclusions: The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. copyright 2015 AACR. JF - Clinical Cancer Research AU - Rothermel, Luke D AU - Sabesan, Arvind C AU - Stephens, Daniel J AU - Chandran, Smita S AU - Paria, Biman C AU - Srivastava, Abhishek K AU - Somerville, Robert AU - Wunderlich, John R AU - Lee, Chyi-Chia R AU - Xi, Liqiang AU - Pham, Trinh H AU - Raffeld, Mark AU - Jailwala, Parthav AU - Kasoji, Manjula AU - Kammula, Udai S AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, udai_kammula@nih.gov Y1 - 2016/05/01/ PY - 2016 DA - 2016 May 01 SP - 2237 EP - 2249 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 United States VL - 22 IS - 9 SN - 1078-0432, 1078-0432 KW - Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Pigmentation KW - Melanin KW - Immunotherapy KW - Cell culture KW - Tumors KW - CD8 antigen KW - Radiology KW - Tumor cells KW - Cancer KW - Melanoma KW - Metastases KW - Differentiation KW - CD4 antigen KW - Immunogenicity KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Liver KW - Antitumor activity KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808674312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Identification+of+an+Immunogenic+Subset+of+Metastatic+Uveal+Melanoma&rft.au=Rothermel%2C+Luke+D%3BSabesan%2C+Arvind+C%3BStephens%2C+Daniel+J%3BChandran%2C+Smita+S%3BParia%2C+Biman+C%3BSrivastava%2C+Abhishek+K%3BSomerville%2C+Robert%3BWunderlich%2C+John+R%3BLee%2C+Chyi-Chia+R%3BXi%2C+Liqiang%3BPham%2C+Trinh+H%3BRaffeld%2C+Mark%3BJailwala%2C+Parthav%3BKasoji%2C+Manjula%3BKammula%2C+Udai+S&rft.aulast=Rothermel&rft.aufirst=Luke&rft.date=2016-05-01&rft.volume=22&rft.issue=9&rft.spage=2237&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-2294 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Pigmentation; Melanin; Immunotherapy; Cell culture; CD8 antigen; Tumors; Radiology; Tumor cells; Cancer; Melanoma; Metastases; Differentiation; CD4 antigen; Immunogenicity; Antigen (tumor-associated); Liver; Lymphocytes T; Antitumor activity DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-2294 ER - TY - JOUR T1 - Preclinical Dose-Escalation Study of Intravitreal AAV-RS1 Gene Therapy in a Mouse Model of X-linked Retinoschisis: Dose-Dependent Expression and Improved Retinal Structure and Function AN - 1808661510; PQ0003174207 AB - Gene therapy for inherited retinal diseases has been shown to ameliorate functional and structural defects in both animal models and in human clinical trials. X-linked retinoschisis (XLRS) is an early-age onset macular dystrophy resulting from loss of an extracellular matrix protein (RS1). In preparation for a human clinical gene therapy trial, we conducted a dose-range efficacy study of the clinical vector, a self-complementary AAV delivering a human retinoschisin (RS1) gene under control of the RS1 promoter and an interphotoreceptor binding protein enhancer (AAV8-scRS/IRBPhRS), in the retinoschisin knockout (Rs1-KO) mouse. The therapeutic vector at 1106 to 2.5109 (1E6-2.5E9) vector genomes (vg)/eye or vehicle was administered to one eye of 229 male Rs1-KO mice by intravitreal injection at 22 plus or minus 3 days postnatal age (PN). Analysis of retinal function (dark-adapted electroretinogram, ERG), structure (cavities and outer nuclear layer thickness) by in vivo retinal imaging using optical coherence tomography, and retinal immunohistochemistry (IHC) for RS1 was done 3-4 months and/or 6-9 months postinjection (PI). RS1 IHC staining was dose dependent across doses greater than or equal to 1E7 vg/eye, and the threshold for significant improvement in all measures of retinal structure and function was 1E8 vg/eye. Higher doses, however, did not produce additional improvement. At all doses showing efficacy, RS1 staining in Rs1-KO mouse was less than that in wild-type mice. Improvement in the ERG and RS1 staining was unchanged or greater at 6-9 months than at 3-4 months PI. This study demonstrates that vitreal administration of AAV8 scRS/IRBPhRS produces significant improvement in retinal structure and function in the mouse model of XLRS over a vector dose range that can be extended to a human trial. It indicates that a fully normal level of RS1 expression is not necessary for a therapeutic effect. JF - Human Gene Therapy AU - Bush, Ronald A AU - Zeng, Yong AU - Colosi, Peter AU - Kjellstrom, Sten AU - Hiriyanna, Suja AU - Vijayasarathy, Camasamudram AU - Santos, Maria AU - Li, Jinbo AU - Wu, Zhijian AU - Sieving, Paul A AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 376 EP - 389 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 United States VL - 27 IS - 5 SN - 1043-0342, 1043-0342 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Cavities KW - Age KW - Eye KW - Gene therapy KW - Retina KW - X chromosome KW - Animal models KW - Clinical trials KW - Adeno-associated virus KW - Expression vectors KW - Enhancers KW - Promoters KW - retinoschisis KW - Dystrophy KW - Electroretinograms KW - Structure-function relationships KW - Extracellular matrix KW - Computed tomography KW - Tomography KW - Immunohistochemistry KW - W 30905:Medical Applications KW - G 07870:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808661510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Preclinical+Dose-Escalation+Study+of+Intravitreal+AAV-RS1+Gene+Therapy+in+a+Mouse+Model+of+X-linked+Retinoschisis%3A+Dose-Dependent+Expression+and+Improved+Retinal+Structure+and+Function&rft.au=Bush%2C+Ronald+A%3BZeng%2C+Yong%3BColosi%2C+Peter%3BKjellstrom%2C+Sten%3BHiriyanna%2C+Suja%3BVijayasarathy%2C+Camasamudram%3BSantos%2C+Maria%3BLi%2C+Jinbo%3BWu%2C+Zhijian%3BSieving%2C+Paul+A&rft.aulast=Bush&rft.aufirst=Ronald&rft.date=2016-05-01&rft.volume=27&rft.issue=5&rft.spage=376&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2Fhum.2015.142 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 42 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Cavities; Age; Retina; Gene therapy; Eye; X chromosome; Animal models; Clinical trials; Expression vectors; retinoschisis; Promoters; Enhancers; Structure-function relationships; Electroretinograms; Dystrophy; Extracellular matrix; Computed tomography; Tomography; Immunohistochemistry; Adeno-associated virus DO - http://dx.doi.org/10.1089/hum.2015.142 ER - TY - JOUR T1 - Coarse- and fine-grained phenotypic divergenceamong threespine stickleback from alternating lake and stream habitats AN - 1808661456; PQ0003463034 AB - Background: Habitat characteristics can vary over small spatial scales at which gene flow is expected to swamp any effect of divergent natural selection. However, fine-grained ('microgeographic') adaptive divergence may still be feasible if individuals exhibit dispersal behaviours that improve the match between their phenotype and habitat. For example, threespine stickleback (Gasterosteus aculeatus) from lake and stream habitats maintain differences across a narrow ecotone because of non-random gene flow. However, it is unknown whether dispersal bias might also contribute to even finer-scale divergence within habitats, in response to microhabitat variation within lakes and within streams. Question: Does stickleback morphology co-vary with flow regime within stream populations, controlling for distance from adjoining lake populations? Data: We sampled stickleback along a transect through alternating lake and stream habitats. Within each stream, multiple traps were set at 50 m intervals. We recorded microhabitat data (flow rate and depth) at each trap. We measured morphology (gill rakers, head shape, fin shape, standard length) of more than 900 stickleback captured from these traps. Analysis: We used multivariate analyses of covariance and linear models to test for: (1) phenotypic divergence between lake and stream stickleback, (2) divergence among stream sites as a function of their distance from an adjoining lake, and (3) covariation between local flow regime (at each trap) and the morphology of stickleback captured from that trap. Conclusions: Fish from different flow regimes within a stream show phenotypic variation that is not due to clinal transitions from lake to stream. We found covariation between local flow regime and either fin morphology or gill raker length in different streams. The total effect size of stream microhabitat on morphology was greater than the effect size of habitat (lake vs. stream), for overall multivariate data and for a subset of univariate traits. These findings imply that local adaptation can occur on a finer spatial scale than is typically expected, perhaps as a result of non-random dispersal. JF - Evolutionary Ecology Research AU - Izen, Rebecca AU - Stuart, Yoel E AU - Jiang, Yuexin AU - Bolnick, Daniel I AD - Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA, rebecca.izen@gmail.com Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 437 EP - 457 PB - Evolutionary Ecology Ltd., Department of Ecology & Evolutionary Biology Tucson AZ 85721 United States VL - 17 SN - 1522-0613, 1522-0613 KW - Environment Abstracts; ASFA 1: Biological Sciences & Living Resources; Ecology Abstracts KW - cline KW - Gasterosteus aculeatus KW - habitat preference KW - matching habitat choice KW - microgeographic variation KW - threespine stickleback KW - Spatial distribution KW - Ecological distribution KW - Microhabitats KW - Freshwater KW - Freshwater fish KW - Habitat selection KW - Natural selection KW - Streams KW - Phenotypes KW - Flow rates KW - Models KW - Ecology KW - Lakes KW - Genes KW - Multivariate analysis KW - Gene flow KW - Swamps KW - Gills KW - Data processing KW - Adaptations KW - Head KW - Phenotypic variations KW - Habitat KW - Ecotones KW - Adaptability KW - Scales KW - Stream KW - Morphology KW - Microenvironments KW - Traps KW - Fish KW - Dispersal KW - Evolution KW - ENA 13:Population Planning & Control KW - Q1 08463:Habitat community studies KW - D 04040:Ecosystem and Ecology Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808661456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Evolutionary+Ecology+Research&rft.atitle=Coarse-+and+fine-grained+phenotypic+divergenceamong+threespine+stickleback+from+alternating+lake+and+stream+habitats&rft.au=Izen%2C+Rebecca%3BStuart%2C+Yoel+E%3BJiang%2C+Yuexin%3BBolnick%2C+Daniel+I&rft.aulast=Izen&rft.aufirst=Rebecca&rft.date=2016-05-01&rft.volume=17&rft.issue=&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Evolutionary+Ecology+Research&rft.issn=15220613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Genes; Ecological distribution; Stream; Microhabitats; Phenotypic variations; Habitat selection; Freshwater fish; Phenotypes; Gills; Adaptations; Data processing; Head; Habitat; Ecotones; Streams; Natural selection; Models; Ecology; Lakes; Multivariate analysis; Scales; Gene flow; Traps; Microenvironments; Dispersal; Swamps; Evolution; Spatial distribution; Flow rates; Adaptability; Morphology; Fish; Gasterosteus aculeatus; Freshwater ER - TY - JOUR T1 - Disease models for the development of therapies for lysosomal storage diseases AN - 1808648817; PQ0003293852 AB - Lysosomal storage diseases (LSDs) are a group of rare diseases in which the function of the lysosome is disrupted by the accumulation of macromolecules. The complexity underlying the pathogenesis of LSDs and the small, often pediatric, population of patients make the development of therapies for these diseases challenging. Current treatments are only available for a small subset of LSDs and have not been effective at treating neurological symptoms. Disease-relevant cellular and animal models with high clinical predictability are critical for the discovery and development of new treatments for LSDs. In this paper, we review how LSD patient primary cells and induced pluripotent stem cell-derived cellular models are providing novel assay systems in which phenotypes are more similar to those of the human LSD physiology. Furthermore, larger animal disease models are providing additional tools for evaluation of the efficacy of drug candidates. Early predictors of efficacy and better understanding of disease biology can significantly affect the translational process by focusing efforts on those therapies with the higher probability of success, thus decreasing overall time and cost spent in clinical development and increasing the overall positive outcomes in clinical trials. JF - Annals of the New York Academy of Sciences AU - Xu, Miao AU - Motabar, Omid AU - Ferrer, Marc AU - Marugan, Juan J AU - Zheng, Wei AU - Ottinger, Elizabeth A AD - National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 15 EP - 29 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1371 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts KW - Storage KW - Reviews KW - Physiology KW - Animal models KW - Clinical trials KW - Drugs KW - Animal diseases KW - ENA 13:Population Planning & Control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808648817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Disease+models+for+the+development+of+therapies+for+lysosomal+storage+diseases&rft.au=Xu%2C+Miao%3BMotabar%2C+Omid%3BFerrer%2C+Marc%3BMarugan%2C+Juan+J%3BZheng%2C+Wei%3BOttinger%2C+Elizabeth+A&rft.aulast=Xu&rft.aufirst=Miao&rft.date=2016-05-01&rft.volume=1371&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13052 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Storage; Reviews; Physiology; Animal models; Drugs; Clinical trials; Animal diseases DO - http://dx.doi.org/10.1111/nyas.13052 ER - TY - JOUR T1 - Blood levels of trace metals and amyotrophic lateral sclerosis AN - 1808646682; PQ0003165121 AB - Some trace metals may increase risk of amyotrophic lateral sclerosis (ALS), whereas others may be beneficial. Our goal was to examine associations of ALS with blood levels of selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn). We conducted a case-control study of 163 neurologist confirmed patients from the National Registry of Veterans with ALS and 229 frequency-matched veteran controls. We measured metal levels in blood using inductively coupled plasma mass spectrometry and estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between ALS and a doubling of metal levels using unconditional logistic regression, adjusting for age, gender, and race/ethnicity. ALS was inversely associated with both Se (OR=0.4, 95% CI: 0.2-0.8) and Zn (OR=0.4, 95% CI: 0.2-0.8). Inverse associations with Se were stronger in patients with bulbar compared to spinal onset, worse function, longer diagnostic delay, and longer collection delay; inverse associations with Zn were stronger for those with worse function and longer collection delay. In contrast, ALS was positively associated with Cu (OR=3.4, 95% CI: 1.5-7.9). For Mn, no linear trend was evident (OR=0.9, 95% CI: 0.6-1.3, Ptrend =0.51). Associations of Se, Zn, Cu, and Mn with ALS were independent of one another. Adjustment for lead levels attenuated the positive association of ALS with Cu but did not change associations with Se, Zn, or Mn. In conclusion, Se and Zn were inversely associated with ALS, particularly among those with worse function, suggesting that supplementation with these metals may benefit such patients, while Cu was positively associated with ALS. Deficiencies of Se and Zn and excess Cu may have a role in ALS etiology. JF - Neurotoxicology AU - Peters, Tracy L AU - Beard, John D AU - Umbach, David M AU - Allen, Kelli AU - Keller, Jean AU - Mariosa, Daniela AU - Sandler, Dale P AU - Schmidt, Silke AU - Fang, Fang AU - Ye, Weimin AU - Kamel, Freya AD - Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 119 EP - 126 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 54 SN - 0161-813X, 0161-813X KW - Environment Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - AIC Akaike information criterion KW - ALS amyotrophic lateral sclerosis KW - ALSFRS-R revised ALS functional rating scale KW - CI confidence interval KW - CSF cerebral spinal fluid KW - Cu copper KW - GENEVA Genes and Environmental Exposures in Veterans with ALS KW - ICPMS inductively coupled plasma mass spectrometry KW - Mn manganese KW - MND motor neuron disease KW - NHANES National Health and Nutrition Examination Survey ns not statistically significant KW - OR odds ratio KW - Pb lead KW - RBCs red blood cells KW - RR relative risk KW - SD standard deviation KW - Se selenium KW - SOD1 superoxide dismutase 1 KW - VA Department of Veterans Affairs KW - VALE veterans with ALS and lead exposure KW - Zn zinc KW - Amyotrophic lateral sclerosis KW - Motor neuron disease KW - Risk factors KW - Trace metals KW - Case-Control study KW - Age KW - Heavy metals KW - Mass spectrometry KW - Copper KW - Lead KW - Supplementation KW - Mass spectroscopy KW - Selenium KW - Zinc KW - Manganese KW - Races KW - Ethnic groups KW - Metals KW - Etiology KW - Blood levels KW - Blood KW - Gender KW - X 24360:Metals KW - N3 11027:Neurology & neuropathology KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808646682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Blood+levels+of+trace+metals+and+amyotrophic+lateral+sclerosis&rft.au=Peters%2C+Tracy+L%3BBeard%2C+John+D%3BUmbach%2C+David+M%3BAllen%2C+Kelli%3BKeller%2C+Jean%3BMariosa%2C+Daniela%3BSandler%2C+Dale+P%3BSchmidt%2C+Silke%3BFang%2C+Fang%3BYe%2C+Weimin%3BKamel%2C+Freya&rft.aulast=Peters&rft.aufirst=Tracy&rft.date=2016-05-01&rft.volume=54&rft.issue=&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/10.1016%2Fj.neuro.2016.03.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Etiology; Age; Heavy metals; Copper; Mass spectroscopy; Supplementation; Blood levels; Selenium; Amyotrophic lateral sclerosis; Zinc; Manganese; Trace metals; Ethnic groups; Races; Metals; Mass spectrometry; Lead; Blood; Gender DO - http://dx.doi.org/10.1016/j.neuro.2016.03.022 ER - TY - JOUR T1 - Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia AN - 1808643432; PQ0003174206 AB - Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut0) or partial (mut-) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals, especially those with mut0 MMA, has led centers to use elective liver transplantation as a treatment for these patients. We have previously demonstrated the efficacy of systemic adeno-associated viral (AAV) gene delivery as a treatment for MMA in a murine model and therefore sought to survey AAV antibody titers against serotypes 2, 8, and 9 in a group of well-characterized MMA patients, accrued via a dedicated natural history study (clinicaltrials.gov ID: NCT00078078). Plasma samples provided by 42 patients (8 mut- and 34 mut0; 10 had received organ transplantation), who ranged in age between 2 and 31 years, were analyzed to examine AAV2 (n=35), AAV8 (n=41), and AAV9 (n=42) antibody titers. In total, the seroprevalence of antibodies against AAV2, AAV8, or AAV9 was 20%, 22%, and 24%, respectively. We observed a lower-than-expected seropositivity rate (titers greater than or equal to 1:20) in the pediatric MMA patients (2-18 years) for both AAV2 (p<0.05) and AAV8 (p<0.01) neutralizing antibodies (NAbs) compared with historical controls. Those with positive NAb titers were typically older than 18 years (p<0.05 all serotypes) or had received solid organ transplantation (p<0.01 AAV8, AAV9). The mut0 patients who had not been transplanted (n=24)-that is, the subset with the greatest need for improved treatments-represented the seronegative majority, with 21 out of 24 patients lacking Abs against all AAV capsids tested. The unexpected lack of NAbs against AAV in this patient population has encouraging implications for systemic gene delivery as a treatment for mut MMA. JF - Human Gene Therapy AU - Harrington, Elizabeth A AU - Sloan, Jennifer L AU - Manoli, Irini AU - Chandler, Randy J AU - Schneider, Mark AU - McGuire, Peter J AU - Calcedo, Roberto AU - Wilson, James M AU - Venditti, Charles P AD - Organic Acid Research Section, Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 345 EP - 353 PB - Mary Ann Liebert, Inc., 2 Madison Ave Larchmont NY 10538 United States VL - 27 IS - 5 SN - 1043-0342, 1043-0342 KW - Genetics Abstracts; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Capsids KW - Methylmalonyl-CoA mutase KW - Mortality KW - Age KW - Serotypes KW - Gene therapy KW - Pediatrics KW - Inborn errors of metabolism KW - Animal models KW - Enzymes KW - Adeno-associated virus KW - Liver transplantation KW - Antibodies KW - Gene transfer KW - Allografts KW - Liver KW - W 30905:Medical Applications KW - V 22410:Animal Diseases KW - G 07870:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808643432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Neutralizing+Antibodies+Against+Adeno-Associated+Viral+Capsids+in+Patients+with+mut+Methylmalonic+Acidemia&rft.au=Harrington%2C+Elizabeth+A%3BSloan%2C+Jennifer+L%3BManoli%2C+Irini%3BChandler%2C+Randy+J%3BSchneider%2C+Mark%3BMcGuire%2C+Peter+J%3BCalcedo%2C+Roberto%3BWilson%2C+James+M%3BVenditti%2C+Charles+P&rft.aulast=Harrington&rft.aufirst=Elizabeth&rft.date=2016-05-01&rft.volume=27&rft.issue=5&rft.spage=345&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2Fhum.2015.092 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 46 N1 - Last updated - 2016-08-04 N1 - SubjectsTermNotLitGenreText - Capsids; Mortality; Methylmalonyl-CoA mutase; Age; Serotypes; Gene therapy; Pediatrics; Inborn errors of metabolism; Animal models; Enzymes; Liver transplantation; Antibodies; Gene transfer; Allografts; Liver; Adeno-associated virus DO - http://dx.doi.org/10.1089/hum.2015.092 ER - TY - JOUR T1 - Epithelial-mesenchymal transition: a new target in anticancer drug discovery AN - 1805506836; PQ0003041754 AB - The conversion of cells with an epithelial phenotype into cells with a mesenchymal phenotype, referred to as epithelial-mesenchymal transition, is a critical process for embryonic development that also occurs in adult life, particularly during tumour progression. Tumour cells undergoing epithelial-mesenchymal transition acquire the capacity to disarm the body's antitumour defences, resist apoptosis and anticancer drugs, disseminate throughout the organism, and act as a reservoir that replenishes and expands the tumour cell population. Epithelial-mesenchymal transition is therefore becoming a target of prime interest for anticancer therapy. Here, we discuss the screening and classification of compounds that affect epithelial-mesenchymal transition, highlight some compounds of particular interest, and address issues related to their clinical application. JF - Nature Reviews: Drug Discovery AU - Marcucci, Fabrizio AU - Stassi, Giorgio AU - De Maria, Ruggero AD - Scientific Directorate, Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144 Rome, Italy. Present address: Department of Pharmacological and Biomolecular Sciences, University of Milan, via Trentacoste 2, 20133 Milan, Italy. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 311 EP - 325 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 15 IS - 5 SN - 1474-1776, 1474-1776 KW - Biotechnology and Bioengineering Abstracts KW - Embryogenesis KW - Apoptosis KW - Therapeutic applications KW - Mesenchyme KW - Antitumor agents KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1805506836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Reviews%3A+Drug+Discovery&rft.atitle=Epithelial-mesenchymal+transition%3A+a+new+target+in+anticancer+drug+discovery&rft.au=Marcucci%2C+Fabrizio%3BStassi%2C+Giorgio%3BDe+Maria%2C+Ruggero&rft.aulast=Marcucci&rft.aufirst=Fabrizio&rft.date=2016-05-01&rft.volume=15&rft.issue=5&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Drug+Discovery&rft.issn=14741776&rft_id=info:doi/10.1038%2Fnrd.2015.13 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Embryogenesis; Apoptosis; Therapeutic applications; Mesenchyme; Antitumor agents DO - http://dx.doi.org/10.1038/nrd.2015.13 ER - TY - JOUR T1 - Synthetic cathinone pharmacokinetics, analytical methods, and toxicological findings from human performance and postmortem cases. AN - 1801424748; 27249313 AB - Synthetic cathinones are commonly abused novel psychoactive substances (NPS). We present a comprehensive systematic review addressing in vitro and in vivo synthetic cathinone pharmacokinetics, analytical methods for detection and quantification in biological matrices, and toxicological findings from human performance and postmortem toxicology cases. Few preclinical administration studies examined synthetic cathinone pharmacokinetic profiles (absorption, distribution, metabolism, and excretion), and only one investigated metabolite pharmacokinetics. Synthetic cathinone metabolic profiling studies, primarily with human liver microsomes, elucidated metabolite structures and identified suitable biomarkers to extend detection windows beyond those provided by parent compounds. Generally, cathinone derivatives underwent ketone reduction, carbonylation of the pyrrolidine ring, and oxidative reactions, with phase II metabolites also detected. Reliable analytical methods are necessary for cathinone identification in biological matrices to document intake and link adverse events to specific compounds and concentrations. NPS analytical methods are constrained in their ability to detect new emerging synthetic cathinones due to limited commercially available reference standards and continuous development of new analogs. Immunoassay screening methods are especially affected, but also gas-chromatography and liquid-chromatography mass spectrometry confirmation methods. Non-targeted high-resolution-mass spectrometry screening methods are advantageous, as they allow for retrospective data analysis and easier addition of new synthetic cathinones to existing methods. Lack of controlled administration studies in humans complicate interpretation of synthetic cathinones in biological matrices, as dosing information is typically unknown. Furthermore, antemortem and postmortem concentrations often overlap and the presence of other psychoactive substances are typically found in combination with cathinones derivatives, further confounding result interpretation. JF - Drug metabolism reviews AU - Ellefsen, Kayla N AU - Concheiro, Marta AU - Huestis, Marilyn A AD - a Chemistry and Drug Metabolism, IRP , National Institute on Drug Abuse, National Institutes of Health , Baltimore , MD , USA ; ; c Department of Sciences, John Jay College of Criminal Justice , City University of New York , New York , NY , USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 237 EP - 265 VL - 48 IS - 2 KW - Index Medicus KW - Analytical methods KW - GC-MS KW - metabolism KW - novel psychoactive substances KW - LC-MS/MS KW - pharmacokinetics KW - synthetic cathinones UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1801424748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Synthetic+cathinone+pharmacokinetics%2C+analytical+methods%2C+and+toxicological+findings+from+human+performance+and+postmortem+cases.&rft.au=Ellefsen%2C+Kayla+N%3BConcheiro%2C+Marta%3BHuestis%2C+Marilyn+A&rft.aulast=Ellefsen&rft.aufirst=Kayla&rft.date=2016-05-01&rft.volume=48&rft.issue=2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=1097-9883&rft_id=info:doi/10.1080%2F03602532.2016.1188937 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-07-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/03602532.2016.1188937 ER - TY - JOUR T1 - Multicenter Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Study for Identification of Clinically Relevant Nocardia spp. AN - 1794499062; PQ0003096691 AB - This multicenter study analyzed Nocardia spp., including extraction, spectral acquisition, Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identification, and score interpretation, using three Nocardia libraries, the Bruker, National Institutes of Health (NIH), and The Ohio State University (OSU) libraries, and compared the results obtained by each center. A standardized study protocol, 150 Nocardia isolates, and NIH and OSU Nocardia MALDI-TOF MS libraries were distributed to three centers. Following standardized culture, extraction, and MALDI-TOF MS analysis, isolates were identified using score cutoffs of greater than or equal to 2.0 for species/species complex-level identification and greater than or equal to 1.8 for genus-level identification. Isolates yielding a score of <2.0 underwent a single repeat extraction and analysis. The overall score range for all centers was 1.3 to 2.7 (average, 2.2 plus or minus 0.3), with common species generally producing higher average scores than less common ones. Score categorization and isolate identification demonstrated 86% agreement between centers; 118 of 150 isolates were correctly identified to the species/species complex level by all centers. Nine strains (6.0%) were not identified by any center, and six (4.0%) of these were uncommon species with limited library representation. A categorical score discrepancy among centers occurred for 21 isolates (14.0%). There was an overall benefit of 21.2% from repeat extraction of low-scoring isolates and a center-dependent benefit for duplicate spotting (range, 2 to 8.7%). Finally, supplementation of the Bruker Nocardia MALDI-TOF MS library with both the OSU and NIH libraries increased the genus-level and species-level identification by 18.2% and 36.9%, respectively. Overall, this study demonstrates the ability of diverse clinical microbiology laboratories to utilize MALDI-TOF MS for the rapid identification of clinically relevant Nocardia spp. and to implement MALDI-TOF MS libraries developed by single laboratories across institutions. JF - Journal of Clinical Microbiology AU - Blosser, Sara J AU - Drake, Steven K AU - Andrasko, Jennifer L AU - Henderson, Christina M AU - Kamboj, Kamal AU - Antonara, Stella AU - Mijares, Lilia AU - Conville, Patricia AU - Frank, Karen M AU - Harrington, Susan M AD - << + $0, azelazny@mail.nih.gov. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1251 EP - 1258 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 54 IS - 5 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - Lasers KW - Nocardia KW - Mass spectroscopy KW - Supplementation KW - J 02300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794499062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Multicenter+Matrix-Assisted+Laser+Desorption+Ionization-Time+of+Flight+Mass+Spectrometry+Study+for+Identification+of+Clinically+Relevant+Nocardia+spp.&rft.au=Blosser%2C+Sara+J%3BDrake%2C+Steven+K%3BAndrasko%2C+Jennifer+L%3BHenderson%2C+Christina+M%3BKamboj%2C+Kamal%3BAntonara%2C+Stella%3BMijares%2C+Lilia%3BConville%2C+Patricia%3BFrank%2C+Karen+M%3BHarrington%2C+Susan+M&rft.aulast=Blosser&rft.aufirst=Sara&rft.date=2016-05-01&rft.volume=54&rft.issue=5&rft.spage=1251&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.02942-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-06-01 N1 - Number of references - 18 N1 - Last updated - 2016-07-20 N1 - SubjectsTermNotLitGenreText - Lasers; Supplementation; Mass spectroscopy; Nocardia DO - http://dx.doi.org/10.1128/JCM.02942-15 ER - TY - JOUR T1 - Lower core body temperature and greater body fat are components of a human thrifty phenotype AN - 1790966133; PQ0003041724 AB - Background/ Objectives: In small studies, a thrifty human phenotype, defined by a greater 24-hour energy expenditure (EE) decrease with fasting, is associated with less weight loss during caloric restriction. In rodents, models of diet-induced obesity often have a phenotype including a reduced EE and decreased core body temperature. We assessed whether a thrifty human phenotype associates with differences in core body temperature or body composition.Subjects/ Methods: Data for this cross-sectional analysis were obtained from 77 individuals participating in one of two normal physiology studies while housed on our clinical research unit. Twenty-four-hour EE using a whole-room indirect calorimeter and 24-h core body temperature were measured during 24 h each of fasting and 200% overfeeding with a diet consisting of 50% carbohydrates, 20% protein and 30% fat. Body composition was measured by dual X-ray absorptiometry. To account for the effects of body size on EE, changes in EE were expressed as a percentage change from 24-hour EE (%EE) during energy balance. Results: A greater %EE decrease with fasting correlated with a smaller %EE increase with overfeeding (r=0.27, P=0.02). The %EE decrease with fasting was associated with both fat mass and abdominal fat mass, even after accounting for covariates ( beta =-0.16 (95% CI: -0.26, -0.06) %EE per kg fat mass, P=0.003; beta =-0.0004 (-0.0007, -0.00004) %EE kg super(-1) abdominal fat mass, P=0.03). In men, a greater %EE decrease in response to fasting was associated with a lower 24- h core body temperature, even after adjusting for covariates ( beta =1.43 (0.72, 2.15) %EE per 0.1 degree C, P=0.0003). Conclusions: Thrifty individuals, as defined by a larger EE decrease with fasting, were more likely to have greater overall and abdominal adiposity as well as lower core body temperature consistent with a more efficient metabolism. JF - International Journal of Obesity AU - Reinhardt, M AU - Schlogl, M AU - Bonfiglio, S AU - Votruba, S B AU - Krakoff, J AU - Thearle, M S AD - Department of Health and Human Services, Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA; Department of Diagnostic and Interventional Radiology, University Leipzig, Leipzig, Germany Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 754 EP - 760 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 40 IS - 5 SN - 0307-0565, 0307-0565 KW - Health & Safety Science Abstracts KW - Diets KW - Obesity KW - Energy KW - Physiology KW - Temperature KW - Body size KW - Proteins KW - Carbohydrates KW - Clinical trials KW - Rodents KW - Metabolism KW - H 6000:Natural Disasters/Civil Defense/Emergency Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790966133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Obesity&rft.atitle=Lower+core+body+temperature+and+greater+body+fat+are+components+of+a+human+thrifty+phenotype&rft.au=Reinhardt%2C+M%3BSchlogl%2C+M%3BBonfiglio%2C+S%3BVotruba%2C+S+B%3BKrakoff%2C+J%3BThearle%2C+M+S&rft.aulast=Reinhardt&rft.aufirst=M&rft.date=2016-05-01&rft.volume=40&rft.issue=5&rft.spage=754&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Obesity&rft.issn=03070565&rft_id=info:doi/10.1038%2Fijo.2015.229 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Diets; Obesity; Energy; Physiology; Body size; Temperature; Proteins; Carbohydrates; Clinical trials; Metabolism; Rodents DO - http://dx.doi.org/10.1038/ijo.2015.229 ER - TY - JOUR T1 - Functional Equivalence of OspA and OspB, but Not OspC, in Tick Colonization by Borrelia burgdorferi AN - 1790964346; PQ0003049545 AB - Borrelia burgdorferi, a Lyme disease agent, makes different major outer surface lipoproteins at different stages of its mouse-tick infectious cycle. Outer surface protein A (OspA) coats the spirochetes from the time they enter ticks until they are transmitted to a mammal. OspA is required for normal tick colonization and has been shown to bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin. Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is derived from mice that do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, which will not recognize tick-specific proteins such as OspA. To further study the importance of OspA during tick colonization, we constructed a form of B. burgdorferi in which the ospA open reading frame, on lp54, was replaced with the ospC gene or the ospB gene, encoding a mammal-specific or tick-specific lipoprotein, respectively. These fusions yielded a strain that produces OspC within a tick (from the fusion gene) and during early mammalian infection (from the normal ospC locus) and a strain that produces OspB in place of OspA within ticks. Here we show that the related, tick-specific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein OspC cannot. These data were derived from three different methods of infecting ticks, and they confirm and extend previous studies indicating that OspA both protects spirochetes within ticks from mammalian antibody and serves an additional role during tick colonization. JF - Infection and Immunity AU - Tilly, Kit AU - Bestor, Aaron AU - Rosa, Patricia A Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1565 EP - 1573 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 84 IS - 5 SN - 0019-9567, 0019-9567 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Adhesins KW - Data processing KW - Borrelia burgdorferi KW - Ixodidae KW - Blood meals KW - Infection KW - OspA protein KW - Spirochetes KW - Colonization KW - Antibodies KW - outer surface protein A KW - Lipoproteins KW - ospC gene KW - Fusion protein KW - Midgut KW - Open reading frames KW - Lyme disease KW - J 02350:Immunology KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790964346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Functional+Equivalence+of+OspA+and+OspB%2C+but+Not+OspC%2C+in+Tick+Colonization+by+Borrelia+burgdorferi&rft.au=Tilly%2C+Kit%3BBestor%2C+Aaron%3BRosa%2C+Patricia+A&rft.aulast=Tilly&rft.aufirst=Kit&rft.date=2016-05-01&rft.volume=84&rft.issue=5&rft.spage=1565&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.00063-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 50 N1 - Last updated - 2016-07-07 N1 - SubjectsTermNotLitGenreText - Adhesins; Data processing; Blood meals; Infection; OspA protein; Colonization; Spirochetes; Antibodies; outer surface protein A; Lipoproteins; ospC gene; Midgut; Fusion protein; Open reading frames; Lyme disease; Borrelia burgdorferi; Ixodidae DO - http://dx.doi.org/10.1128/IAI.00063-16 ER - TY - JOUR T1 - Lifetime Number of Ovulatory Cycles and Risks of Ovarian and Endometrial Cancer Among Postmenopausal Women AN - 1790955839; PQ0003078034 AB - Previous studies have shown that a greater number of ovulatory cycles, cumulatively summed as lifetime number of ovulatory cycles (LOC), increases ovarian cancer risk, but there is no uniform algorithm with which to compute LOC. The association between LOC and endometrial cancer is less certain. Accordingly, we identified 14 different LOC algorithms in a literature review and calculated LOCs in the Polish Cancer Study (2001-2003). We evaluated the associations of LOC with ovarian and endometrial cancer risks using unconditional logistic regression, with and without adjustment for individual risk factors used in the LOC computations. Our analysis included 302 ovarian cancer cases with 1,356 controls and 532 endometrial cancer cases with 1,286 controls. We found a high correlation between LOC values among the combined controls (r greater than or equal to 0.88) and identified 5 groups of similar LOC algorithms. A LOC value in the highest quartile was associated with ovarian cancer risk as computed by 2 algorithms (odds ratio (OR) = 2.22 (95% confidence interval (CI): 1.07, 4.62) and OR = 2.44 (95% CI: 1.22, 4.87)) and with endometrial cancer risk as computed by 1 algorithm (OR = 1.95, 95% CI: 1.11, 3.44). LOC algorithms using a core set of variables widely available in epidemiologic studies may be independently associated with risk of gynecological cancers beyond the contribution of the individual risk factors, such as ages at menopause and menarche. JF - American Journal of Epidemiology AU - Yang, Hannah P AU - Murphy, Kelsey R AU - Pfeiffer, Ruth M AU - George, Neena AU - Garcia-Closas, Montserrat AU - Lissowska, Jolanta AU - Brinton, Louise A AU - Wentzensen, Nicolas AD - Correspondence to Dr. Hannah P. Yang, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room 7E-238 Rockville, MD 20892. Y1 - 2016/05/01/ PY - 2016 DA - 2016 May 01 SP - 800 EP - 814 PB - Oxford University Press, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 183 IS - 9 SN - 0002-9262, 0002-9262 KW - Health & Safety Science Abstracts KW - age at menarche KW - age at menopause KW - endometrial cancer KW - incessant ovulation KW - lifetime ovulatory cycles KW - ovarian cancer KW - ovulation KW - Health risks KW - Age KW - Literature reviews KW - Post-menopause KW - Risk factors KW - Ovarian carcinoma KW - Females KW - Cancer KW - Menopause KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790955839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Lifetime+Number+of+Ovulatory+Cycles+and+Risks+of+Ovarian+and+Endometrial+Cancer+Among+Postmenopausal+Women&rft.au=Yang%2C+Hannah+P%3BMurphy%2C+Kelsey+R%3BPfeiffer%2C+Ruth+M%3BGeorge%2C+Neena%3BGarcia-Closas%2C+Montserrat%3BLissowska%2C+Jolanta%3BBrinton%2C+Louise+A%3BWentzensen%2C+Nicolas&rft.aulast=Yang&rft.aufirst=Hannah&rft.date=2016-05-01&rft.volume=183&rft.issue=9&rft.spage=800&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/10.1093%2Faje%2Fkwv308 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-07-07 N1 - SubjectsTermNotLitGenreText - Health risks; Age; Literature reviews; Post-menopause; Risk factors; Ovarian carcinoma; Females; Menopause; Cancer DO - http://dx.doi.org/10.1093/aje/kwv308 ER - TY - JOUR T1 - Complementation of Arginine Auxotrophy for Genetic Transformation of Coxiella burnetii by Use of a Defined Axenic Medium AN - 1790934206; PQ0003096599 AB - Host cell-free (axenic) culture of Coxiella burnetii in acidified citrate cysteine medium-2 (ACCM-2) has provided important opportunities for investigating the biology of this naturally obligate intracellular pathogen and enabled the development of tools for genetic manipulation. However, ACCM-2 has complex nutrient sources that preclude a detailed study of nutritional factors required for C. burnetii growth. Metabolic reconstruction of C. burnetii predicts that the bacterium cannot synthesize all amino acids and therefore must sequester some from the host. To examine C. burnetii amino acid auxotrophies, we developed a nutritionally defined medium with known amino acid concentrations, termed ACCM-D. Compared to ACCM-2, ACCM-D supported longer logarithmic growth, a more gradual transition to stationary phase, and approximately 5- to 10-fold greater overall replication. Small-cell-variant morphological forms generated in ACCM-D also showed increased viability relative to that generated in ACCM-2. Lack of growth in amino acid-deficient formulations of ACCM-D revealed C. burnetii auxotrophy for 11 amino acids, including arginine. Heterologous expression of Legionella pneumophila argGH in C. burnetii permitted growth in ACCM-D missing arginine and supplemented with citrulline, thereby providing a nonantibiotic means of selection of C. burnetii genetic transformants. Consistent with bioinformatic predictions, the elimination of glucose did not impair C. burnetii replication. Together, these results highlight the advantages of a nutritionally defined medium in investigations of C. burnetii metabolism and the development of genetic tools. IMPORTANCE Host cell-free growth and genetic manipulation of Coxiella burnetii have revolutionized research of this intracellular bacterial pathogen. Nonetheless, undefined components of growth medium have made studies of C. burnetii physiology difficult and have precluded the development of selectable markers for genetic transformation based on nutritional deficiencies. Here, we describe a medium, containing only amino acids as the sole source of carbon and energy, which supports robust growth and improved viability of C. burnetii. Growth studies confirmed that C. burnetii cannot replicate in medium lacking arginine. However, genetic transformation of the bacterium with constructs containing the last two genes in the L. pneumophila arginine biosynthesis pathway (argGH) allowed growth on defined medium missing arginine but supplemented with the arginine precursor citrulline. Our results advance the field by facilitating studies of C. burnetii metabolism and allowing non-antibiotic-based selection of C. burnetii genetic transformants, an important achievement considering that selectable makers based on antibiotic resistance are limited. JF - Antimicrobial Agents & Chemotherapy AU - Sandoz, Kelsi M AU - Beare, Paul A AU - Cockrell, Diane C AU - Heinzen, Robert A Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 3042 EP - 3051 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 82 IS - 10 SN - 0099-2240, 0099-2240 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Pure culture KW - Transformation KW - Legionella pneumophila KW - Amino acids KW - Replication KW - Arginine KW - citrulline KW - Glucose KW - Pathogens KW - Auxotrophy KW - stationary phase KW - Coxiella burnetii KW - Nutrient deficiency KW - Carbon KW - Complementation KW - Cysteine KW - Energy KW - Nutrient sources KW - Bioinformatics KW - Antibiotic resistance KW - Metabolism KW - Citric acid KW - J 02320:Cell Biology KW - A 01300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790934206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Complementation+of+Arginine+Auxotrophy+for+Genetic+Transformation+of+Coxiella+burnetii+by+Use+of+a+Defined+Axenic+Medium&rft.au=Sandoz%2C+Kelsi+M%3BBeare%2C+Paul+A%3BCockrell%2C+Diane+C%3BHeinzen%2C+Robert+A&rft.aulast=Sandoz&rft.aufirst=Kelsi&rft.date=2016-05-01&rft.volume=82&rft.issue=10&rft.spage=3042&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00992240&rft_id=info:doi/10.1128%2FAEM.00261-16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 74 N1 - Last updated - 2016-07-07 N1 - SubjectsTermNotLitGenreText - Transformation; Pure culture; Amino acids; Arginine; Replication; citrulline; Glucose; Auxotrophy; Pathogens; stationary phase; Nutrient deficiency; Complementation; Carbon; Cysteine; Energy; Bioinformatics; Nutrient sources; Metabolism; Antibiotic resistance; Citric acid; Legionella pneumophila; Coxiella burnetii DO - http://dx.doi.org/10.1128/AEM.00261-16 ER - TY - JOUR T1 - 2-Deoxy-d-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and BNP as Potential Early Cardiac Safety Biomarkers AN - 1790931029; PQ0003094147 AB - 2-Deoxy- d -glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in rats. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity. In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed. Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials. JF - International Journal of Toxicology AU - Terse, P S AU - Joshi, P S AU - Bordelon, N R AU - Brys, A M AU - Patton, K M AU - Arndt, T P AU - Sutula, T P AD - 1 .National Center for Advancing Translational Sciences, Bethesda, MD, USA, tersep@mail.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 284 EP - 293 PB - Sage Publications, Inc., 2 Park Square Oxford OX14 4RN United Kingdom VL - 35 IS - 3 SN - 1091-5818, 1091-5818 KW - Environment Abstracts; Toxicology Abstracts KW - 2-deoxy-d-glucose KW - NT-proBNP KW - BNP KW - vacuolar degeneration KW - Autopsy KW - Atrial natriuretic peptide KW - Histopathology KW - Clinical trials KW - Neurodegeneration KW - Rats KW - Endothelial cells KW - Brain natriuretic peptide KW - Creatine kinase KW - Lesions KW - Calcium-binding protein KW - Sex KW - Bioindicators KW - Heart KW - Safety KW - Brain KW - Troponin KW - Toxicity KW - biomarkers KW - Hypertrophy KW - Epilepsy KW - Anticonvulsants KW - X 24310:Pharmaceuticals KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790931029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Toxicology&rft.atitle=2-Deoxy-d-Glucose+%282-DG%29-Induced+Cardiac+Toxicity+in+Rat%3A+NT-proBNP+and+BNP+as+Potential+Early+Cardiac+Safety+Biomarkers&rft.au=Terse%2C+P+S%3BJoshi%2C+P+S%3BBordelon%2C+N+R%3BBrys%2C+A+M%3BPatton%2C+K+M%3BArndt%2C+T+P%3BSutula%2C+T+P&rft.aulast=Terse&rft.aufirst=P&rft.date=2016-05-01&rft.volume=35&rft.issue=3&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Toxicology&rft.issn=10915818&rft_id=info:doi/10.1177%2F1091581815624397 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 27 N1 - Last updated - 2016-07-20 N1 - SubjectsTermNotLitGenreText - Heart; Autopsy; Atrial natriuretic peptide; Troponin; Toxicity; biomarkers; Neurodegeneration; Clinical trials; Endothelial cells; Brain natriuretic peptide; Hypertrophy; Creatine kinase; Epilepsy; Calcium-binding protein; Anticonvulsants; Sex; Rats; Bioindicators; Safety; Brain; Lesions; Histopathology DO - http://dx.doi.org/10.1177/1091581815624397 ER - TY - JOUR T1 - MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy. AN - 1790467515; 26755334 AB - Spinal and bulbar muscular atrophy (SBMA) is a currently untreatable adult-onset neuromuscular disease caused by expansion of a polyglutamine repeat in the androgen receptor (AR). In SBMA, as in other polyglutamine diseases, a toxic gain of function in the mutant protein is an important factor in the disease mechanism; therefore, reducing the mutant protein holds promise as an effective treatment strategy. In this work, we evaluated a microRNA (miRNA) to reduce AR expression. From a list of predicted miRNAs that target human AR, we selected microRNA-298 (miR-298) for its ability to downregulate AR mRNA and protein levels when transfected in cells overexpressing wild-type and mutant AR and in SBMA patient-derived fibroblasts. We showed that miR-298 directly binds to the 3'-untranslated region of the human AR transcript, and counteracts AR toxicity in vitro. Intravenous delivery of miR-298 with adeno-associated virus serotype 9 vector resulted in efficient transduction of muscle and spinal cord and amelioration of the disease phenotype in SBMA mice. Our findings support the development of miRNAs as a therapeutic strategy for SBMA and other neurodegenerative disorders caused by toxic proteins. JF - Molecular therapy : the journal of the American Society of Gene Therapy AU - Pourshafie, Naemeh AU - Lee, Philip R AU - Chen, Ke-Lian AU - Harmison, George G AU - Bott, Laura C AU - Katsuno, Masahisa AU - Sobue, Gen AU - Burnett, Barrington G AU - Fischbeck, Kenneth H AU - Rinaldi, Carlo AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. ; Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child and Human Development, National Institutes of Health, Bethesda, Maryland, USA. ; Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan. ; Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hebert School of Medicine, Bethesda, Maryland, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 937 EP - 945 VL - 24 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790467515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.atitle=MiR-298+Counteracts+Mutant+Androgen+Receptor+Toxicity+in+Spinal+and+Bulbar+Muscular+Atrophy.&rft.au=Pourshafie%2C+Naemeh%3BLee%2C+Philip+R%3BChen%2C+Ke-Lian%3BHarmison%2C+George+G%3BBott%2C+Laura+C%3BKatsuno%2C+Masahisa%3BSobue%2C+Gen%3BBurnett%2C+Barrington+G%3BFischbeck%2C+Kenneth+H%3BRinaldi%2C+Carlo&rft.aulast=Pourshafie&rft.aufirst=Naemeh&rft.date=2016-05-01&rft.volume=24&rft.issue=5&rft.spage=937&rft.isbn=&rft.btitle=&rft.title=Molecular+therapy+%3A+the+journal+of+the+American+Society+of+Gene+Therapy&rft.issn=1525-0024&rft_id=info:doi/10.1038%2Fmt.2016.13 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-20 N1 - Date revised - 2017-01-24 N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/mt.2016.13 ER - TY - JOUR T1 - Relationship between a Centers for Disease Control and Prevention expanded HIV testing initiative and past-year testing by race/ethnicity: a multilevel analysis of the Behavioral Risk Factor Surveillance System AN - 1789532027 AB - The Centers for Disease Control and Prevention's (CDC) expanded testing initiative (ETI) aims to bolster HIV testing among populations disproportionately affected by the HIV epidemic by providing additional funding to health departments serving these communities. ETI prioritizes testing in clinical settings; therefore, we examined the relationship between state-level ETI participation and past-year HIV testing among a racially/ethnically diverse sample of adult respondents to the 2012 Behavioral Risk Factor Surveillance System who accessed health services within the 12 months prior to being interviewed. Controlling for individual- and state-level characteristics in a multilevel logistic regression model, ETI participation was independently and positively associated with past-year testing, but this association varied by race/ethnicity. Hispanics had higher odds (adjusted odds ratio [AOR]: 1.49; 95% CI: 1.11-2.02) and American Indian/Alaska Natives had lower odds (AOR: 0.66; 95% CI: 0.43-0.99) of testing if they resided in states with (vs. without) ETI participation. State-level ETI participation did not significantly alter past-year testing among other racial/ethnic groups. Prioritizing public health resources in states most affected by HIV can improve testing patterns, but other mechanisms likely influence which racial/ethnic groups undergo testing. JF - AIDS Care AU - Gaines, Tommi L AU - Caldwell, Julia T AU - Ford, Chandra L AU - Mulatu, Mesfin S AU - Godette, Dionne C AD - Division of Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA ; Department of Community Health Sciences, Fielding School of Public Health, University of California at Los Angeles, Los Angeles, CA, USA ; Independent Researcher, Atlanta, GA, USA ; Division of Epidemiology and Prevention Research, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 554 EP - 560 CY - London PB - Taylor & Francis Ltd. VL - 28 IS - 5 SN - 0954-0121 KW - Medical Sciences--Psychiatry And Neurology KW - HIV/AIDS KW - screening KW - race/ethnic differences KW - testing initiative KW - multilevel KW - Alaska Native people KW - American Indian people KW - Ethnic groups KW - Ethnicity KW - Financing KW - Health services KW - HIV KW - Multilevel analysis KW - Preventive health care KW - Prioritizing KW - Public health KW - Race KW - Risk behaviour KW - Sex education KW - Surveillance systems KW - Testing KW - Acquired immune deficiency syndrome--AIDS KW - Health risk assessment KW - Surveillance KW - Human immunodeficiency virus--HIV KW - Medical tests KW - Disease prevention KW - Disease control KW - Alaska UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789532027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Care&rft.atitle=Relationship+between+a+Centers+for+Disease+Control+and+Prevention+expanded+HIV+testing+initiative+and+past-year+testing+by+race%2Fethnicity%3A+a+multilevel+analysis+of+the+Behavioral+Risk+Factor+Surveillance+System&rft.au=Gaines%2C+Tommi+L%3BCaldwell%2C+Julia+T%3BFord%2C+Chandra+L%3BMulatu%2C+Mesfin+S%3BGodette%2C+Dionne+C&rft.aulast=Gaines&rft.aufirst=Tommi&rft.date=2016-05-01&rft.volume=28&rft.issue=5&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=AIDS+Care&rft.issn=09540121&rft_id=info:doi/10.1080%2F09540121.2015.1131968 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Name - Centers for Disease Control & Prevention--CDC N1 - Copyright - © 2016 Informa UK Limited, trading as Taylor & Francis Group N1 - Last updated - 2016-06-13 N1 - SubjectsTermNotLitGenreText - Alaska DO - http://dx.doi.org/10.1080/09540121.2015.1131968 ER - TY - JOUR T1 - Potential of breastmilk analysis to inform early events in breast carcinogenesis: rationale and considerations. AN - 1789033544; 27107568 AB - This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g., hormones) is often complicated by the requirement to accurately account for menstrual cycle date. Accordingly, novel approaches are needed to understand how events such as pregnancy, breastfeeding, weaning, and post-weaning breast remodeling influence breast cancer risk. Analysis of breastmilk offers opportunities to understand mechanisms related to carcinogenesis in the breast, and to identify risk markers that may inform efforts to identify high-risk women early in the carcinogenic process. In addition, analysis of breastmilk could have value in early detection or diagnosis of breast cancer. In this article, we describe the potential for using breastmilk to characterize the microenvironment of the lactating breast with the goal of advancing research on risk assessment, prevention, and detection of breast cancer. JF - Breast cancer research and treatment AU - Murphy, Jeanne AU - Sherman, Mark E AU - Browne, Eva P AU - Caballero, Ana I AU - Punska, Elizabeth C AU - Pfeiffer, Ruth M AU - Yang, Hannah P AU - Lee, Maxwell AU - Yang, Howard AU - Gierach, Gretchen L AU - Arcaro, Kathleen F AD - Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. jeanne.murphy@nih.gov. ; Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. ; Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, USA. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. ; Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 13 EP - 22 VL - 157 IS - 1 KW - Index Medicus KW - Prevention KW - Methods KW - Human breastmilk KW - Breast cancer KW - Biomarkers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1789033544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Potential+of+breastmilk+analysis+to+inform+early+events+in+breast+carcinogenesis%3A+rationale+and+considerations.&rft.au=Murphy%2C+Jeanne%3BSherman%2C+Mark+E%3BBrowne%2C+Eva+P%3BCaballero%2C+Ana+I%3BPunska%2C+Elizabeth+C%3BPfeiffer%2C+Ruth+M%3BYang%2C+Hannah+P%3BLee%2C+Maxwell%3BYang%2C+Howard%3BGierach%2C+Gretchen+L%3BArcaro%2C+Kathleen+F&rft.aulast=Murphy&rft.aufirst=Jeanne&rft.date=2016-05-01&rft.volume=157&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=1573-7217&rft_id=info:doi/10.1007%2Fs10549-016-3796-x LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10549-016-3796-x ER - TY - JOUR T1 - Methamphetamine addiction: involvement of CREB and neuroinflammatory signaling pathways AN - 1787987225; PQ0002977806 AB - Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models are also helping to decipher the neurobiological substrates of associated neuropsychiatric complications. This review summarizes our work on the influence of METH self-administration on dopamine systems, transcription and immune responses in the brain. We used the rat model of METH self-administration with extended access (15 h/day for eight consecutive days) to investigate the effects of voluntary METH intake on the markers of dopamine system integrity and changes in gene expression observed in the brain at 2 h-1 month after cessation of drug exposure. Extended access to METH self-administration caused changes in the rat brain that are consistent with clinical findings reported in neuroimaging and postmortem studies of human METH addicts. In addition, gene expression studies using striatal tissues from METH self-administering rats revealed increased expression of genes involved in cAMP response element binding protein (CREB) signaling pathway and in the activation of neuroinflammatory response in the brain. These data show an association of METH exposure with activation of neuroplastic and neuroinflammatory cascades in the brain. The neuroplastic changes may be involved in promoting METH addiction. Neuroinflammatory processes in the striatum may underlie cognitive deficits, depression, and parkinsonism reported in METH addicts. Therapeutic approaches that include suppression of neuroinflammation may be beneficial to addicted patients. JF - Psychopharmacology AU - Krasnova, Irina N AU - Justinova, Zuzana AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Research Branch, Intramural Research Program, NIDA, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD, 21224, USA, ikrasnov@intra.nida.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1945 EP - 1962 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 233 IS - 10 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Neuroimaging KW - Addicts KW - Regulatory sequences KW - Animal models KW - Drug abuse KW - Inflammation KW - Gene expression KW - Methamphetamine KW - Dopamine KW - Movement disorders KW - Cognitive ability KW - Reviews KW - Neostriatum KW - Self-administration KW - Immune response KW - Addiction KW - Basal ganglia KW - Signal transduction KW - Cyclic AMP response element-binding protein KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787987225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Methamphetamine+addiction%3A+involvement+of+CREB+and+neuroinflammatory+signaling+pathways&rft.au=Krasnova%2C+Irina+N%3BJustinova%2C+Zuzana%3BCadet%2C+Jean+Lud&rft.aulast=Krasnova&rft.aufirst=Irina&rft.date=2016-05-01&rft.volume=233&rft.issue=10&rft.spage=1945&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-016-4235-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 157 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Addicts; Regulatory sequences; Animal models; Drug abuse; Inflammation; Gene expression; Methamphetamine; Movement disorders; Dopamine; Cognitive ability; Reviews; Neostriatum; Self-administration; Addiction; Immune response; Basal ganglia; Cyclic AMP response element-binding protein; Signal transduction DO - http://dx.doi.org/10.1007/s00213-016-4235-8 ER - TY - JOUR T1 - Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders AN - 1787986472; PQ0002977800 AB - The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants able to cause substance use disorders (SUD). Caffeine produces psychomotor-activating, reinforcing, and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. A model that considers the striatal adenosine A sub(2A)-dopamine D sub(2) receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally, the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives, synthetic cathinones, and energy drinks with alcohol, and the higher sensitivity of children and adolescents to the psychostimulant effects of caffeine and its potential to increase vulnerability to SUD. The striatal A sub(2A)-D sub(2) receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants. JF - Psychopharmacology AU - Ferre, Sergi AD - Integrative Neurobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Triad Technology Building, 333 Cassell Drive, Baltimore, MD, 21224, USA, sferre@intra.nida.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1963 EP - 1979 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 233 IS - 10 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Dopamine D2 receptors KW - Learning KW - Beverages KW - Arousal KW - Adolescence KW - Denervation KW - Children KW - Drug abuse KW - Models KW - Long-term effects KW - Reviews KW - Energy KW - Rotational behavior KW - Neostriatum KW - alcohols KW - Caffeine KW - Amphetamine KW - Cocaine KW - Adenosine KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787986472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Mechanisms+of+the+psychostimulant+effects+of+caffeine%3A+implications+for+substance+use+disorders&rft.au=Ferre%2C+Sergi&rft.aulast=Ferre&rft.aufirst=Sergi&rft.date=2016-05-01&rft.volume=233&rft.issue=10&rft.spage=1963&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-016-4212-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 209 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Dopamine D2 receptors; Learning; Beverages; Arousal; Adolescence; Drug abuse; Children; Denervation; Models; Long-term effects; Rotational behavior; Energy; Reviews; Neostriatum; alcohols; Amphetamine; Caffeine; Cocaine; Adenosine DO - http://dx.doi.org/10.1007/s00213-016-4212-2 ER - TY - JOUR T1 - Contributions to drug abuse research of Steven R. Goldberg's behavioral analysis of stimulus-stimulus contingencies AN - 1787986456; PQ0002977797 AB - By the mid-1960s, the concept that drugs can function as reinforcing stimuli through response-reinforcer contingencies had created a paradigm shift in drug abuse science. Steve Goldberg's first several publications focused instead on stimulus-stimulus contingencies (respondent conditioning) in examining Abraham Wikler's two-factor hypothesis of relapse involving conditioned withdrawal and reinforcing effects of drugs. Goldberg provided a compelling demonstration that histories of contingencies among stimuli could produce lasting withdrawal reactions in primates formerly dependent on opioids. Other studies conducted by Goldberg extended the analysis of effects of stimulus-stimulus contingencies on behavior maintained by opioid reinforcing effects and showed that withdrawal-inducing antagonist administration can produce conditioned increases in self-administration. Subsequent studies of the effects of stimuli associated with cocaine injection under second-order schedules showed that the maintenance of behavior with drug injections was in most important aspects similar to the maintenance of behavior with more conventional reinforcers when the behavior-disrupting pharmacological effects of the drugs were minimized. Studies on second-order schedules demonstrated a wide array of conditions under which behavior could be maintained by drug injection and further influenced by stimulus-stimulus contingencies. These schedules present opportunities to produce in the laboratory complex situations involving response- and stimulus-stimulus contingencies, which go beyond simplistic pairings of stimuli and more closely approximate those found with human drug abusers. A focus on the response- and stimulus-stimulus contingencies, and resulting quantifiable changes in objective and quantifiable behavioral endpoints exemplified by the studies by Steve Goldberg, remains the most promising way forward for studying problems of drug dependence. JF - Psychopharmacology AU - Katz, Jonathan L AD - Psychobiology Section, NIDA Intramural Research Program, Baltimore, MD, USA, jkatz@intra.nida.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1921 EP - 1932 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 233 IS - 10 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts; Animal Behavior Abstracts; CSA Neurosciences Abstracts KW - Drug dependence KW - Withdrawal KW - Second-order schedule KW - Reinforcement KW - Opioids KW - Drug abuse KW - Cocaine KW - Contingency KW - Drug self-administration KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience KW - Y 25070:Learning, Memory, Reinforcement, and Motivation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787986456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Contributions+to+drug+abuse+research+of+Steven+R.+Goldberg%27s+behavioral+analysis+of+stimulus-stimulus+contingencies&rft.au=Katz%2C+Jonathan+L&rft.aulast=Katz&rft.aufirst=Jonathan&rft.date=2016-05-01&rft.volume=233&rft.issue=10&rft.spage=1921&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-015-4149-x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 52 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Drug dependence; Withdrawal; Reinforcement; Second-order schedule; Opioids; Cocaine; Drug abuse; Contingency; Drug self-administration DO - http://dx.doi.org/10.1007/s00213-015-4149-x ER - TY - JOUR T1 - Differential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on nicotine versus cocaine self-administration and relapse in squirrel monkeys AN - 1787986249; PQ0002977792 AB - Group II metabotropic glutamate receptors (mGluR2 and mGluR3) have been suggested to play an important role in mediation of drug-reinforced behaviors, as well as in the mechanisms underlying relapse in abstinent subjects. The prototypical mGluR2/3 agonist, LY379268, has been shown to attenuate nicotine reinforcement and cue-induced reinstatement of drug seeking in rats, as well as reinstatement induced by drug-associated stimuli and contexts across different drugs of abuse (i.e., cocaine, heroin, and methamphetamine). However, in primates, LY379268 has been shown to produce conflicting results on abuse-related effects of cocaine, and there are no data available for nicotine. To explore the therapeutic potential of mGluR2/3 agonists, we compared the effects of LY379268 (0.03-1.0 mg/kg) on nicotine, cocaine, and food self-administration under a fixed-ratio (FR10) schedule in three separate groups of squirrel monkeys. Moreover, we studied the effects of LY379268 on nicotine/cocaine priming-induced and cue-induced reinstatement of drug-seeking behavior in nicotine- and cocaine-experienced groups of animals. LY379268 blocked nicotine, but not cocaine, self-administration in monkeys. There was a partial overlap between doses that affected nicotine and food self-administration. In abstinent monkeys, LY379268 dose-dependently blocked nicotine, but not cocaine, priming-induced reinstatement of drug seeking. In both cocaine-experienced and nicotine-experienced groups of animals, LY379268 potently reduced cue-induced reinstatement of drug-seeking behavior. The present findings provide strong support for the potential utility of mGlu2/3 receptor agonists for the treatment of nicotine dependence and suggest their utility for prevention of relapse induced by environmental cues associated with drug taking. JF - Psychopharmacology AU - Justinova, Zuzana AU - Le Foll, Bernard AU - Redhi, Godfrey H AU - Markou, Athina AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA, zjustino@intra.nida.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1791 EP - 1800 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 233 IS - 10 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts; Animal Behavior Abstracts; CSA Neurosciences Abstracts KW - Glutamic acid receptors (metabotropic) KW - Data processing KW - Heroin KW - Food KW - Drug abuse KW - Reinstatement KW - Glutamic acid receptors KW - Saimiri KW - Drug dependence KW - Methamphetamine KW - Nicotine KW - Reinforcement KW - Drug addiction KW - Cocaine KW - Drug self-administration KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience KW - Y 25110:Biochemical & Neurophysiological Correlates, Lesions and Stimuli UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787986249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Differential+effects+of+the+metabotropic+glutamate+2%2F3+receptor+agonist+LY379268+on+nicotine+versus+cocaine+self-administration+and+relapse+in+squirrel+monkeys&rft.au=Justinova%2C+Zuzana%3BLe+Foll%2C+Bernard%3BRedhi%2C+Godfrey+H%3BMarkou%2C+Athina%3BGoldberg%2C+Steven+R&rft.aulast=Justinova&rft.aufirst=Zuzana&rft.date=2016-05-01&rft.volume=233&rft.issue=10&rft.spage=1791&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-015-3994-y LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 46 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Glutamic acid receptors (metabotropic); Data processing; Heroin; Food; Drug abuse; Glutamic acid receptors; Reinstatement; Drug dependence; Methamphetamine; Nicotine; Reinforcement; Cocaine; Drug addiction; Drug self-administration; Saimiri DO - http://dx.doi.org/10.1007/s00213-015-3994-y ER - TY - JOUR T1 - Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats AN - 1787983628; PQ0002977794 AB - In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement. We trained rats to self-administer heroin (0.05-0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone-light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub arrow right NAc shell and vSub arrow right vmPFC projections are functionally involved in this reinstatement. Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. Anatomical disconnection of the vSub arrow right NAc shell projection, but not the vSub arrow right vmPFC projection, decreased this reinstatement. Our data indicate that the vSub arrow right NAc shell glutamatergic projection, but not the vSub arrow right vmPFC projection, contributes to context-induced reinstatement of heroin seeking. JF - Psychopharmacology AU - Bossert, Jennifer M AU - Adhikary, Sweta AU - St Laurent, Robyn AU - Marchant, Nathan J AU - Wang, Hui-Ling AU - Morales, Marisela AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, IRP-NIDA, NIH, Baltimore, MD, USA, jbossert@intra.nida.nih.gov Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1991 EP - 2004 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 233 IS - 10 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Nucleus accumbens KW - Data processing KW - Extinction KW - Hippocampus KW - Heroin KW - Drug abuse KW - Reinstatement KW - Fos protein KW - Tracers KW - Glutamatergic transmission KW - Neurons KW - Glutamic acid KW - Cortex (prefrontal) KW - X 24380:Social Poisons & Drug Abuse KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787983628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Role+of+projections+from+ventral+subiculum+to+nucleus+accumbens+shell+in+context-induced+reinstatement+of+heroin+seeking+in+rats&rft.au=Bossert%2C+Jennifer+M%3BAdhikary%2C+Sweta%3BSt+Laurent%2C+Robyn%3BMarchant%2C+Nathan+J%3BWang%2C+Hui-Ling%3BMorales%2C+Marisela%3BShaham%2C+Yavin&rft.aulast=Bossert&rft.aufirst=Jennifer&rft.date=2016-05-01&rft.volume=233&rft.issue=10&rft.spage=1991&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/10.1007%2Fs00213-015-4060-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 81 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Nucleus accumbens; Data processing; Extinction; Heroin; Hippocampus; Drug abuse; Reinstatement; Fos protein; Tracers; Glutamatergic transmission; Neurons; Glutamic acid; Cortex (prefrontal) DO - http://dx.doi.org/10.1007/s00213-015-4060-5 ER - TY - JOUR T1 - E-Waste and Harm to Vulnerable Populations: A Growing Global Problem. AN - 1787089508; 26418733 AB - Electronic waste (e-waste) is produced in staggering quantities, estimated globally to be 41.8 million tonnes in 2014. Informal e-waste recycling is a source of much-needed income in many low- to middle-income countries. However, its handling and disposal in underdeveloped countries is often unsafe and leads to contaminated environments. Rudimentary and uncontrolled processing methods often result in substantial harmful chemical exposures among vulnerable populations, including women and children. E-waste hazards have not yet received the attention they deserve in research and public health agendas. We provide an overview of the scale and health risks. We review international efforts concerned with environmental hazards, especially affecting children, as a preface to presenting next steps in addressing health issues stemming from the global e-waste problem. The e-waste problem has been building for decades. Increased observation of adverse health effects from e-waste sites calls for protecting human health and the environment from e-waste contamination. Even if e-waste exposure intervention and prevention efforts are implemented, legacy contamination will remain, necessitating increased awareness of e-waste as a major environmental health threat. Global, national, and local levels efforts must aim to create safe recycling operations that consider broad security issues for people who rely on e-waste processing for survival. Paramount to these efforts is reducing pregnant women and children's e-waste exposures to mitigate harmful health effects. With human environmental health in mind, novel dismantling methods and remediation technologies and intervention practices are needed to protect communities. Heacock M, Kelly CB, Asante KA, Birnbaum LS, Bergman AL, Bruné MN, Buka I, Carpenter DO, Chen A, Huo X, Kamel M, Landrigan PJ, Magalini F, Diaz-Barriga F, Neira M, Omar M, Pascale A, Ruchirawat M, Sly L, Sly PD, Van den Berg M, Suk WA. 2016. E-waste and harm to vulnerable populations: a growing global problem. Environ Health Perspect 124:550-555; http://dx.doi.org/10.1289/ehp.1509699. JF - Environmental health perspectives AU - Heacock, Michelle AU - Kelly, Carol Bain AU - Asante, Kwadwo Ansong AU - Birnbaum, Linda S AU - Bergman, Åke Lennart AU - Bruné, Marie-Noel AU - Buka, Irena AU - Carpenter, David O AU - Chen, Aimin AU - Huo, Xia AU - Kamel, Mostafa AU - Landrigan, Philip J AU - Magalini, Federico AU - Diaz-Barriga, Fernando AU - Neira, Maria AU - Omar, Magdy AU - Pascale, Antonio AU - Ruchirawat, Mathuros AU - Sly, Leith AU - Sly, Peter D AU - Van den Berg, Martin AU - Suk, William A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 550 EP - 555 VL - 124 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787089508?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=E-Waste+and+Harm+to+Vulnerable+Populations%3A+A+Growing+Global+Problem.&rft.au=Heacock%2C+Michelle%3BKelly%2C+Carol+Bain%3BAsante%2C+Kwadwo+Ansong%3BBirnbaum%2C+Linda+S%3BBergman%2C+%C3%85ke+Lennart%3BBrun%C3%A9%2C+Marie-Noel%3BBuka%2C+Irena%3BCarpenter%2C+David+O%3BChen%2C+Aimin%3BHuo%2C+Xia%3BKamel%2C+Mostafa%3BLandrigan%2C+Philip+J%3BMagalini%2C+Federico%3BDiaz-Barriga%2C+Fernando%3BNeira%2C+Maria%3BOmar%2C+Magdy%3BPascale%2C+Antonio%3BRuchirawat%2C+Mathuros%3BSly%2C+Leith%3BSly%2C+Peter+D%3BVan+den+Berg%2C+Martin%3BSuk%2C+William+A&rft.aulast=Heacock&rft.aufirst=Michelle&rft.date=2016-05-01&rft.volume=124&rft.issue=5&rft.spage=550&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1509699 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-04 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Environ Health Perspect. 1998 Jun;106 Suppl 3:787-94 [9646038] Environ Sci Technol. 2007 Nov 15;41(22):7668-74 [18075072] Sci Total Environ. 2009 Dec 20;408(2):183-91 [19846207] Environ Sci Technol. 2011 Jan 15;45(2):400-5 [21128659] Environ Health Perspect. 2011 Apr;119(4):431-8 [21081302] Environ Int. 2011 Jul;37(5):921-8 [21470682] Sci Total Environ. 2012 May 1;424:63-73 [22446112] Waste Manag. 2012 Nov;32(11):2134-46 [22560019] Rev Environ Health. 2013;28(1):59-65 [23612529] Lancet. 2013 Jun 29;381(9885):2223 [23809544] Ecotoxicol Environ Saf. 2013 Oct;96:205-12 [23849468] Rev Environ Health. 2014;29(1-2):1-2 [24552954] Environ Sci Technol. 2014;48(15):8735-43 [25007134] Lancet Glob Health. 2013 Dec;1(6):e350-61 [25104600] Lancet Glob Health. 2014 Mar;2(3):e129-30 [25102838] Environ Health Perspect. 2003 Aug;111(10):1340-7 [12896856] Int J Occup Med Environ Health. 2004;17(1):103-10 [15212212] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1509699 ER - TY - JOUR T1 - Developmental Effects of the ToxCast™ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits. AN - 1787088181; 26496690 AB - Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. The nematode Caenorhabditis elegans (C. elegans) was used to screen the U.S. Environmental Protection Agency's (EPA's) ToxCast™ Phase I and Phase II libraries, which contain 292 and 676 chemicals, respectively, for chemicals leading to decreased larval development and growth. Chemical toxicity was evaluated using three parameters: a biologically defined effect size threshold, half-maximal activity concentration (AC50), and lowest effective concentration (LEC). Across both the Phase I and Phase II libraries, 62% of the chemicals were classified as active ≤ 200 μM in the C. elegans assay. Chemical activities and potencies in C. elegans were compared with those from two zebrafish embryonic development toxicity studies and developmental toxicity data for rats and rabbits. Concordance of chemical activity was higher between C. elegans and one zebrafish assay across Phase I chemicals (79%) than with a second zebrafish assay (59%). Using C. elegans or zebrafish to predict rat or rabbit developmental toxicity resulted in balanced accuracies (the average value of the sensitivity and specificity for an assay) ranging from 45% to 53%, slightly lower than the concordance between rat and rabbit (58%). Here, we present an assay that quantitatively and reliably describes the effects of chemical toxicants on C. elegans growth and development. We found significant overlap in the activity of chemicals in the ToxCast™ libraries between C. elegans and zebrafish developmental screens. Incorporating C. elegans toxicological assays as part of a battery of in vitro and in vivo assays provides additional information for the development of models to predict a chemical's potential toxicity to humans. Boyd WA, Smith MV, Co CA, Pirone JR, Rice JR, Shockley KR, Freedman JH. 2016. Developmental effects of the ToxCast™ Phase I and II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environ Health Perspect 124:586-593; http://dx.doi.org/10.1289/ehp.1409645. JF - Environmental health perspectives AU - Boyd, Windy A AU - Smith, Marjolein V AU - Co, Caroll A AU - Pirone, Jason R AU - Rice, Julie R AU - Shockley, Keith R AU - Freedman, Jonathan H AD - Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 586 EP - 593 VL - 124 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787088181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Developmental+Effects+of+the+ToxCast%E2%84%A2+Phase+I+and+Phase+II+Chemicals+in+Caenorhabditis+elegans+and+Corresponding+Responses+in+Zebrafish%2C+Rats%2C+and+Rabbits.&rft.au=Boyd%2C+Windy+A%3BSmith%2C+Marjolein+V%3BCo%2C+Caroll+A%3BPirone%2C+Jason+R%3BRice%2C+Julie+R%3BShockley%2C+Keith+R%3BFreedman%2C+Jonathan+H&rft.aulast=Boyd&rft.aufirst=Windy&rft.date=2016-05-01&rft.volume=124&rft.issue=5&rft.spage=586&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1409645 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-04 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Toxicol Sci. 2007 Jan;95(1):5-12 [16963515] Methods Mol Biol. 2006;351:275-86 [16988441] PLoS One. 2007;2(12):e1259 [18060055] Reprod Toxicol. 2009 Sep;28(2):209-19 [19446433] Environ Health Perspect. 2009 Mar;117(3):392-9 [19337514] Science. 2008 Feb 15;319(5865):906-7 [18276874] PLoS One. 2009;4(9):e7024 [19753116] PLoS One. 2009;4(9):e7018 [19753303] Neurotoxicol Teratol. 2010 Jan-Feb;32(1):68-73 [19166924] Environ Health Perspect. 2011 Jan;119(1):20-8 [20797931] ALTEX. 2011;28(1):9-15 [21311847] J Vis Exp. 2011;(51). pii: 2745. doi: 10.3791/2745 [21633332] PLoS One. 2011;6(5):e20085 [21647448] Birth Defects Res C Embryo Today. 2011 Sep;93(3):256-67 [21932434] Toxicol Sci. 2011 Nov;124(1):109-27 [21873373] Reprod Toxicol. 2012 Apr;33(2):174-87 [22182468] Environ Sci Technol. 2014;48(1):804-10 [24328182] Lancet Neurol. 2014 Mar;13(3):330-8 [24556010] Methods. 2014 Aug 1;68(3):529-35 [24990146] Neurotoxicology. 2014 Jul;43:134-42 [24674958] Environ Health Perspect. 2010 Apr;118(4):485-92 [20368123] Toxicol Appl Pharmacol. 2010 Jun 1;245(2):153-9 [20206647] Toxicol Appl Pharmacol. 2004 Feb 1;194(3):248-56 [14761681] Genetics. 1974 May;77(1):71-94 [4366476] Dev Biol. 1976 Jul 1;51(1):23-33 [988845] Toxicol Ind Health. 1988 Dec;4(4):469-78 [3188044] Arch Environ Contam Toxicol. 1997 Jan;32(1):110-4 [9002442] Nat Rev Drug Discov. 2006 May;5(5):387-98 [16672925] Biochem Biophys Res Commun. 2007 May 25;357(1):200-5 [17418813] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1409645 ER - TY - JOUR T1 - Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood AN - 1786772688 AB - Childhood trauma is a major precipitating factor in psychiatric disease. Emerging data suggest that stress susceptibility is genetically determined, and that risk is mediated by changes in limbic brain circuitry. There is a need to identify markers of disease vulnerability, and it is critical that these markers be investigated in childhood and adolescence, a time when neural networks are particularly malleable and when psychiatric disorders frequently emerge. In this preliminary study, we evaluated whether a common variant in the brain-derived neurotrophic factor (BDNF) gene (Val66Met; rs6265) interacts with childhood trauma to predict limbic gray matter volume in a sample of 55 youth high in sociodemographic risk. We found trauma-by-BDNF interactions in the right subcallosal area and right hippocampus, wherein BDNF-related gray matter changes were evident in youth without histories of trauma. In youth without trauma exposure, lower hippocampal volume was related to higher symptoms of anxiety. These data provide preliminary evidence for a contribution of a common BDNF gene variant to the neural correlates of childhood trauma among high-risk urban youth. Altered limbic structure in early life may lay the foundation for longer term patterns of neural dysfunction, and hold implications for understanding the psychiatric and psychobiological consequences of traumatic stress on the developing brain. JF - European Child & Adolescent Psychiatry AU - Marusak, Hilary A AU - Kuruvadi, Nisha AU - Vila, Angela M AU - Shattuck, David W AU - Joshi, Shantanu H AU - Joshi, Anand A AU - Jella, Pavan K AU - Thomason, Moriah E AD - Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, USA; Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA ; Liberty University College of Osteopathic Medicine, Lynchburg, VA, USA ; Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, USA ; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA ; Brain and Creativity Institute, University of Southern California, Los Angeles, CA, USA; Signal and Image Processing Institute, University of Southern California, Los Angeles, CA, USA ; Department of Radiology, Wayne State University, Detroit, MI, USA ; Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, USA; Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA; Perinatology Research Branch, NICHD/NIH/DHSS, Detroit, MI, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 509 EP - 518 CY - Dordrecht PB - Springer Science & Business Media VL - 25 IS - 5 SN - 1018-8827 KW - Medical Sciences--Psychiatry And Neurology KW - Brain-derived neurotrophic factor KW - Early adversity KW - Mood disorders KW - Gray matter volume KW - Medial prefrontal cortex KW - Adolescence KW - Sociodemographic aspects KW - Young people KW - Brain KW - Childhood abuse KW - High risk KW - Psychological trauma KW - Dysfunction KW - Susceptibility KW - Vulnerability KW - Psychiatric disorders KW - Traumatic stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1786772688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Child+%26+Adolescent+Psychiatry&rft.atitle=Interactive+effects+of+BDNF+Val66Met+genotype+and+trauma+on+limbic+brain+anatomy+in+childhood&rft.au=Marusak%2C+Hilary+A%3BKuruvadi%2C+Nisha%3BVila%2C+Angela+M%3BShattuck%2C+David+W%3BJoshi%2C+Shantanu+H%3BJoshi%2C+Anand+A%3BJella%2C+Pavan+K%3BThomason%2C+Moriah+E&rft.aulast=Marusak&rft.aufirst=Hilary&rft.date=2016-05-01&rft.volume=25&rft.issue=5&rft.spage=509&rft.isbn=&rft.btitle=&rft.title=European+Child+%26+Adolescent+Psychiatry&rft.issn=10188827&rft_id=info:doi/10.1007%2Fs00787-015-0759-4 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer-Verlag Berlin Heidelberg 2016 N1 - Last updated - 2016-05-19 DO - http://dx.doi.org/10.1007/s00787-015-0759-4 ER - TY - JOUR T1 - Anxiety in childhood across the globe: findings from meta-regression analyses of the past 15 years (1998-2013) AN - 1786772604 JF - European Child & Adolescent Psychiatry AU - Gosmann, N P AU - Vaz, L V AU - Desousa, D A AU - Koller, S H AU - Pine, D S AU - Manfro, G G AU - Salum, G A AD - Anxiety Disorders Outpatient Program for Child and Adolescent Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil ; Center for Psychological Studies on At-Risk Populations, Institute of Psychology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Anxiety Disorders Outpatient Program for Child and Adolescent Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil; Center for Psychological Studies on At-Risk Populations, Institute of Psychology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil ; Emotion and Development Branch, Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 557 EP - 561 CY - Dordrecht PB - Springer Science & Business Media VL - 25 IS - 5 SN - 1018-8827 KW - Medical Sciences--Psychiatry And Neurology KW - Childhood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1786772604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Child+%26+Adolescent+Psychiatry&rft.atitle=Anxiety+in+childhood+across+the+globe%3A+findings+from+meta-regression+analyses+of+the+past+15+years+%281998-2013%29&rft.au=Gosmann%2C+N+P%3BVaz%2C+L+V%3BDesousa%2C+D+A%3BKoller%2C+S+H%3BPine%2C+D+S%3BManfro%2C+G+G%3BSalum%2C+G+A&rft.aulast=Gosmann&rft.aufirst=N&rft.date=2016-05-01&rft.volume=25&rft.issue=5&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=European+Child+%26+Adolescent+Psychiatry&rft.issn=10188827&rft_id=info:doi/10.1007%2Fs00787-015-0785-2 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Springer-Verlag Berlin Heidelberg 2016 N1 - Last updated - 2016-05-19 DO - http://dx.doi.org/10.1007/s00787-015-0785-2 ER - TY - JOUR T1 - Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial. AN - 1785753710; 27035363 AB - We report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy (SBRT) for low (LR) and select intermediate risk (IR) prostate cancer (PCa) patients. Eligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA ≤ 20 or Gleason 7 with PSA ≤ 15 and clinical stage ≤ T2b. For the phase I portion of the study patients in cohorts of 15 received 45, 47.5, or 50 Gray (Gy) in five fractions. Since the maximally tolerated dose was not met in the phase I study, an additional 47 patients received 50 Gy in five fractions in the phase II study. Toxicity using Common Toxicity Criteria for Adverse Events v. 3.0, quality of life, and outcome data was collected. A total of 91 patients are included for analysis; 63.7% had NCCN IR and 36.3% had LR PCa. At a median follow up of 54 months the actuarial freedom from biochemical failure was 100% at 3 years and 98.6% at 5 years. Actuarial distant metastasis free survival was 100% at 3 and 5 years. Overall survival was 94% at 3 years and 89.7% at 5 years with no deaths attributed to PCa. Acute and late urinary grade ≥ III toxicity occurred in 0% and 5.5% of patients, respectively. Gastrointestinal (GI) acute and late toxicity of grade ≥ III occurred in 2% and 7% of patients, respectively. A total of four men experienced grade IV toxicity (three GI, one genitourinary). SBRT treatment results in excellent biochemical control rates at 5 years for LR and IR PCa patients although doses greater than 47.5 Gy in five fractions led to increased severe late toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - European journal of cancer (Oxford, England : 1990) AU - Hannan, Raquibul AU - Tumati, Vasu AU - Xie, Xian-Jin AU - Cho, L Chinsoo AU - Kavanagh, Brian D AU - Brindle, Jeffrey AU - Raben, David AU - Nanda, Akash AU - Cooley, Susan AU - Kim, D W Nathan AU - Pistenmaa, David AU - Lotan, Yair AU - Timmerman, Robert AD - Department of Radiation Oncology, University of Texas Southwestern Medical Center, USA. ; Department of Clinical Sciences, University of Texas Southwestern Medical Center, USA. ; Department of Radiation Oncology, University of Minnesota, USA. ; Department of Radiation Oncology, University of Colorado, USA. ; Department of Radiation Oncology, Prairie Lakes Hospital, USA. ; Department of Radiation Oncology, Orlando Health, USA. ; Texas Oncology-Waco, USA. ; Radiation Research Program, NCI, USA. ; Department of Urology, University of Texas Southwestern Medical Center, USA. ; Department of Radiation Oncology, University of Texas Southwestern Medical Center, USA. Electronic address: Robert.Timmerman@utsouthwestern.edu. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 142 EP - 151 VL - 59 KW - Index Medicus KW - Stereotactic body radiation therapy KW - Prostate cancer KW - Dose constraints KW - SBRT UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785753710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Stereotactic+body+radiation+therapy+for+low+and+intermediate+risk+prostate+cancer-Results+from+a+multi-institutional+clinical+trial.&rft.au=Hannan%2C+Raquibul%3BTumati%2C+Vasu%3BXie%2C+Xian-Jin%3BCho%2C+L+Chinsoo%3BKavanagh%2C+Brian+D%3BBrindle%2C+Jeffrey%3BRaben%2C+David%3BNanda%2C+Akash%3BCooley%2C+Susan%3BKim%2C+D+W+Nathan%3BPistenmaa%2C+David%3BLotan%2C+Yair%3BTimmerman%2C+Robert&rft.aulast=Hannan&rft.aufirst=Raquibul&rft.date=2016-05-01&rft.volume=59&rft.issue=&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=1879-0852&rft_id=info:doi/10.1016%2Fj.ejca.2016.02.014 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-30 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ejca.2016.02.014 ER - TY - JOUR T1 - Survival After Surgical Treatment of Lung Cancer Arising in the Population Exposed to Illegal Dumping of Toxic Waste in the Land of Fires ('Terra dei Fuochi') of Southern Italy. AN - 1785743610; 27127112 AB - Terra dei Fuochi (TdF), the so-called 'Land of Fires' in Southern Italy, is an agricultural territory characterized by illegal dumping of toxic waste known to occur since the 1980s. It is unknown whether prognosis of patients developing cancer and living in that area may differ compared to those living in areas not exposed to this specific type of pollution. We retrospectively analyzed the 5-year survival rates of patients originating from the TdF diagnosed with lung cancer compared to patients from other areas. Patients consecutively operated on for non-small cell lung cancer (NSCLC) between November 2004 and April 2013 at the Division of Thoracic Surgery of the National Cancer Institute of Naples were eligible. The study outcome was overall survival (OS). In addition, the TdF and non-TdF groups were compared through propensity score matching (PSM). Overall, 439 patients with resectable NSCLC were operated on, 123 (28%) from the TdF and 316 (72%) from other referral centers of our catchment area. There were 301 males and 138 females; the median age of the entire surgical population was 65 years (range=25-83) years. Apart from a different prevalence of hypertension and underweight patients, preoperative factors were evenly distributed between the two groups. At univariate analysis, OS was not different between the TdF and non TdF group (median 72 and 68 months, respectively; p=0.75 log-rank test). Multivariable analysis confirmed that living in the TdF area had no prognostic impact (hazard ratio=1.05; 95% confidence interval=0.70-1.57; p=0.78) on OS. PSM confirmed no statistically significant difference of OS (hazard ratio=1.01, 95% confidence interval=0.67-1.52; p=0.93). Following surgery for lung cancer, TdF and non-TdF surgical candidates had similar long-term survival. Originating from the TdF does not seem to be associated with worse outcomes after surgical treatment of patients with lung cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. JF - Anticancer research AU - Rocco, Gaetano AU - Petitti, Tommasangelo AU - Martucci, Nicola AU - Piccirillo, Maria Carmela AU - LA Rocca, Antonello AU - LA Manna, Carmine AU - DE Luca, Giuseppe AU - Morabito, Alessandro AU - Chirico, Andrea AU - Franco, Renato AU - Accardo, Rosanna AU - Normanno, Nicola AU - Botti, Gerardo AU - Lodato, Sergio AU - Ciliberto, Gennaro AU - Pedicini, Tonino AU - Giordano, Antonio AD - Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy g.rocco@istitutotumori.na.it. ; Hygiene, Public Health an Statistics Research Unit, University Campus Biomedico, Rome, Italy. ; Division of Thoracic Surgery, Department of Thoracic Surgery and Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Clinical Trials Unit, Department of Experimental Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Division of Medical Oncology, Department of Thoracic Surgery and Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Department of Psychology of Developmental and Socialization Processes, Sapienza University of Rome, Rome, Italy Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, U.S.A. ; Division of Pathology, Department of Experimental Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Division of Anesthesiology, Department of Experimental Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Division of Cell Biology, Department of Experimental Oncology, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Strategic Direction, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Scientific Direction, G. Pascale Foundation, National Cancer Institute, IRCCS, Naples, Italy. ; Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, U.S.A. Department of Medicine, Surgery & Neuroscience, University of Siena, Siena, Italy. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 2119 EP - 2124 VL - 36 IS - 5 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - waste dumping KW - Terra dei Fuochi KW - pollution KW - surgery KW - Lung cancer KW - Survival Rate KW - Humans KW - Retrospective Studies KW - Prognosis KW - Aged KW - Middle Aged KW - Male KW - Italy KW - Female KW - Carcinoma, Non-Small-Cell Lung -- chemically induced KW - Environmental Pollutants -- toxicity KW - Carcinoma, Non-Small-Cell Lung -- surgery KW - Lung Neoplasms -- chemically induced KW - Lung Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785743610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Survival+After+Surgical+Treatment+of+Lung+Cancer+Arising+in+the+Population+Exposed+to+Illegal+Dumping+of+Toxic+Waste+in+the+Land+of+Fires+%28%27Terra+dei+Fuochi%27%29+of+Southern+Italy.&rft.au=Rocco%2C+Gaetano%3BPetitti%2C+Tommasangelo%3BMartucci%2C+Nicola%3BPiccirillo%2C+Maria+Carmela%3BLA+Rocca%2C+Antonello%3BLA+Manna%2C+Carmine%3BDE+Luca%2C+Giuseppe%3BMorabito%2C+Alessandro%3BChirico%2C+Andrea%3BFranco%2C+Renato%3BAccardo%2C+Rosanna%3BNormanno%2C+Nicola%3BBotti%2C+Gerardo%3BLodato%2C+Sergio%3BCiliberto%2C+Gennaro%3BPedicini%2C+Tonino%3BGiordano%2C+Antonio&rft.aulast=Rocco&rft.aufirst=Gaetano&rft.date=2016-05-01&rft.volume=36&rft.issue=5&rft.spage=2119&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=1791-7530&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-30 N1 - Date created - 2016-04-29 N1 - Date revised - 2017-02-01 N1 - Last updated - 2017-02-01 ER - TY - JOUR T1 - Influenza A and methicillin-resistant Staphylococcus aureus co-infection in rhesus macaques - A model of severe pneumonia AN - 1785243507; PQ0002916925 AB - Background Influenza results in up to 500,000 deaths annually. Seasonal influenza vaccines have an estimated 60% effectiveness, but provide little or no protection against novel subtypes, and may be less protective in high-risk groups. Neuraminidase inhibitors are recommended for the treatment of severe influenza infection, but are not proven to reduce mortality in severe disease. Preclinical models of severe influenza infection that closely correlate to human disease are needed to assess efficacy of new vaccines and therapeutics. Methods We developed a nonhuman primate model of influenza and bacterial co-infection that recapitulates severe pneumonia in humans. Animals were infected with influenza A virus via intra-bronchial or small-particle aerosol inoculation, methicillin-resistant Staphylococcus aureus, or co-infected with influenza and methicillin-resistant S. aureus combined. We assessed the severity of disease in animals over the course of our study using tools available to evaluate critically ill human patients including high-resolution computed tomography imaging of the lungs, arterial blood gas analyses, and bronchoalveolar lavage. Results Using an intra-bronchial route of inoculation we successfully induced severe pneumonia following influenza infection alone and following influenza and bacterial co-infection. Peak illness was observed at day 6 post-influenza infection, manifested by bilateral pulmonary infiltrates and hypoxemia. The timing of radiographic and physiologic manifestations of disease in our model closely match those observed in severe human influenza infection. Discussion This was the first nonhuman primate study of influenza and bacterial co-infection where high-resolution computed tomography scanning of the lungs was used to quantitatively assess pneumonia over the course of illness and where hypoxemia was correlated with pneumonia severity. With additional validation this model may serve as a pathway for regulatory approval of vaccines and therapeutics for the prevention and treatment of severe influenza pneumonia. JF - Antiviral Research AU - Chertow, Daniel S AU - Kindrachuk, Jason AU - Sheng, Zong-Mei AU - Pujanauski, Lindsey M AU - Cooper, Kurt AU - Nogee, Daniel AU - Claire, Marisa St AU - Solomon, Jeffrey AU - Perry, Donna AU - Sayre, Philip AU - Janosko, Krisztina B AU - Lackemeyer, Matthew G AU - Bohannon, Jordan K AU - Kash, John C AU - Jahrling, Peter B AU - Taubenberger, Jeffery K AD - Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 120 EP - 129 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 129 SN - 0166-3542, 0166-3542 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Influenza KW - Co-infection KW - Pneumonia KW - Vaccines KW - Therapies KW - Mortality KW - Aerosols KW - Hypoxemia KW - Drug resistance KW - Influenza A KW - Animal models KW - Infection KW - imaging KW - Alveoli KW - Blood KW - Bronchus KW - Scanning KW - Lung KW - Influenza A virus KW - Computed tomography KW - Inoculation KW - Risk groups KW - Macaca mulatta KW - Exo- alpha -sialidase KW - Staphylococcus aureus KW - A 01340:Antibiotics & Antimicrobials KW - J 02400:Human Diseases KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785243507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+Research&rft.atitle=Influenza+A+and+methicillin-resistant+Staphylococcus+aureus+co-infection+in+rhesus+macaques+-+A+model+of+severe+pneumonia&rft.au=Chertow%2C+Daniel+S%3BKindrachuk%2C+Jason%3BSheng%2C+Zong-Mei%3BPujanauski%2C+Lindsey+M%3BCooper%2C+Kurt%3BNogee%2C+Daniel%3BClaire%2C+Marisa+St%3BSolomon%2C+Jeffrey%3BPerry%2C+Donna%3BSayre%2C+Philip%3BJanosko%2C+Krisztina+B%3BLackemeyer%2C+Matthew+G%3BBohannon%2C+Jordan+K%3BKash%2C+John+C%3BJahrling%2C+Peter+B%3BTaubenberger%2C+Jeffery+K&rft.aulast=Chertow&rft.aufirst=Daniel&rft.date=2016-05-01&rft.volume=129&rft.issue=&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2Fj.antiviral.2016.02.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-07-07 N1 - SubjectsTermNotLitGenreText - Mortality; Aerosols; Hypoxemia; Influenza A; Drug resistance; Animal models; Infection; imaging; Alveoli; Blood; Scanning; Bronchus; Lung; Computed tomography; Inoculation; Risk groups; Vaccines; Exo- alpha -sialidase; Pneumonia; Influenza A virus; Macaca mulatta; Staphylococcus aureus DO - http://dx.doi.org/10.1016/j.antiviral.2016.02.013 ER - TY - JOUR T1 - Non-thyroid cancer incidence in Belarusian residents exposed to Chernobyl fallout in childhood and adolescence: Standardized Incidence Ratio analysis, 1997-2011 AN - 1785242848; PQ0002920618 AB - Background While an increased risk of thyroid cancer from post-Chernobyl exposure to Iodine-131 (I-131) in children and adolescents has been well-documented, risks of other cancers or leukemia as a result of residence in radioactively contaminated areas remain uncertain. Methods We studied non-thyroid cancer incidence in a cohort of about 12,000 individuals from Belarus exposed under age of 18 years to Chernobyl fallout (median age at the time of Chernobyl accident of 7.9 years). During 15 years of follow-up from1997 through 2011, 54 incident cancers excluding thyroid were identified in the study cohort with 142,968 person-years at risk. We performed Standardized Incidence Ratio (SIR) analysis of all solid cancers excluding thyroid (n=42), of leukemia (n=6) and of lymphoma (n=6). Results We found no significant increase in the incidence of non-thyroid solid cancer (SIR=0.83, 95% Confidence Interval [CI]: 0.61; 1.11), lymphoma (SIR=0.66, 95% CI: 0.26; 1.33) or leukemia (SIR=1.78, 95% CI: 0.71; 3.61) in the study cohort as compared with the sex-, age- and calendar-time-specific national rates. These findings may in part reflect the relatively young age of study subjects (median attained age of 33.4 years), and long latency for some radiation-related solid cancers. Conclusions We found no evidence of statistically significant increases in solid cancer, lymphoma and leukemia incidence 25 years after childhood exposure in the study cohort; however, it is important to continue follow-up non-thyroid cancers in individuals exposed to low-level radiation at radiosensitive ages. JF - Environmental Research AU - Ostroumova, Evgenia AU - Hatch, Maureen AU - Brenner, Alina AU - Nadyrov, Eldar AU - Veyalkin, Ilya AU - Polyanskaya, Olga AU - Yauseyenka, Vasilina AU - Polyakov, Semion AU - Levin, Leonid AU - Zablotska, Lydia AU - Rozhko, Alexander AU - Mabuchi, Kiyohiko AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9609 Medical Center Drive, MSC 9776, Bethesda, 20892 MD, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 44 EP - 49 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 147 SN - 0013-9351, 0013-9351 KW - Toxicology Abstracts; Pollution Abstracts; Environment Abstracts KW - Standardized Incidence Ratio (SIR) KW - Solid cancer KW - Leukemia KW - Lymphoma KW - Chernobyl KW - Belarus KW - Ukraine, Chernobyl KW - Age KW - Statistical analysis KW - Fallout KW - Accidents KW - Radiation KW - thyroid cancer KW - Adolescents KW - Adolescence KW - Thyroid KW - Children KW - Cancer KW - Health risks KW - Nuclear power plants KW - Radioactive fallout KW - Standards KW - X 24390:Radioactive Materials KW - P 6000:TOXICOLOGY AND HEALTH KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785242848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=Non-thyroid+cancer+incidence+in+Belarusian+residents+exposed+to+Chernobyl+fallout+in+childhood+and+adolescence%3A+Standardized+Incidence+Ratio+analysis%2C+1997-2011&rft.au=Ostroumova%2C+Evgenia%3BHatch%2C+Maureen%3BBrenner%2C+Alina%3BNadyrov%2C+Eldar%3BVeyalkin%2C+Ilya%3BPolyanskaya%2C+Olga%3BYauseyenka%2C+Vasilina%3BPolyakov%2C+Semion%3BLevin%2C+Leonid%3BZablotska%2C+Lydia%3BRozhko%2C+Alexander%3BMabuchi%2C+Kiyohiko&rft.aulast=Ostroumova&rft.aufirst=Evgenia&rft.date=2016-05-01&rft.volume=147&rft.issue=&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1016%2Fj.envres.2016.01.025 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Fallout; Leukemia; Accidents; Age; Radiation; Adolescence; thyroid cancer; Statistical analysis; Children; Lymphoma; Nuclear power plants; Health risks; Radioactive fallout; Thyroid; Standards; Adolescents; Cancer; Belarus; Ukraine, Chernobyl DO - http://dx.doi.org/10.1016/j.envres.2016.01.025 ER - TY - JOUR T1 - Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma. AN - 1785215073; 26784951 AB - For recipients of liver transplantations (LTs) for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus (SRL), an immunosuppressant with anticarcinogenic properties, may reduce HCC recurrence and improve survival. In our study, the US Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early SRL use with recurrence, cancer-specific mortality, and all-cause mortality, adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of interleukin 2 induction therapy, and allocated and calculated Model for End-Stage Liver Disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Among the 3936 included HCC LTs, 234 (6%) were SRL users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in SRL users and nonusers (adjusted hazard ratio [aHR], 1.01; 95% CI, 0.73-1.39). HCC recurrence and cancer-specific mortality rates appeared lower in SRL users, but associations were not statistically significant (recurrence aHR, 0.86; 95% CI, 0.45-1.65; cancer-specific mortality aHR, 0.80; 95% CI, 0.43-1.50). Among recipients >55 years old, associations were suggestive of better outcomes for SRL users (all-cause mortality aHR, 0.62; 95% CI, 0.38-1.01; recurrence aHR, 0.52; 95% CI, 0.19-1.44; cancer-specific mortality aHR, 0.34; 95% CI, 0.11-1.09), whereas among recipients ≤55 years old, SRL users had worse outcomes (all-cause mortality aHR, 1.76; 95% CI, 1.12-2.75; recurrence aHR, 1.49; 95% CI, 0.62-3.61; cancer-specific mortality aHR, 1.54; 95% CI, 0.71-3.32). In conclusion, among HCC liver recipients overall, SRL did not appear beneficial in reducing all-cause mortality. However, there were suggestions of reductions in recurrence and cancer-specific mortality, and effects appeared to be modified by age at transplantation. Liver Transplantation 22 627-634 2016 AASLD. © 2016 American Association for the Study of Liver Diseases. JF - Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society AU - Yanik, Elizabeth L AU - Chinnakotla, Srinath AU - Gustafson, Sally K AU - Snyder, Jon J AU - Israni, Ajay K AU - Segev, Dorry L AU - Engels, Eric A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD. ; Department of Surgery, School of Medicine, University of Minnesota, Minneapolis, MN. ; Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN. ; Department of Epidemiology and Community Health, School of Medicine, University of Minnesota, Minneapolis, MN. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 627 EP - 634 VL - 22 IS - 5 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785215073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+transplantation+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.atitle=Effects+of+maintenance+immunosuppression+with+sirolimus+after+liver+transplant+for+hepatocellular+carcinoma.&rft.au=Yanik%2C+Elizabeth+L%3BChinnakotla%2C+Srinath%3BGustafson%2C+Sally+K%3BSnyder%2C+Jon+J%3BIsrani%2C+Ajay+K%3BSegev%2C+Dorry+L%3BEngels%2C+Eric+A&rft.aulast=Yanik&rft.aufirst=Elizabeth&rft.date=2016-05-01&rft.volume=22&rft.issue=5&rft.spage=627&rft.isbn=&rft.btitle=&rft.title=Liver+transplantation+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.issn=1527-6473&rft_id=info:doi/10.1002%2Flt.24395 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-27 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Hepatol. 2012 Jan;56(1):285-7 [21781945] Transplant Proc. 2012 Jul-Aug;44(6):1565-7 [22841215] Liver Transpl. 2012 Sep;18(9):1029-36 [22641474] Aliment Pharmacol Ther. 2013 Feb;37(4):411-9 [23278125] Transplant Rev (Orlando). 2013 Apr;27(2):50-6 [23481320] JAMA. 2014 Jul 2;312(1):57-67 [25058218] Clin Cancer Res. 2015 Apr 15;21(8):1951-61 [25248380] Transplantation. 2016 Jan;100(1):116-25 [26555945] Nat Rev Cancer. 2004 May;4(5):335-48 [15122205] N Engl J Med. 1996 Mar 14;334(11):693-9 [8594428] J Clin Oncol. 1999 Jan;17(1):324-31 [10458250] N Engl J Med. 2004 Dec 23;351(26):2715-29 [15616206] Nat Rev Drug Discov. 2006 Aug;5(8):671-88 [16883305] Transplantation. 2007 Feb 27;83(4):425-32 [17318075] Liver Transpl. 2008 May;14(5):633-8 [18324656] Transplant Proc. 2008 Dec;40(10):3548-53 [19100435] Liver Transpl. 2009 Dec;15(12):1834-42 [19938137] Aliment Pharmacol Ther. 2010 Feb 15;31(4):461-76 [19925500] Hepatology. 2010 Apr;51(4):1237-43 [20187107] Med Oncol. 2010 Jun;27(2):255-61 [19301157] BMC Cancer. 2010;10:190 [20459775] Am J Transplant. 2011 Oct;11(10):2031-5 [21831154] Future Oncol. 2011 Oct;7(10):1149-67 [21992728] J Hepatol. 2012 Jan;56(1):288-90 [21741926] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/lt.24395 ER - TY - JOUR T1 - Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy. AN - 1783921086; 26963343 AB - Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. JF - The American journal of pathology AU - Kuraoka, Mutsuki AU - Kimura, En AU - Nagata, Tetsuya AU - Okada, Takashi AU - Aoki, Yoshitsugu AU - Tachimori, Hisateru AU - Yonemoto, Naohiro AU - Imamura, Michihiro AU - Takeda, Shin'ichi AD - Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurology and Neurological Science, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan. ; Department of Mental Health Policy and Evaluation, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Psychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. Electronic address: takeda@ncnp.go.jp. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1302 EP - 1312 VL - 186 IS - 5 KW - Abridged Index Medicus KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1783921086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Serum+Osteopontin+as+a+Novel+Biomarker+for+Muscle+Regeneration+in+Duchenne+Muscular+Dystrophy.&rft.au=Kuraoka%2C+Mutsuki%3BKimura%2C+En%3BNagata%2C+Tetsuya%3BOkada%2C+Takashi%3BAoki%2C+Yoshitsugu%3BTachimori%2C+Hisateru%3BYonemoto%2C+Naohiro%3BImamura%2C+Michihiro%3BTakeda%2C+Shin%27ichi&rft.aulast=Kuraoka&rft.aufirst=Mutsuki&rft.date=2016-05-01&rft.volume=186&rft.issue=5&rft.spage=1302&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=1525-2191&rft_id=info:doi/10.1016%2Fj.ajpath.2016.01.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ajpath.2016.01.002 ER - TY - JOUR T1 - High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress. AN - 1782832812; 27034412 AB - Astrocytes are the predominant cell type in the nervous system and play a significant role in maintaining neuronal health and homeostasis. Recently, astrocyte dysfunction has been implicated in the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Astrocytes are thus an attractive new target for drug discovery for neurological disorders. Using astrocytes differentiated from human embryonic stem cells, we have developed an assay to identify compounds that protect against oxidative stress, a condition associated with many neurodegenerative diseases. This phenotypic oxidative stress assay has been optimized for high-throughput screening in a 1,536-well plate format. From a screen of approximately 4,100 bioactive tool compounds and approved drugs, we identified a set of 22 that acutely protect human astrocytes from the consequences of hydrogen peroxide-induced oxidative stress. Nine of these compounds were also found to be protective of induced pluripotent stem cell-differentiated astrocytes in a related assay. These compounds are thought to confer protection through hormesis, activating stress-response pathways and preconditioning astrocytes to handle subsequent exposure to hydrogen peroxide. In fact, four of these compounds were found to activate the antioxidant response element/nuclear factor-E2-related factor 2 pathway, a protective pathway induced by toxic insults. Our results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. Astrocytes play a key role in neurological diseases. Drug discovery efforts that target astrocytes can identify novel therapeutics. Human astrocytes are difficult to obtain and thus are challenging to use for high-throughput screening, which requires large numbers of cells. Using human embryonic stem cell-derived astrocytes and an optimized astrocyte differentiation protocol, it was possible to screen approximately 4,100 compounds in titration to identify 22 that are cytoprotective of astrocytes. This study is the largest-scale high-throughput screen conducted using human astrocytes, with a total of 17,536 data points collected in the primary screen. The results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. ©AlphaMed Press. JF - Stem cells translational medicine AU - Thorne, Natasha AU - Malik, Nasir AU - Shah, Sonia AU - Zhao, Jean AU - Class, Bradley AU - Aguisanda, Francis AU - Southall, Noel AU - Xia, Menghang AU - McKew, John C AU - Rao, Mahendra AU - Zheng, Wei AD - National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA Natasha.Thorne@fda.hhs.gov wzheng@mail.nih.gov. ; Laboratory of Stem Cell Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. ; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA. ; NIH Center for Regenerative Medicine, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 613 EP - 627 VL - 5 IS - 5 SN - 2157-6564, 2157-6564 KW - Antioxidants KW - 0 KW - NF-E2-Related Factor 2 KW - NFE2L2 protein, human KW - Oxidants KW - Small Molecule Libraries KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Stem cells KW - Astrocytes KW - Oxidative stress KW - High-throughput screening KW - Neurodegenerative disease KW - Antioxidant Response Elements -- drug effects KW - Oxidants -- pharmacology KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Humans KW - NF-E2-Related Factor 2 -- genetics KW - Cytoprotection KW - NF-E2-Related Factor 2 -- metabolism KW - Hydrogen Peroxide -- toxicity KW - Phenotype KW - Hep G2 Cells KW - Gene Expression Regulation, Developmental KW - Neurogenesis KW - Embryonic Stem Cells -- metabolism KW - Embryonic Stem Cells -- drug effects KW - Antioxidants -- pharmacology KW - Astrocytes -- drug effects KW - Oxidative Stress -- drug effects KW - High-Throughput Screening Assays -- methods KW - Drug Discovery -- methods KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1782832812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+translational+medicine&rft.atitle=High-Throughput+Phenotypic+Screening+of+Human+Astrocytes+to+Identify+Compounds+That+Protect+Against+Oxidative+Stress.&rft.au=Thorne%2C+Natasha%3BMalik%2C+Nasir%3BShah%2C+Sonia%3BZhao%2C+Jean%3BClass%2C+Bradley%3BAguisanda%2C+Francis%3BSouthall%2C+Noel%3BXia%2C+Menghang%3BMcKew%2C+John+C%3BRao%2C+Mahendra%3BZheng%2C+Wei&rft.aulast=Thorne&rft.aufirst=Natasha&rft.date=2016-05-01&rft.volume=5&rft.issue=5&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Stem+cells+translational+medicine&rft.issn=21576564&rft_id=info:doi/10.5966%2Fsctm.2015-0170 LA - English DB - ProQuest Environmental Science Collection N1 - 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Last updated - 2017-01-19 DO - http://dx.doi.org/10.5966/sctm.2015-0170 ER - TY - JOUR T1 - Cerebrospinal Fluid from Sporadic Amyotrophic Lateral Sclerosis Patients Induces Mitochondrial and Lysosomal Dysfunction. AN - 1782216883; 26646005 AB - In our laboratory, we have developed (1) an in vitro model of sporadic Amyotrophic Lateral Sclerosis (sALS) involving exposure of motor neurons to cerebrospinal fluid (CSF) from sALS patients and (2) an in vivo model involving intrathecal injection of sALS-CSF into rat pups. In the current study, we observed that spinal cord extract from the in vivo sALS model displayed elevated reactive oxygen species (ROS) and mitochondrial dysfunction. Quantitative proteomic analysis of sub-cellular fractions from spinal cord of the in vivo sALS model revealed down-regulation of 35 mitochondrial proteins and 4 lysosomal proteins. Many of the down-regulated mitochondrial proteins contribute to alterations in respiratory chain complexes and organellar morphology. Down-regulated lysosomal proteins Hexosaminidase, Sialidase and Aryl sulfatase also displayed lowered enzyme activity, thus validating the mass spectrometry data. Proteomic analysis and validation by western blot indicated that sALS-CSF induced the over-expression of the pro-apoptotic mitochondrial protein BNIP3L. In the in vitro model, sALS-CSF induced neurotoxicity and elevated ROS, while it lowered the mitochondrial membrane potential in rat spinal cord mitochondria in the in vivo model. Ultra structural alterations were evident in mitochondria of cultured motor neurons exposed to ALS-CSF. These observations indicate the first line evidence that sALS-CSF mediated mitochondrial and lysosomal defects collectively contribute to the pathogenesis underlying sALS. JF - Neurochemical research AU - Sharma, Aparna AU - Varghese, Anu Mary AU - Vijaylakshmi, Kalyan AU - Sumitha, Rajendrarao AU - Prasanna, V K AU - Shruthi, S AU - Chandrasekhar Sagar, B K AU - Datta, Keshava K AU - Gowda, Harsha AU - Nalini, Atchayaram AU - Alladi, Phalguni Anand AU - Christopher, Rita AU - Sathyaprabha, Talakad N AU - Raju, Trichur R AU - Srinivas Bharath, M M AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India. ; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India. ; Institute of Bioinformatics, Discoverer Building, International Tech Park, Whitefield, Bangalore, 560066, India. ; Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India. ; Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India. ; Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India. bharath@nimhans.kar.nic.in. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 965 EP - 984 VL - 41 IS - 5 KW - BNIP3L protein, human KW - 0 KW - Membrane Proteins KW - Mitochondrial Proteins KW - Proteome KW - Proto-Oncogene Proteins KW - Reactive Oxygen Species KW - Tissue Extracts KW - Tumor Suppressor Proteins KW - Index Medicus KW - Cerebrospinal fluid KW - Oxidative stress KW - Proteomics KW - Lysosome KW - Mitochondria KW - Respiratory chain complexes KW - Motor neuron disease KW - Motor Neurons -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Humans KW - Membrane Proteins -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Motor Neurons -- ultrastructure KW - Membrane Potential, Mitochondrial KW - Cells, Cultured KW - Injections, Spinal KW - Tumor Suppressor Proteins -- metabolism KW - Oxidative Stress KW - Adult KW - Rats, Wistar KW - Proteome -- metabolism KW - Middle Aged KW - Mitochondrial Proteins -- metabolism KW - Female KW - Male KW - Mitochondria -- physiology KW - Amyotrophic Lateral Sclerosis -- metabolism KW - Amyotrophic Lateral Sclerosis -- cerebrospinal fluid KW - Tissue Extracts -- pharmacology KW - Lysosomes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1782216883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemical+research&rft.atitle=Cerebrospinal+Fluid+from+Sporadic+Amyotrophic+Lateral+Sclerosis+Patients+Induces+Mitochondrial+and+Lysosomal+Dysfunction.&rft.au=Sharma%2C+Aparna%3BVarghese%2C+Anu+Mary%3BVijaylakshmi%2C+Kalyan%3BSumitha%2C+Rajendrarao%3BPrasanna%2C+V+K%3BShruthi%2C+S%3BChandrasekhar+Sagar%2C+B+K%3BDatta%2C+Keshava+K%3BGowda%2C+Harsha%3BNalini%2C+Atchayaram%3BAlladi%2C+Phalguni+Anand%3BChristopher%2C+Rita%3BSathyaprabha%2C+Talakad+N%3BRaju%2C+Trichur+R%3BSrinivas+Bharath%2C+M+M&rft.aulast=Sharma&rft.aufirst=Aparna&rft.date=2016-05-01&rft.volume=41&rft.issue=5&rft.spage=965&rft.isbn=&rft.btitle=&rft.title=Neurochemical+research&rft.issn=1573-6903&rft_id=info:doi/10.1007%2Fs11064-015-1779-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-04-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11064-015-1779-7 ER - TY - JOUR T1 - Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model. AN - 1782215693; 26852374 AB - The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans. Copyright © 2016 Elsevier GmbH. All rights reserved. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Yoshizawa, Katsuhiko AU - Yuki, Michiko AU - Kinoshita, Yuichi AU - Emoto, Yuko AU - Yuri, Takashi AU - Shikata, Nobuaki AU - Elmore, Susan A AU - Tsubura, Airo AD - Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan. Electronic address: yoshizak@hirakata.kmu.ac.jp. ; Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan. ; Department of Pathology II, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; Division of Diagnostic Cytopathology and Histopathology, Kansai Medical University Takii Hospital, Fumizono 10-15, Moriguchi, Osaka 570-8507, Japan. ; Division of Diagnostic Cytopathology and Histopathology, Kansai Medical University Takii Hospital, Fumizono 10-15, Moriguchi, Osaka 570-8507, Japan. ; Cellular & Molecular Pathology Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 263 EP - 270 VL - 68 IS - 5 KW - Carcinogens KW - 0 KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Breast cancer KW - Mammary adenocarcinoma KW - Immunohistochemistry KW - N-methyl-N-nitrosourea KW - Male rat KW - Rats KW - Animals KW - Mammary Glands, Animal -- drug effects KW - Mammary Glands, Animal -- pathology KW - Humans KW - Male KW - Female KW - Carcinogens -- pharmacology KW - Mammary Neoplasms, Animal -- pathology KW - Adenocarcinoma -- chemically induced KW - Breast Neoplasms, Male -- chemically induced KW - Methylnitrosourea -- pharmacology KW - Disease Models, Animal KW - Mammary Neoplasms, Animal -- chemically induced KW - Breast Neoplasms, Male -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1782215693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=Characterization+of+mammary+adenocarcinomas+in+male+rats+after+N-methyl-N-nitrosourea+exposure--Potential+for+human+male+breast+cancer+model.&rft.au=Yoshizawa%2C+Katsuhiko%3BYuki%2C+Michiko%3BKinoshita%2C+Yuichi%3BEmoto%2C+Yuko%3BYuri%2C+Takashi%3BShikata%2C+Nobuaki%3BElmore%2C+Susan+A%3BTsubura%2C+Airo&rft.aulast=Yoshizawa&rft.aufirst=Katsuhiko&rft.date=2016-05-01&rft.volume=68&rft.issue=5&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=1618-1433&rft_id=info:doi/10.1016%2Fj.etp.2016.01.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-11 N1 - Date created - 2016-04-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.etp.2016.01.005 ER - TY - JOUR T1 - Real-time magnetic resonance imaging-guided transcatheter aortic valve replacement. AN - 1782214474; 26725711 AB - To demonstrate the feasibility of Real-time magnetic resonance imaging (rtMRI) guided transcatheter aortic valve replacement (TAVR) with an active guidewire and an MRI compatible valve delivery catheter system in a swine model. The CoreValve system was minimally modified to be MRI-compatible by replacing the stainless steel components with fluoroplastic resin and high-density polyethylene components. Eight swine weighing 60-90 kg underwent rtMRI-guided TAVR with an active guidewire through a left subclavian approach. Two imaging planes (long-axis view and short-axis view) were used simultaneously for real-time imaging during implantation. Successful deployment was performed without rapid ventricular pacing or cardiopulmonary bypass. Postdeployment images were acquired to evaluate the final valve position in addition to valvular and cardiac function. Our results show that the CoreValve can be easily and effectively deployed through a left subclavian approach using rtMRI guidance, a minimally modified valve delivery catheter system, and an active guidewire. This method allows superior visualization before deployment, thereby allowing placement of the valve with pinpoint accuracy. rtMRI has the added benefit of the ability to perform immediate postprocedural functional assessment, while eliminating the morbidity associated with radiation exposure, rapid ventricular pacing, contrast media renal toxicity, and a more invasive procedure. Use of a commercially available device brings this rtMRI-guided approach closer to clinical reality. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved. JF - The Journal of thoracic and cardiovascular surgery AU - Miller, Justin G AU - Li, Ming AU - Mazilu, Dumitru AU - Hunt, Tim AU - Horvath, Keith A AD - Cardiothoracic Surgery Research Program, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md. ; Cardiothoracic Surgery Research Program, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md. Electronic address: horvathka@mail.nih.gov. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1269 EP - 1277 VL - 151 IS - 5 KW - Abridged Index Medicus KW - Index Medicus KW - swine animal model KW - real-time magnetic resonance image KW - Medtronic CoreValve KW - transcatheter aortic valve replacement KW - Swine KW - Sensitivity and Specificity KW - Minimally Invasive Surgical Procedures -- adverse effects KW - Animals KW - Prosthesis Failure KW - Random Allocation KW - Disease Models, Animal KW - Postoperative Complications -- physiopathology KW - Heart Valve Prosthesis KW - Prosthesis Design KW - Postoperative Complications -- epidemiology KW - Female KW - Male KW - Minimally Invasive Surgical Procedures -- methods KW - Operative Time KW - Bioprosthesis KW - Aortic Valve Stenosis -- surgery KW - Transcatheter Aortic Valve Replacement -- methods KW - Transcatheter Aortic Valve Replacement -- adverse effects KW - Magnetic Resonance Imaging, Cine -- methods KW - Aortic Valve Stenosis -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1782214474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.atitle=Real-time+magnetic+resonance+imaging-guided+transcatheter+aortic+valve+replacement.&rft.au=Miller%2C+Justin+G%3BLi%2C+Ming%3BMazilu%2C+Dumitru%3BHunt%2C+Tim%3BHorvath%2C+Keith+A&rft.aulast=Miller&rft.aufirst=Justin&rft.date=2016-05-01&rft.volume=151&rft.issue=5&rft.spage=1269&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.issn=1097-685X&rft_id=info:doi/10.1016%2Fj.jtcvs.2015.11.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-07 N1 - Date created - 2016-04-18 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Ann Thorac Surg. 2014 Dec;98(6):2194-9 [25468087] J Thorac Cardiovasc Surg. 2015 Apr;149(4):1067-72 [25466854] Magn Reson Med. 2003 Aug;50(2):315-21 [12876708] Heart. 2000 Aug;84(2):211-8 [10908267] J Cardiovasc Magn Reson. 2001;3(3):ix [11816624] Magn Reson Med. 2002 Dec;48(6):1091-5 [12465124] Allergy Asthma Proc. 2002 Sep-Oct;23(5):347-51 [12476546] Circulation. 2003 Dec 9;108(23):2899-904 [14656911] Magn Reson Med. 2004 Jan;51(1):200-4 [14705062] AJR Am J Roentgenol. 2004 May;182(5):1111-4 [15100103] Circulation. 1968 Jul;38(1 Suppl):61-7 [4894151] Am J Cardiol. 1988 Jan 1;61(1):123-30 [3337000] Schweiz Med Wochenschr. 1988 Apr 9;118(14):508-16 [3375789] J Am Coll Cardiol. 1997 Mar 1;29(3):630-4 [9060903] Am J Med. 1997 Nov;103(5):368-75 [9375704] Anesth Analg. 1999 Oct;89(4):870-84 [10512257] Circulation. 2005 Nov 8;112(19):3009-17 [16275886] Lancet. 2006 Sep 16;368(9540):1005-11 [16980116] Circulation. 2006 Oct 10;114(15):1616-24 [17015786] Magn Reson Med. 2006 Nov;56(5):958-64 [17036300] Annu Rev Biomed Eng. 2007;9:351-87 [17439358] Semin Thorac Cardiovasc Surg. 2007 Winter;19(4):330-5 [18395633] Rev Cardiovasc Med. 2008 Fall;9(4):232-8 [19122581] JACC Cardiovasc Imaging. 2008 Jan;1(1):15-24 [19356400] J Magn Reson Imaging. 2009 Aug;30(2):461-5 [19629968] J Thorac Cardiovasc Surg. 2010 Feb;139(2):424-30 [19969312] Mayo Clin Proc. 2010 May;85(5):483-500 [20435842] N Engl J Med. 2010 Oct 21;363(17):1597-607 [20961243] J Cardiovasc Magn Reson. 2010;12:58 [20942968] Eur J Cardiothorac Surg. 2011 Jun;39(6):822-8 [20971017] JACC Cardiovasc Interv. 2011 Jul;4(7):751-7 [21777882] Circ Cardiovasc Interv. 2011 Aug;4(4):387-95 [21846898] Int J Cardiovasc Imaging. 2012 Jan;28(1):117-37 [21359519] J Am Coll Cardiol. 2012 Apr 3;59(14):1275-86 [22365424] JACC Cardiovasc Imaging. 2012 Apr;5(4):441-55 [22498335] J Cardiovasc Magn Reson. 2012;14:21 [22453050] Heart. 2012 Aug;98(15):1146-52 [22773684] Int J Cardiol. 2012 Jul 26;158(3):353-8 [21315460] Eur J Radiol. 2012 Dec;81(12):3912-7 [22889591] Expert Rev Med Devices. 2013 Jan;10(1):15-26 [23278219] J Am Soc Echocardiogr. 2013 Apr;26(4):359-69 [23484436] Circ Res. 2013 Jul 5;113(2):179-85 [23833292] Catheter Cardiovasc Interv. 2013 Aug 1;82(2):292-7 [23554013] Curr Opin Cardiol. 2013 Sep;28(5):512-7 [23852025] Int J Cardiol. 2013 Oct 9;168(4):3431-8 [23688431] Cardiovasc Revasc Med. 2014 Jun;15(4):200-3 [24746865] J Am Coll Cardiol. 2014 Jul 1;63(25 Pt A):2852-61 [24814496] Magn Reson Imaging. 2015 May;33(4):497-501 [25620522] Comment In: J Thorac Cardiovasc Surg. 2016 May;151(5):1278-9 [26778378] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jtcvs.2015.11.024 ER - TY - JOUR T1 - Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes. AN - 1782214015; 26254731 AB - Induced pluripotent stem cells (iPSC) and their differentiated derivatives offer a unique source of human primary cells for toxicity screens. Here, we report on the comparative cytotoxicity of 80 compounds (neurotoxicants, developmental neurotoxicants, and environmental compounds) in iPSC as well as isogenic iPSC-derived neural stem cells (NSC), neurons, and astrocytes. All compounds were tested over a 24-h period at 10 and 100 μM, in duplicate, with cytotoxicity measured using the MTT assay. Of the 80 compounds tested, 50 induced significant cytotoxicity in at least one cell type; per cell type, 32, 38, 46, and 41 induced significant cytotoxicity in iPSC, NSC, neurons, and astrocytes, respectively. Four compounds (valinomycin, 3,3',5,5'-tetrabromobisphenol, deltamethrin, and triphenyl phosphate) were cytotoxic in all four cell types. Retesting these compounds at 1, 10, and 100 μM using the same exposure protocol yielded consistent results as compared with the primary screen. Using rotenone, we extended the testing to seven additional iPSC lines of both genders; no substantial difference in the extent of cytotoxicity was detected among the cell lines. Finally, the cytotoxicity assay was simplified by measuring luciferase activity using lineage-specific luciferase reporter iPSC lines which were generated from the parental iPSC line. This article is part of a Special Issue entitled SI: PSC and the brain. Copyright © 2015. Published by Elsevier B.V. JF - Brain research AU - Pei, Ying AU - Peng, Jun AU - Behl, Mamta AU - Sipes, Nisha S AU - Shockley, Keith R AU - Rao, Mahendra S AU - Tice, Raymond R AU - Zeng, Xianmin AD - XCell Science Inc., Novato, CA, USA. ; Buck Institute for Research on Aging, Novato, CA, USA. ; National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27713, USA. ; NxCell Science, Novato, CA, USA. ; XCell Science Inc., Novato, CA, USA; Buck Institute for Research on Aging, Novato, CA, USA. Electronic address: xzeng@xcellscience.com. Y1 - 2016/05/01/ PY - 2016 DA - 2016 May 01 SP - 57 EP - 73 VL - 1638 KW - Index Medicus KW - Lineage-specific reporter lines KW - Astrocytes KW - Neurons KW - iPSC KW - Neurotoxicity KW - Drug screening KW - Neural stem cells KW - Cells, Cultured KW - Humans KW - Neurotoxicity Syndromes -- etiology KW - Neurotoxicity Syndromes -- metabolism KW - Cell Differentiation -- drug effects KW - Cell Line KW - Astrocytes -- cytology KW - Neurons -- metabolism KW - Astrocytes -- drug effects KW - Neurons -- drug effects KW - Neural Stem Cells -- drug effects KW - Neural Stem Cells -- cytology KW - Induced Pluripotent Stem Cells -- metabolism KW - Induced Pluripotent Stem Cells -- drug effects KW - Neurons -- cytology KW - Neural Stem Cells -- metabolism KW - Induced Pluripotent Stem Cells -- cytology KW - Drug Evaluation, Preclinical -- methods KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1782214015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Comparative+neurotoxicity+screening+in+human+iPSC-derived+neural+stem+cells%2C+neurons+and+astrocytes.&rft.au=Pei%2C+Ying%3BPeng%2C+Jun%3BBehl%2C+Mamta%3BSipes%2C+Nisha+S%3BShockley%2C+Keith+R%3BRao%2C+Mahendra+S%3BTice%2C+Raymond+R%3BZeng%2C+Xianmin&rft.aulast=Pei&rft.aufirst=Ying&rft.date=2016-05-01&rft.volume=1638&rft.issue=&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=1872-6240&rft_id=info:doi/10.1016%2Fj.brainres.2015.07.048 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-31 N1 - Date created - 2016-04-18 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.brainres.2015.07.048 ER - TY - JOUR T1 - Selective inhibition by aspirin and naproxen of mainstream cigarette smoke-induced genotoxicity and lung tumors in female mice. AN - 1781541887; 26104855 AB - The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used. JF - Archives of toxicology AU - Balansky, Roumen AU - Ganchev, Gancho AU - Iltcheva, Marietta AU - Micale, Rosanna T AU - La Maestra, Sebastiano AU - D'Oria, Chiara AU - Steele, Vernon E AU - De Flora, Silvio AD - National Center of Oncology, Sofia, 1756, Bulgaria. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132, Genoa, Italy. ; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, 20892, USA. ; Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132, Genoa, Italy. sdf@unige.it. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1251 EP - 1260 VL - 90 IS - 5 KW - Anticarcinogenic Agents KW - 0 KW - Cyclooxygenase Inhibitors KW - Estrogen Receptor Modulators KW - Naproxen KW - 57Y76R9ATQ KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Lung tumors KW - Cigarette smoke KW - Chemoprevention KW - Animals KW - Cell Transformation, Neoplastic -- pathology KW - Sex Factors KW - Risk Factors KW - Cell Transformation, Neoplastic -- drug effects KW - Mice KW - Time Factors KW - Male KW - Female KW - Cell Transformation, Neoplastic -- genetics KW - Estrogen Receptor Modulators -- pharmacology KW - Neoplasms, Experimental -- etiology KW - Neoplasms, Experimental -- genetics KW - Naproxen -- pharmacology KW - Smoking -- adverse effects KW - Neoplasms, Experimental -- prevention & control KW - Lung -- metabolism KW - Lung -- pathology KW - Neoplasms, Experimental -- pathology KW - Cyclooxygenase Inhibitors -- pharmacology KW - DNA Damage -- drug effects KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- pharmacology KW - Lung -- drug effects KW - Lung Neoplasms -- genetics KW - Aspirin -- pharmacology KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781541887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+toxicology&rft.atitle=Selective+inhibition+by+aspirin+and+naproxen+of+mainstream+cigarette+smoke-induced+genotoxicity+and+lung+tumors+in+female+mice.&rft.au=Balansky%2C+Roumen%3BGanchev%2C+Gancho%3BIltcheva%2C+Marietta%3BMicale%2C+Rosanna+T%3BLa+Maestra%2C+Sebastiano%3BD%27Oria%2C+Chiara%3BSteele%2C+Vernon+E%3BDe+Flora%2C+Silvio&rft.aulast=Balansky&rft.aufirst=Roumen&rft.date=2016-05-01&rft.volume=90&rft.issue=5&rft.spage=1251&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=1432-0738&rft_id=info:doi/10.1007%2Fs00204-015-1550-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-24 N1 - Date created - 2016-04-14 N1 - Date revised - 2017-01-26 N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1007/s00204-015-1550-5 ER - TY - JOUR T1 - Immunohistochemical Expression of Cyclin D1, Cytokeratin 20, and Uroplakin III in Proliferative Urinary Bladder Lesions Induced by o-Nitroanisole in Fischer 344/N Rats. AN - 1781533812; 26319780 AB - o-Nitroanisole is an intermediate in the manufacture of azo dyes. In a National Toxicology Program stop-exposure study,o-nitroanisole induced hyperplasia, papillomas, and papillary carcinomas in the urinary bladder of Fischer 344/N rats.o-Nitroanisole was investigated since occupational or environmental exposure to aniline and azo dyes is a risk factor for urinary bladder cancer in humans. The current study describes the morphology of urinary bladder neoplasms seen in rats with respect to those observed in humans. This study also evaluated immunohistochemical expression of the cell cycle-related proteins cyclin D1 and p53 and the differentiation markers cytokeratin 20 and uroplakin III in hyperplastic (n= 11) and neoplastic (n= 6 papillomas,n= 11 carcinomas) lesions of the urinary bladder epithelium from rats treated with o-nitroanisole and in normal (n= 6) urinary bladders from untreated rats. The tumors observed were more similar to the papillary type rather than the muscle-invasive type of urinary bladder cancer in humans. The preneoplastic and neoplastic lesions observed suggest progression from hyperplasia to papilloma to papillary carcinoma. With neoplastic progression (hyperplasia to papilloma to carcinoma), cyclin D1 immunoreactivity progressively increased in intensity, percentage of cells staining, and distribution. Overexpression of p53 was not found. Cytokeratin 20 staining decreased in superficial cells, while uroplakin III staining increased in intermediate and basal cells with progression from hyperplasia to carcinoma. The results are consistent with increased cell cycle dysregulation or proliferation (cyclin D1), decreased differentiation (cytokeratin 20), and abnormal differentiation (uroplakin III) as lesions progress toward malignancy. © The Author(s) 2015. JF - Veterinary pathology AU - Willson, C J AU - Flake, G P AU - Sills, R C AU - Kissling, G E AU - Cesta, M F AD - Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Integrated Laboratory Systems, Inc, Research Triangle Park, NC, USA. ; Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA cesta@niehs.nih.gov. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 682 EP - 690 VL - 53 IS - 3 KW - Index Medicus KW - uroplakin III KW - urinary bladder KW - immunohistochemistry KW - o-nitroanisole KW - cytokeratin 20 KW - urothelial carcinoma KW - rats KW - cyclin D1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781533812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Veterinary+pathology&rft.atitle=Immunohistochemical+Expression+of+Cyclin+D1%2C+Cytokeratin+20%2C+and+Uroplakin+III+in+Proliferative+Urinary+Bladder+Lesions+Induced+by+o-Nitroanisole+in+Fischer+344%2FN+Rats.&rft.au=Willson%2C+C+J%3BFlake%2C+G+P%3BSills%2C+R+C%3BKissling%2C+G+E%3BCesta%2C+M+F&rft.aulast=Willson&rft.aufirst=C&rft.date=2016-05-01&rft.volume=53&rft.issue=3&rft.spage=682&rft.isbn=&rft.btitle=&rft.title=Veterinary+pathology&rft.issn=1544-2217&rft_id=info:doi/10.1177%2F0300985815603432 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0300985815603432 ER - TY - JOUR T1 - The relationship of health behaviors with sleep and fatigue in transplant caregivers AN - 1781528768 AB - Objective The burden and psychological impact of providing care to a loved one with cancer is significant and associated with a number of problems including sleep disturbance and fatigue. While engaging in healthy behaviors such as proper nutrition, exercise, and stress reduction may improve sleep and fatigue, few studies have focused on this relationship. The objective of this study is to examine the relationship of health behaviors with sleep quality and fatigue in transplant caregivers. Methods Data were analyzed from a cross-sectional survey of 78 caregivers of patients undergoing allogeneic hematopoietic stem cell transplantation. Measures included: Health-Promoting Lifestyle Profile II (HPLP-II), Brief Symptom Inventory (Distress), Caregiver Reaction Assessment (Caregiver Burden), Pittsburgh Sleep Quality Index, and the Multidimensional Fatigue Symptom Inventory Short-Form. Results Controlling for age, gender, BMI, burden and distress, health behaviors predicted sleep quality (B=-0.408, p=0.021) and fatigue (B=-0.966, p<0.001). Stress management (B=-0.450, p=0.001), nutrition (B=-0.249, p=0.048), and interpersonal relationships (B=-0.319, p=0.049) were the HPLP-II subscales that significantly predicted sleep quality; nearly every HPLP-II subscale predicted fatigue. Conclusions Despite the burden and distress associated with caregiving, engaging in healthy behaviors may help to improve sleep and fatigue in transplant caregivers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. JF - Psycho-Oncology AU - Ross, A AU - Yang, L AU - Klagholz, S D AU - Wehrlen, L AU - Bevans, M F AD - National Institutes of Health Clinical Center, Nursing Department, Bethesda, MD, USA Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 506 EP - 512 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 25 IS - 5 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Sleep KW - Body Mass Index KW - Burden KW - Cancer KW - Carers KW - Caretaker syndrome KW - Exercise KW - Fatigue KW - Health behaviour KW - Health promotion KW - Healthy habits KW - Interpersonal relationships KW - Lifestyle KW - Nutrition KW - Psychological distress KW - Public domain KW - Sleep problems KW - Stress management KW - Transplants & implants KW - Health behavior KW - Inventory KW - Caregivers KW - Quality KW - United States--US KW - Pittsburgh Pennsylvania UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781528768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=The+relationship+of+health+behaviors+with+sleep+and+fatigue+in+transplant+caregivers&rft.au=Ross%2C+A%3BYang%2C+L%3BKlagholz%2C+S+D%3BWehrlen%2C+L%3BBevans%2C+M+F&rft.aulast=Ross&rft.aufirst=A&rft.date=2016-05-01&rft.volume=25&rft.issue=5&rft.spage=506&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.3860 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 John Wiley & Sons, Ltd. N1 - Last updated - 2016-05-18 N1 - SubjectsTermNotLitGenreText - Pittsburgh Pennsylvania; United States--US DO - http://dx.doi.org/10.1002/pon.3860 ER - TY - JOUR T1 - Impact of depression on health utility value in cancer patients AN - 1781528660 AB - Objective The quality-adjusted life year, which is usually calculated from the health utility value, is now a standard measurement used in political decision-making in health. Although depression is the leading cause of decrement in health utility in general population, impact of comorbid depression among cancer patients has not been studied sufficiently. Therefore, this study aimed to measure the impact of depression on cancer patients' health utility score, according to the severity of depression. Methods Impact of depression severity (measured by the Patient Health Questionnaire) on health utility score (measured by the EuroQoL-5 scale) was evaluated in a sample of 328 Japanese cancer patients, controlling for performance status, symptom burden, and demographic variables. Results The patients with depression had significantly lower health utility value than those without depression (mean decrement=0.14). Decrements in health utility of 0.13, 0.18, and 0.19 were observed for mild, moderate, and moderately severe to severe level of depression, respectively. The difference was significant between groups. Depression severity was a significant predictor for health utility (standardized coefficient beta=-0.25), which was comparable with physical symptom burden and performance status. Participants' age, gender, cancer stage, and comorbid illness were not significant. The model explained 37.9% of the variance. Conclusions Even mild level of depression caused clinically meaningful decrement in health utility value in cancer patients, which was comparable with decrements due to major physical complications of cancer. Influence of depression should be carefully investigated when interpreting the quality-adjusted life year among cancer patients. Copyright © 2015 John Wiley & Sons, Ltd. JF - Psycho-Oncology AU - Fujisawa, Daisuke AU - Inoguchi, Hironobu AU - Shimoda, Haruki AU - Yoshiuchi, Kazuhiro AU - Inoue, Shinichiro AU - Ogawa, Asao AU - Okuyama, Toru AU - Akechi, Tatsuo AU - Mimura, Masaru AU - Shimizu, Ken AU - Uchitomi, Yosuke AD - Department of Neuropsychiatry and Palliative Care Center, Keio University School of Medicine, Japan; Department of Psycho-Oncology, National Cancer Center, Japan ; Department of Psycho-Oncology, National Cancer Center, Japan ; Department of Mental Health Policy and Evaluation, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan; Department of Mental Health, University of Tokyo, Japan ; Department of Stress Science and Psychosomatic Medicine, University of Tokyo, Japan ; Department of Neuropsychiatry, Okayama University, Japan ; Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University, Japan ; Department of Neuropsychiatry and Palliative Care Center, Keio University School of Medicine, Japan ; Innovation Center for Supportive, Palliative and Psychosocial Care, National Cancer Center, Japan Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 491 EP - 495 CY - Chichester PB - Wiley Subscription Services, Inc. VL - 25 IS - 5 SN - 1057-9249 KW - Medical Sciences--Psychiatry And Neurology KW - Measurement KW - Comorbidity KW - Decision making KW - Health KW - Depression KW - Severity KW - Burden KW - Cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781528660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psycho-Oncology&rft.atitle=Impact+of+depression+on+health+utility+value+in+cancer+patients&rft.au=Fujisawa%2C+Daisuke%3BInoguchi%2C+Hironobu%3BShimoda%2C+Haruki%3BYoshiuchi%2C+Kazuhiro%3BInoue%2C+Shinichiro%3BOgawa%2C+Asao%3BOkuyama%2C+Toru%3BAkechi%2C+Tatsuo%3BMimura%2C+Masaru%3BShimizu%2C+Ken%3BUchitomi%2C+Yosuke&rft.aulast=Fujisawa&rft.aufirst=Daisuke&rft.date=2016-05-01&rft.volume=25&rft.issue=5&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Psycho-Oncology&rft.issn=10579249&rft_id=info:doi/10.1002%2Fpon.3945 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 John Wiley & Sons, Ltd. N1 - Last updated - 2016-08-17 DO - http://dx.doi.org/10.1002/pon.3945 ER - TY - JOUR T1 - The ups and downs of exercise and insulin sensitivity: a role for the myokine myostatin in glucose metabolism? AN - 1780536215; PQ0002864957 JF - Acta Physiologica AU - McPherron, A C AD - National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 6 EP - 10 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 217 IS - 1 SN - 1748-1708, 1748-1708 KW - Physical Education Index UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780536215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+Physiologica&rft.atitle=The+ups+and+downs+of+exercise+and+insulin+sensitivity%3A+a+role+for+the+myokine+myostatin+in+glucose+metabolism%3F&rft.au=McPherron%2C+A+C&rft.aulast=McPherron&rft.aufirst=A&rft.date=2016-05-01&rft.volume=217&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Acta+Physiologica&rft.issn=17481708&rft_id=info:doi/10.1111%2Fapha.12650 LA - English DB - Physical Education Index N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-04-13 DO - http://dx.doi.org/10.1111/apha.12650 ER - TY - JOUR T1 - Maternal Weight Gain During Pregnancy: Comparing Methods to Address Bias Due to Length of Gestation in Epidemiological Studies AN - 1780526127; PQ0002888024 AB - Background Studies examining total gestational weight gain (GWG) and outcomes associated with gestational age (GA) are potentially biased. The z-score has been proposed to mitigate this bias. We evaluated a regression-based adjustment for GA to remove the correlation between GWG and GA, and compared it to published weight-gain-for-gestational-age z-scores when applied to a study sample with different underlying population characteristics. Methods Using 65 643 singleton deliveries to normal weight women at 12 US clinical sites, we simulated a null association between GWG and neonatal mortality. Logistic regression was used to estimate approximate relative risks (RR) of neonatal mortality associated with GWG, unadjusted and adjusted for GA, and the z-score, overall and within study sites. Average RRs across 5000 replicates were calculated with 95% coverage probability to indicate model bias and precision, where 95% is nominal. Results Under a simulated null association, total GWG resulted in a biased mortality estimate (RR = 0.87; coverage = 0%); estimates adjusted for GA were unbiased (RR = 1.00; coverage = 94%). Quintile-specific RRs ranged from 0.97-1.03. Similar results were observed for site-specific analyses. The overall z-score RR was 0.97 (84% coverage) with quintile-specific RRs ranging from 0.64-0.90. Estimates were close to 1.0 at most sites, with coverage from 70-94%. Sites 1 and 6 were biased with RRs of 0.66 and 1.43, respectively, and coverage of 70% and 80%. Conclusions Adjusting for GA achieves unbiased estimates of the association between total GWG and neonatal mortality, providing an accessible alternative to the weight-gain-for-gestational-age z-scores without requiring assumptions concerning underlying population characteristics. JF - Paediatric and Perinatal Epidemiology AU - Hinkle, Stefanie N AU - Mitchell, Emily M AU - Grantz, Katherine L AU - Ye, Aijun AU - Schisterman, Enrique F AD - Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 294 EP - 304 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 30 IS - 3 SN - 0269-5022, 0269-5022 KW - Health & Safety Science Abstracts KW - Mortality KW - Obesity KW - Age KW - Body weight KW - Population characteristics KW - Neonates KW - Pregnancy KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780526127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Paediatric+and+Perinatal+Epidemiology&rft.atitle=Maternal+Weight+Gain+During+Pregnancy%3A+Comparing+Methods+to+Address+Bias+Due+to+Length+of+Gestation+in+Epidemiological+Studies&rft.au=Hinkle%2C+Stefanie+N%3BMitchell%2C+Emily+M%3BGrantz%2C+Katherine+L%3BYe%2C+Aijun%3BSchisterman%2C+Enrique+F&rft.aulast=Hinkle&rft.aufirst=Stefanie&rft.date=2016-05-01&rft.volume=30&rft.issue=3&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Paediatric+and+Perinatal+Epidemiology&rft.issn=02695022&rft_id=info:doi/10.1111%2Fppe.12284 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-04-29 N1 - SubjectsTermNotLitGenreText - Obesity; Mortality; Age; Population characteristics; Body weight; Neonates; Pregnancy DO - http://dx.doi.org/10.1111/ppe.12284 ER - TY - JOUR T1 - Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach. AN - 1780517083; 26995226 AB - Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Gomez-Verjan, J C AU - Estrella-Parra, E AU - Vazquez-Martinez, E R AU - Gonzalez-Sanchez, I AU - Guerrero-Magos, G AU - Mendoza-Villanueva, D AU - Isus, L AU - Alfaro, A AU - Cerbón-Cervantes, M AU - Aloy, P AU - Reyes-Chilpa, R AD - Departamento de Productos Naturales, Instituto de Química, UNAM, Mexico City, Mexico. Electronic address: carlosverjan@comunidad.unam.mx. ; Departamento de Productos Naturales, Instituto de Química, UNAM, Mexico City, Mexico. ; Unidad de Investigacion en Reproduccion Humana, Instituto Nacional de Perinatologia-Facultad de Química, UNAM, Mexico City, Mexico. ; Laboratorio de Fitofarmacología, Departamento de Farmacología, Facultad de Medicina, UNAM, México City, Mexico. ; Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, USA. ; Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Catalonia, Spain. ; Unidad de Medicina Genómica, Facultad de Medicina, UNAM/Hospital General de México, Ciudad de México, Mexico. ; Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. ; Departamento de Productos Naturales, Instituto de Química, UNAM, Mexico City, Mexico. Electronic address: chilpa@unam.mx. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 117 EP - 129 VL - 91 KW - Coumarins KW - 0 KW - Index Medicus KW - Mammea A/BA+A/BB KW - Toxicology KW - Toxicogenomics KW - Soulatrolide KW - Calophyllum brasiliense KW - Animals KW - Mice KW - Male KW - Risk Assessment KW - Toxicogenetics KW - Coumarins -- toxicity KW - Calophyllum -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780517083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Risk+assessment+of+Soulatrolide+and+Mammea+%28A%2FBA%2BA%2FBB%29+coumarins+from+Calophyllum+brasiliense+by+a+toxicogenomic+and+toxicological+approach.&rft.au=Gomez-Verjan%2C+J+C%3BEstrella-Parra%2C+E%3BVazquez-Martinez%2C+E+R%3BGonzalez-Sanchez%2C+I%3BGuerrero-Magos%2C+G%3BMendoza-Villanueva%2C+D%3BIsus%2C+L%3BAlfaro%2C+A%3BCerb%C3%B3n-Cervantes%2C+M%3BAloy%2C+P%3BReyes-Chilpa%2C+R&rft.aulast=Gomez-Verjan&rft.aufirst=J&rft.date=2016-05-01&rft.volume=91&rft.issue=&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=1873-6351&rft_id=info:doi/10.1016%2Fj.fct.2016.03.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-04-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.fct.2016.03.010 ER - TY - JOUR T1 - Keratinocyte p38δ loss inhibits Ras-induced tumor formation, while systemic p38δ loss enhances skin inflammation in the early phase of chemical carcinogenesis in mouse skin. AN - 1780511427; 25753147 AB - p38δ expression and/or activity are increased in human cutaneous malignancies, including invasive squamous cell carcinoma (SCC) and head and neck SCC, but the role of p38δ in cutaneous carcinogenesis has not been well-defined. We have reported that mice with germline loss of p38δ exhibited a reduced susceptibility to skin tumor development compared with wild-type mice in the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38δ gene ablation inhibited the growth of tumors generated from v-ras(Ha) -transformed keratinocytes in skin orthografts to nude mice, indicating that keratinocyte-intrinsic p38δ is required for Ras-induced tumorigenesis. Gene expression profiling of v-ras(Ha) -transformed p38δ-null keratinocytes revealed transcriptional changes associated with cellular responses linked to tumor suppression, such as reduced proliferation and increased differentiation, cell adhesion, and cell communications. Notably, a short-term DMBA/TPA challenge, modeling the initial stages of chemical skin carcinogenesis treatment, elicited an enhanced inflammation in p38δ-null skin compared with skin of wild-type mice, as assessed by measuring the expression of pro-inflammatory cytokines, including IL-1β, IL-6, IL-17, and TNFα. Additionally, p38δ-null skin and p38δ-null keratinocytes exhibited increased p38α activation and signaling in response to acute inflammatory challenges, suggesting a role for p38α in stimulating the elevated inflammatory response in p38δ-null skin during the initial phases of the DMBA/TPA treatment compared with similarly treated p38δ(+/+) skin. Altogether, our results indicate that p38δ signaling regulates skin carcinogenesis not only by keratinocyte cell-autonomous mechanisms, but also by influencing the interaction between between the epithelial compartment of the developing skin tumor and its stromal microenvironment. © 2015 Wiley Periodicals, Inc. JF - Molecular carcinogenesis AU - Kiss, Alexi AU - Koppel, Aaron C AU - Anders, Joanna AU - Cataisson, Christophe AU - Yuspa, Stuart H AU - Blumenberg, Miroslav AU - Efimova, Tatiana AD - Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri. ; Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. ; R. O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 563 EP - 574 VL - 55 IS - 5 KW - Benz(a)Anthracenes KW - 0 KW - Mitogen-Activated Protein Kinase 13 KW - EC 2.7.1.- KW - ras Proteins KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - p38α KW - p38δ KW - knockout mice KW - orthotopic skin grafts KW - skin inflammation KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Cell Transformation, Neoplastic -- pathology KW - Cell Transformation, Neoplastic -- metabolism KW - Inflammation -- chemically induced KW - Inflammation -- genetics KW - Mice, Nude KW - Mice KW - Inflammation -- metabolism KW - Benz(a)Anthracenes -- toxicity KW - Cell Transformation, Neoplastic -- genetics KW - Skin Neoplasms -- genetics KW - ras Proteins -- genetics KW - Skin -- drug effects KW - Skin Neoplasms -- chemically induced KW - Skin -- metabolism KW - Skin -- pathology KW - Skin Neoplasms -- pathology KW - ras Proteins -- pharmacology KW - Skin Neoplasms -- metabolism KW - Mitogen-Activated Protein Kinase 13 -- metabolism KW - Mitogen-Activated Protein Kinase 13 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780511427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Keratinocyte+p38%CE%B4+loss+inhibits+Ras-induced+tumor+formation%2C+while+systemic+p38%CE%B4+loss+enhances+skin+inflammation+in+the+early+phase+of+chemical+carcinogenesis+in+mouse+skin.&rft.au=Kiss%2C+Alexi%3BKoppel%2C+Aaron+C%3BAnders%2C+Joanna%3BCataisson%2C+Christophe%3BYuspa%2C+Stuart+H%3BBlumenberg%2C+Miroslav%3BEfimova%2C+Tatiana&rft.aulast=Kiss&rft.aufirst=Alexi&rft.date=2016-05-01&rft.volume=55&rft.issue=5&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=1098-2744&rft_id=info:doi/10.1002%2Fmc.22303 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-06 N1 - Date created - 2016-04-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/mc.22303 ER - TY - JOUR T1 - Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis. AN - 1780509123; 26965985 AB - Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. U.S. Government work not protected by U.S. copyright. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Yan, Tingting AU - Wang, Hong AU - Zhao, Min AU - Yagai, Tomoki AU - Chai, Yingying AU - Krausz, Kristopher W AU - Xie, Cen AU - Cheng, Xuefang AU - Zhang, Jun AU - Che, Yuan AU - Li, Feiyan AU - Wu, Yuzheng AU - Brocker, Chad N AU - Gonzalez, Frank J AU - Wang, Guangji AU - Hao, Haiping AD - State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.). ; State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China (Ti.Y., H.W., M.Z., Yi.C., X.C., J.Z., Yu.C., F.L., Y.W., G.W., H.H.); Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Ti.Y., To.Y., K.W.K., C.X., C.N.B., F.J.G.) guangjiwang@hotmail.com haipinghao@cpu.edu.cn. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 720 EP - 731 VL - 44 IS - 5 KW - Protective Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Acetaminophen KW - 362O9ITL9D KW - Glycyrrhizic Acid KW - 6FO62043WK KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Receptor-Interacting Protein Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Index Medicus KW - Receptor-Interacting Protein Serine-Threonine Kinases -- metabolism KW - Animals KW - Hepatocytes -- drug effects KW - Humans KW - Mitochondria, Liver -- metabolism KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Mice KW - Mitochondria, Liver -- drug effects KW - Activation, Metabolic -- drug effects KW - Mice, Inbred C57BL KW - Cell Line KW - Male KW - Hepatocytes -- metabolism KW - Glycyrrhizic Acid -- pharmacology KW - Liver -- drug effects KW - Apoptosis -- drug effects KW - Acetaminophen -- adverse effects KW - Liver -- metabolism KW - Protective Agents -- pharmacology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Chemical and Drug Induced Liver Injury -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780509123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Glycyrrhizin+Protects+against+Acetaminophen-Induced+Acute+Liver+Injury+via+Alleviating+Tumor+Necrosis+Factor+%CE%B1-Mediated+Apoptosis.&rft.au=Yan%2C+Tingting%3BWang%2C+Hong%3BZhao%2C+Min%3BYagai%2C+Tomoki%3BChai%2C+Yingying%3BKrausz%2C+Kristopher+W%3BXie%2C+Cen%3BCheng%2C+Xuefang%3BZhang%2C+Jun%3BChe%2C+Yuan%3BLi%2C+Feiyan%3BWu%2C+Yuzheng%3BBrocker%2C+Chad+N%3BGonzalez%2C+Frank+J%3BWang%2C+Guangji%3BHao%2C+Haiping&rft.aulast=Yan&rft.aufirst=Tingting&rft.date=2016-05-01&rft.volume=44&rft.issue=5&rft.spage=720&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=1521-009X&rft_id=info:doi/10.1124%2Fdmd.116.069419 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-27 N1 - Date created - 2016-04-09 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cancer Lett. 1999 Oct 18;145(1-2):35-42 [10530767] Gastroenterology. 1998 Dec;115(6):1541-51 [9834283] Drug Metab Dispos. 2005 Mar;33(3):449-57 [15576447] J Biol Chem. 2005 Mar 18;280(11):10556-63 [15642733] Basic Clin Pharmacol Toxicol. 2005 Jul;97(1):8-14 [15943753] Life Sci. 2006 Mar 6;78(15):1670-6 [16226279] J Biol Chem. 2008 Feb 22;283(8):4543-59 [18093979] Hepatology. 2008 Jun;47(6):1905-15 [18452148] Science. 2009 Jul 17;325(5938):332-6 [19498109] J Toxicol Sci. 2010 Apr;35(2):163-73 [20371967] Hepatology. 2011 Feb;53(2):718-9 [21274895] Cell. 2012 Jan 20;148(1-2):213-27 [22265413] Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5322-7 [22421439] J Leukoc Biol. 2012 Jun;91(6):967-76 [22422925] Cell. 2012 Jul 20;150(2):339-50 [22817896] Hepatology. 2013 Jan;57(1):373-84 [22821628] J Hepatol. 2013 Feb;58(2):297-305 [23046676] PLoS One. 2013;8(1):e53662 [23341968] Chin J Nat Med. 2013 May;11(3):309-13 [23725847] Int J Neurosci. 2013 Nov;123(11):745-51 [23594088] Crit Care Med. 2013 Nov;41(11):2543-50 [23949472] Hepatology. 2013 Dec;58(6):2099-108 [23744808] BMJ. 2014;348:g356 [24452448] Eur J Pharmacol. 2014 Feb 5;724:43-50 [24378346] JAMA. 2014 Feb 12;311(6):563 [24519283] Toxicol Lett. 2014 Mar 21;225(3):445-53 [24440347] Expert Rev Clin Pharmacol. 2014 May;7(3):341-8 [24678654] Trends Pharmacol Sci. 2014 Apr;35(4):168-77 [24582872] Biochim Biophys Acta. 2014 Jun;1840(6):1755-64 [24462946] Cell Death Dis. 2014;5:e1278 [24901049] J Hepatol. 2014 Jul;61(1):166-8 [24780816] Biomed Res Int. 2014;2014:872139 [24963489] Phytother Res. 2014 Jun;28(6):933-6 [25032255] Drug Metab Dispos. 2014 Dec;42(12):1982-90 [25217484] Toxicol Sci. 2015 Jan;143(1):107-15 [25319358] Arch Toxicol. 2015 Feb;89(2):193-9 [25537186] Shock. 2015 Apr;43(4):412-21 [25526376] Int Immunopharmacol. 2015 May;26(1):112-8 [25812767] Drug Discov Today. 2015 May;20(5):562-8 [25849660] Nat Rev Cardiol. 2015 Jun;12(6):374 [25917150] Hepatology. 2015 Dec;62(6):1847-57 [26077809] Toxicol Sci. 2000 Apr;54(2):509-16 [10774834] Clin Pharmacol Ther. 2000 Mar;67(3):275-82 [10741631] Sci Rep. 2016;6:18751 [26728993] Pharmacol Toxicol. 2002 Jan;90(1):38-50 [12005112] Hepatology. 2002 Jul;36(1):55-64 [12085349] Pharmacol Res. 2002 Sep;46(3):221-7 [12220964] Hepatology. 2003 Jun;37(6):1425-34 [12774022] Toxicol Appl Pharmacol. 2003 Dec 1;193(2):218-27 [14644624] J Pharm Pharmacol. 1994 Feb;46(2):135-7 [8021802] J Biol Chem. 1996 May 17;271(20):12063-7 [8662637] J Pharm Pharmacol. 1996 Sep;48(9):902-5 [8910850] Gastroenterology. 2004 Dec;127(6):1760-74 [15578514] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/dmd.116.069419 ER - TY - JOUR T1 - Mapping and modeling of a strain-specific epitope in the Norwalk virus capsid inner shell. AN - 1779879263; 26971245 AB - Noroviruses are diverse positive-strand RNA viruses associated with acute gastroenteritis. Cross-reactive epitopes have been mapped primarily to conserved sequences in the capsid VP1 Shell (S) domain, and strain-specific epitopes to the highly variable Protruding (P) domain. In this work, we investigated a strain-specific linear epitope defined by MAb NV10 that was raised against prototype (Genogroup I.1) strain Norwalk virus (NV). Using peptide scanning and mutagenesis, the epitope was mapped to amino acids 21-32 (LVPEVNASDPLA) of the NV S domain, and its specificity was verified by epitope transfer and reactivity with a recombinant MAb NV10 single-chain variable fragment (scFv). Comparative structural modeling of the NV10 strain-specific and the broadly cross-reactive TV20 epitopes identified two internal non-overlapping sites in the NV shell, corresponding to variable and conserved amino acid sequences among strains, respectively. The S domain, like the P domain, contains strain-specific epitopes that contribute to the antigenic diversity among the noroviruses. Published by Elsevier Inc. JF - Virology AU - Parra, Gabriel I AU - Sosnovtsev, Stanislav V AU - Abente, Eugenio J AU - Sandoval-Jaime, Carlos AU - Bok, Karin AU - Dolan, Michael A AU - Green, Kim Y AD - Caliciviruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Caliciviruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: kgreen@niaid.nih.gov. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 232 EP - 241 VL - 492 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Viral KW - Capsid Proteins KW - Epitopes KW - Single-Chain Antibodies KW - Index Medicus KW - Noroviruses KW - Epitope-tagging KW - Caliciviruses KW - Antibodies, Monoclonal -- biosynthesis KW - Animals KW - Calicivirus, Feline -- metabolism KW - Models, Molecular KW - Gene Expression KW - Amino Acid Sequence KW - Capsid -- chemistry KW - Mice KW - Antibodies, Monoclonal -- chemistry KW - Mice, Inbred BALB C KW - Capsid -- immunology KW - Sequence Alignment KW - Calicivirus, Feline -- genetics KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Epitope Mapping KW - Single-Chain Antibodies -- chemistry KW - Single-Chain Antibodies -- biosynthesis KW - Epitopes -- genetics KW - Capsid Proteins -- immunology KW - Norwalk virus -- immunology KW - Antibodies, Viral -- chemistry KW - Norwalk virus -- genetics KW - Epitopes -- chemistry KW - Epitopes -- immunology KW - Capsid Proteins -- genetics KW - Capsid Proteins -- chemistry KW - Antibodies, Viral -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1779879263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Mapping+and+modeling+of+a+strain-specific+epitope+in+the+Norwalk+virus+capsid+inner+shell.&rft.au=Parra%2C+Gabriel+I%3BSosnovtsev%2C+Stanislav+V%3BAbente%2C+Eugenio+J%3BSandoval-Jaime%2C+Carlos%3BBok%2C+Karin%3BDolan%2C+Michael+A%3BGreen%2C+Kim+Y&rft.aulast=Parra&rft.aufirst=Gabriel&rft.date=2016-05-01&rft.volume=492&rft.issue=&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=1096-0341&rft_id=info:doi/10.1016%2Fj.virol.2016.02.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-16 N1 - Date created - 2016-04-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.virol.2016.02.019 ER - TY - JOUR T1 - Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. AN - 1779020507; 26988606 AB - Chronic oral treatment of tetrabromobisphenol A (TBBPA) to female Wistar Han rats resulted in increased incidence of cell proliferation at 250mg/kg and tumor formation in the uterus at higher doses. The present study was designed to test the hypothesis that disruption of estrogen homeostasis was a major mode-of-action for the observed effects. Biological changes were assessed in serum, liver, and the proximal (nearest the cervix) and distal (nearest the ovaries) sections of the uterine horn of Wistar Han rats 24h following administration of the last of five daily oral doses of 250mg/kg. Expression of genes associated with receptors, biosynthesis, and metabolism of estrogen was altered in the liver and uterus. TBBPA treatment also resulted in changes in expression of genes associated with cell division and growth. Changes were also observed in the concentration of thyroxine in serum and in expression of genes in the liver and uterus associated with thyroid hormone receptors. Differential expression of some genes was tissue-dependent or specific to tissue location in the uterus. The biological responses observed in the present study support the hypothesis that perturbation of estrogen homeostasis is a major mode-of-action for TBBPA-mediated cell proliferation and tumorigenesis previously observed in the uterus of TBBPA-treated Wistar Han rats. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Sanders, J Michael AU - Coulter, Sherry J AU - Knudsen, Gabriel A AU - Dunnick, June K AU - Kissling, Grace E AU - Birnbaum, Linda S AD - Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States. Electronic address: sander10@mail.nih.gov. ; Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States. ; National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States. Y1 - 2016/05/01/ PY - 2016 DA - 2016 May 01 SP - 31 EP - 39 VL - 298 KW - Environmental Pollutants KW - 0 KW - Estrogen Receptor alpha KW - Estrogen Receptor beta KW - Estrogens KW - Polybrominated Biphenyls KW - tetrabromobisphenol A KW - FQI02RFC3A KW - Index Medicus KW - Rats KW - Gene expression KW - TBBPA KW - Tetrabromobisphenol A KW - Estrogen homeostasis KW - Uterine toxicity KW - Cell Proliferation -- drug effects KW - Animals KW - Liver -- pathology KW - Estrogen Receptor alpha -- genetics KW - Liver -- drug effects KW - Dose-Response Relationship, Drug KW - Rats, Wistar KW - Liver -- metabolism KW - Female KW - Estrogen Receptor beta -- genetics KW - Uterus -- metabolism KW - Gene Expression -- drug effects KW - Environmental Pollutants -- toxicity KW - Estrogens -- metabolism KW - Homeostasis -- genetics KW - Uterus -- pathology KW - Polybrominated Biphenyls -- toxicity KW - Homeostasis -- drug effects KW - Uterus -- drug effects KW - Estrogens -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1779020507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Disruption+of+estrogen+homeostasis+as+a+mechanism+for+uterine+toxicity+in+Wistar+Han+rats+treated+with+tetrabromobisphenol+A.&rft.au=Sanders%2C+J+Michael%3BCoulter%2C+Sherry+J%3BKnudsen%2C+Gabriel+A%3BDunnick%2C+June+K%3BKissling%2C+Grace+E%3BBirnbaum%2C+Linda+S&rft.aulast=Sanders&rft.aufirst=J&rft.date=2016-05-01&rft.volume=298&rft.issue=&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.03.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-15 N1 - Date created - 2016-04-05 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Toxicol Sci. 2012 Feb;125(2):359-67 [22086976] Aquat Toxicol. 2012 Feb;108:106-11 [22100034] J Clin Endocrinol Metab. 2012 Nov;97(11):4228-35 [22969138] Environ Pollut. 2014 Oct;193:181-8 [25038377] Environ Health Perspect. 2013 Oct;121(10):1194-9 [23959441] CA Cancer J Clin. 2013 Jan;63(1):11-30 [23335087] Toxicol Pathol. 2015 Jun;43(4):464-73 [25476797] Toxicol Sci. 2007 Apr;96(2):237-45 [17234645] J Cell Biochem. 1999;Suppl 32-33:166-72 [10629116] Endocr Rev. 2000 Feb;21(1):40-54 [10696569] Toxicol Sci. 2000 Jul;56(1):95-104 [10869457] J Natl Cancer Inst Monogr. 2000;(27):113-24 [10963623] Endocrinology. 2000 Sep;141(9):3430-9 [10965916] Xenobiotica. 2000 Sep;30(9):881-90 [11055266] Environ Health Perspect. 2001 Apr;109(4):399-407 [11335189] Cancer Res. 2001 Sep 15;61(18):6716-22 [11559542] Biochem Biophys Res Commun. 2002 Apr 26;293(1):554-9 [12054637] Genome Biol. 2002 Jun 18;3(7):RESEARCH0034 [12184808] Virchows Arch. 2004 Mar;444(3):213-23 [14747944] J Pharmacol Exp Ther. 1984 Feb;228(2):407-13 [6694118] Cancer Res. 1995 Apr 15;55(8):1780-6 [7712488] Xenobiotica. 1996 Jun;26(6):597-611 [8810031] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937-42 [9380738] J Endocrinol. 1958 Sep;17(3):307-13 [13587836] Toxicol Sci. 2005 Apr;84(2):249-59 [15635150] Biotech Histochem. 2005 Mar-Apr;80(2):79-87 [16195173] Int J Gynecol Cancer. 2005 Nov-Dec;15(6):1243-8 [16343224] Mol Cell Endocrinol. 2006 Mar 27;248(1-2):136-40 [16406263] Exp Oncol. 2006 Mar;28(1):44-8 [16614707] Aquat Toxicol. 2006 Jun 30;78(3):292-302 [16678281] Toxicol Sci. 2006 Jul;92(1):157-73 [16601080] Toxicol Appl Pharmacol. 2008 Jul 1;230(1):17-22 [18342900] PLoS Genet. 2008 Jun;4(6):e1000108 [18584035] Cancer Res. 2008 Sep 15;68(18):7386-93 [18794126] World J Surg Oncol. 2010;8:60 [20642852] Sci Total Environ. 2010 Jul 1;408(15):2885-918 [19815253] Folia Biol (Praha). 2011;57(1):35-9 [21457653] J Steroid Biochem Mol Biol. 2011 Sep;126(3-5):78-86 [21600284] Toxicol Sci. 2011 Aug;122(2):372-82 [21622942] Mol Med Rep. 2012 Mar;5(3):761-6 [22179484] Chemosphere. 2012 May;87(7):782-8 [22277881] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.03.007 ER - TY - JOUR T1 - BE-POSITIVE: Beyond progression after tyrosine kinase inhibitor in EGFR- positive non small cell lung cancer patients: Results from a multicenter Italian observational study. AN - 1778708842; 27040855 AB - Non-small-cell-lung-cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations develop drug resistance after 9-12 months of EGFR tyrosine kinase inhibitors (TKIs) therapy pointing out the issue of the second-line treatment choice. From June 2009 until May 2013 patients affected by advanced NSCLC harbouring EGFR mutations receiving first-line TKI were collected mainly retrospectively in 24 Italian Centers. Primary objective was to describe the percentage of EGFR mutated patients receiving second-line therapy after progression to first-line EGFR-TKIs assessing the type, the activity in terms of objective response rate (ORR), efficacy in terms of progression free survival (PFS) and overall survival (OS), and safety of second-line treatment. Secondary objective was to describe the efficacy of first-line EGFR-TKIs. 312 patients were included. Most of them were females (203, 65.1%), never smokers (200, 64.1%), with adenocarcinoma histology (290, 92.9%). The most common mutations were EGFR exon 19 deletion and L858R, detected in 186 and 97 cases (59.6% and 31.1%), respectively. At data cut-off, 274 patients (95.1%) received any second-line treatment (including best supportive care or local treatments only). A total of 163 patients received second-line systemic therapy with an ORR of 20.9% (95% CI:14.62-27.10), a median PFS and OS of 4.7 (95% CI:3.81-5.26) and 24.5 (95% CI:21.65-27.37) months, respectively. Grade 3-4 hematological and non-hematological toxicities were reported in 9% and 6.3% of 144 patients treated with chemotherapy while non-hematological toxicity was reported in 4 cases of the 17 patients receiving second-line target agents. BE-Positive is the first multicenter observational study reporting outcomes of therapies in a "real-life Caucasian EGFR-mutated population", highlighting the need of further researches about new treatment strategies in this setting. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Lung cancer (Amsterdam, Netherlands) AU - Vavalà, Tiziana AU - Follador, Alessandro AU - Tiseo, Marcello AU - Galetta, Domenico AU - Morabito, Alessandro AU - Di Maio, Massimo AU - Martelli, Olga AU - Caffo, Orazio AU - Piovano, Pier Luigi AU - Cortinovis, Diego AU - Zilembo, Nicoletta AU - Casartelli, Clelia AU - Banna, Giuseppe Luigi AU - Ardizzoia, Antonio AU - Barzelloni, Maria Luisa AU - Bearz, Alessandra AU - Genestreti, Giovenzio AU - Mucciarini, Claudia AU - Filipazzi, Virginio AU - Menis, Jessica AU - Rizzo, Elisa AU - Barbieri, Fausto AU - Rijavec, Erika AU - Cecere, Fabiana AU - Bria, Emilio AU - Spitaleri, Gianluca AU - Rossi, Antonio AU - Novello, Silvia AD - Department of Oncology, University of Torino AOU San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy. ; Department of Oncology, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy. ; Medical Oncology Unit, University Hospital of Parma, via Gramsci, 14, 43126 Parma, Italy. ; Medical Oncology Unit, Clinical Cancer Center Giovanni Paolo II, viale Orazio Flacco, 65, 70124 Bari, Italy. ; Thoracic Medical Oncology, National Cancer Institute, Fondazione "G.Pascale", via Mariano Semmola 80131, Napoli, Italy. ; Clinical Trials Unit, National Cancer Institute, Fondazione "G.Pascale", via Mariano Semmola, 80131 Napoli, Italy. ; Medical Oncology, S.Giovanni-Addolorata Hospital, via di S. Stefano Rotondo 5a, 00184 Roma, Italy. ; Medical Oncology Unit, Santa Chiara Hospital, Largo Medaglie D'oro 9, 38122 Trento, Italy. ; Medical Oncology Unit, AO SS. Antonio Biagio e Cesare Arrigo, via S. Pio V 5, Alessandria, Italy. ; Medical Oncology Unit, AOU San Gerardo, via Giambattista Pergolesi 33, 20900 Monza, Italy. ; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, Milano, Italy. ; Medical Oncology Unit, Valduce Hospital, via Dante Alighieri 11, 22100 Como, Italy. ; Division of Medical Oncology, AO Cannizzaro Hospital, via Messina 829, 95126 Catania, Italy. ; Medical Oncology Unit, A.Manzoni Hospital via dell'Eremo 9/11, 23900 Lecco, Italy. ; AOU San Giovanni di Dio e Ruggi d' Aragona c/o P.O. G. da Procida, largo Città di Ippocrate, 84131 Salerno, Italy. ; Department of Medical Oncology, National Institute for Cancer Research, via Franco Gallini 2, Aviano (PN), Italy. ; Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via Piero Maroncelli 40, 47014 Meldola, Italy. ; Department of Oncological Medicine, Ramazzini Hospital, via Guido Molinari 2, 41012 Carpi (MO), Italy. ; UOC Medical Oncology, AO Luigi Sacco, via Giovanni Battista Grassi 74, 20157 Milano,Italy. ; EORTC Headquarters, Avenue E. Mounier 83, 1200 Bruxelles, Belgium. ; Department of Oncology and Hemathology, AOU of Modena, viale del pozzo 71, Modena, Italy. ; Lung Cancer Unit, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genova, Italy. ; Medical Oncology Unit, University Hospital Careggi, Largo Brambilla 3, 50134 Firenze, Italy. ; Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, P.zza L. A. Scuro 10, 37134 Verona, Italy. ; Division of Thoracic Oncology, European Institute of Oncology, via Ripamonti 435, 20141 Milano, Italy. ; Division of Medical Oncology, S.G. Moscati Hospital, Contrada Amoretta Avellino, Italy. ; Department of Oncology, University of Torino AOU San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy. Electronic address: silvia.novello@unito.it. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 73 EP - 81 VL - 95 KW - Protein Kinase Inhibitors KW - 0 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Second line KW - Non small cell lung cancer KW - EGFR tyrosine kinase inhibitors KW - EGFR mutation KW - First line KW - Acquired resistance KW - Neoplasm Staging KW - Humans KW - Disease Progression KW - Aged KW - Drug Resistance, Neoplasm KW - Italy KW - Aged, 80 and over KW - Risk Factors KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Retreatment KW - Mutation KW - Female KW - Male KW - Receptor, Epidermal Growth Factor -- antagonists & inhibitors KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Lung Neoplasms -- drug therapy KW - Protein Kinase Inhibitors -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- diagnosis KW - Lung Neoplasms -- diagnosis KW - Receptor, Epidermal Growth Factor -- genetics KW - Protein Kinase Inhibitors -- therapeutic use KW - Protein Kinase Inhibitors -- adverse effects KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- mortality KW - Carcinoma, Non-Small-Cell Lung -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1778708842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=BE-POSITIVE%3A+Beyond+progression+after+tyrosine+kinase+inhibitor+in+EGFR-+positive+non+small+cell+lung+cancer+patients%3A+Results+from+a+multicenter+Italian+observational+study.&rft.au=Vaval%C3%A0%2C+Tiziana%3BFollador%2C+Alessandro%3BTiseo%2C+Marcello%3BGaletta%2C+Domenico%3BMorabito%2C+Alessandro%3BDi+Maio%2C+Massimo%3BMartelli%2C+Olga%3BCaffo%2C+Orazio%3BPiovano%2C+Pier+Luigi%3BCortinovis%2C+Diego%3BZilembo%2C+Nicoletta%3BCasartelli%2C+Clelia%3BBanna%2C+Giuseppe+Luigi%3BArdizzoia%2C+Antonio%3BBarzelloni%2C+Maria+Luisa%3BBearz%2C+Alessandra%3BGenestreti%2C+Giovenzio%3BMucciarini%2C+Claudia%3BFilipazzi%2C+Virginio%3BMenis%2C+Jessica%3BRizzo%2C+Elisa%3BBarbieri%2C+Fausto%3BRijavec%2C+Erika%3BCecere%2C+Fabiana%3BBria%2C+Emilio%3BSpitaleri%2C+Gianluca%3BRossi%2C+Antonio%3BNovello%2C+Silvia&rft.aulast=Vaval%C3%A0&rft.aufirst=Tiziana&rft.date=2016-05-01&rft.volume=95&rft.issue=&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=1872-8332&rft_id=info:doi/10.1016%2Fj.lungcan.2016.02.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-19 N1 - Date created - 2016-04-04 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.lungcan.2016.02.011 ER - TY - JOUR T1 - Non-Wilsonian hepatolenticular degeneration: Clinical and MRI observations in four families from south India. AN - 1778400221; 26765764 AB - Non-Wilsonian hepatolenticular degeneration (NWHD) is a heterogeneous neurological disorder occurring secondary to chronic acquired liver disease. Genetically determined familial NWHD is rare, poorly understood, and often mistaken for Wilson's disease (WD). We analysed clinical and MRI profiles of NWHD patients who did not have obvious cause for acquired liver disease, such as alcohol intake or hepatitis. Six patients from four families (four males, two females, mean age: 17.0±standard deviation 7.9years), presenting with chronic extrapyramidal disorder resembling WD and imaging (abdominal ultrasound/MRI) evidence of cirrhosis were studied. They lacked Kayser-Fleischer rings or biochemical and/or genetic evidence of WD. Clinical features included dystonia (n=6), parkinsonism (n=3), tremor (n=1), cerebellar ataxia (n=3), orofacial dyskinesia (n=1), behavioural abnormalities (n=3), and cognitive decline (n=1). Brain MRI revealed T1-weighted hyperintensity in the pallidum (n=6), crus cerebri (n=4), putamen (n=1), caudate (n=1), thalamus (n=1), and red nucleus (n=1) with T2-weighted shortening in some of these regions. Additional findings included giant cisterna magna (n=1), face of giant panda sign (n=1) and thin corpus callosum (n=1). Areas of "blooming" on susceptibility weighted images were noted in two patients in the caudate (n=2) and putamen (n=1). The finding of T1 shortening is distinct from that of WD where the majority of lesions are T1-hypointense and T2-hyperintense. Extrapallidal T1-hyperintensity is also an exceptional observation in NWHD. The MRI appearance of intense T1 shortening coupled with the lack of increased susceptibility changes suggests that the most likely mineral deposited is manganese. The association of this neurological disorder and cirrhosis of the liver in the absence of an acquired liver disease is a distinct disease entity. This syndrome may represent a disorder of manganese metabolism resulting in its toxic deposition. Copyright © 2015 Elsevier Ltd. All rights reserved. JF - Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia AU - Nagappa, Madhu AU - Sinha, Sanjib AU - Saini, Jitender S AU - Kallolimath, Pradeep AU - Singh, Nivedita AU - Kumar, Arun AU - Bindu, Parayil S AU - Taly, Arun B AD - Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India. ; Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore 560 029, Karnataka, India. Electronic address: sanjib_sinha2004@yahoo.co.in. ; Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India. ; Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science (IISc), Bangalore, India. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 91 EP - 94 VL - 27 KW - Manganese KW - 42Z2K6ZL8P KW - Index Medicus KW - Non-Wilsonian hepatolenticular degeneration KW - Wilson’s disease KW - MRI KW - Liver dysfunction KW - Pallidal hyperintensity KW - Pedigree KW - Magnetic Resonance Imaging KW - Humans KW - Adult KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - India KW - Liver Cirrhosis -- pathology KW - Manganese -- metabolism KW - Liver Cirrhosis -- metabolism KW - Basal Ganglia Diseases -- pathology KW - Liver Cirrhosis -- complications KW - Basal Ganglia Diseases -- metabolism KW - Basal Ganglia Diseases -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1778400221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+neuroscience+%3A+official+journal+of+the+Neurosurgical+Society+of+Australasia&rft.atitle=Non-Wilsonian+hepatolenticular+degeneration%3A+Clinical+and+MRI+observations+in+four+families+from+south+India.&rft.au=Nagappa%2C+Madhu%3BSinha%2C+Sanjib%3BSaini%2C+Jitender+S%3BKallolimath%2C+Pradeep%3BSingh%2C+Nivedita%3BKumar%2C+Arun%3BBindu%2C+Parayil+S%3BTaly%2C+Arun+B&rft.aulast=Nagappa&rft.aufirst=Madhu&rft.date=2016-05-01&rft.volume=27&rft.issue=&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+neuroscience+%3A+official+journal+of+the+Neurosurgical+Society+of+Australasia&rft.issn=1532-2653&rft_id=info:doi/10.1016%2Fj.jocn.2015.06.035 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-04-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jocn.2015.06.035 ER - TY - JOUR T1 - Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. AN - 1777979991; 26867988 AB - Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear. We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges' g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects. A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = -1.00, 95% CI -1.28 to -0.73, p < 0.001), and loosing superiority by days 10-12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5-8 (Hedges' g = -0.37, 95% CI -0.66 to -0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3-5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3-5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant. A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance. JF - Psychological medicine AU - Kishimoto, T AU - Chawla, J M AU - Hagi, K AU - Zarate, C A AU - Kane, J M AU - Bauer, M AU - Correll, C U AD - Keio University School of Medicine,Tokyo,Japan. ; The Zucker Hillside Hospital,Psychiatry Research,Northwell Health System,Glen Oaks,NY,USA. ; National Institute of Mental Health,Bethesda,Northwell Health System,MD,USA. ; Klinik und Poliklinik für Psychiatrie und Psychotherapie,Universitätsklinikum Carl Gustav Carus,Technische Universität,Dresden,Germany. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 1459 EP - 1472 VL - 46 IS - 7 KW - Antidepressive Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Ketamine KW - 690G0D6V8H KW - Index Medicus KW - ketamine KW - meta-analyses KW - N-methyl-d-aspartate receptor antagonists KW - trajectories KW - Bipolar depression KW - depression KW - Humans KW - Ketamine -- pharmacokinetics KW - Antidepressive Agents -- pharmacology KW - Excitatory Amino Acid Antagonists -- administration & dosage KW - Antidepressive Agents -- adverse effects KW - Ketamine -- administration & dosage KW - Ketamine -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Ketamine -- adverse effects KW - Depressive Disorder, Major -- drug therapy KW - Antidepressive Agents -- administration & dosage KW - Antidepressive Agents -- pharmacokinetics KW - Bipolar Disorder -- drug therapy KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Outcome Assessment (Health Care) -- statistics & numerical data KW - Excitatory Amino Acid Antagonists -- adverse effects KW - Excitatory Amino Acid Antagonists -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777979991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychological+medicine&rft.atitle=Single-dose+infusion+ketamine+and+non-ketamine+N-methyl-d-aspartate+receptor+antagonists+for+unipolar+and+bipolar+depression%3A+a+meta-analysis+of+efficacy%2C+safety+and+time+trajectories.&rft.au=Kishimoto%2C+T%3BChawla%2C+J+M%3BHagi%2C+K%3BZarate%2C+C+A%3BKane%2C+J+M%3BBauer%2C+M%3BCorrell%2C+C+U&rft.aulast=Kishimoto&rft.aufirst=T&rft.date=2016-05-01&rft.volume=46&rft.issue=7&rft.spage=1459&rft.isbn=&rft.btitle=&rft.title=Psychological+medicine&rft.issn=1469-8978&rft_id=info:doi/10.1017%2FS0033291716000064 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-02 N1 - Date created - 2016-04-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1017/S0033291716000064 ER - TY - JOUR T1 - Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH-AARP diet and health cohort. AN - 1767623951; 26666579 AB - Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white and processed meat intake, meat cooking methods and doneness and heme iron and mutagen intake in relation to pancreatic cancer in the NIH-AARP Diet and Health Study cohort. A total of 322,846 participants (187,265 men and 135,581 women) successfully completed and returned the food frequency questionnaire between 1995 and 1996. After a mean follow-up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men and 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, body mass index, self-reported diabetes and energy-adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1: HR = 1.20, 95% CI 1.02-1.42, p-trend = 0.03), red meat (HR = 1.22, 95% CI 1.01-1.48, p-trend = 0.02), high-temperature cooked meat (HR = 1.21, 95% CI 1.00-1.45, p-trend = 0.02), grilled/barbequed meat (HR = 1.24, 95% CI 1.03-1.50, p-trend = 0.007), well/very well done meat (HR = 1.32, 95% CI 1.10-1.58, p-trend = 0.005) and heme iron from red meat (Q4 vs. Q1: HR = 1.21, 95% CI 1.01-1.45, p-trend = 0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR = 1.33, 95% CI 1.02-1.74, p-trend = 0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk. © 2015 UICC. JF - International journal of cancer AU - Taunk, Pulkit AU - Hecht, Eric AU - Stolzenberg-Solomon, Rachael AD - Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL. ; Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD. Y1 - 2016/05/01/ PY - 2016 DA - 2016 May 01 SP - 2172 EP - 2189 VL - 138 IS - 9 KW - Iron, Dietary KW - 0 KW - Heme KW - 42VZT0U6YR KW - Index Medicus KW - pancreatic cancer KW - meat KW - heme iron KW - Risk Factors KW - Humans KW - Cooking KW - Cohort Studies KW - Diet Surveys KW - Aged KW - Middle Aged KW - Heme -- adverse effects KW - Male KW - Female KW - Proportional Hazards Models KW - Heme -- administration & dosage KW - Meat -- adverse effects KW - Iron, Dietary -- adverse effects KW - Pancreatic Neoplasms -- epidemiology KW - Diet KW - Feeding Behavior KW - Iron, Dietary -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767623951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Are+meat+and+heme+iron+intake+associated+with+pancreatic+cancer%3F+Results+from+the+NIH-AARP+diet+and+health+cohort.&rft.au=Taunk%2C+Pulkit%3BHecht%2C+Eric%3BStolzenberg-Solomon%2C+Rachael&rft.aulast=Taunk&rft.aufirst=Pulkit&rft.date=2016-05-01&rft.volume=138&rft.issue=9&rft.spage=2172&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.29964 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-18 N1 - Date created - 2016-02-22 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Mol Nutr Food Res. 2005 Jul;49(7):648-55 [15986387] Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):655-61 [17416754] Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2664-75 [18086772] PLoS Med. 2007 Dec;4(12):e325 [18076279] Int J Cancer. 2009 Sep 1;125(5):1118-26 [19452526] Am J Epidemiol. 2010 Jan 15;171(2):233-41 [20022893] Ann Oncol. 2011 Jan;22(1):202-6 [20530201] Cancer Epidemiol Biomarkers Prev. 2011 Apr;20(4):711-4 [21278328] Mol Carcinog. 2012 Jan;51(1):128-37 [22162237] Cancer Epidemiol. 2012 Feb;36(1):60-7 [22018953] Br J Cancer. 2012 Jan 31;106(3):603-7 [22240790] Cancer Epidemiol Biomarkers Prev. 2012 Apr;21(4):619-28 [22301828] Surg Oncol. 2014 Jun;23(2):61-71 [24746917] Am J Clin Nutr. 2015 Jan;101(1):126-34 [25527756] Am J Epidemiol. 2000 Aug 1;152(3):279-86 [10933275] Am J Epidemiol. 2001 Dec 15;154(12):1119-25 [11744517] Mutat Res. 2002 Sep 30;506-507:225-31 [12351162] Am J Epidemiol. 2003 Jun 15;157(12):1115-25 [12796048] J Natl Cancer Inst. 2003 Jul 2;95(13):948-60 [12837831] Mutat Res. 1975 Dec;31(6):347-64 [768755] Int J Cancer. 1991 Jan 2;47(1):1-6 [1845960] Am J Epidemiol. 1991 Jul 15;134(2):167-79 [1862800] Cancer Causes Control. 1991 Sep;2(5):291-7 [1932541] Int J Epidemiol. 1993 Feb;22(1):30-7 [8449644] Cancer Res. 1995 Oct 15;55(20):4516-9 [7553619] Int J Cancer. 2012 Oct 1;131(7):E1134-47 [22438075] Carcinogenesis. 2013 Jul;34(7):1628-35 [23455377] Cancer Epidemiol Biomarkers Prev. 2013 Jul;22(7):1336-9 [23632817] Br J Cancer. 2013 Aug 6;109(3):756-60 [23695021] Am J Clin Nutr. 2013 Oct;98(4):1057-65 [23985810] Nutr J. 2013;12:102 [23866833] CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 [24399786] Meat Sci. 2014 Aug;97(4):583-96 [24769880] Food Chem Toxicol. 1998 Apr;36(4):279-87 [9651044] Food Chem Toxicol. 1998 Apr;36(4):289-97 [9651045] J Natl Cancer Inst. 1998 Nov 18;90(22):1710-9 [9827525] J Gastroenterol. 2005 Mar;40(3):297-301 [15830290] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.29964 ER - TY - JOUR T1 - Body Mass Index and Treatment Outcomes in Metastatic Breast Cancer Patients Treated With Eribulin. AN - 1760901607; 26449308 AB - Eribulin has shown survival advantage and manageable toxicity in heavily pre-treated metastatic breast cancer (mBC). We assessed whether body mass index (BMI) impacts treatment outcomes in 101 patients treated with eribulin at six Italian Oncologic Centers. BMI was addressed as a categorical variable (18.5-24.9 vs. at least 25). Clinical benefit rate (CBR) was assessed overall and in subgroups defined by BMI, line of therapy (LOT), and hormone receptor (HR) status. Analysis of CBR by LOT and HR status were further stratified by BMI. Survival curves were compared using the Kaplan-Meier method and log-rank test. Predictors of survival were tested in Cox models. Patients treated with eribulin as third line showed greater CBR when their BMI was in the lowest category (77.8 vs. 58.1%, P = 0.03). Median progression free survival (PFS) and overall survival (OS) in normal and overweight patients were 4 (95% CI, 3-5) versus 3 (2.1-4) months, P = 0.02 and 13 (11-15) versus 12 (6-18) months, P = 0.96, respectively. Median PFS and OS in estrogen receptor (ER) positive and negative tumours were 4 (3-5) versus 3 (2-4) months, P = 0.005 and 14 (10-18) versus 7 (4-10), P = 0.02, respectively. In multivariate analyses, BMI impacted PFS at a nearly significant extent (P = 0.05), while ER expression significantly affected PFS and OS (P = 0.01 and 0.02, respectively). No relevant findings emerged concerning toxicity. We found evidence of greater efficacy of eribulin in leaner mBC patients, particularly if given as third line and in ER positive tumors. Further studies are warranted to confirm our findings. © 2015 Wiley Periodicals, Inc. JF - Journal of cellular physiology AU - Barba, Maddalena AU - Pizzuti, Laura AU - Sperduti, Isabella AU - Natoli, Clara AU - Gamucci, Teresa AU - Sergi, Domenico AU - Di Lauro, Luigi AU - Moscetti, Luca AU - Izzo, Fiorentino AU - Rinaldi, Massimo AU - Mentuccia, Lucia AU - Vaccaro, Angela AU - Iezzi, Laura AU - Grassadonia, Antonino AU - Michelotti, Andrea AU - Landucci, Elisabetta AU - Perracchio, Letizia AU - Pescarmona, Edoardo AU - Di Filippo, Franco AU - Giordano, Antonio AU - Maugeri-Saccà, Marcello AU - Vici, Patrizia AD - Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy. ; Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy. ; Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy. ; Medical Oncology Unit-ASL Frosinone, Italy. ; Medical Oncology Unit, Belcolle Hospital, Viterbo, Italy. ; Oncology Unit I, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. ; Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy. ; Surgery Division A, Regina Elena National Cancer Institute, Rome, Italy. ; Sbarro Institute for Cancer Research and Molecular Medicine e del Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania. Y1 - 2016/05// PY - 2016 DA - May 2016 SP - 986 EP - 991 VL - 231 IS - 5 KW - Furans KW - 0 KW - Ketones KW - Receptors, Estrogen KW - eribulin KW - LR24G6354G KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Adult KW - Treatment Outcome KW - Neoplasm Metastasis KW - Aged KW - Middle Aged KW - Receptors, Estrogen -- metabolism KW - Female KW - Breast Neoplasms -- drug therapy KW - Furans -- pharmacology KW - Breast Neoplasms -- pathology KW - Furans -- therapeutic use KW - Body Mass Index KW - Ketones -- therapeutic use KW - Ketones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760901607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Body+Mass+Index+and+Treatment+Outcomes+in+Metastatic+Breast+Cancer+Patients+Treated+With+Eribulin.&rft.au=Barba%2C+Maddalena%3BPizzuti%2C+Laura%3BSperduti%2C+Isabella%3BNatoli%2C+Clara%3BGamucci%2C+Teresa%3BSergi%2C+Domenico%3BDi+Lauro%2C+Luigi%3BMoscetti%2C+Luca%3BIzzo%2C+Fiorentino%3BRinaldi%2C+Massimo%3BMentuccia%2C+Lucia%3BVaccaro%2C+Angela%3BIezzi%2C+Laura%3BGrassadonia%2C+Antonino%3BMichelotti%2C+Andrea%3BLanducci%2C+Elisabetta%3BPerracchio%2C+Letizia%3BPescarmona%2C+Edoardo%3BDi+Filippo%2C+Franco%3BGiordano%2C+Antonio%3BMaugeri-Sacc%C3%A0%2C+Marcello%3BVici%2C+Patrizia&rft.aulast=Barba&rft.aufirst=Maddalena&rft.date=2016-05-01&rft.volume=231&rft.issue=5&rft.spage=986&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=1097-4652&rft_id=info:doi/10.1002%2Fjcp.25213 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-07 N1 - Date created - 2016-01-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/jcp.25213 ER - TY - JOUR T1 - Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry. AN - 1775633118; 27003044 AB - AMB (methyl (1-pentyl-1H-indazole-3-carbonyl)-L-valinate)) and its fluoro analog 5F-AMB (methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L-valinate) are two new synthetic cannabinoids that are structural analogs of AB-PINACA and 5F-AB-PINACA, respectively. 5F-AMB is scheduled as an illicit drug in China, Germany, Singapore and Japan, and no metabolism data are currently available for either drug. The aim of the present work was to investigate the metabolism of AMB and 5F-AMB and propose appropriate markers to identify their intake in clinical or forensic cases. AMB and 5F-AMB were incubated in human hepatocytes (10 μmol/L) to generate phase I and II metabolites, which were identified with a TripleTOF 5600(+) high-resolution mass spectrometer. AMB and 5F-AMB metabolic stability studies also were performed with human liver microsomes (HLM) to evaluate metabolic clearances, and to adequately design the human hepatocyte experiment. AMB and 5F-AMB were quickly metabolized in HLM with a 1.1 ± 0.1 and 1.0 ± 0.2 min T1/2, respectively. The predominant metabolic pathway for AMB and 5F-AMB in hepatocytes was ester hydrolysis, and further oxidation and/or glucuronidation. In total, 19 metabolites were identified for AMB and 17 for 5F-AMB. We describe metabolites to differentiate AMB from 5F-AMB, and metabolites that are common to both analytes due to oxidative defluorination of 5F-AMB. For the first time, AMB and 5F-AMB metabolism profiles were characterized, providing valuable data for identifying these two novel psychoactive substances. The difficulties of differentiating AMB and 5F-AMB from AB-PINACA/5F-AB-PINACA metabolites also were examined. These data improve the interpretation of urinary markers after AMB and 5F-AMB intake. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Rapid communications in mass spectrometry : RCM AU - Andersson, Maria AU - Diao, Xingxing AU - Wohlfarth, Ariane AU - Scheidweiler, Karl B AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. Y1 - 2016/04/30/ PY - 2016 DA - 2016 Apr 30 SP - 1067 EP - 1078 VL - 30 IS - 8 KW - Cannabinoids KW - 0 KW - Index Medicus KW - Cells, Cultured KW - Humans KW - Metabolomics -- methods KW - Cannabinoids -- metabolism KW - Microsomes, Liver -- metabolism KW - Cannabinoids -- chemistry KW - Mass Spectrometry -- methods KW - Hepatocytes -- metabolism KW - Cannabinoids -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775633118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Rapid+communications+in+mass+spectrometry+%3A+RCM&rft.atitle=Metabolic+profiling+of+new+synthetic+cannabinoids+AMB+and+5F-AMB+by+human+hepatocyte+and+liver+microsome+incubations+and+high-resolution+mass+spectrometry.&rft.au=Andersson%2C+Maria%3BDiao%2C+Xingxing%3BWohlfarth%2C+Ariane%3BScheidweiler%2C+Karl+B%3BHuestis%2C+Marilyn+A&rft.aulast=Andersson&rft.aufirst=Maria&rft.date=2016-04-30&rft.volume=30&rft.issue=8&rft.spage=1067&rft.isbn=&rft.btitle=&rft.title=Rapid+communications+in+mass+spectrometry+%3A+RCM&rft.issn=1097-0231&rft_id=info:doi/10.1002%2Frcm.7538 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/rcm.7538 ER - TY - JOUR T1 - Evolutionary constraints over microsatellite abundance in larger mammals as a potential mechanism against carcinogenic burden. AN - 1785736761; 27125812 AB - Larger organisms tend to live longer, have more potentially carcinogenic cells, and undergo more cell divisions. While one might intuitively expect cancer incidence to scale with body size, this assertion does not hold over the range of different mammals. Explaining this lack of correlation, so-called 'Peto's paradox' can likely increase our understanding of how cancer defense mechanisms are shaped by natural selection. Here, we study the occurrence of microsatellite in mammal genomes and observe that animals with expanded body size restrain the number of microsatellite. To take into account of higher mutation rate in the microsatellite region compared to that of genome, limiting the abundance of somatic mutations might explain how larger organisms could overcome the burden of cancer. These observations may serve as the basis to better understand how evolution has modeled protective mechanisms against cancer development. JF - Scientific reports AU - Park, Jung Youn AU - An, Yong-Rock AU - An, Chul-Min AU - Kang, Jung-Ha AU - Kim, Eun Mi AU - Kim, Heebal AU - Cho, Seoae AU - Kim, Jaemin AD - Biotechnology Research Division, National Fisheries Research &Development Institute, Gijang gun, Busan, 619-705, Republic of Korea. ; Cetacean Research Institute, National Fisheries Research &Development Institute, Nam-gu, Ulsan 680-050, Republic of Korea. ; Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea. ; C&K Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. ; National Human Genome Research Institute, National Institutes of Health, Bethesda MD 20892, USA. Y1 - 2016/04/29/ PY - 2016 DA - 2016 Apr 29 SP - 25246 VL - 6 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785736761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Evolutionary+constraints+over+microsatellite+abundance+in+larger+mammals+as+a+potential+mechanism+against+carcinogenic+burden.&rft.au=Park%2C+Jung+Youn%3BAn%2C+Yong-Rock%3BAn%2C+Chul-Min%3BKang%2C+Jung-Ha%3BKim%2C+Eun+Mi%3BKim%2C+Heebal%3BCho%2C+Seoae%3BKim%2C+Jaemin&rft.aulast=Park&rft.aufirst=Jung&rft.date=2016-04-29&rft.volume=6&rft.issue=&rft.spage=25246&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep25246 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-29 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D154-9 [15608167] Cancer Res. 1998 Nov 15;58(22):5248-57 [9823339] J Exp Biol. 2005 Aug;208(Pt 16):3015-35 [16081601] Genome Biol. 2009;10(4):R42 [19393038] Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a001198 [20516129] PLoS Genet. 2010 Aug;6(8). pii: e1001080. doi: 10.1371/journal.pgen.1001080 [20865118] Trends Ecol Evol. 2011 Apr;26(4):175-82 [21296451] BMC Cancer. 2012;12:387 [22943484] PLoS Pathog. 2014 Jul;10(7):e1004214 [25033295] BMC Genomics. 2015;16:13 [25609461] Sci Rep. 2015;5:10008 [25943793] Philos Trans R Soc Lond B Biol Sci. 2015 Jul 19;370(1673). pii: 20140177. doi: 10.1098/rstb.2014.0177 [26056361] Philos Trans R Soc Lond B Biol Sci. 2015 Jul 19;370(1673). pii: 20140223. doi: 10.1098/rstb.2014.0223 [26056367] Philos Trans R Soc Lond B Biol Sci. 2015 Jul 19;370(1673). pii: 20140225. doi: 10.1098/rstb.2014.0225 [26056369] JAMA. 2015 Nov 3;314(17):1850-60 [26447779] Nucleic Acids Res. 1999 Jan 15;27(2):573-80 [9862982] Genome Res. 2000 Jul;10(7):967-81 [10899146] Science. 2001 Sep 21;293(5538):2248-51 [11567137] Nucleic Acids Res. 2002 Jan 1;30(1):38-41 [11752248] Nat Genet. 2002 Feb;30(2):194-200 [11799393] Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):776-81 [12552134] Exp Gerontol. 2003 Mar;38(3):333-7 [12581799] Bioinformatics. 2004 Jan 22;20(2):289-90 [14734327] Nat Rev Genet. 2004 Jun;5(6):435-45 [15153996] Br J Cancer. 1975 Oct;32(4):411-26 [1212409] Genomics. 1990 Aug;7(4):524-30 [1974878] Proc Natl Acad Sci U S A. 1993 May 1;90(9):4087-91 [8483925] Nature. 1993 Jun 10;363(6429):558-61 [8505985] Trends Genet. 1993 Apr;9(4):138-41 [8516849] Cell. 1993 Dec 3;75(5):1027-38 [8252616] Bioessays. 1996 May;18(5):421-5 [8639165] Trends Genet. 1997 Feb;13(2):74-8 [9055609] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):140-5 [15618408] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep25246 ER - TY - JOUR T1 - Investigation of the Structure-Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase I Poisons. AN - 1785731369; 27070999 AB - Several indenoisoquinolines have shown promise as anticancer agents in clinical trials. Incorporation of a nitrogen atom into the indenoisoquinoline scaffold offers the possibility of favorably modulating ligand-binding site interactions, physicochemical properties, and biological activities. Four series of aza-A-ring indenoisoquinolines were synthesized in which the nitrogen atom was systematically rotated through positions 1, 2, 3, and 4. The resulting compounds were tested to establish the optimal nitrogen position for topoisomerase IB (Top1) enzyme poisoning activity and cytotoxicity to human cancer cells. The 4-aza compounds were the most likely to yield derivatives with high Top1 inhibitory activity. However, the relationship between structure and cytotoxicity was more complicated since the potency was influenced strongly by the side chains on the lactam nitrogen. The most cytotoxic azaindenoisoquinolines 45 and 46 had nitrogen in the 2- or 3-positions and a 3'-dimethylaminopropyl side chain, and they had MGM GI50 values that were slightly better than the corresponding indenoisoquinoline 64. JF - Journal of medicinal chemistry AU - Beck, Daniel E AU - Reddy, P V Narasimha AU - Lv, Wei AU - Abdelmalak, Monica AU - Tender, Gabrielle S AU - Lopez, Sophia AU - Agama, Keli AU - Marchand, Christophe AU - Pommier, Yves AU - Cushman, Mark AD - Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and the Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States. ; Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. Y1 - 2016/04/28/ PY - 2016 DA - 2016 Apr 28 SP - 3840 EP - 3853 VL - 59 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785731369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Investigation+of+the+Structure-Activity+Relationships+of+Aza-A-Ring+Indenoisoquinoline+Topoisomerase+I+Poisons.&rft.au=Beck%2C+Daniel+E%3BReddy%2C+P+V+Narasimha%3BLv%2C+Wei%3BAbdelmalak%2C+Monica%3BTender%2C+Gabrielle+S%3BLopez%2C+Sophia%3BAgama%2C+Keli%3BMarchand%2C+Christophe%3BPommier%2C+Yves%3BCushman%2C+Mark&rft.aulast=Beck&rft.aufirst=Daniel&rft.date=2016-04-28&rft.volume=59&rft.issue=8&rft.spage=3840&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=1520-4804&rft_id=info:doi/10.1021%2Facs.jmedchem.6b00003 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jmedchem.6b00003 ER - TY - JOUR T1 - ZP2 peptide beads select human sperm in vitro, decoy mouse sperm in vivo, and provide reversible contraception AN - 1808726847; PQ0003314784 AB - Gamete recognition in the female reproductive tract occurs at the surface of the zona pellucida surrounding ovulated eggs. The acellular zona matrix is composed of three (mouse) or four (human) proteins (ZP1 to ZP4), and the amino terminus of ZP2 is the primary sperm-binding ligand. Mouse and human sperm bind, respectively, to recombinant moZP2 super(35-149) and huZP2 super(39-154) peptides attached to agarose beads. Mouse ZP2 peptide beads markedly inhibited fertilization of ovulated mouse eggs inseminated in vitro and incubated overnight. Similarly, human ZP2 peptide beads prevented sperm binding and penetration of transgenic ZP2Rescue zonae pellucidae, in which human ZP2 replaced mouse ZP2. When mouse ZP2 peptide beads were transcervically deposited into the uterus, there was no change in mating behavior and copulatory plugs were present, but bound sperm did not progress into the oviduct and female mice were infertile. On average, contraception lasted >10 estrus cycles but was reversible with no detectable pathology in the reproductive tract. Despite the long-term contraceptive effect, initial sperm binding to the peptide beads was reversible in vitro. We exploited this observation to select human sperm that were better able to penetrate the zonae of human ZP2Rescue eggs, and the approach holds promise for identifying superior sperm for human assisted reproductive technologies (ART). We conclude that the amino-terminal ZP2 peptide supports sperm binding, which is initially reversible but, with time, becomes irreversible. Short-term, reversible binding may be useful in selecting sperm for ART, and long-term binding decoys sperm and results in effective contraception in mice. JF - Science Translational Medicine AU - Avella, Matteo A AU - Baibakov, Boris A AU - Jimenez-Movilla, Maria AU - Sadusky, Anna Burkart AU - Dean, Jurrien AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, jurriend@helix.nih.gov Y1 - 2016/04/27/ PY - 2016 DA - 2016 Apr 27 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 United States VL - 8 IS - 336 SN - 1946-6234, 1946-6234 KW - Biotechnology and Bioengineering Abstracts KW - Mating behavior KW - Translation KW - Uterus KW - Gametes KW - Sperm KW - Reproductive system KW - Eggs KW - Fertilization KW - Oviduct KW - Estrus KW - Contraception KW - Zona pellucida KW - Reproduction KW - Contraceptives KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808726847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+Translational+Medicine&rft.atitle=ZP2+peptide+beads+select+human+sperm+in+vitro%2C+decoy+mouse+sperm+in+vivo%2C+and+provide+reversible+contraception&rft.au=Avella%2C+Matteo+A%3BBaibakov%2C+Boris+A%3BJimenez-Movilla%2C+Maria%3BSadusky%2C+Anna+Burkart%3BDean%2C+Jurrien&rft.aulast=Avella&rft.aufirst=Matteo&rft.date=2016-04-27&rft.volume=8&rft.issue=336&rft.spage=336ra60&rft.isbn=&rft.btitle=&rft.title=Science+Translational+Medicine&rft.issn=19466234&rft_id=info:doi/10.1126%2Fscitranslmed.aad9946 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Mating behavior; Translation; Uterus; Gametes; Sperm; Eggs; Reproductive system; Fertilization; Estrus; Oviduct; Zona pellucida; Contraception; Reproduction; Contraceptives DO - http://dx.doi.org/10.1126/scitranslmed.aad9946 ER - TY - JOUR T1 - Comparison of SYBR green I real-time RT-PCR with conventional agarose gel-based RT-PCR for the diagnosis of infectious bronchitis virus infection in chickens in Morocco. AN - 1784461526; 27106608 AB - A rapid, sensitive, and specific molecular method for the diagnosis of infectious bronchitis virus (IBV) infection is important in curbing infectious bronchitis outbreaks in Morocco and other countries. In this study, an easy-to-perform SYBR green I real-time reverse transcriptase polymerase chain reaction (RT-PCR) targeting the nucleocapsid gene of IBV was developed and compared with conventional agarose gel-based RT-PCR for the detection of IBV infection. We found that the SYBR green I real-time RT-PCR was at least 10 times more sensitive than the agarose gel electrophoresis detection method. The assay exhibited high specificity for IBV infection. All negative controls, such as Newcastle disease virus, infectious bursal disease virus, and avian influenza virus, were not detected. The SYBR green I real-time RT-PCR test described herein can be used to rapidly distinguish IBV from other respiratory pathogens, which is important for diagnosis and control of infectious bronchitis outbreaks in Morocco. The test is a valuable and useful method as a routine assay for diagnosis of clinical IBV infection in commercial chickens. JF - BMC research notes AU - Fellahi, Siham AU - El Harrak, Mehdi AU - Kuhn, Jens H AU - Sebbar, Ghizlane AU - Bouaiti, El Arbi AU - Khataby, Khadija AU - Fihri, Ouafae Fassi AU - El Houadfi, Mohammed AU - Ennaji, My Mustapha AD - Unit of Avian Pathology, Agronomic and Veterinary Institute Hassan II, B.P. 6202, Rabat, Morocco. ; Laboratory of Molecular Biology-Society of Biological Products and Veterinary Pharmaceuticals (Biopharma), B.P. 4569, Km 2, Route de Casa, Rabat, Morocco. ; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, B-8200 Research Plaza, Fort Detrick, Frederick, MD, 21702, USA. ; Laboratory of Epidemiology and Clinical Research. Faculty of Medicine, B.P. 1014, 4, Avenue Ibn Battouta, Rabat, Morocco. ; Laboratory of Virology, Microbiology and Quality/Ecotoxicology & Biodiversity, Faculty of Sciences and Techniques-University Hassan II Mohammedia, PO Box 146, Quartier Yasmina-Mohammedia, 20650, Casablanca, Morocco. ; Laboratory of Virology, Microbiology and Quality/Ecotoxicology & Biodiversity, Faculty of Sciences and Techniques-University Hassan II Mohammedia, PO Box 146, Quartier Yasmina-Mohammedia, 20650, Casablanca, Morocco. m.ennaji@yahoo.fr. Y1 - 2016/04/22/ PY - 2016 DA - 2016 Apr 22 SP - 231 VL - 9 KW - Nucleocapsid Proteins KW - 0 KW - Organic Chemicals KW - RNA, Viral KW - nucleocapsid protein, Coronavirus KW - SYBR Green I KW - 163795-75-3 KW - Index Medicus KW - Real time RT-PCR KW - Coronavirus KW - RT-PCR KW - Infectious bronchitis virus KW - Gammacoronavirus KW - IBV KW - SYBR green KW - Sensitivity and Specificity KW - Animals KW - Chickens KW - Reproducibility of Results KW - Morocco -- epidemiology KW - Disease Outbreaks -- prevention & control KW - Nucleocapsid Proteins -- genetics KW - RNA, Viral -- genetics KW - Electrophoresis, Agar Gel -- methods KW - Bird Diseases -- virology KW - Bird Diseases -- diagnosis KW - Coronavirus Infections -- virology KW - Coronavirus Infections -- diagnosis KW - Coronavirus Infections -- epidemiology KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Bird Diseases -- epidemiology KW - Infectious bronchitis virus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1784461526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+research+notes&rft.atitle=Comparison+of+SYBR+green+I+real-time+RT-PCR+with+conventional+agarose+gel-based+RT-PCR+for+the+diagnosis+of+infectious+bronchitis+virus+infection+in+chickens+in+Morocco.&rft.au=Fellahi%2C+Siham%3BEl+Harrak%2C+Mehdi%3BKuhn%2C+Jens+H%3BSebbar%2C+Ghizlane%3BBouaiti%2C+El+Arbi%3BKhataby%2C+Khadija%3BFihri%2C+Ouafae+Fassi%3BEl+Houadfi%2C+Mohammed%3BEnnaji%2C+My+Mustapha&rft.aulast=Fellahi&rft.aufirst=Siham&rft.date=2016-04-22&rft.volume=9&rft.issue=&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=BMC+research+notes&rft.issn=1756-0500&rft_id=info:doi/10.1186%2Fs13104-016-2037-z LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-20 N1 - Date created - 2016-04-23 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Immunol. 1981 Apr;126(4):1614-9 [7009746] Clin Microbiol Infect. 2004 Mar;10(3):190-212 [15008940] Avian Dis. 1992 Oct-Dec;36(4):903-15 [1336663] Avian Dis. 1993 Jan-Mar;37(1):194-202 [8095782] Vet Microbiol. 1993 Mar;34(3):249-57 [8384739] Avian Dis. 1997 Jan-Mar;41(1):105-10 [9087326] Adv Virus Res. 1997;48:1-100 [9233431] Avian Dis. 1998 Apr-Jun;42(2):275-84 [9645318] J Virol Methods. 2007 Jan;139(1):31-8 [17030068] J Virol Methods. 2006 Dec;138(1-2):60-5 [16934878] Adv Exp Med Biol. 2006;581:133-8 [17037519] Arch Virol. 2007 Jan;152(1):41-58 [16941059] Vet Res. 2007 Mar-Apr;38(2):281-97 [17296157] Avian Dis. 2007 Dec;51(4):974-8 [18251411] Microbiol Res. 2008;163(5):556-63 [16971101] J Virol Methods. 2010 Feb;163(2):190-4 [19781572] J Virol. 2010 Jun;84(11):5565-73 [20219929] Biosci Biotechnol Biochem. 2012;76(12):2255-60 [23221700] Mol Cell Probes. 2013 Oct-Dec;27(5-6):184-92 [23810983] Avian Dis. 2000 Apr-Jun;44(2):325-35 [10879913] J Clin Microbiol. 2002 Mar;40(3):1060-2 [11880439] Adv Exp Med Biol. 1990;276:369-72 [1966424] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13104-016-2037-z ER - TY - JOUR T1 - Status of hepatic DNA methylome predetermines and modulates the severity of non-alcoholic fatty liver injury in mice. AN - 1783914531; 27103143 AB - Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and Western countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD; nonetheless, the effect of inter-individual differences in the normal liver epigenome with regard to the susceptibility to NAFLD has not been determined. In the present study, we investigated the association between the DNA methylation status in the livers of A/J and WSB/EiJ mice and the severity of NAFLD-associated liver injury. We demonstrate that A/J and WSB/EiJ mice, which are characterized by significant differences in the severity of liver injury induced by a choline- and folate-deficient (CFD) diet exhibit substantial differences in cytosine DNA methylation in their normal livers. Furthermore, feeding A/J and WSB/EiJ mice a CFD diet for 12 weeks resulted in different trends and changes in hepatic cytosine DNA methylation. Our findings indicate a primary role of hepatic DNA methylation in the pathogenesis of NAFLD and suggest that individual variations in DNA methylation across the genome may be a factor determining and influencing the vulnerability to NAFLD. JF - BMC genomics AU - Tryndyak, Volodymyr P AU - Han, Tao AU - Fuscoe, James C AU - Ross, Sharon A AU - Beland, Frederick A AU - Pogribny, Igor P AD - Division of Biochemical Toxicology, National Center for Toxicological Research, FDA, 3900 NCTR Rd, Jefferson, AR, 72079, USA. ; Division of Systems Biology, National Center for Toxicological Research, FDA, Jefferson, AR, USA. ; Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. ; Division of Biochemical Toxicology, National Center for Toxicological Research, FDA, 3900 NCTR Rd, Jefferson, AR, 72079, USA. igor.pogribny@fda.hhs.gov. Y1 - 2016/04/22/ PY - 2016 DA - 2016 Apr 22 SP - 298 VL - 17 KW - Histones KW - 0 KW - Cytosine KW - 8J337D1HZY KW - Folic Acid KW - 935E97BOY8 KW - DNA (Cytosine-5-)-Methyltransferase KW - EC 2.1.1.37 KW - DNA (cytosine-5-)-methyltransferase 1 KW - DNA methyltransferase 3A KW - Choline KW - N91BDP6H0X KW - Index Medicus KW - Inter-strain differences KW - DNA methylation KW - Non-alcoholic fatty liver injury KW - Mouse KW - Susceptibility KW - Mice, Inbred Strains KW - Mice, Inbred A KW - Animals KW - Cytosine -- chemistry KW - Histones -- metabolism KW - CpG Islands KW - Mice KW - Diet KW - DNA (Cytosine-5-)-Methyltransferase -- metabolism KW - Non-alcoholic Fatty Liver Disease -- genetics KW - Liver -- physiopathology KW - DNA Methylation KW - Epigenesis, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1783914531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+genomics&rft.atitle=Status+of+hepatic+DNA+methylome+predetermines+and+modulates+the+severity+of+non-alcoholic+fatty+liver+injury+in+mice.&rft.au=Tryndyak%2C+Volodymyr+P%3BHan%2C+Tao%3BFuscoe%2C+James+C%3BRoss%2C+Sharon+A%3BBeland%2C+Frederick+A%3BPogribny%2C+Igor+P&rft.aulast=Tryndyak&rft.aufirst=Volodymyr&rft.date=2016-04-22&rft.volume=17&rft.issue=&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=BMC+genomics&rft.issn=1471-2164&rft_id=info:doi/10.1186%2Fs12864-016-2617-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-09 N1 - Date created - 2016-04-22 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cell Metab. 2013 Aug 6;18(2):296-302 [23931760] Gut. 2013 Sep;62(9):1356-63 [22879518] Liver Int. 2014 Feb;34(2):281-95 [23834235] Hepatology. 2014 Feb;59(2):471-82 [23913408] Arch Toxicol. 2014 Apr;88(4):967-82 [24469900] Int J Mol Sci. 2014;15(5):8591-638 [24830559] J Hum Genet. 2014 May;59(5):241-6 [24621583] Hepatology. 2015 Feb;61(2):515-25 [25302781] J Hepatol. 2015 May;62(5):1148-55 [25477264] Gastroenterology. 2015 May;148(5):1012-1023.e14 [25701738] J Hepatol. 2015 Apr;62(1 Suppl):S65-75 [25920092] PLoS One. 2015;10(5):e0127991 [26017539] Cell Metab. 2015 Jun 2;21(6):905-17 [26039453] JAMA. 2015 Jun 9;313(22):2263-73 [26057287] J Hepatol. 2015 Aug;63(2):494-502 [25776890] Sci Rep. 2015;5:12931 [26263022] Semin Liver Dis. 2015 Aug;35(3):270-90 [26378644] Clin Res Hepatol Gastroenterol. 2015 Sep;39 Suppl 1:S46-50 [26160474] J Dig Dis. 2015 Oct;16(10):541-57 [26406351] Hepatology. 2004 Dec;40(6):1266-74 [15562441] Nat Protoc. 2008;3(6):1101-8 [18546601] J Hepatol. 2009 Jul;51(1):176-86 [19450891] Methods Mol Biol. 2009;563:379-98 [19597796] Gastroenterology. 2010 Nov;139(5):1567-76, 1576.e1-6 [20708005] Gene. 2011 Mar 1;473(2):150-6 [21167261] Expert Rev Gastroenterol Hepatol. 2011 Apr;5(2):253-63 [21476920] Nature. 2011 May 5;473(7345):43-9 [21441907] Antioxid Redox Signal. 2011 Jul 15;15(2):535-50 [21126212] Science. 2011 Jun 24;332(6037):1519-23 [21700865] PLoS One. 2012;7(1):e30014 [22238690] Gastroenterol Hepatol. 2012 Jan;35(1):32-41 [22093607] J Mol Med (Berl). 2012 Feb;90(2):105-18 [21894552] J Hepatol. 2012 Jun;56(6):1384-91 [22326465] Toxicol Appl Pharmacol. 2012 Jul 1;262(1):52-9 [22561871] FASEB J. 2012 Nov;26(11):4592-602 [22872676] Biochim Biophys Acta. 2013 Apr;1831(4):803-18 [23318274] Gastroenterology. 2013 Nov;145(5):1076-87 [23916847] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s12864-016-2617-2 ER - TY - JOUR T1 - Disposition of the emerging brominated flame retardant, bis(2-ethylhexyl) tetrabromophthalate, in female Sprague Dawley rats: effects of dose, route and repeated administration. AN - 1826681472; 27098498 AB - 1. Bis(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP; CAS No. 26040-51-7; PubChem CID: 117291; MW 706.15 g/mol, elsewhere: TeBrDEPH, TBPH, or BEHTBP) is used as an additive brominated flame retardant in consumer products. 2. Female Sprague Dawley rats eliminated 92-98% of [14C]-BEH-TEBP unchanged in feces after oral administration (0.1 or 10 μmol/kg). A minor amount of each dose (0.8-1%) was found in urine after 72 h. Disposition of orally administered BEH-TEBP in male B6C3F1/Tac mice was similar to female rats. 3. Bioaccumulation of [14C]-radioactivity was observed in liver and adrenals following 10 daily oral administrations (0.1 μmol/kg/day). These tissues contained 5- and 10-fold higher concentrations of [14C]-radioactivity, respectively, versus a single dose. 4. IV-administered [14C]-BEH-TEBP (0.1 μmol/kg) was slowly eliminated in feces, with >15% retained in tissues after 72 h. Bile and fecal extracts from these rats contained the metabolite mono-ethylhexyl tetrabromophthalate (TBMEHP). 5. BEH-TEBP was poorly absorbed, minimally metabolized and eliminated mostly by the fecal route after oral administration. Repeated exposure to BEH-TEBP led to accumulation in some tissues. The toxicological significance of this effect remains to be determined. This work was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Project ZIA BC 011476). JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Knudsen, Gabriel A AU - Sanders, J Michael AU - Birnbaum, Linda S AD - a NCI Laboratory of Toxicology and Toxicokinetics , NC , USA. Y1 - 2016/04/21/ PY - 2016 DA - 2016 Apr 21 SP - 1 EP - 10 KW - brominated flame retardant KW - ADME KW - phthalate ester KW - persistent organic pollutant KW - bioaccumulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826681472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Disposition+of+the+emerging+brominated+flame+retardant%2C+bis%282-ethylhexyl%29+tetrabromophthalate%2C+in+female+Sprague+Dawley+rats%3A+effects+of+dose%2C+route+and+repeated+administration.&rft.au=Knudsen%2C+Gabriel+A%3BSanders%2C+J+Michael%3BBirnbaum%2C+Linda+S&rft.aulast=Knudsen&rft.aufirst=Gabriel&rft.date=2016-04-21&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=1366-5928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency AN - 1808707955; PQ0003314780 AB - X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain ([gamma]c) of several interleukin receptors. Gamma-retroviral ([gamma]RV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector [gamma]c transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1. JF - Science Translational Medicine AU - De Ravin, Suk See AU - Wu, Xiaolin AU - Moir, Susan AU - Kardava, Lela AU - Anaya-O'Brien, Sandra AU - Kwatemaa, Nana AU - Littel, Patricia AU - Theobald, Narda AU - Choi, Uimook AU - Su, Ling AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA, sderavin@niaid.nih.gov Y1 - 2016/04/20/ PY - 2016 DA - 2016 Apr 20 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 United States VL - 8 IS - 335 SN - 1946-6234, 1946-6234 KW - Immunology Abstracts; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Autografts KW - Translation KW - Data processing KW - Gene therapy KW - Lymphocytes B KW - X chromosome KW - Interleukins KW - Natural killer cells KW - Children KW - Immunization KW - Expression vectors KW - Stem cells KW - Busulfan KW - Lymphocytes T KW - Severe combined immunodeficiency KW - Immune response KW - Mutation KW - Infants KW - W 30905:Medical Applications KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808707955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+Translational+Medicine&rft.atitle=Lentiviral+hematopoietic+stem+cell+gene+therapy+for+X-linked+severe+combined+immunodeficiency&rft.au=De+Ravin%2C+Suk+See%3BWu%2C+Xiaolin%3BMoir%2C+Susan%3BKardava%2C+Lela%3BAnaya-O%27Brien%2C+Sandra%3BKwatemaa%2C+Nana%3BLittel%2C+Patricia%3BTheobald%2C+Narda%3BChoi%2C+Uimook%3BSu%2C+Ling&rft.aulast=De+Ravin&rft.aufirst=Suk&rft.date=2016-04-20&rft.volume=8&rft.issue=335&rft.spage=335ra57&rft.isbn=&rft.btitle=&rft.title=Science+Translational+Medicine&rft.issn=19466234&rft_id=info:doi/10.1126%2Fscitranslmed.aad8856 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-10-26 N1 - SubjectsTermNotLitGenreText - Autografts; Translation; Data processing; Gene therapy; Lymphocytes B; X chromosome; Natural killer cells; Interleukins; Children; Immunization; Expression vectors; Stem cells; Busulfan; Lymphocytes T; Severe combined immunodeficiency; Immune response; Mutation; Infants DO - http://dx.doi.org/10.1126/scitranslmed.aad8856 ER - TY - JOUR T1 - Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials. AN - 1781539247; 26926682 AB - The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Lee, Shing M AU - Backenroth, Daniel AU - Cheung, Ying Kuen Ken AU - Hershman, Dawn L AU - Vulih, Diana AU - Anderson, Barry AU - Ivy, Percy AU - Minasian, Lori AD - Shing M. Lee, Daniel Backenroth, Ying Kuen Ken Cheung, and Dawn L. Hershman, Columbia University, New York, NY; Diana Vulih and Barry Anderson, Theradex Systems, Princeton, NJ; and Percy Ivy and Lori Minasian, National Cancer Institute, Bethesda, MD. sml2114@columbia.edu. ; Shing M. Lee, Daniel Backenroth, Ying Kuen Ken Cheung, and Dawn L. Hershman, Columbia University, New York, NY; Diana Vulih and Barry Anderson, Theradex Systems, Princeton, NJ; and Percy Ivy and Lori Minasian, National Cancer Institute, Bethesda, MD. Y1 - 2016/04/20/ PY - 2016 DA - 2016 Apr 20 SP - 1395 EP - 1401 VL - 34 IS - 12 KW - Antineoplastic Agents KW - 0 KW - Proteasome Inhibitors KW - Bortezomib KW - 69G8BD63PP KW - Index Medicus KW - Kaplan-Meier Estimate KW - Disease-Free Survival KW - Humans KW - Treatment Outcome KW - Retrospective Studies KW - Molecular Targeted Therapy KW - Maximum Tolerated Dose KW - Time Factors KW - Proportional Hazards Models KW - Bortezomib -- adverse effects KW - Neoplasms -- drug therapy KW - Bortezomib -- administration & dosage KW - Neoplasms -- pathology KW - Neoplasms -- enzymology KW - Antineoplastic Agents -- administration & dosage KW - Proteasome Inhibitors -- administration & dosage KW - Drug Dosage Calculations KW - Research Design KW - Proteasome Inhibitors -- adverse effects KW - Clinical Trials as Topic -- methods KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1781539247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Case+Example+of+Dose+Optimization+Using+Data+From+Bortezomib+Dose-Finding+Clinical+Trials.&rft.au=Lee%2C+Shing+M%3BBackenroth%2C+Daniel%3BCheung%2C+Ying+Kuen+Ken%3BHershman%2C+Dawn+L%3BVulih%2C+Diana%3BAnderson%2C+Barry%3BIvy%2C+Percy%3BMinasian%2C+Lori&rft.aulast=Lee&rft.aufirst=Shing&rft.date=2016-04-20&rft.volume=34&rft.issue=12&rft.spage=1395&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/10.1200%2FJCO.2015.66.0662 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-06 N1 - Date created - 2016-04-14 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1200/JCO.2015.66.0662 ER - TY - JOUR T1 - Use of Existing Diagnostic Reverse-Transcription Polymerase Chain Reaction Assays for Detection of Ebola Virus RNA in Semen AN - 1794503934; PQ0003139855 AB - Sexual transmission of Ebola virus in Liberia has now been documented and associated with new clusters in regions previously declared Ebola free. Assays that have Emergency Use Authorization (EUA) and are routinely used to detect Ebola virus RNA in whole blood and plasma specimens at the Liberian Institute for Biomedical Research were tested for their suitability in detecting the presence of Ebola virus RNA in semen. Qiagen AVL extraction protocols, as well as the Ebola Zaire Target 1 and major groove binder quantitative reverse-transcription polymerase chain reaction assays, were demonstrably suitable for this purpose and should facilitate epidemiologic investigations, including those involving long-term survivors of Ebola. JF - Journal of Infectious Diseases AU - Pettitt, James AU - Higgs, Elizabeth S AU - Adams, Rick D AU - Jahrling, Peter B AU - Hensley, Lisa E AD - Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, jahrlingp@niaid.nih.gov Y1 - 2016/04/15/ PY - 2016 DA - 2016 Apr 15 SP - 1237 EP - 1239 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 8 SN - 0022-1899, 0022-1899 KW - Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - Ebola KW - PCR KW - semen KW - diagnosis KW - Viruses KW - Assays KW - Ebola virus KW - RNA viruses KW - Disease transmission KW - Liberia KW - Blood KW - ASE, Angola, Zaire KW - Infectious diseases KW - RNA KW - Semen KW - Polymerase chain reaction KW - V 22300:Methods KW - N 14830:RNA KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794503934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Use+of+Existing+Diagnostic+Reverse-Transcription+Polymerase+Chain+Reaction+Assays+for+Detection+of+Ebola+Virus+RNA+in+Semen&rft.au=Pettitt%2C+James%3BHiggs%2C+Elizabeth+S%3BAdams%2C+Rick+D%3BJahrling%2C+Peter+B%3BHensley%2C+Lisa+E&rft.aulast=Pettitt&rft.aufirst=James&rft.date=2016-04-15&rft.volume=213&rft.issue=8&rft.spage=1237&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiv454 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-06-01 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Blood; RNA; Polymerase chain reaction; Semen; RNA viruses; Disease transmission; Infectious diseases; Viruses; Assays; Ebola virus; Liberia; ASE, Angola, Zaire DO - http://dx.doi.org/10.1093/infdis/jiv454 ER - TY - JOUR T1 - rcellminer: exploring molecular profiles and drug response of the NCI-60 cell lines in R. AN - 1787472282; 26635141 AB - The rcellminer R package provides a wide range of functionality to help R users access and explore molecular profiling and drug response data for the NCI-60. The package enables flexible programmatic access to CellMiner's unparalleled breadth of NCI-60 data, including gene and protein expression, copy number, whole exome mutations, as well as activity data for ∼21K compounds, with information on their structure, mechanism of action and repeat screens. Functions are available to easily visualize compound structures, activity patterns and molecular feature profiles. Additionally, embedded R Shiny applications allow interactive data exploration. rcellminer is compatible with R 3.2 and above on Windows, Mac OS X and Linux. The package, documentation, tutorials and Shiny-based applications are available through Bioconductor (http://www.bioconductor.org/packages/rcellminer); ongoing updates will occur according to the Bioconductor release schedule with new CellMiner data. The package is free and open-source (LGPL 3). lunaa@cbio.mskcc.org or vinodh.rajapakse@nih.gov. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US. JF - Bioinformatics (Oxford, England) AU - Luna, Augustin AU - Rajapakse, Vinodh N AU - Sousa, Fabricio G AU - Gao, Jianjiong AU - Schultz, Nikolaus AU - Varma, Sudhir AU - Reinhold, William AU - Sander, Chris AU - Pommier, Yves AD - Computer Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. ; Developmental Therapeutic Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. ; Centro De Estudos Em Células Tronco, Terapia Celular E Genética Toxicológica, Programa De Pós-Graduação Em Farmácia, Universidade Federal De Mato Grosso Do Sul, Campo Grande, MS 79070-900, Brazil and. ; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. Y1 - 2016/04/15/ PY - 2016 DA - 2016 Apr 15 SP - 1272 EP - 1274 VL - 32 IS - 8 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787472282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics+%28Oxford%2C+England%29&rft.atitle=rcellminer%3A+exploring+molecular+profiles+and+drug+response+of+the+NCI-60+cell+lines+in+R.&rft.au=Luna%2C+Augustin%3BRajapakse%2C+Vinodh+N%3BSousa%2C+Fabricio+G%3BGao%2C+Jianjiong%3BSchultz%2C+Nikolaus%3BVarma%2C+Sudhir%3BReinhold%2C+William%3BSander%2C+Chris%3BPommier%2C+Yves&rft.aulast=Luna&rft.aufirst=Augustin&rft.date=2016-04-15&rft.volume=32&rft.issue=8&rft.spage=1272&rft.isbn=&rft.btitle=&rft.title=Bioinformatics+%28Oxford%2C+England%29&rft.issn=1367-4811&rft_id=info:doi/10.1093%2Fbioinformatics%2Fbtv701 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/bioinformatics/btv701 ER - TY - JOUR T1 - Beyond the dose-limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials of the Cancer Therapeutics Evaluation Program. AN - 1780511925; 26916138 AB - Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date. Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)-sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug-related dermatologic AEs were described and compared. The timing of worst drug-related dermatologic AEs was summarized. In total, 3517 patients with solid tumors and 6165 unique, drug-related dermatologic AEs were analyzed, including 1545 patients on MTA-only trials, 671 on cytotoxic-only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug-related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug-related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug-related AEs was highest in patients who received MTA-only therapy (P < .001) and differed by dose level (P < .001). In patients who received MTA-only therapy, drug-related AEs were most common for combination kinase inhibitor-containing therapy (P < .001). A substantial proportion of drug-related dermatologic AEs occur after the traditional dose-limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities. © 2016 American Cancer Society. JF - Cancer AU - Drilon, Alexander AU - Eaton, Anne A AU - Schindler, Katja AU - Gounder, Mrinal M AU - Spriggs, David R AU - Harris, Pamela AU - Ivy, S Percy AU - Iasonos, Alexia AU - Lacouture, Mario E AU - Hyman, David M AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. ; Dermatology Department, Medical University of Vienna, Vienna, Austria. ; Cancer Therapeutics and Evaluation Program, National Cancer Institute, Bethesda, Maryland. Y1 - 2016/04/15/ PY - 2016 DA - 2016 Apr 15 SP - 1228 EP - 1237 VL - 122 IS - 8 KW - Antineoplastic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - dermatologic toxicity KW - molecularly targeted agents KW - phase 1 trial KW - dose-limiting toxicity (DLT) period KW - Cancer Therapeutics Evaluation Program (CTEP) KW - Severity of Illness Index KW - Survival Rate KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials, Phase I as Topic KW - Retrospective Studies KW - Databases, Factual KW - Incidence KW - Follow-Up Studies KW - Maximum Tolerated Dose KW - Male KW - Female KW - Risk Assessment KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Drug Eruptions -- etiology KW - Drug Eruptions -- physiopathology KW - Antineoplastic Agents -- therapeutic use KW - Drug Eruptions -- epidemiology KW - Molecular Targeted Therapy -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780511925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Beyond+the+dose-limiting+toxicity+period%3A+Dermatologic+adverse+events+of+patients+on+phase+1+trials+of+the+Cancer+Therapeutics+Evaluation+Program.&rft.au=Drilon%2C+Alexander%3BEaton%2C+Anne+A%3BSchindler%2C+Katja%3BGounder%2C+Mrinal+M%3BSpriggs%2C+David+R%3BHarris%2C+Pamela%3BIvy%2C+S+Percy%3BIasonos%2C+Alexia%3BLacouture%2C+Mario+E%3BHyman%2C+David+M&rft.aulast=Drilon&rft.aufirst=Alexander&rft.date=2016-04-15&rft.volume=122&rft.issue=8&rft.spage=1228&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=1097-0142&rft_id=info:doi/10.1002%2Fcncr.29918 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-22 N1 - Date created - 2016-04-11 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cncr.29918 ER - TY - JOUR T1 - Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress. AN - 1778707517; 26883165 AB - Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities. Published by Elsevier B.V. JF - Brain research AU - Akbar, Mohammed AU - Essa, Musthafa Mohamed AU - Daradkeh, Ghazi AU - Abdelmegeed, Mohamed A AU - Choi, Youngshim AU - Mahmood, Lubna AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. ; Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman; Ageing and Dementia Research Group, Sultan Qaboos University, Oman. ; Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman. ; Department of Nutritional Sciences, Qatar University, Qatar. Y1 - 2016/04/15/ PY - 2016 DA - 2016 Apr 15 SP - 34 EP - 55 VL - 1637 KW - Antioxidants KW - 0 KW - DNA, Mitochondrial KW - Mitochondrial Proteins KW - Reactive Oxygen Species KW - Glutamic Acid KW - 3KX376GY7L KW - Index Medicus KW - Neuronal cell death KW - Neurodegenerative diseases KW - Oxidative stress KW - Post-translational protein modifications KW - Translational research KW - Mitochondrial dysfunction KW - Oxidation-Reduction KW - Reactive Oxygen Species -- metabolism KW - Antioxidants -- metabolism KW - Age Factors KW - Glutamic Acid -- metabolism KW - Humans KW - Apoptosis -- physiology KW - DNA, Mitochondrial -- metabolism KW - Mitochondrial Proteins -- metabolism KW - Lipid Metabolism KW - Oxidative Stress -- physiology KW - Neurodegenerative Diseases -- metabolism KW - Neurodegenerative Diseases -- pathology KW - Mitochondria -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1778707517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Mitochondrial+dysfunction+and+cell+death+in+neurodegenerative+diseases+through+nitroxidative+stress.&rft.au=Akbar%2C+Mohammed%3BEssa%2C+Musthafa+Mohamed%3BDaradkeh%2C+Ghazi%3BAbdelmegeed%2C+Mohamed+A%3BChoi%2C+Youngshim%3BMahmood%2C+Lubna%3BSong%2C+Byoung-Joon&rft.aulast=Akbar&rft.aufirst=Mohammed&rft.date=2016-04-15&rft.volume=1637&rft.issue=&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=1872-6240&rft_id=info:doi/10.1016%2Fj.brainres.2016.02.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-24 N1 - Date created - 2016-04-04 N1 - Date revised - 2017-01-26 N1 - SuppNotes - Cited By: J Alzheimers Dis. 2010;20(2):369-93 [20164570] Methods Enzymol. 2010;473:251-64 [20513482] J Alzheimers Dis. 2010;20 Suppl 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[19342591] Nat Med. 1999 Dec;5(12):1403-9 [10581083] J Biol Chem. 2000 Jan 7;275(1):322-7 [10617621] Alzheimer Dis Assoc Disord. 2000;14 Suppl 1:S47-53 [10850730] J Neurochem. 2001 May;77(3):849-63 [11331414] Sci STKE. 2000 Oct 10;2000(53):pe1 [11752613] Biochem Pharmacol. 2002 Sep;64(5-6):781-8 [12213570] Nature. 2002 Oct 31;419(6910):939-44 [12410314] J Neurochem. 2002 Nov;83(4):992-1001 [12421372] J Clin Invest. 2003 Mar;111(6):785-93 [12639981] N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1016/j.brainres.2016.02.016 ER - TY - JOUR T1 - Temporal-spatially transformed synthesis and formation mechanism of gold bellflowers. AN - 1777982754; 26525291 AB - Anisotropic gold nanostructures with unique plasmonic properties, specifically the strong absorption of light in the near-infrared region (650-900 nm) due to the excitation of plasmon oscillations, have been widely employed as photothermal conversion agents (PTCAs) for cancer photothermal therapy (PTT). However, the reported PTCAs show suboptimal photothermal conversion efficiency (η), even gold nanocages (η = 63%), which limits their biomedical applications. Herein, we fabricated gold bellflowers (GBFs) with an ultrahigh photothermal conversion efficiency (η = 74%) via a novel liquid/liquid/gas triphasic interface system, using chloroauric acid as a gold source, and o-phenetidine as a reducing agent. The well-defined GBFs with multiple-branched petals show adjustable localized surface plasmon resonance (LSPR) from 760 to 1100 nm by tuning the petal length and circular bottom diameter. Originating from the monophasic and biphasic systems used in the creation of gold nanourchins (GNUs) and gold microspheres (GMPs) respectively, the triphasic interface system successfully produced GBFs. The possible formation mechanisms of GNUs, GMPs, and GBFs in the different systems were also investigated and discussed. We found that the formation mechanism of GNUs and GBFs followed classical crystallization, while the formation of GMPs followed non-classical crystallization. JF - Nanoscale AU - Lin, Jing AU - Zhang, Molly G AU - Tang, Yuxia AU - Wen, Bronte AU - Hu, Hao AU - Song, Jibing AU - Liu, Yijing AU - Huang, Peng AU - Chen, Xiaoyuan AD - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen 518060, China. peng.huang@nih.gov and Laboratory of Cellular Imaging and Macromolecular Biophysics (LCIMB), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA. ; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA. shawn.chen@nih.gov. ; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen 518060, China. peng.huang@nih.gov and Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA. shawn.chen@nih.gov. Y1 - 2016/04/14/ PY - 2016 DA - 2016 Apr 14 SP - 7430 EP - 7434 VL - 8 IS - 14 KW - Index Medicus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777982754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nanoscale&rft.atitle=Temporal-spatially+transformed+synthesis+and+formation+mechanism+of+gold+bellflowers.&rft.au=Lin%2C+Jing%3BZhang%2C+Molly+G%3BTang%2C+Yuxia%3BWen%2C+Bronte%3BHu%2C+Hao%3BSong%2C+Jibing%3BLiu%2C+Yijing%3BHuang%2C+Peng%3BChen%2C+Xiaoyuan&rft.aulast=Lin&rft.aufirst=Jing&rft.date=2016-04-14&rft.volume=8&rft.issue=14&rft.spage=7430&rft.isbn=&rft.btitle=&rft.title=Nanoscale&rft.issn=2040-3372&rft_id=info:doi/10.1039%2Fc5nr04430h LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-03-31 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nat Mater. 2009 Aug;8(8):683-9 [19597500] Biomaterials. 2011 Dec;32(36):9796-809 [21917309] J Am Chem Soc. 2011 Jun 8;133(22):8506-9 [21563806] Nat Mater. 2011 Apr;10(4):324-32 [21423187] Adv Drug Deliv Rev. 2010 Aug 30;62(11):1052-63 [20709124] Chem Commun (Camb). 2010 Jul 14;46(26):4800-2 [20502783] Phys Chem Chem Phys. 2006 Jul 28;8(28):3271-87 [16835675] Lasers Med Sci. 2008 Jul;23(3):217-28 [17674122] Angew Chem Int Ed Engl. 2009;48(1):60-103 [19053095] Bioconjug Chem. 2011 Oct 19;22(10):1879-903 [21830812] Chem Soc Rev. 2012 Mar 21;41(6):2256-82 [22130549] Angew Chem Int Ed Engl. 2013 Apr 8;52(15):4169-73 [23494970] J Am Chem Soc. 2014 Jun 11;136(23):8307-13 [24842342] Mol Pharm. 2010 Feb 1;7(1):94-104 [19891496] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1039/c5nr04430h ER - TY - JOUR T1 - Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2. AN - 1795866410; 26993806 AB - The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hodson, Daniel J AU - Shaffer, Arthur L AU - Xiao, Wenming AU - Wright, George W AU - Schmitz, Roland AU - Phelan, James D AU - Yang, Yandan AU - Webster, Daniel E AU - Rui, Lixin AU - Kohlhammer, Holger AU - Nakagawa, Masao AU - Waldmann, Thomas A AU - Staudt, Louis M AD - Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Department of Haematology, University of Cambridge, Cambridge, CB2 0AH, United Kingdom. ; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; ; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; lstaudt@mail.nih.gov. Y1 - 2016/04/05/ PY - 2016 DA - 2016 Apr 05 SP - E2039 EP - E2046 VL - 113 IS - 14 KW - Organic Cation Transport Proteins KW - 0 KW - Slc22a2 protein, mouse KW - Index Medicus KW - cancer biology KW - germinal center KW - lymphoma KW - Animals KW - Mice KW - Cell Line, Tumor KW - Mice, Knockout KW - Organic Cation Transport Proteins -- physiology KW - B-Lymphocytes -- cytology KW - Lymphoma, Large B-Cell, Diffuse -- pathology KW - Cell Differentiation KW - Organic Cation Transport Proteins -- genetics KW - Cell Survival UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1795866410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Regulation+of+normal+B-cell+differentiation+and+malignant+B-cell+survival+by+OCT2.&rft.au=Hodson%2C+Daniel+J%3BShaffer%2C+Arthur+L%3BXiao%2C+Wenming%3BWright%2C+George+W%3BSchmitz%2C+Roland%3BPhelan%2C+James+D%3BYang%2C+Yandan%3BWebster%2C+Daniel+E%3BRui%2C+Lixin%3BKohlhammer%2C+Holger%3BNakagawa%2C+Masao%3BWaldmann%2C+Thomas+A%3BStaudt%2C+Louis+M&rft.aulast=Hodson&rft.aufirst=Daniel&rft.date=2016-04-05&rft.volume=113&rft.issue=14&rft.spage=E2039&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=1091-6490&rft_id=info:doi/10.1073%2Fpnas.1600557113 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-06-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1073/pnas.1600557113 ER - TY - JOUR T1 - Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety AN - 1811890306; PQ0003207743 AB - Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed-some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds. JF - Substance Abuse AU - Litten, Raye Z AU - Wilford, Bonnie B AU - Falk, Daniel E AU - Ryan, Megan L AU - Fertig, Joanne B AD - NIAAA's Clinical Investigations Group (NCIG), Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA Y1 - 2016/04/02/ PY - 2016 DA - 2016 Apr 02 SP - 286 EP - 298 PB - Taylor & Francis Group Ltd., 2 Park Square Oxford OX14 4RN United Kingdom VL - 37 IS - 2 SN - 0889-7077, 0889-7077 KW - Physical Education Index KW - Evaluation KW - Alcohol KW - Genetics KW - Food and Drug Administration KW - Collaboration KW - Medications KW - Medicine KW - Abuse KW - Self efficacy KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811890306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+Abuse&rft.atitle=Potential+medications+for+the+treatment+of+alcohol+use+disorder%3A+An+evaluation+of+clinical+efficacy+and+safety&rft.au=Litten%2C+Raye+Z%3BWilford%2C+Bonnie+B%3BFalk%2C+Daniel+E%3BRyan%2C+Megan+L%3BFertig%2C+Joanne+B&rft.aulast=Litten&rft.aufirst=Raye&rft.date=2016-04-02&rft.volume=37&rft.issue=2&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Substance+Abuse&rft.issn=08897077&rft_id=info:doi/10.1080%2F08897077.2015.1133472 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Evaluation; Genetics; Alcohol; Collaboration; Food and Drug Administration; Medications; Medicine; Abuse; Self efficacy DO - http://dx.doi.org/10.1080/08897077.2015.1133472 ER - TY - JOUR T1 - Tackling Noncommunicable Diseases in Africa: Caveat Lector AN - 1811898790; PQ0002906699 AB - Noncommunicable disease (NCD), principally cardiovascular diseases, cancer, chronic lung disease, and diabetes, constitutes the major cause of death worldwide. Evidence of a continuing increase in the global burden of these diseases has generated recent urgent calls for global action to tackle and reduce related death and disability. Because the majority of NCD deaths occur in low- and middle-income countries, increased attention has been focused on this group of countries. However, in sub-Saharan Africa, where all countries are members of the low- and middle-income grouping, NCDs are not the leading causes of death or potential life years lost. Thus, strategies to tackle NCDs in sub-Saharan Africa are best conceived and executed in alignment with existing strategies for the prevention, treatment, and control of the actual leading causes of death in this region. This commentary addresses caveats to be considered as strategies are developed to tackle NCDs in sub-Saharan Africa as part of the global effort to prevent, treat, and control NCDs. JF - Health Education & Behavior AU - Airhihenbuwa, Collins O AU - Ogedegbe, Gbenga AU - Mensah, George A Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 7S EP - 13S PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 43 IS - 1_suppl SN - 1090-1981, 1090-1981 KW - Physical Education Index KW - Africa KW - chronic diseases KW - demographic changes KW - noncommunicable diseases KW - risk factors KW - urbanization KW - Handicapped KW - Death KW - Preventive health KW - Strategy KW - Health (behavior) KW - Chronic diseases KW - Cardiorespiratory KW - Diabetes KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1811898790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Education+%26+Behavior&rft.atitle=Tackling+Noncommunicable+Diseases+in+Africa%3A+Caveat+Lector&rft.au=Airhihenbuwa%2C+Collins+O%3BOgedegbe%2C+Gbenga%3BMensah%2C+George+A&rft.aulast=Airhihenbuwa&rft.aufirst=Collins&rft.date=2016-04-01&rft.volume=43&rft.issue=1_suppl&rft.spage=7S&rft.isbn=&rft.btitle=&rft.title=Health+Education+%26+Behavior&rft.issn=10901981&rft_id=info:doi/10.1177%2F1090198116633454 LA - English DB - Physical Education Index N1 - Date revised - 2016-08-01 N1 - Number of references - 35 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Handicapped; Death; Preventive health; Strategy; Health (behavior); Cardiorespiratory; Chronic diseases; Diabetes DO - http://dx.doi.org/10.1177/1090198116633454 ER - TY - JOUR T1 - Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: a re-analysis of case-control studies using bi-dimensional spline models AN - 1808739656; PQ0003205179 AB - The synergistic effect of tobacco smoking and alcohol consumption on the risk of head and neck cancers has been mainly investigated as a cross-product of categorical exposure, thus leading to loss of information. We propose a bi-dimensional logistic spline model to investigate the interacting dose-response relationship of two continuous exposures (i.e., ethanol intake and tobacco smoking) on the risk of head and neck cancers, representing results through three-dimensional graphs. This model was applied to a pool of hospital-based case-control studies on head and neck cancers conducted in Italy and in the Vaud Swiss Canton between 1982 and 2000, including 1569 cases and 3147 controls. Among never drinkers and for all levels of ethanol intake, the risk of head and neck cancers steeply increased with increasing smoking intensity, starting from 1 cigarette/day. The risk associated to ethanol intake increased with incrementing exposure among smokers, and a threshold effect at approximately 50 g/day emerged among never smokers. Compared to abstainers from both tobacco and alcohol consumption, the combined exposure to ethanol and/or cigarettes led to a steep increase of cancer risk up to a 35-fold higher risk (95 % confidence interval 27.30-43.61) among people consuming 84 g/day of ethanol and 10 cigarettes/day. The highest risk was observed at the highest levels of alcohol and tobacco consumption. Our findings confirmed a combined effect of tobacco smoking and alcohol drinking on head and neck cancers risk, providing evidence that bi-dimensional spline models could be a feasible and flexible method to explore the pattern of risks associated to two interacting continuous-exposure variables. JF - European Journal of Epidemiology AU - Dal Maso, Luigino AU - Torelli, Nicola AU - Biancotto, Elisa AU - Di Maso, Matteo AU - Gini, Andrea AU - Franchin, Gianni AU - Levi, Fabio AU - La Vecchia, Carlo AU - Serraino, Diego AU - Polesel, Jerry AD - Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy, polesel@cro.it Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 385 EP - 393 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 31 IS - 4 SN - 0393-2990, 0393-2990 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - MED, Italy KW - Alcohol KW - Tobacco smoking KW - Synergistic effects KW - Cigarettes KW - Cancer KW - Models KW - Health risks KW - Risk factors KW - Dose-response effects KW - Cigarette smoking KW - Tobacco KW - Head and neck cancer KW - Drinking behavior KW - Ethanol KW - X 24380:Social Poisons & Drug Abuse KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808739656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Epidemiology&rft.atitle=Combined+effect+of+tobacco+smoking+and+alcohol+drinking+in+the+risk+of+head+and+neck+cancers%3A+a+re-analysis+of+case-control+studies+using+bi-dimensional+spline+models&rft.au=Dal+Maso%2C+Luigino%3BTorelli%2C+Nicola%3BBiancotto%2C+Elisa%3BDi+Maso%2C+Matteo%3BGini%2C+Andrea%3BFranchin%2C+Gianni%3BLevi%2C+Fabio%3BLa+Vecchia%2C+Carlo%3BSerraino%2C+Diego%3BPolesel%2C+Jerry&rft.aulast=Dal+Maso&rft.aufirst=Luigino&rft.date=2016-04-01&rft.volume=31&rft.issue=4&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Epidemiology&rft.issn=03932990&rft_id=info:doi/10.1007%2Fs10654-015-0028-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 22 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Tobacco smoking; Cigarettes; Dose-response effects; Risk factors; Drinking behavior; Head and neck cancer; Cancer; Models; Ethanol; Alcohol; Health risks; Synergistic effects; Cigarette smoking; Tobacco; MED, Italy DO - http://dx.doi.org/10.1007/s10654-015-0028-3 ER - TY - JOUR T1 - Modeling Smith-Lemli-Opitz syndrome with induced pluripotent stem cells reveals a causal role for Wnt/ beta -catenin defects in neuronal cholesterol synthesis phenotypes AN - 1805512146; PQ0002901525 AB - Smith-Lemli-Opitz syndrome (SLOS) is a malformation disorder caused by mutations in DHCR7, which impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. SLOS results in cognitive impairment, behavioral abnormalities and nervous system defects, though neither affected cell types nor impaired signaling pathways are fully understood. Whether 7DHC accumulation or cholesterol loss is primarily responsible for disease pathogenesis is also unclear. Using induced pluripotent stem cells (iPSCs) from subjects with SLOS, we identified cellular defects that lead to precocious neuronal specification within SLOS derived neural progenitors. We also demonstrated that 7DHC accumulation, not cholesterol deficiency, is critical for SLOS-associated defects. We further identified downregulation of Wnt/ beta -catenin signaling as a key initiator of aberrant SLOS iPSC differentiation through the direct inhibitory effects of 7DHC on the formation of an active Wnt receptor complex. Activation of canonical Wnt signaling prevented the neural phenotypes observed in SLOS iPSCs, suggesting that Wnt signaling may be a promising therapeutic target for SLOS. JF - Nature Medicine AU - Francis, Kevin R AU - Ton, Amy N AU - Xin, Yao AU - O'Halloran, Peter E AU - Wassif, Christopher A AU - Malik, Nasir AU - Williams, Ian M AU - Cluzeau, Celine V AU - Trivedi, Niraj S AU - Pavan, William J AU - Cho, Wonhwa AU - Westphal, Heiner AU - Porter, Forbes D AD - Program in Genomics of Differentiation, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA.; Program in Developmental Endocrinology and Genetics, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 388 EP - 396 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 22 IS - 4 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Wnt protein KW - Inhibitory postsynaptic potentials KW - Cholesterol KW - 7-Dehydrocholesterol reductase KW - Differentiation KW - Nervous system KW - Stem cells KW - catenin KW - Cognitive ability KW - Congenital defects KW - Mutation KW - Neural stem cells KW - Signal transduction KW - W 30965:Miscellaneous, Reviews KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1805512146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Modeling+Smith-Lemli-Opitz+syndrome+with+induced+pluripotent+stem+cells+reveals+a+causal+role+for+Wnt%2F+beta+-catenin+defects+in+neuronal+cholesterol+synthesis+phenotypes&rft.au=Francis%2C+Kevin+R%3BTon%2C+Amy+N%3BXin%2C+Yao%3BO%27Halloran%2C+Peter+E%3BWassif%2C+Christopher+A%3BMalik%2C+Nasir%3BWilliams%2C+Ian+M%3BCluzeau%2C+Celine+V%3BTrivedi%2C+Niraj+S%3BPavan%2C+William+J%3BCho%2C+Wonhwa%3BWestphal%2C+Heiner%3BPorter%2C+Forbes+D&rft.aulast=Francis&rft.aufirst=Kevin&rft.date=2016-04-01&rft.volume=22&rft.issue=4&rft.spage=388&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2Fnm.4067 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Wnt protein; Inhibitory postsynaptic potentials; Cholesterol; 7-Dehydrocholesterol reductase; Differentiation; Stem cells; Nervous system; catenin; Cognitive ability; Congenital defects; Neural stem cells; Mutation; Signal transduction DO - http://dx.doi.org/10.1038/nm.4067 ER - TY - JOUR T1 - Mathematical Modeling of Extinction of Inhomogeneous Populations AN - 1802200898; PQ0003085732 AB - Mathematical models of population extinction have a variety of applications in such areas as ecology, paleontology and conservation biology. Here we propose and investigate two types of sub-exponential models of population extinction. Unlike the more traditional exponential models, the life duration of sub-exponential models is finite. In the first model, the population is assumed to be composed of clones that are independent from each other. In the second model, we assume that the size of the population as a whole decreases according to the sub-exponential equation. We then investigate the "unobserved heterogeneity," i.e., the underlying inhomogeneous population model, and calculate the distribution of frequencies of clones for both models. We show that the dynamics of frequencies in the first model is governed by the principle of minimum of Tsallis information loss. In the second model, the notion of "internal population time" is proposed; with respect to the internal time, the dynamics of frequencies is governed by the principle of minimum of Shannon information loss. The results of this analysis show that the principle of minimum of information loss is the underlying law for the evolution of a broad class of models of population extinction. Finally, we propose a possible application of this modeling framework to mechanisms underlying time perception. JF - Bulletin of Mathematical Biology AU - Karev, G P AU - Kareva, I AD - National Center for Biotechnology Information, National Institutes of Health - Bldg. 38A, 8600 Rockville Pike, Bethesda, MD, 20894, USA, karev@ncbi.nlm.nih.gov Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 834 EP - 858 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 78 IS - 4 SN - 0092-8240, 0092-8240 KW - Ecology Abstracts KW - Mathematical models KW - Extinction KW - Temporal perception KW - Conservation KW - Paleontology KW - Evolution KW - D 04030:Models, Methods, Remote Sensing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1802200898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bulletin+of+Mathematical+Biology&rft.atitle=Mathematical+Modeling+of+Extinction+of+Inhomogeneous+Populations&rft.au=Karev%2C+G+P%3BKareva%2C+I&rft.aulast=Karev&rft.aufirst=G&rft.date=2016-04-01&rft.volume=78&rft.issue=4&rft.spage=834&rft.isbn=&rft.btitle=&rft.title=Bulletin+of+Mathematical+Biology&rft.issn=00928240&rft_id=info:doi/10.1007%2Fs11538-016-0166-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Number of references - 42 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Mathematical models; Extinction; Temporal perception; Conservation; Paleontology; Evolution DO - http://dx.doi.org/10.1007/s11538-016-0166-0 ER - TY - JOUR T1 - Combined Couples' Therapy: A Qualitative Study of Individual and Conjoint Sessions AN - 1788991960 AB - Combined couples' therapy is an integrative format of couple therapy where the therapist combines the use of individual and conjoint sessions in therapy. However, little is known about the processes that occur in this type of therapy. In this study, a qualitative analysis of written records was undertaken to identify certain characteristics of combined couples' therapy themes and goals. There were 15 cases identified for inclusion in this study. The majority of the clients were young educated couples in their first family life cycle stage, from middle to upper socioeconomic status, having dual careers. Results show that while dyadic/systemic issues are discussed in individual and conjoint sessions, the sessions differ in goals addressed. Moreover, certain themes like self-in-marriage concerns, unresolved past conflicts, violence, and resistance for conjoint sessions are addressed exclusively in individual sessions. The findings have implications for individual and conjoint sessions in couples' therapy. JF - Journal of Family Psychotherapy AU - Shah, Anisha AU - Nagpal, Ashmeet AU - V, Manjula AU - Rynjah, Ila Lyngksiar AD - Department of Clinical Psychology, National Institute of Mental Health and Neurosciences, Bengaluru, India Y1 - 2016///Apr/Jun PY - 2016 DA - Apr/Jun 2016 SP - 99 EP - 108 CY - Abingdon PB - Taylor & Francis Ltd. VL - 27 IS - 2 SN - 0897-5353 KW - Psychology KW - Conjoint sessions KW - couple therapy KW - goals KW - India KW - individual sessions KW - themes KW - Careers KW - Life Cycle KW - Family Violence KW - Couples KW - Marriage KW - Family Life KW - Resistance KW - Qualitative Methods KW - Socioeconomic Status KW - 6142:mental & emotional health problems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1788991960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Family+Psychotherapy&rft.atitle=Combined+Couples%27+Therapy%3A+A+Qualitative+Study+of+Individual+and+Conjoint+Sessions&rft.au=Shah%2C+Anisha%3BNagpal%2C+Ashmeet%3BV%2C+Manjula%3BRynjah%2C+Ila+Lyngksiar&rft.aulast=Shah&rft.aufirst=Anisha&rft.date=2016-04-01&rft.volume=27&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Journal+of+Family+Psychotherapy&rft.issn=08975353&rft_id=info:doi/10.1080%2F08975353.2016.1169019 LA - English DB - Social Services Abstracts N1 - Copyright - © 2016 Taylor & Francis Group, LLC N1 - Last updated - 2016-08-16 DO - http://dx.doi.org/10.1080/08975353.2016.1169019 ER - TY - JOUR T1 - Distributions of autofluorescence after compensation: Be panglossian, fret not AN - 1787981735; PQ0002966169 AB - In this technical note, I describe an in silico model of multiparameter fluorescence measurements that takes into account intrinsic cellular autofluorescence and stained dye fluorescence distributions, fluorescence spectrum spillovers, and photon counting statistics. Using this model, it is easy to manipulate spectral variables as well as error terms to understand the impact of each on the distributions of estimated cell-associated dyes (e.g., conjugated monoclonal antibodies in immunophenotyping). An application of this model was to understand the genesis of "unusual" autofluorescence distributions that occasionally happen in multi-color immunophenotyping. These unusual distributions show striking correlated patterns (diagonals) for graphs of certain pairs of parameters. Here I show that these arise from combinations of spillover-spreading from unviewed parameters. While disconcerting to researchers taught to look for diagonals in distributions as heralding improper compensation, these distributions are in fact appropriate. In general, one can ignore the characteristics of cell distributions within the same limits as background (e.g., as proscribed by a fluorescence-minus-one, or FMO, control), as there is essentially no information content in that region. Published 2016 International Society for Advancement of Cytometry. This article is a US Government work, and as such, is in the public domain in the USA. JF - Cytometry Part A AU - Roederer, Mario AD - Flow Cytometry Core and ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 398 EP - 402 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 89 IS - 4 SN - 1552-4922, 1552-4922 KW - Biotechnology and Bioengineering Abstracts KW - Statistics KW - Dyes KW - Photons KW - Monoclonal antibodies KW - Statistical analysis KW - fluorescence resonance energy transfer KW - Enumeration KW - Cytometry KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787981735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytometry+Part+A&rft.atitle=Distributions+of+autofluorescence+after+compensation%3A+Be+panglossian%2C+fret+not&rft.au=Roederer%2C+Mario&rft.aulast=Roederer&rft.aufirst=Mario&rft.date=2016-04-01&rft.volume=89&rft.issue=4&rft.spage=398&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+A&rft.issn=15524922&rft_id=info:doi/10.1002%2Fcyto.a.22820 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Statistics; Photons; Dyes; Monoclonal antibodies; Statistical analysis; fluorescence resonance energy transfer; Enumeration; Cytometry DO - http://dx.doi.org/10.1002/cyto.a.22820 ER - TY - JOUR T1 - Loss of Folliculin Disrupts Hematopoietic Stem Cell Quiescence and Homeostasis Resulting in Bone Marrow Failure AN - 1787977169; PQ0002952951 AB - Folliculin (FLCN) is an autosomal dominant tumor suppressor gene that modulates diverse signaling pathways required for growth, proliferation, metabolism, survival, motility, and adhesion. FLCN is an essential protein required for murine embryonic development, embryonic stem cell (ESC) commitment, and Drosophila germline stem cell maintenance, suggesting that Flcn may be required for adult stem cell homeostasis. Conditional inactivation of Flcn in adult hematopoietic stem/progenitor cells (HSPCs) drives hematopoietic stem cells (HSC) into proliferative exhaustion resulting in the rapid depletion of HSPC, loss of all hematopoietic cell lineages, acute bone marrow (BM) failure, and mortality after 40 days. HSC that lack Flcn fail to reconstitute the hematopoietic compartment in recipient mice, demonstrating a cell-autonomous requirement for Flcn in HSC maintenance. BM cells showed increased phosphorylation of Akt and mTorc1, and extramedullary hematopoiesis was significantly reduced by treating mice with rapamycin in vivo, suggesting that the mTorc1 pathway was activated by loss of Flcn expression in hematopoietic cells in vivo. Tfe3 was activated and preferentially localized to the nucleus of Flcn knockout (KO) HSPCs. Tfe3 overexpression in HSPCs impaired long-term hematopoietic reconstitution in vivo, recapitulating the Flcn KO phenotype, and supporting the notion that abnormal activation of Tfe3 contributes to the Flcn KO phenotype. Flcn KO mice develop an acute histiocytic hyperplasia in multiple organs, suggesting a novel function for Flcn in macrophage development. Thus, Flcn is intrinsically required to maintain adult HSC quiescence and homeostasis, and Flcn loss leads to BM failure and mortality in mice. Stem Cells 2016; 34:1068-1082 JF - Stem Cells AU - Baba, Masaya AU - Toyama, Hirofumi AU - Sun, Lei AU - Takubo, Keiyo AU - Suh, Hyung-Chan AU - Hasumi, Hisashi AU - Nakamura-Ishizu, Ayako AU - Hasumi, Yukiko AU - Klarmann, Kimberly D AU - Nakagata, Naomi AU - Schmidt, Laura S AU - Linehan, WMarston AU - Suda, Toshio AU - Keller, Jonathan R AD - Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 1068 EP - 1082 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 4 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Macrophages KW - Cell lineage KW - Tumor suppressor genes KW - Mortality KW - Bone marrow KW - Homeostasis KW - Hyperplasia KW - Stem cells KW - Embryogenesis KW - Motility KW - Phosphorylation KW - Embryo cells KW - AKT protein KW - Hemopoiesis KW - Nuclei KW - Drosophila KW - Rapamycin KW - Metabolism KW - Signal transduction KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787977169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Loss+of+Folliculin+Disrupts+Hematopoietic+Stem+Cell+Quiescence+and+Homeostasis+Resulting+in+Bone+Marrow+Failure&rft.au=Baba%2C+Masaya%3BToyama%2C+Hirofumi%3BSun%2C+Lei%3BTakubo%2C+Keiyo%3BSuh%2C+Hyung-Chan%3BHasumi%2C+Hisashi%3BNakamura-Ishizu%2C+Ayako%3BHasumi%2C+Yukiko%3BKlarmann%2C+Kimberly+D%3BNakagata%2C+Naomi%3BSchmidt%2C+Laura+S%3BLinehan%2C+WMarston%3BSuda%2C+Toshio%3BKeller%2C+Jonathan+R&rft.aulast=Baba&rft.aufirst=Masaya&rft.date=2016-04-01&rft.volume=34&rft.issue=4&rft.spage=1068&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2293 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-06-22 N1 - SubjectsTermNotLitGenreText - Cell lineage; Macrophages; Mortality; Tumor suppressor genes; Bone marrow; Homeostasis; Motility; Embryogenesis; Stem cells; Hyperplasia; Embryo cells; Phosphorylation; AKT protein; Hemopoiesis; Nuclei; Metabolism; Rapamycin; Signal transduction; Drosophila DO - http://dx.doi.org/10.1002/stem.2293 ER - TY - JOUR T1 - Adverse outcome pathways: From research to regulation scientific workshop report AN - 1787972295; PQ0003003256 AB - An adverse outcome pathway (AOP) helps to organize existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. JF - Regulatory Toxicology and Pharmacology AU - Kleinstreuer, Nicole C AU - Sullivan, Kristie AU - Allen, David AU - Edwards, Stephen AU - Mendrick, Donna L AU - Embry, Michelle AU - Matheson, Joanna AU - Rowlands, JCraig AU - Munn, Sharon AU - Maull, Elizabeth AU - Casey, Warren AD - National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 39 EP - 50 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 76 SN - 0273-2300, 0273-2300 KW - Environment Abstracts; Toxicology Abstracts KW - AOP KW - Workshop KW - Toxicology KW - Pathway KW - Regulatory KW - Quantitative KW - Application KW - Acceptance KW - Criteria KW - Computational KW - AO adverse outcome KW - AOP adverse outcome pathway KW - AOP-KB AOP Knowledge Base KW - EAGMST Extended Advisory Group for Molecular Screening and Toxicogenomics KW - EPA U.S. Environmental Protection Agency KW - IATA integrated approaches to testing and assessment KW - IT Information Technology KW - KE key event KW - KER key event relationship KW - MIE molecular initiating event KW - MoA mode of action KW - NCATS National Center for Advancing Translational Sciences KW - NICEATM National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods KW - OECD Organisation for Economic Co-operation and Development KW - PCRM Physicians Committee for Responsible Medicine KW - Conferences KW - Interest groups KW - Toxicity KW - ANW, USA, Maryland KW - X 24310:Pharmaceuticals KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787972295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+Toxicology+and+Pharmacology&rft.atitle=Adverse+outcome+pathways%3A+From+research+to+regulation+scientific+workshop+report&rft.au=Kleinstreuer%2C+Nicole+C%3BSullivan%2C+Kristie%3BAllen%2C+David%3BEdwards%2C+Stephen%3BMendrick%2C+Donna+L%3BEmbry%2C+Michelle%3BMatheson%2C+Joanna%3BRowlands%2C+JCraig%3BMunn%2C+Sharon%3BMaull%2C+Elizabeth%3BCasey%2C+Warren&rft.aulast=Kleinstreuer&rft.aufirst=Nicole&rft.date=2016-04-01&rft.volume=76&rft.issue=&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Regulatory+Toxicology+and+Pharmacology&rft.issn=02732300&rft_id=info:doi/10.1016%2Fj.yrtph.2016.01.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-07-07 N1 - SubjectsTermNotLitGenreText - Conferences; Toxicity; Interest groups; Toxicology; ANW, USA, Maryland DO - http://dx.doi.org/10.1016/j.yrtph.2016.01.007 ER - TY - JOUR T1 - Intelligent navigation to improve obstetrical sonography AN - 1785246576; PQ0002911129 AB - 'Manual navigation' by the operator is the standard method used to obtain information from two-dimensional and volumetric sonography. Two-dimensional sonography is highly operator dependent and requires extensive training and expertise to assess fetal anatomy properly. Most of the sonographic examination time is devoted to acquisition of images, while 'retrieval' and display of diagnostic planes occurs rapidly (essentially instantaneously). In contrast, volumetric sonography has a rapid acquisition phase, but the retrieval and display of relevant diagnostic planes is often time-consuming, tedious and challenging. We propose the term 'intelligent navigation' to refer to a new method of interrogation of a volume dataset whereby identification and selection of key anatomical landmarks allow the system to: 1) generate a geometrical reconstruction of the organ of interest; and 2) automatically navigate, find, extract and display specific diagnostic planes. This is accomplished using operator-independent algorithms that are both predictable and adaptive. Virtual Intelligent Sonographer Assistance (VIS-Assistance registered ) is a tool that allows operator-independent sonographic navigation and exploration of the surrounding structures in previously identified diagnostic planes. The advantage of intelligent (over manual) navigation in volumetric sonography is the short time required for both acquisition and retrieval and display of diagnostic planes. Intelligent navigation technology automatically realigns the volume, and reorients and standardizes the anatomical position, so that the fetus and the diagnostic planes are consistently displayed in the same manner each time, regardless of the fetal position or the initial orientation. Automatic labeling of anatomical structures, subject orientation and each of the diagnostic planes is also possible. Intelligent navigation technology can operate on conventional computers, and is not dependent on specific ultrasound platforms or on the use of software to perform manual navigation of volume datasets. Diagnostic planes and VIS-Assistance videoclips can be transmitted by telemedicine so that expert consultants can evaluate the images to provide an opinion. The end result is a user-friendly, simple, fast and consistent method of obtaining sonographic images with decreased operator dependency. Intelligent navigation is one approach to improve obstetrical sonography. JF - Ultrasound in Obstetrics and Gynecology AU - Yeo, Lami AU - Romero, Roberto AD - Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 403 EP - 409 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 47 IS - 4 SN - 0960-7692, 0960-7692 KW - Biotechnology and Bioengineering Abstracts KW - Computer programs KW - software KW - Gynecology KW - Computers KW - Algorithms KW - Ultrasound KW - Obstetrics KW - Fetuses KW - Telemedicine KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785246576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ultrasound+in+Obstetrics+and+Gynecology&rft.atitle=Intelligent+navigation+to+improve+obstetrical+sonography&rft.au=Yeo%2C+Lami%3BRomero%2C+Roberto&rft.aulast=Yeo&rft.aufirst=Lami&rft.date=2016-04-01&rft.volume=47&rft.issue=4&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Ultrasound+in+Obstetrics+and+Gynecology&rft.issn=09607692&rft_id=info:doi/10.1002%2Fuog.12562 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Computer programs; software; Gynecology; Computers; Algorithms; Obstetrics; Ultrasound; Telemedicine; Fetuses DO - http://dx.doi.org/10.1002/uog.12562 ER - TY - JOUR T1 - Prospective evaluation of the fetal heart using Fetal Intelligent Navigation Echocardiography (FINE) AN - 1785246383; PQ0002911125 AB - Objective To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. Methods In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop(TM) to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance registered ) were calculated. Results One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient ( n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. Conclusions In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. JF - Ultrasound in Obstetrics and Gynecology AU - Garcia, M AU - Yeo, L AU - Romero, R AU - Haggerty, D AU - Giardina, I AU - Hassan, S S AU - Chaiworapongsa, T AU - Hernandez-Andrade, E AD - Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 450 EP - 459 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 47 IS - 4 SN - 0960-7692, 0960-7692 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Spine KW - Gynecology KW - Aortic arch KW - Respiration KW - Echocardiography KW - Gestation KW - Ultrasound KW - Obstetrics KW - Fetuses KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785246383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ultrasound+in+Obstetrics+and+Gynecology&rft.atitle=Prospective+evaluation+of+the+fetal+heart+using+Fetal+Intelligent+Navigation+Echocardiography+%28FINE%29&rft.au=Garcia%2C+M%3BYeo%2C+L%3BRomero%2C+R%3BHaggerty%2C+D%3BGiardina%2C+I%3BHassan%2C+S+S%3BChaiworapongsa%2C+T%3BHernandez-Andrade%2C+E&rft.aulast=Garcia&rft.aufirst=M&rft.date=2016-04-01&rft.volume=47&rft.issue=4&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Ultrasound+in+Obstetrics+and+Gynecology&rft.issn=09607692&rft_id=info:doi/10.1002%2Fuog.15676 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Heart; Spine; Gynecology; Aortic arch; Respiration; Gestation; Echocardiography; Obstetrics; Ultrasound; Fetuses DO - http://dx.doi.org/10.1002/uog.15676 ER - TY - JOUR T1 - Targeted gene addition in human CD34 super(+) hematopoietic cells for correction of X-linked chronic granulomatous disease AN - 1785229748; PQ0002901560 AB - Gene therapy with genetically modified human CD34 super(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus super(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in 15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. JF - Nature Biotechnology AU - De Ravin, Suk See AU - Reik, Andreas AU - Liu, Pei-Qi AU - Li, Linhong AU - Wu, Xiaolin AU - Su, Ling AU - Raley, Castle AU - Theobald, Narda AU - Choi, Uimook AU - Song, Alexander H AU - Chan, Andy AU - Pearl, Jocelynn R AU - Paschon, David E AU - Lee, Janet AU - Newcombe, Hannah AU - Koontz, Sherry AU - Sweeney, Colin AU - Shivak, David A AU - Zarember, Kol A AU - Peshwa, Madhusudan V AU - Gregory, Philip D AU - Urnov, Fyodor D AU - Malech, Harry L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 424 EP - 429 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 34 IS - 4 SN - 1087-0156, 1087-0156 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Donors KW - Gene therapy KW - Electroporation KW - X chromosome KW - Transgenes KW - Bone marrow KW - Leukocytes (neutrophilic) KW - Zinc finger proteins KW - Nuclease KW - CD34 antigen KW - Adeno-associated virus KW - mRNA KW - Integration KW - Allografts KW - Hemopoiesis KW - NAD(P)H oxidase KW - genomics KW - Chronic granulomatous disease KW - Mutation KW - Bone marrow transplantation KW - W 30905:Medical Applications KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785229748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Targeted+gene+addition+in+human+CD34+super%28%2B%29+hematopoietic+cells+for+correction+of+X-linked+chronic+granulomatous+disease&rft.au=De+Ravin%2C+Suk+See%3BReik%2C+Andreas%3BLiu%2C+Pei-Qi%3BLi%2C+Linhong%3BWu%2C+Xiaolin%3BSu%2C+Ling%3BRaley%2C+Castle%3BTheobald%2C+Narda%3BChoi%2C+Uimook%3BSong%2C+Alexander+H%3BChan%2C+Andy%3BPearl%2C+Jocelynn+R%3BPaschon%2C+David+E%3BLee%2C+Janet%3BNewcombe%2C+Hannah%3BKoontz%2C+Sherry%3BSweeney%2C+Colin%3BShivak%2C+David+A%3BZarember%2C+Kol+A%3BPeshwa%2C+Madhusudan+V%3BGregory%2C+Philip+D%3BUrnov%2C+Fyodor+D%3BMalech%2C+Harry+L&rft.aulast=De+Ravin&rft.aufirst=Suk&rft.date=2016-04-01&rft.volume=34&rft.issue=4&rft.spage=424&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt.3513 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Donors; Electroporation; Gene therapy; Transgenes; X chromosome; Leukocytes (neutrophilic); Bone marrow; Nuclease; Zinc finger proteins; CD34 antigen; mRNA; Integration; Allografts; Hemopoiesis; NAD(P)H oxidase; genomics; Chronic granulomatous disease; Mutation; Bone marrow transplantation; Adeno-associated virus DO - http://dx.doi.org/10.1038/nbt.3513 ER - TY - JOUR T1 - Human rabies in India: an audit from a rabies diagnostic laboratory AN - 1780526398; PQ0002888168 AB - Objectives Rabies, an acute progressive encephalomyelitis, continues to be a serious public health problem in India and many other countries in Asia and Africa. The low level of commitment to rabies control is partly attributable to challenges in laboratory diagnosis and lack of adequate surveillance to indicate the disease burden. A laboratory audit of human rabies cases was undertaken to disseminate information on the clinical, demographic, prophylactic and most importantly the laboratory diagnostic aspects of rabies. Methods A retrospective analysis of all clinically suspected human rabies cases, whose samples were received at a rabies diagnostic laboratory in South India in the last 3 years, was performed. Clinical and demographic details of patients were obtained. The clinical samples included cerebrospinal fluid (CSF), serum, saliva and nuchal skin biopsy collected antemortem, and brain tissue obtained post-mortem. Various laboratory tests were performed for diagnosis. Results Clinical samples from 128 patients with suspected rabies, from 11 states in India, were received for diagnostic confirmation. About 94% of the victims reported dog-bites, more than a third of them were children and most of the victims did not receive adequate post-exposure prophylaxis. Antemortem confirmation of rabies by a combination of laboratory diagnostic assays (detection of viral RNA in CSF, skin and saliva, and neutralising antibodies in CSF) could be achieved in 40.6%cases. Conclusions Increasing awareness about adequate post-exposure prophylaxis, additional rabies diagnostic facilities, and enhanced human and animal rabies surveillance to indicate the true disease burden are essential to control this fatal disease.Original Abstract: Objectifs La rage, une encephalomyelite aiguee progressive, continue d'etre un serieux probleme de sante publique en Inde et dans de nombreux autres pays d'Asie et d'Afrique. Le faible niveau d'engagement dans la lutte contre la rage est en partie attribuable a des defis en matiere de diagnostic de laboratoire et au manque de surveillance adequate pour indiquer la charge de morbidite. Un audit de laboratoire sur les cas de rage humaine a ete entrepris afin de divulguer des informations sur les aspects cliniques, demographiques, prophylactiques et surtout du diagnostic de laboratoire de la rage. Methodes Une analyse retrospective de tous les cas cliniquement suspects de la rage humaine dont les echantillons ont ete recus dans un laboratoire de diagnostic de la rage dans le sud de l'Inde au cours des 3 dernieres annees, a ete realisee. Les details cliniques et demographiques des patients ont ete obtenus. Les echantillons cliniques comprenaient: le liquide cephalorachidien (LCR), le serum, la salive et la biopsie cutanee de la nuque recueillie ante-mortem, ainsi que le tissu cerebral obtenu post-mortem. Differents tests de laboratoire ont ete realises pour le diagnostic. Resultats Des echantillons cliniques provenant de 128 patients suspectes de la rage dans 11 Etats de l'Inde ont ete recus pour la confirmation du diagnostic. 94% des victimes ont declare une morsure de chien, plus d'un tiers d'entre eux etaient des enfants et la plupart des victimes n'ont pas recu de prophylaxie post-exposition adequate. La confirmation ante-mortem de la rage par une combinaison de tests de diagnostic de laboratoire (detection de l'ARN viral dans le LCR, la peau et la salive, et des anticorps neutralisants dans le LCR) a pu etre obtenue dans 40,6% des cas. Conclusions L'augmentation de la sensibilisation a la prophylaxie post-exposition adequate, des centres additionnels de diagnostic de la rage et une meilleure surveillance de la rage humaine et animale pour indiquer la veritable charge de morbidite, sont essentiels pour lutter contre cette maladie mortelle. JF - Tropical Medicine and International Health AU - Mani, Reeta Subramaniam AU - Anand, Ashwini Manoor AU - Madhusudana, Shampur Narayan AD - Department of Neurovirology, National Institute of Mental Health and Neurosciences, WHO Collaborating Centre for Reference and Research on Rabies, Bangalore, India. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 556 EP - 563 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 21 IS - 4 SN - 1360-2276, 1360-2276 KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - Skin KW - Laboratory testing KW - Brain KW - Encephalomyelitis KW - Biopsy KW - Children KW - India KW - Public health KW - Demography KW - Antibodies KW - Cerebrospinal fluid KW - RNA KW - Rabies KW - Prophylaxis KW - Africa KW - Saliva KW - Asia KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780526398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tropical+Medicine+and+International+Health&rft.atitle=Human+rabies+in+India%3A+an+audit+from+a+rabies+diagnostic+laboratory&rft.au=Mani%2C+Reeta+Subramaniam%3BAnand%2C+Ashwini+Manoor%3BMadhusudana%2C+Shampur+Narayan&rft.aulast=Mani&rft.aufirst=Reeta&rft.date=2016-04-01&rft.volume=21&rft.issue=4&rft.spage=556&rft.isbn=&rft.btitle=&rft.title=Tropical+Medicine+and+International+Health&rft.issn=13602276&rft_id=info:doi/10.1111%2Ftmi.12669 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Skin; Brain; Biopsy; Encephalomyelitis; Children; Public health; Demography; Cerebrospinal fluid; Antibodies; RNA; Rabies; Prophylaxis; Saliva; Laboratory testing; Africa; Asia; India DO - http://dx.doi.org/10.1111/tmi.12669 ER - TY - JOUR T1 - Red and processed meat, nitrite, and heme iron intakes and postmenopausal breast cancer risk in the NIH-AARP Diet and Health Study AN - 1780515909; PQ0002803727 AB - Previous studies have shown inconsistent associations between red and processed meat intake and breast cancer risk. N-nitroso compounds and heme iron have been hypothesized as contributing factors. We followed 193,742 postmenopausal women in the NIH-AARP Diet and Health Study and identified 9,305 incident breast cancers (1995-2006). Dietary intake was assessed using a food frequency questionnaire at baseline. We adjusted daily intakes of meat, nitrite and heme iron for energy intake using the nutrient density method. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by quintiles of dietary exposures for all breast cancer, by stage (in-situ, localized, regional/distant) and by estrogen/progesterone receptor (ER/PR) status using Cox proportional hazards regression. Total red meat intake was positively associated with risk of regional/distant cancer (p-trend=0.02). The risk was 25% higher in the highest vs. lowest intake quintile (95% CI=1.03-1.52). Higher processed red meat intake (Q5 vs. Q1) was associated with 27% higher risk of localized breast cancer (95% CI=1.01-1.27, p-trend=0.03) and a 19% higher risk of regional/distant cancer (95% CI=0.98-1.44, p-trend=0.10). In addition, higher nitrite intake from processed red meat was positively associated with localized cancer (HR for Q5 vs. Q1=1.23, 95% CI=1.09-1.39, p-trend<0.0001). Heme iron intake was positively associated with breast cancer risk overall and all cancer stages (p-trend=0.02-0.05). No heterogeneity was observed in risk associations by hormone receptor status. Our findings suggest that high consumption of red meat and processed meat may increase risk of postmenopausal breast cancer. Added nitrite and heme iron may partly contribute to these observed associations. What's new? Associations between red and processed meat intakes and breast cancer have been inconclusive with few studies considering whether risk associations differ by cancer stage and hormone receptor status. We found that higher red meat intake was associated with regional/distant breast cancer. Higher processed red meat intake was also associated with localized cancer. Heme iron and nitrite may partly contribute to these observed associations. No heterogeneity was observed in risk associations by hormone receptor status. JF - International Journal of Cancer AU - Inoue-Choi, Maki AU - Sinha, Rashmi AU - Gierach, Gretchen L AU - Ward, Mary H AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 1609 EP - 1618 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 138 IS - 7 SN - 0020-7136, 0020-7136 KW - Toxicology Abstracts KW - Inventories KW - Estrogens KW - Heme KW - Food KW - Energy intake KW - Nutrients KW - Dietary intake KW - Hormones KW - Meat KW - Progesterone receptors KW - N-Nitroso compounds KW - Post-menopause KW - Risk factors KW - Breast cancer KW - Nitrite KW - Estrogen receptors KW - Iron KW - X 24320:Food Additives & Contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780515909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Red+and+processed+meat%2C+nitrite%2C+and+heme+iron+intakes+and+postmenopausal+breast+cancer+risk+in+the+NIH-AARP+Diet+and+Health+Study&rft.au=Inoue-Choi%2C+Maki%3BSinha%2C+Rashmi%3BGierach%2C+Gretchen+L%3BWard%2C+Mary+H&rft.aulast=Inoue-Choi&rft.aufirst=Maki&rft.date=2016-04-01&rft.volume=138&rft.issue=7&rft.spage=1609&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.29901 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Inventories; Estrogens; Heme; Food; Energy intake; Nutrients; Hormones; Dietary intake; Meat; Progesterone receptors; N-Nitroso compounds; Post-menopause; Risk factors; Breast cancer; Nitrite; Iron; Estrogen receptors DO - http://dx.doi.org/10.1002/ijc.29901 ER - TY - JOUR T1 - Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48-hour continuous infusion in patients with cancer AN - 1780515878; PQ0002778429 AB - The histone deacetylase inhibitor belinostat is eliminated through glucuronidation by UGT1A1. Polymorphisms that reduce UGT1A1 function could result in increased belinostat exposure and toxicities. We wanted to determine which single-nucleotide polymorphisms alter belinostat exposure and toxicity. In a phase 1 trial (belinostat over 48 hours in combination with cisplatin and etoposide), belinostat (400, 500, 600, or 800mg/m super(2)/24h, 48-hour continuous infusion) was administered to patients with cancer in combination with cisplatin and etoposide (n=25). Patients were genotyped for UGT1A1 variants associated with reduced function: UGT1A1*6, UGT1A1*28, and UGT1A1*60. End points were associations between UGT1A1 genotype and belinostat pharmacokinetics (PK), toxicities, and global protein lysine acetylation (AcK). Belinostat AUC was increased (P=.003), and t sub(1/2) increased (P=.0009) in UGT1A1*28 and UGT1A1*60 carriers who received more than 400mg/m super(2)/24h. The incidence of grades 3-4 thrombocytopenia (P=.0081) was associated with UGT1A1 polymorphisms. The US Food and Drug Administration-approved package insert recommends dose adjustment of belinostat for UGT1A1*28. However, our data suggest dose adjustment is also necessary for UGT1A1*60. UGT1A1 polymorphisms were associated with increased systemic belinostat exposure, increased AcK, and increased incidence of toxicities, particularly at doses > 400mg/m super(2)/24h. JF - Journal of Clinical Pharmacology AU - Goey, Andrew KL AU - Sissung, Tristan M AU - Peer, Cody J AU - Trepel, Jane B AU - Lee, Min-Jung AU - Tomita, Yusuke AU - Ehrlich, Sheryl AU - Bryla, Christine AU - Balasubramaniam, Sanjeeve AU - Piekarz, Richard AU - Steinberg, Seth M AU - Bates, Susan E AU - Figg, William D AD - Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 461 EP - 473 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 56 IS - 4 SN - 0091-2700, 0091-2700 KW - Toxicology Abstracts KW - Histone deacetylase KW - Data processing KW - Food KW - Lysine KW - Toxicity KW - Clinical trials KW - Pharmacokinetics KW - Cancer KW - Acetylation KW - Thrombocytopenia KW - Cisplatin KW - Single-nucleotide polymorphism KW - Etoposide KW - Drugs KW - Pharmacodynamics KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780515878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Pharmacology&rft.atitle=Effects+of+UGT1A1+genotype+on+the+pharmacokinetics%2C+pharmacodynamics%2C+and+toxicities+of+belinostat+administered+by+48-hour+continuous+infusion+in+patients+with+cancer&rft.au=Goey%2C+Andrew+KL%3BSissung%2C+Tristan+M%3BPeer%2C+Cody+J%3BTrepel%2C+Jane+B%3BLee%2C+Min-Jung%3BTomita%2C+Yusuke%3BEhrlich%2C+Sheryl%3BBryla%2C+Christine%3BBalasubramaniam%2C+Sanjeeve%3BPiekarz%2C+Richard%3BSteinberg%2C+Seth+M%3BBates%2C+Susan+E%3BFigg%2C+William+D&rft.aulast=Goey&rft.aufirst=Andrew&rft.date=2016-04-01&rft.volume=56&rft.issue=4&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Pharmacology&rft.issn=00912700&rft_id=info:doi/10.1002%2Fjcph.625 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Histone deacetylase; Data processing; Food; Lysine; Toxicity; Clinical trials; Cancer; Pharmacokinetics; Acetylation; Thrombocytopenia; Cisplatin; Single-nucleotide polymorphism; Drugs; Etoposide; Pharmacodynamics DO - http://dx.doi.org/10.1002/jcph.625 ER - TY - JOUR T1 - Diastereoselective Synthesis of 6″-(Z)- and 6″-(E)-Fluoro Analogues of Anti-hepatitis B Virus Agent Entecavir and Its Evaluation of the Activity and Toxicity Profile of the Diastereomers. AN - 1777987024; 27009432 AB - A method for the diastereoselective synthesis of 6″-(Z)- and 6″-(E)-fluorinated analogues of the anti-HBV agent entecavir has been developed. Construction of the methylenecyclopentane skeleton of the target molecules has been accomplished by radical-mediated 5-exo-dig cyclization of the selenides 6 and 15 having the phenylsulfanylethynyl structure as a radical accepting moiety. In the radical reaction of the TBS-protected precursor 6, (Z)-anti-12 was formed as a major product. On the other hand, TIPS-protected 15 gave (E)-anti-12. The sulfur-extrusive stannylation of anti-12 furnished a mixture of geometric isomers of the respective vinylstannane, whereas benzoyl-protected 17 underwent the stannylation in the manner of retention of configuration. Following XeF2-mediated fluorination, introduction of the purine base and deoxygenation of the resulting carbocyclic guanosine gave the target (E)- and (Z)-3 after deprotection. Evaluation of the anti-HBV activity of 3 revealed that fluorine-substitution at the 6″-position of entecavir gave rise to a reduction in the cytotoxicity in HepG2 cells with retention of the antiviral activity. JF - The Journal of organic chemistry AU - Kumamoto, Hiroki AU - Fukano, Misato AU - Nakano, Tomohiko AU - Iwagami, Keito AU - Takeyama, Chiaki AU - Kohgo, Satoru AU - Imoto, Shuhei AU - Amano, Masayuki AU - Kuwata-Higashi, Nobuyo AU - Aoki, Manabu AU - Abe, Hiroshi AU - Mitsuya, Hiroaki AU - Fukuhara, Kiyoshi AU - Haraguchi, Kazuhiro AD - School of Pharmacy, Showa University , 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. ; Center for Clinical Sciences, National Center for Global Health and Medicine , 1-21-1 Toyama, Shinjuku, Tokyo 162-8655, Japan. ; Faculty of Pharmaceutical Sciences, Sojo University , 4-22-1 Ikeda, Kumamoto 860-0082, Japan. ; Department of Infectious Diseases and Hematology, Kumamoto University School of Medicine , Kumamoto 860-8556, Japan. ; Department of Medical Technology, Kumamoto Heath Science University , 325 Izumimachi, Kumamoto 861-5598, Japan. ; Department of Chemistry, Graduate School of Science, Nagoya University , Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. ; Nihon Pharmaceutical University , 10281 Komuro, Inamachi, Kita-adachi-gun, Saitama 362-0806, Japan. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 2827 EP - 2836 VL - 81 IS - 7 KW - Antiviral Agents KW - 0 KW - Guanosine KW - 12133JR80S KW - entecavir KW - 5968Y6H45M KW - Guanine KW - 5Z93L87A1R KW - Index Medicus KW - Stereoisomerism KW - Humans KW - Hepatitis B virus -- drug effects KW - Structure-Activity Relationship KW - Antiviral Agents -- chemical synthesis KW - Hep G2 Cells -- chemistry KW - Guanine -- chemistry KW - Antiviral Agents -- pharmacology KW - Antiviral Agents -- chemistry KW - Guanine -- chemical synthesis KW - Guanine -- analogs & derivatives KW - Guanosine -- chemistry KW - HIV-1 -- drug effects KW - Guanine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777987024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+organic+chemistry&rft.atitle=Diastereoselective+Synthesis+of+6%E2%80%B3-%28Z%29-+and+6%E2%80%B3-%28E%29-Fluoro+Analogues+of+Anti-hepatitis+B+Virus+Agent+Entecavir+and+Its+Evaluation+of+the+Activity+and+Toxicity+Profile+of+the+Diastereomers.&rft.au=Kumamoto%2C+Hiroki%3BFukano%2C+Misato%3BNakano%2C+Tomohiko%3BIwagami%2C+Keito%3BTakeyama%2C+Chiaki%3BKohgo%2C+Satoru%3BImoto%2C+Shuhei%3BAmano%2C+Masayuki%3BKuwata-Higashi%2C+Nobuyo%3BAoki%2C+Manabu%3BAbe%2C+Hiroshi%3BMitsuya%2C+Hiroaki%3BFukuhara%2C+Kiyoshi%3BHaraguchi%2C+Kazuhiro&rft.aulast=Kumamoto&rft.aufirst=Hiroki&rft.date=2016-04-01&rft.volume=81&rft.issue=7&rft.spage=2827&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+organic+chemistry&rft.issn=1520-6904&rft_id=info:doi/10.1021%2Facs.joc.6b00105 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-23 N1 - Date created - 2016-04-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.joc.6b00105 ER - TY - JOUR T1 - Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics. AN - 1777986813; 26804983 AB - Chronic pain negatively impacts the quality of life in a variety of patient populations. The current therapeutic repertoire is inadequate in managing patient pain and warrants the development of new therapeutics. Adenosine and its four cognate receptors (A1 , A2A , A2B and A3 ) have important roles in physiological and pathophysiological states, including chronic pain. Preclinical and clinical studies have revealed that while adenosine and agonists of the A1 and A2A receptors have antinociceptive properties, their therapeutic utility is limited by adverse cardiovascular side effects. In contrast, our understanding of the A3 receptor is only in its infancy, but exciting preclinical observations of A3 receptor antinociception, which have been bolstered by clinical trials of A3 receptor agonists in other disease states, suggest pain relief without cardiovascular side effects and with sufficient tolerability. Our goal herein is to briefly discuss adenosine and its receptors in the context of pathological pain and to consider the current data regarding A3 receptor-mediated antinociception. We will highlight recent findings regarding the impact of the A3 receptor on pain pathways and examine the current state of selective A3 receptor agonists used for these studies. The adenosine-to-A3 receptor pathway represents an important endogenous system that can be targeted to provide safe, effective pain relief from chronic pain. © 2016 The British Pharmacological Society. JF - British journal of pharmacology AU - Janes, K AU - Symons-Liguori, A M AU - Jacobson, K A AU - Salvemini, D AD - Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO, USA. ; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 1253 EP - 1267 VL - 173 IS - 8 KW - Adenosine A3 Receptor Agonists KW - 0 KW - Analgesics, Non-Narcotic KW - Receptor, Adenosine A3 KW - Index Medicus KW - Humans KW - Analgesics, Non-Narcotic -- pharmacology KW - Adenosine A3 Receptor Agonists -- pharmacology KW - Adenosine A3 Receptor Agonists -- chemistry KW - Receptor, Adenosine A3 -- metabolism KW - Analgesics, Non-Narcotic -- chemistry KW - Chronic Pain -- drug therapy KW - Chronic Pain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777986813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Identification+of+A3+adenosine+receptor+agonists+as+novel+non-narcotic+analgesics.&rft.au=Janes%2C+K%3BSymons-Liguori%2C+A+M%3BJacobson%2C+K+A%3BSalvemini%2C+D&rft.aulast=Janes&rft.aufirst=K&rft.date=2016-04-01&rft.volume=173&rft.issue=8&rft.spage=1253&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=1476-5381&rft_id=info:doi/10.1111%2Fbph.13446 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-26 N1 - Date created - 2016-03-31 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/bph.13446 ER - TY - JOUR T1 - Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer. AN - 1777985852; 26553749 AB - The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men. We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade-matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored. Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. ©2015 American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Yang, Yijun AU - Jia, Dingwu AU - Kim, Hogyoung AU - Abd Elmageed, Zakaria Y AU - Datta, Amrita AU - Davis, Rodney AU - Srivastav, Sudesh AU - Moroz, Krzysztof AU - Crawford, Byron E AU - Moparty, Krishnarao AU - Thomas, Raju AU - Hudson, Robert S AU - Ambs, Stefan AU - Abdel-Mageed, Asim B AD - Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana. ; Department of Biostatistics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana. ; Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana. Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana. ; Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana. ; Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana. Division of Urology, Southeast Louisiana Veterans Health Care System, New Orleans, Louisiana. ; Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana. Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana. ; Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland. ; Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana. Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana. Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana. amageed@tulane.edu. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 1744 EP - 1756 VL - 22 IS - 7 SN - 1078-0432, 1078-0432 KW - Androgens KW - 0 KW - Anilides KW - Antineoplastic Agents KW - Heterogeneous-Nuclear Ribonucleoprotein Group F-H KW - MIRN212 microRNA, human KW - MicroRNAs KW - Nitriles KW - Receptors, Androgen KW - Tosyl Compounds KW - bicalutamide KW - A0Z3NAU9DP KW - Nuclear Receptor Coactivator 3 KW - EC 2.3.1.48 KW - Index Medicus KW - Tosyl Compounds -- pharmacology KW - Nitriles -- pharmacology KW - Gene Silencing KW - Humans KW - Disease Progression KW - Cell Line, Tumor KW - Cell Proliferation KW - Protein Binding KW - Anilides -- pharmacology KW - Gene Expression Profiling KW - Nuclear Receptor Coactivator 3 -- metabolism KW - Alternative Splicing KW - Drug Resistance, Neoplasm -- genetics KW - Middle Aged KW - Response Elements KW - RNA Interference KW - Antineoplastic Agents -- pharmacology KW - Cluster Analysis KW - Male KW - Androgens -- metabolism KW - Prostatic Neoplasms, Castration-Resistant -- diagnosis KW - Gene Expression Regulation, Neoplastic KW - Prostatic Neoplasms, Castration-Resistant -- metabolism KW - MicroRNAs -- genetics KW - Receptors, Androgen -- genetics KW - Heterogeneous-Nuclear Ribonucleoprotein Group F-H -- metabolism KW - Prostatic Neoplasms, Castration-Resistant -- genetics KW - Receptors, Androgen -- metabolism KW - Heterogeneous-Nuclear Ribonucleoprotein Group F-H -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777985852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Dysregulation+of+miR-212+Promotes+Castration+Resistance+through+hnRNPH1-Mediated+Regulation+of+AR+and+AR-V7%3A+Implications+for+Racial+Disparity+of+Prostate+Cancer.&rft.au=Yang%2C+Yijun%3BJia%2C+Dingwu%3BKim%2C+Hogyoung%3BAbd+Elmageed%2C+Zakaria+Y%3BDatta%2C+Amrita%3BDavis%2C+Rodney%3BSrivastav%2C+Sudesh%3BMoroz%2C+Krzysztof%3BCrawford%2C+Byron+E%3BMoparty%2C+Krishnarao%3BThomas%2C+Raju%3BHudson%2C+Robert+S%3BAmbs%2C+Stefan%3BAbdel-Mageed%2C+Asim+B&rft.aulast=Yang&rft.aufirst=Yijun&rft.date=2016-04-01&rft.volume=22&rft.issue=7&rft.spage=1744&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-1606 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-19 N1 - Date created - 2016-04-02 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-1606 ER - TY - JOUR T1 - Microbial sphingomyelinase induces RhoA-mediated reorganization of the apical brush border membrane and is protective against invasion. AN - 1777983122; 26864627 AB - The apical brush border membrane (BBM) of intestinal epithelial cells forms a highly structured and dynamic environmental interface that serves to regulate cellular physiology and block invasion by intestinal microbes and their products. How the BBM dynamically responds to pathogenic and commensal bacterial signals can define intestinal homeostasis and immune function. We previously found that in model intestinal epithelium, the conversion of apical membrane sphingomyelin to ceramide by exogenous bacterial sphingomyelinase (SMase) protected against the endocytosis and toxicity of cholera toxin. Here we elucidate a mechanism of action by showing that SMase induces a dramatic, reversible, RhoA-dependent alteration of the apical cortical F-actin network. Accumulation of apical membrane ceramide is necessary and sufficient to induce the actin phenotype, and this coincides with altered membrane structure and augmented innate immune function as evidenced by resistance to invasion by Salmonella. © 2016 Saslowsky, Thiagarajah, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). JF - Molecular biology of the cell AU - Saslowsky, David E AU - Thiagarajah, Jay R AU - McCormick, Beth A AU - Lee, Jean C AU - Lencer, Wayne I AD - Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA 02115 Harvard Digestive Diseases Center, Boston Children's Hospital, Boston, MA 02115 Harvard Medical School, Boston, MA 02115 david.saslowsky@nih.gov. ; Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA 02115 Harvard Digestive Diseases Center, Boston Children's Hospital, Boston, MA 02115 Harvard Medical School, Boston, MA 02115. ; Harvard Digestive Diseases Center, Boston Children's Hospital, Boston, MA 02115 Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655. ; Harvard Medical School, Boston, MA 02115 Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 1120 EP - 1130 VL - 27 IS - 7 KW - Actins KW - 0 KW - Ceramides KW - Sphingomyelin Phosphodiesterase KW - EC 3.1.4.12 KW - rhoA GTP-Binding Protein KW - EC 3.6.5.2 KW - Index Medicus KW - Bacterial Infections -- metabolism KW - Humans KW - Bacterial Infections -- immunology KW - Immunity, Innate KW - Salmonella typhimurium KW - Ceramides -- biosynthesis KW - Staphylococcus aureus -- enzymology KW - Microvilli -- microbiology KW - Microvilli -- immunology KW - Intestinal Mucosa -- immunology KW - Microvilli -- metabolism KW - Sphingomyelin Phosphodiesterase -- metabolism KW - Intestinal Mucosa -- microbiology KW - Actin Cytoskeleton -- immunology KW - Intestinal Mucosa -- metabolism KW - Actin Cytoskeleton -- microbiology KW - rhoA GTP-Binding Protein -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777983122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Microbial+sphingomyelinase+induces+RhoA-mediated+reorganization+of+the+apical+brush+border+membrane+and+is+protective+against+invasion.&rft.au=Saslowsky%2C+David+E%3BThiagarajah%2C+Jay+R%3BMcCormick%2C+Beth+A%3BLee%2C+Jean+C%3BLencer%2C+Wayne+I&rft.aulast=Saslowsky&rft.aufirst=David&rft.date=2016-04-01&rft.volume=27&rft.issue=7&rft.spage=1120&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=1939-4586&rft_id=info:doi/10.1091%2Fmbc.E15-05-0293 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-13 N1 - Date created - 2016-03-31 N1 - Date revised - 2017-01-26 N1 - SuppNotes - Cited By: J Biol Chem. 2013 Sep 6;288(36):25804-9 [23884419] J Clin Invest. 1988 Nov;82(5):1516-24 [3141478] Biochemistry. 1988 Aug 23;27(17):6197-202 [3064805] Infect Immun. 1989 Apr;57(4):1290-8 [2647635] J Cell Biol. 1989 Oct;109(4 Pt 1):1597-608 [2507553] J Cell Biol. 1991 Jun;113(6):1267-79 [2045412] J Cell Sci. 1991 Jun;99 ( Pt 2):283-96 [1909337] Annu Rev Cell Biol. 1991;7:337-74 [1839710] J Clin Invest. 1992 May;89(5):1501-11 [1569187] J Biol Chem. 1994 Feb 4;269(5):3125-8 [8106344] J Clin Invest. 1995 Mar;95(3):1026-31 [7883950] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10094-8 [7479732] Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10629-33 [7479854] Mol Microbiol. 1995 Nov;18(3):479-90 [8748032] Mol Microbiol. 1995 Nov;18(4):715-27 [8817493] Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12895-900 [25136128] World J Gastroenterol. 2004 Jun 15;10(12):1802-5 [15188510] Cell. 2004 Jul 23;118(2):203-16 [15260990] Immunol Lett. 2004 Jul 15;94(3):247-52 [15275973] Am J Physiol Cell Physiol. 2004 Nov;287(5):C1453-62 [15294854] Biochem Biophys Res Commun. 2004 Nov 12;324(2):901-8 [15474513] Biochem Soc Trans. 1984 Apr;12(2):198-200 [6427037] Gastroenterology. 1987 May;92(5 Pt 1):1133-45 [3557010] Infect Immun. 1987 Dec;55(12):3103-10 [3679545] Am J Physiol. 1988 Mar;254(3 Pt 1):G416-23 [3279816] Toxicol Appl Pharmacol. 1997 Jan;142(1):208-25 [9007051] Arch Biochem Biophys. 1997 Apr 1;340(1):101-10 [9126282] Nature. 1997 Jun 5;387(6633):569-72 [9177342] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7661-6 [9207149] Am J Physiol. 1997 Nov;273(5 Pt 1):G1014-22 [9374697] Biochem Biophys Res Commun. 1998 Apr 28;245(3):684-90 [9588175] J Biol Chem. 1998 Aug 28;273(35):22298-304 [9712847] Curr Opin Cell Biol. 1999 Feb;11(1):109-16 [10047517] Mol Microbiol. 1999 Aug;33(3):510-23 [10417642] J Biol Chem. 2005 Jun 24;280(25):24072-84 [15840575] J Cell Sci. 2005 Nov 15;118(Pt 22):5325-34 [16263765] Biochim Biophys Acta. 2006 Feb;1758(2):145-53 [16580624] Biochemistry. 2006 Sep 26;45(38):11247-56 [16981685] Cell Microbiol. 2008 Jan;10(1):67-80 [18052945] J Cell Biol. 2008 Apr 21;181(2):335-50 [18426979] FEBS Lett. 2008 Sep 22;582(21-22):3230-6 [18755187] FASEB J. 2009 Jan;23(1):259-70 [18820034] Science. 2010 Jan 1;327(5961):46-50 [20044567] Cell. 2010 Feb 19;140(4):540-53 [20178746] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13795-800 [10570152] Shock. 2000 Dec;14(6):629-34 [11131913] J Cell Sci. 2001 Apr;114(Pt 7):1331-41 [11256999] Clin Microbiol Rev. 2001 Jul;14(3):584-640 [11432815] Gastroenterology. 2001 Sep;121(3):566-79 [11522741] J Neurochem. 2001 Oct;79(2):339-48 [11677262] J Cell Biol. 2001 Oct 29;155(3):331-8 [11684704] Science. 2002 Apr 19;296(5567):535-9 [11964480] J Biol Chem. 2002 May 3;277(18):16249-56 [11859071] Nat Rev Mol Cell Biol. 2002 Aug;3(8):586-99 [12154370] Nat Med. 2003 Mar;9(3):322-30 [12563314] J Lipid Res. 2003 Aug;44(8):1574-80 [12777467] Curr Top Microbiol Immunol. 2004;282:117-63 [14594216] J Biol Chem. 2004 Mar 12;279(11):9997-10004 [14699154] Traffic. 2004 Apr;5(4):241-6 [15030565] Mol Biol Cell. 2004 Jun;15(6):2639-51 [15047870] J Mol Med (Berl). 2004 Jun;82(6):357-63 [15069600] Dev Cell. 2004 Jun;6(6):855-64 [15177033] PLoS One. 2011;6(3):e16953 [21408067] Mol Cell Biol. 2012 Apr;32(8):1396-407 [22331463] Cell. 2012 Jun 8;149(6):1353-67 [22682254] N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1091/mbc.E15-05-0293 ER - TY - JOUR T1 - A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. AN - 1777981979; 26260164 AB - Nephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals. Copyright © 2016 by the American Society of Nephrology. JF - Journal of the American Society of Nephrology : JASN AU - Adler, Melanie AU - Ramm, Susanne AU - Hafner, Marc AU - Muhlich, Jeremy L AU - Gottwald, Esther Maria AU - Weber, Elijah AU - Jaklic, Alenka AU - Ajay, Amrendra Kumar AU - Svoboda, Daniel AU - Auerbach, Scott AU - Kelly, Edward J AU - Himmelfarb, Jonathan AU - Vaidya, Vishal S AD - Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, Massachusetts; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; ; Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, Massachusetts; ; Department of Pharmaceutics, University of Washington, Seattle, Washington; ; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; ; Social and Scientific Systems, Durham, North Carolina; ; National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; ; Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington; and. ; Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, Massachusetts; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts vvaidya@bwh.harvard.edu. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 1015 EP - 1028 VL - 27 IS - 4 KW - Biomarkers KW - 0 KW - Heme Oxygenase-1 KW - EC 1.14.14.18 KW - Index Medicus KW - nephrotoxicity KW - tubule cells KW - acute renal failure KW - Cells, Cultured KW - Humans KW - Biomarkers -- analysis KW - Kidney Tubules, Proximal -- cytology KW - Kidney Diseases -- genetics KW - Heme Oxygenase-1 -- biosynthesis KW - Heme Oxygenase-1 -- analysis KW - Toxicity Tests -- methods KW - Kidney Diseases -- enzymology KW - Heme Oxygenase-1 -- genetics KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777981979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Society+of+Nephrology+%3A+JASN&rft.atitle=A+Quantitative+Approach+to+Screen+for+Nephrotoxic+Compounds+In+Vitro.&rft.au=Adler%2C+Melanie%3BRamm%2C+Susanne%3BHafner%2C+Marc%3BMuhlich%2C+Jeremy+L%3BGottwald%2C+Esther+Maria%3BWeber%2C+Elijah%3BJaklic%2C+Alenka%3BAjay%2C+Amrendra+Kumar%3BSvoboda%2C+Daniel%3BAuerbach%2C+Scott%3BKelly%2C+Edward+J%3BHimmelfarb%2C+Jonathan%3BVaidya%2C+Vishal+S&rft.aulast=Adler&rft.aufirst=Melanie&rft.date=2016-04-01&rft.volume=27&rft.issue=4&rft.spage=1015&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Society+of+Nephrology+%3A+JASN&rft.issn=1533-3450&rft_id=info:doi/10.1681%2FASN.2015010060 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-11 N1 - Date created - 2016-04-01 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Am J Nephrol. 2011;33(5):414-20 [21502755] Drug Discov Today. 2010 Dec;15(23-24):997-1007 [20708096] Environ Health Perspect. 2011 Aug;119(8):1142-8 [21543282] AAPS J. 2011 Dec;13(4):615-31 [21969220] Biomaterials. 2012 Jun;33(18):4700-11 [22444643] J Am Soc Nephrol. 2012 Jun;23(6):1048-57 [22440905] AAPS J. 2012 Sep;14(3):473-80 [22528508] Pflugers Arch. 2012 Dec;464(6):601-11 [23014881] J Antimicrob Chemother. 2013 Jul;68(7):1655-9 [23557927] Environ Health Perspect. 2013 Jul;121(7):756-65 [23603828] Nat Chem Biol. 2013 Aug;9(8):514-20 [23728495] Trans Am Clin Climatol Assoc. 2013;124:111-22 [23874015] Drug Discov Today. 2013 Aug;18(15-16):716-23 [23732176] Curr Opin Nephrol Hypertens. 2014 Jan;23(1):17-24 [24275768] Stem Cell Res Ther. 2013;4 Suppl 1:S17 [24564863] Mol Pharm. 2014 Jul 7;11(7):1982-90 [24495215] Nat Biotechnol. 2014 Aug;32(8):760-72 [25093883] Expert Opin Drug Metab Toxicol. 2014 Dec;10(12):1621-35 [25382677] Neuron. 2000 Nov;28(2):461-73 [11144356] Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):641-8 [11563082] J Pharmacol Exp Ther. 2002 Mar;300(3):918-24 [11861798] Nucleic Acids Res. 2003 Feb 15;31(4):e15 [12582260] Biostatistics. 2003 Apr;4(2):249-64 [12925520] J Biol Chem. 2003 Sep 26;278(39):37561-8 [12860979] Am J Physiol. 1985 Apr;248(4 Pt 2):F536-44 [3985161] Kidney Int. 1994 Jan;45(1):48-57 [8127021] Clin Cancer Res. 2005 May 15;11(10):3790-8 [15897578] Toxicology. 2006 Dec 7;228(2-3):200-18 [16997449] Nat Rev Cancer. 2007 Jan;7(1):54-60 [17186018] Genome Biol. 2006;7(7):R61 [16859521] Clin Sci (Lond). 2007 Apr;112(8):429-40 [17147518] Bioconjug Chem. 2007 Mar-Apr;18(2):494-9 [17279724] Toxicology. 2008 Feb 3;244(1):56-65 [18055091] Pharmacol Rev. 2008 Mar;60(1):79-127 [18323402] Clin J Am Soc Nephrol. 2009 Jul;4(7):1275-83 [19520747] Nature. 2009 Jul 9;460(7252):208-12 [19587762] Annu Rev Pharmacol Toxicol. 2010;50:323-54 [20055707] Adv Chronic Kidney Dis. 2010 May;17(3):254-64 [20439094] Clin Transl Sci. 2008 Dec;1(3):200-8 [19212447] Nat Biotechnol. 2010 May;28(5):436-40 [20458311] Nat Biotechnol. 2010 May;28(5):478-85 [20458318] Diabetes Technol Ther. 2011 Jul;13(7):743-51 [21510766] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1681/ASN.2015010060 ER - TY - JOUR T1 - Bisphenol A, Bisphenol S, and 4-Hydro​xyphenyl 4-Isopro​oxyphenyl​sulfone (BPSIP) in Urine and Blood of Cashiers. AN - 1777980946; 26309242 AB - Bisphenol A (BPA) is a high-production-volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products, including cash register receipt paper; however, little is known about exposure of cashiers to BPA and alternative compounds in receipt paper. We determined whether handling receipt paper results in measurable absorption of BPA or the BPA alternatives bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP). Cashiers (n = 77) and non-cashiers (n = 25) were recruited from the Raleigh-Durham-Chapel Hill region of North Carolina during 2011-2013. Receipts were analyzed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2 hr after completing a shift) were compared with pre-shift samples. Levels of these compounds in urine from cashiers were compared to levels in urine from non-cashiers. Each receipt contained 1-2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. The mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as to increase after a shift, but the mean post-shift concentrations were significantly higher than those in non-cashiers. BPSIP was detected more frequently in the urine of cashiers handling BPSIP receipts than in the urine of non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently. Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP. Thayer KA, Taylor KW, Garantziotis S, Schurman SH, Kissling GE, Hunt D, Herbert B, Church R, Jankowich R, Churchwell MI, Scheri RC, Birnbaum LS, Bucher JR. 2016. Bisphenol A, bisphenol S, and 4-hydro​xyphenyl 4-isopro​oxyphenyl​sulfone (BPSIP) in urine and blood of cashiers. Environ Health Perspect 124:437-444; http://dx.doi.org/10.1289/ehp.1409427. JF - Environmental health perspectives AU - Thayer, Kristina A AU - Taylor, Kyla W AU - Garantziotis, Stavros AU - Schurman, Shepherd H AU - Kissling, Grace E AU - Hunt, Dawn AU - Herbert, Brenda AU - Church, Rebecca AU - Jankowich, Rachael AU - Churchwell, Mona I AU - Scheri, Richard C AU - Birnbaum, Linda S AU - Bucher, John R AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 437 EP - 444 VL - 124 IS - 4 KW - 4-hydroxyphenyl 4-isopropoxyphenylsulfone KW - 0 KW - Benzhydryl Compounds KW - Phenols KW - Sulfones KW - bis(4-hydroxyphenyl)sulfone KW - 80-09-1 KW - bisphenol A KW - MLT3645I99 KW - Index Medicus KW - Humans KW - North Carolina KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Sulfones -- blood KW - Paper KW - Phenols -- blood KW - Sulfones -- urine KW - Benzhydryl Compounds -- blood KW - Phenols -- urine KW - Occupational Exposure -- analysis KW - Benzhydryl Compounds -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777980946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Bisphenol+A%2C+Bisphenol+S%2C+and+4-Hydro%E2%80%8Bxyphenyl+4-Isopro%E2%80%8Boxyphenyl%E2%80%8Bsulfone+%28BPSIP%29+in+Urine+and+Blood+of+Cashiers.&rft.au=Thayer%2C+Kristina+A%3BTaylor%2C+Kyla+W%3BGarantziotis%2C+Stavros%3BSchurman%2C+Shepherd+H%3BKissling%2C+Grace+E%3BHunt%2C+Dawn%3BHerbert%2C+Brenda%3BChurch%2C+Rebecca%3BJankowich%2C+Rachael%3BChurchwell%2C+Mona+I%3BScheri%2C+Richard+C%3BBirnbaum%2C+Linda+S%3BBucher%2C+John+R&rft.aulast=Thayer&rft.aufirst=Kristina&rft.date=2016-04-01&rft.volume=124&rft.issue=4&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1409427 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-24 N1 - Date created - 2016-04-02 N1 - Date revised - 2017-01-26 N1 - SuppNotes - Cited By: Environ Sci Technol. 2011 Nov 1;45(21):9372-9 [21939283] PLoS One. 2014;9(10):e110509 [25337790] Environ Sci Technol. 2012 Jun 19;46(12):6860-6 [22620267] Environ Sci Technol. 2012 Aug 21;46(16):9138-45 [22784190] Toxicol Lett. 2012 Sep 18;213(3):305-8 [22796587] Sci Total Environ. 2012 Oct 1;435-436:30-3 [22846760] Environ Sci Technol. 2012 Nov 6;46(21):11558-65 [23020513] Environ Health Perspect. 2013 Mar;121(3):283-6 [23458838] J Agric Food Chem. 2013 May 15;61(19):4655-62 [23614805] Chemosphere. 2013 Aug;92(9):1190-4 [23484460] Environ Res. 2013 Oct;126:211-4 [23899777] Food Chem Toxicol. 2013 Dec;62:949-63 [23959105] JAMA. 2014 Feb 26;311(8):859-60 [24570250] Breast Cancer Res. 2013;15(5):403 [24083327] J Toxicol Environ Health A. 2008;71(8):471-3 [18338280] NTP CERHR MON. 2008 Sep;(22):v, vii-ix, 1-64 passim [19407859] Reprod Toxicol. 2010 Aug;30(1):131-7 [20214975] Anal Bioanal Chem. 2010 Sep;398(1):571-6 [20623271] Toxicol Appl Pharmacol. 2010 Oct 1;248(1):1-11 [20655935] Rapid Commun Mass Spectrom. 2010 Oct 30;24(20):3011-20 [20872634] Environ Health Perspect. 2011 Jan;119(1):131-7 [21205581] Arch Toxicol. 2011 Sep;85(9):1035-43 [21287149] Toxicol Sci. 2011 Sep;123(1):48-57 [21705716] Toxicol Sci. 2014 May;139(1):4-20 [24496641] Arch Environ Contam Toxicol. 2014 Jul;67(1):50-9 [24639116] Toxicol Lett. 2014 Nov 4;230(3):413-20 [25175590] Environ Sci Technol. 2012 Jun 19;46(12):6515-22 [22591511] N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1289/ehp.1409427 ER - TY - JOUR T1 - Informing 21st-Century Risk Assessments with 21st-Century Science. AN - 1777979389; 27035154 AB - Understanding and preventing adverse impacts from chemicals in the environment is fundamental to protecting public health, and chemical risk assessments are used to inform public health decisions in the United States and around the world. Traditional chemical risk assessments focus on health effects of environmental contaminants on a chemical-by-chemical basis, largely based on data from animal models using exposures that are typically higher than those experienced by humans. Results from environmental epidemiology studies sometimes show effects that are not observed in animal studies at human exposure levels that are lower than those used in animal studies. In addition, new approaches such as Toxicology in the 21st Century (Tox21) and exposure forecasting (ExpoCast) are generating mechanistic data that provide broad coverage of chemical space, chemical mixtures, and potential associated health outcomes, along with improved exposure estimates. It is becoming clear that risk assessments in the future will need to use the full range of available mechanistic, animal, and human data to integrate multiple types of data and to consider nontraditional health outcomes and end points. This perspective was developed at the "Strengthening the Scientific Basis of Chemical Safety Assessments" workshop, which was cosponsored by the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences, where gaps between the emerging science and traditional chemical risk assessments were explored, and approaches for bridging the gaps were considered. JF - Environmental health perspectives AU - Birnbaum, Linda S AU - Burke, Thomas A AU - Jones, James J AD - Office of the Director, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - A60 EP - A63 VL - 124 IS - 4 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - United States KW - Animals KW - United States Environmental Protection Agency KW - Environmental Health KW - Humans KW - Computational Biology -- methods KW - Forecasting KW - Environmental Exposure -- adverse effects KW - National Institute of Environmental Health Sciences (U.S.) KW - Environmental Pollutants -- toxicity KW - Toxicology -- methods KW - Risk Assessment -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777979389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Informing+21st-Century+Risk+Assessments+with+21st-Century+Science.&rft.au=Birnbaum%2C+Linda+S%3BBurke%2C+Thomas+A%3BJones%2C+James+J&rft.aulast=Birnbaum&rft.aufirst=Linda&rft.date=2016-04-01&rft.volume=124&rft.issue=4&rft.spage=A60&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1511135 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-24 N1 - Date created - 2016-04-02 N1 - Date revised - 2017-01-26 N1 - SuppNotes - Cited By: Environ Health Perspect. 2015 May;123(5):458-66 [25622337] Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):E4901-10 [26283345] N1 - Last updated - 2017-01-26 DO - http://dx.doi.org/10.1289/ehp.1511135 ER - TY - JOUR T1 - Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States. AN - 1777487787; 26548585 AB - We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PI-containing as opposed to NNRTI-containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children. JF - AIDS research and human retroviruses AU - Kirmse, Brian AU - Yao, Tzy-Jyun AU - Hofherr, Sean AU - Kacanek, Deborah AU - Williams, Paige L AU - Hobbs, Charlotte V AU - Hazra, Rohan AU - Borkowsky, William AU - Van Dyke, Russell B AU - Summar, Marshall AD - 1 Children's National Health System , Division of Genetics & Metabolism, Washington, DC. ; 2 Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research , Boston, Massachusetts. ; 3 New York University/Langone School of Medicine , Division of Pediatric Infectious Disease and Immunology, New York, New York. ; 4 National Institutes of Health (NICHD) , Maternal and Pediatric Infectious Disease Branch, Bethesda, Maryland. ; 5 Tulane University School of Medicine , New Orleans, Louisiana. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 339 EP - 348 VL - 32 IS - 4 KW - Anti-HIV Agents KW - 0 KW - acylcarnitine KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - AIDS/HIV KW - United States KW - Infant KW - Young Adult KW - Humans KW - Cohort Studies KW - Adult KW - Infant, Newborn KW - Child Development -- drug effects KW - Male KW - Female KW - Pregnancy KW - Child, Preschool KW - Carnitine -- blood KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects KW - Anti-HIV Agents -- administration & dosage KW - Carnitine -- analogs & derivatives KW - Pregnancy Complications, Infectious -- drug therapy KW - Maternal Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777487787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Acylcarnitine+Profiles+in+HIV-Exposed%2C+Uninfected+Neonates+in+the+United+States.&rft.au=Kirmse%2C+Brian%3BYao%2C+Tzy-Jyun%3BHofherr%2C+Sean%3BKacanek%2C+Deborah%3BWilliams%2C+Paige+L%3BHobbs%2C+Charlotte+V%3BHazra%2C+Rohan%3BBorkowsky%2C+William%3BVan+Dyke%2C+Russell+B%3BSummar%2C+Marshall&rft.aulast=Kirmse&rft.aufirst=Brian&rft.date=2016-04-01&rft.volume=32&rft.issue=4&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=AIDS+research+and+human+retroviruses&rft.issn=1931-8405&rft_id=info:doi/10.1089%2FAID.2015.0112 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-30 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Acquir Immune Defic Syndr. 2001 Aug 15;27(5):426-31 [11511818] Am J Obstet Gynecol. 2002 Sep;187(3):715-20 [12237653] N Engl J Med. 2003 Jun 5;348(23):2304-12 [12788994] Dev Biol. 1972 Aug;28(4):537-44 [5049524] Eur J Pediatr. 1995 Nov;154(11):871-7 [8582396] N Engl J Med. 2005 Jan 6;352(1):48-62 [15635112] Hepatology. 2005 Apr;41(4):717-21 [15791615] J Clin Endocrinol Metab. 2005 Jun;90(6):3251-61 [15741249] Endocrine. 2012 Feb;41(1):1-10 [22134974] Annu Rev Physiol. 2012;74:107-30 [21910625] Cell. 2012 Mar 2;148(5):852-71 [22385956] Am Heart J. 2012 May;163(5):844-850.e1 [22607863] J Acquir Immune Defic Syndr. 2012 Aug 15;60 Suppl 3:S96-104 [22797746] Hepatology. 2012 Aug;56(2):594-604 [22407670] Diabetes. 2013 Jan;62(1):1-8 [23258903] Semin Fetal Neonatal Med. 2013 Feb;18(1):48-55 [23164810] Pediatr Infect Dis J. 2013 Feb;32(2):146-50 [22935866] J Infect Dis. 2013 Feb 15;207(4):612-21 [23204173] Heredity (Edinb). 2013 Mar;110(3):253-8 [23149456] PLoS One. 2013;8(4):e61743 [23637898] BMC Infect Dis. 2013;13:203 [23641933] Dev Disabil Res Rev. 2013;17(3):260-8 [23798014] J Inherit Metab Dis. 2013 Jul;36(4):645-58 [23674167] Pediatr Infect Dis J. 2013 Jun;32(6):648-55 [23340561] Pediatr Infect Dis J. 2013 Oct;32(10):e406-13 [24067563] Pediatrics. 2014 Jul;134(1):e37-46 [24913786] Hum Genet. 2014 Aug;133(8):1049-57 [24850141] Pediatr Res. 2005 Jun;57(6):755-9 [15845636] Eur J Clin Nutr. 2007 Dec;61(12):1380-5 [17299469] Genet Med. 2008 Feb;10(2):151-6 [18281923] Lancet. 2008 Jan 26;371(9609):340-57 [18206223] Mol Genet Metab. 2008 May;94(1):16-37 [18243024] Antivir Ther. 2008;13(3):349-55 [18572747] J Nutr. 2009 Jun;139(6):1073-81 [19369366] Biochim Biophys Acta. 2010 May;1801(5):559-66 [20117238] J Inherit Metab Dis. 2010 Oct;33(5):501-6 [20049534] J Inherit Metab Dis. 2010 Oct;33(5):547-53 [20151199] J Inherit Metab Dis. 2010 Oct;33(5):555-61 [20830526] Pediatrics. 2010 Nov;126(5):910-6 [20974783] AIDS Behav. 2010 Dec;14(6):1269-78 [20532607] Methods Mol Biol. 2011;708:55-72 [21207283] AIDS Res Hum Retroviruses. 2011 Jul;27(7):777-83 [21142587] J Acquir Immune Defic Syndr. 2011 Aug 1;57(4):290-6 [21602695] Pediatrics. 2011 Oct;128(4):715-22 [21930552] AIDS Patient Care STDS. 2011 Jul;25(7):385-94 [21992592] Drugs. 2011 Nov 12;71(16):2131-49 [22035514] Pediatr Infect Dis J. 2011 Dec;30(12):1069-74 [22051859] Trends Pharmacol Sci. 2011 Dec;32(12):715-25 [21899897] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1089/AID.2015.0112 ER - TY - JOUR T1 - Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice. AN - 1777076812; 26865715 AB - Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies ofMus musculus Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions ofenvproduced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome.envvariations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region ofenv Outside theenvregion, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributedMussubspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents. Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter- and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Journal of virology AU - Bamunusinghe, Devinka AU - Naghashfar, Zohreh AU - Buckler-White, Alicia AU - Plishka, Ronald AU - Baliji, Surendranath AU - Liu, Qingping AU - Kassner, Joshua AU - Oler, Andrew J AU - Hartley, Janet AU - Kozak, Christine A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. ; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. ; Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. ; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA ckozak@niaid.nih.gov. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 4186 EP - 4198 VL - 90 IS - 8 KW - RNA, Viral KW - 0 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Base Sequence KW - Animals, Laboratory -- virology KW - Molecular Sequence Data KW - Sequence Analysis, RNA KW - Genome, Viral KW - Animals, Wild -- virology KW - Genes, pol KW - Genetic Variation KW - Leukemia Virus, Murine -- genetics KW - Mice -- genetics KW - Leukemia Virus, Murine -- classification KW - Mice -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777076812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Sequence+Diversity%2C+Intersubgroup+Relationships%2C+and+Origins+of+the+Mouse+Leukemia+Gammaretroviruses+of+Laboratory+and+Wild+Mice.&rft.au=Bamunusinghe%2C+Devinka%3BNaghashfar%2C+Zohreh%3BBuckler-White%2C+Alicia%3BPlishka%2C+Ronald%3BBaliji%2C+Surendranath%3BLiu%2C+Qingping%3BKassner%2C+Joshua%3BOler%2C+Andrew+J%3BHartley%2C+Janet%3BKozak%2C+Christine+A&rft.aulast=Bamunusinghe&rft.aufirst=Devinka&rft.date=2016-04-01&rft.volume=90&rft.issue=8&rft.spage=4186&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=1098-5514&rft_id=info:doi/10.1128%2FJVI.03186-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-04 N1 - Date created - 2016-03-29 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Bioinformatics. 2014 Aug 1;30(15):2114-20 [24695404] Bioinformatics. 2014 Oct 15;30(20):2843-51 [24974202] Viruses. 2015 Jan;7(1):1-26 [25549291] Bioinformatics. 2000 Apr;16(4):400-1 [10869039] Genome Res. 2000 Sep;10(9):1307-18 [10984449] J Virol. 2001 Jun;75(11):5049-58 [11333885] Genome Res. 2002 Apr;12(4):656-64 [11932250] Genome Res. 2002 Jun;12(6):996-1006 [12045153] Virology. 2003 Mar 30;308(1):83-91 [12706092] J Virol. 2003 Dec;77(23):12773-81 [14610199] Virology. 2004 Jan 5;318(1):183-91 [14972546] Science. 1971 Oct 8;174(4005):155-6 [4330367] Science. 1973 Dec 14;182(4117):1151-3 [4356281] Virology. 1975 May;65(1):128-34 [167514] Nature. 1982 Jan 7;295(5844):25-31 [6276750] J Virol. 1982 Jul;43(1):26-36 [6287001] J Virol. 1983 Jan;45(1):1-9 [6296423] Proc Natl Acad Sci U S A. 1975 Dec;72(12):5150-5 [1061100] J Virol. 1976 Jul;19(1):13-8 [181592] J Virol. 1976 Jul;19(1):19-25 [59816] Proc Natl Acad Sci U S A. 1977 Feb;74(2):789-92 [191826] Virology. 1977 Dec;83(2):449-52 [929987] Science. 1978 Mar 31;199(4336):1448-9 [204014] Curr Top Microbiol Immunol. 1978;79:215-59 [206407] Clin Immunol Immunopathol. 1980 Mar;15(3):493-501 [7371228] J Virol. 1980 Nov;36(2):499-505 [6253673] J Virol. 1981 Sep;39(3):777-91 [6270351] J Virol. 1984 Jul;51(1):77-80 [6328046] J Virol. 1984 Nov;52(2):695-8 [6092693] Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1655-60 [17234809] Nat Genet. 2007 Sep;39(9):1100-7 [17660819] J Virol. 2007 Oct;81(19):10550-7 [17634227] PLoS Genet. 2007 Oct;3(10):2014-22 [17967065] Bioinformatics. 2009 May 1;25(9):1105-11 [19289445] Proc Natl Acad Sci U S A. 1985 Jan;82(2):459-63 [2578666] Virology. 1985 Jan 30;140(2):239-48 [2982233] J Virol. 1985 Sep;55(3):768-77 [2991595] J Virol. 1987 Jul;61(7):2225-31 [3035222] J Virol. 1987 Sep;61(9):2659-69 [3039159] J Virol. 1987 Oct;61(10):3082-8 [3041030] Mol Biol Evol. 1987 Jul;4(4):406-25 [3447015] Virology. 1988 Aug;165(2):469-75 [2841796] J Virol. 1989 Apr;63(4):1763-74 [2564439] Cell. 1989 May 19;57(4):659-66 [2541919] Genetics. 1989 May;122(1):181-92 [2731728] Virology. 1989 Nov;173(1):58-67 [2554579] J Virol. 1990 Feb;64(2):757-66 [2153240] Genetics. 1990 Feb;124(2):221-36 [2155154] J Virol. 1991 Mar;65(3):1273-85 [1847454] J Virol. 1991 Apr;65(4):1796-802 [1672163] Nucleic Acids Res. 1991 Apr 11;19(7):1707 [1840655] J Virol. 1991 Sep;65(9):4619-28 [1870192] J Virol. 1992 Mar;66(3):1468-75 [1310758] Comput Appl Biosci. 1992 Jun;8(3):275-82 [1633570] J Virol. 1993 Jun;67(6):3489-96 [7684467] J Virol. 1993 Jul;67(7):4056-61 [8510216] Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):78-82 [8278411] J Biomol Struct Dyn. 1994 Feb;11(4):821-36 [8204217] EMBO J. 1997 Mar 17;16(6):1214-23 [9135138] Genome. 1998 Feb;41(1):104-10 [9549063] J Virol. 1998 Jul;72(7):5383-91 [9620992] J Virol. 1998 Dec;72(12):9955-65 [9811733] J Virol. 1999 May;73(5):4327-40 [10196331] J Virol. 1999 Nov;73(11):9362-8 [10516044] Int J Cancer. 2006 Oct 15;119(8):1869-77 [16708391] Virol J. 2006;3:101 [17147829] Retrovirology. 2009;6:87 [19811656] Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15666-7 [20798036] J Virol. 2010 Nov;84(22):11970-80 [20844050] J Virol. 2010 Dec;84(24):12841-9 [20943975] Retrovirology. 2010;7:101 [21118532] PLoS One. 2011;6(6):e20874 [21698104] Nat Genet. 2011 Jul;43(7):648-55 [21623374] Science. 2011 Jul 1;333(6038):97-101 [21628392] Nature. 2011 Sep 15;477(7364):289-94 [21921910] Cancer Biol Ther. 2011 Oct 1;12(7):617-28 [21750403] BMC Bioinformatics. 2012;13 Suppl 3:S13 [22536897] J Virol. 2012 Sep;86(17):9096-104 [22696659] J Virol. 2013 Sep;87(17):9845-55 [23824809] Mol Biol Evol. 2013 Dec;30(12):2725-9 [24132122] Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8595-600 [24912157] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1128/JVI.03186-15 ER - TY - JOUR T1 - Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls. AN - 1777075717; 26721301 AB - An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer's disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V), and zinc (Zn) using inductively coupled plasma sector field mass spectrometry. All metals, with exception of equivalent Pb levels, were lower in the VF, compared to FC. Within-subject comparisons demonstrated that VF levels were not representative of levels within brain tissue. The essential metals Cu, Fe, and Zn were found highest in both compartments. Cd, Hg, and V levels in the VF were below the limit of quantification. In AD cases, FC levels of Fe were higher and As and Cd were lower than levels in controls, while levels of As in the VF were higher. Parameter estimates for FC metal levels indicated an association of Braak stage and higher Fe levels and an association of Braak stage and lower As, Mn, and Zn levels. The data showed no evidence of an accumulation of nonessential metals within the AD brain and, with the exception of As, showed no significant shift in the ratio of FC to VF levels to indicate differential clearance. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Szabo, Steven T AU - Harry, G Jean AU - Hayden, Kathleen M AU - Szabo, David T AU - Birnbaum, Linda AD - *Veterans Affairs Medical Center, Mental Health Service Line, Durham, North Carolina 27705; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27705; steven.szabo@duke.edu. ; Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; ; Department of Psychiatry and Behavioral Sciences, Joseph and Kathleen ADRC, Duke University Medical Center, Durham, North Carolina 27705; ; RAI Services Company, Winston Salem, North Carolina 27102; and. ; National Cancer Institute, National Institutes of Health (NIH), Research Triangle Park, North Carolina 27709. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 292 EP - 300 VL - 150 IS - 2 KW - Metals, Heavy KW - 0 KW - Trace Elements KW - Index Medicus KW - amyloid beta KW - neurodegenerative disease KW - brain KW - heavy metals KW - cerebral spinal fluid KW - Autopsy KW - Aged, 80 and over KW - Humans KW - Case-Control Studies KW - Aged KW - Male KW - Female KW - Trace Elements -- cerebrospinal fluid KW - Metals, Heavy -- metabolism KW - Brain -- pathology KW - Metals, Heavy -- cerebrospinal fluid KW - Brain -- metabolism KW - Alzheimer Disease -- cerebrospinal fluid KW - Alzheimer Disease -- metabolism KW - Trace Elements -- metabolism KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777075717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Comparison+of+Metal+Levels+between+Postmortem+Brain+and+Ventricular+Fluid+in+Alzheimer%27s+Disease+and+Nondemented+Elderly+Controls.&rft.au=Szabo%2C+Steven+T%3BHarry%2C+G+Jean%3BHayden%2C+Kathleen+M%3BSzabo%2C+David+T%3BBirnbaum%2C+Linda&rft.aulast=Szabo&rft.aufirst=Steven&rft.date=2016-04-01&rft.volume=150&rft.issue=2&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=1096-0929&rft_id=info:doi/10.1093%2Ftoxsci%2Fkfv325 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-27 N1 - Date created - 2016-03-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/toxsci/kfv325 ER - TY - JOUR T1 - Self-Reported Physical Activity Among American Indian Adults From Two Diverse Regions AN - 1776784158 AB - Purpose Physical activity may be a protective factor against the disproportionate rates of chronic diseases faced by American Indians. Nevertheless, few studies report any cultural adoptions made to capture physical activity behaviors among this hard-to-reach population. Existing studies reporting the prevalence of physical activity among American Indians are often aggregated and tend to obscure regional, local, and tribal-level variations. This study examines the prevalence of physical activity and inactivity levels, along with associated factors, among rural dwelling American Indian adults from 2 distinct regions. Methods Baseline self-reported data were collected using a culturally modified version of the International Physical Activity Questionnaire (IPAQ) short form during the Obesity Research Prevention and Evaluation of Intervention Effectiveness in Native North Americans trial (OPREVENT) among rural American Indian adults (aged 18-75 years) from 5 tribal communities in Michigan and New Mexico. Findings Most participants were classified as moderately physically active (43.5%), and the majority reported access to physical activity facilities (83.5%). Michigan participants reported engaging in more moderate and total physical activity than those in New Mexico (P < .001) and reported spending less time sitting (P < .001). Conclusions Differences in physical activity among the American Indian communities may be due to regional variations in occupations, climate, and tribal and community support and infrastructure. The unexpected high level of activity evokes uncertainty in the accuracy and appropriateness of the data collection instrument. Research is needed to understand culturally appropriate approaches to measure physical activity and inactivity among rural American Indians. JF - The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association AU - Roberts, Erica Blue AU - Fleischhacker, Sheila AU - Pardilla, Marla AU - Treuth, Margarita AU - Gadhoke, Preety AU - Christiansen, Karina AU - Gittelsohn, Joel AD - Department of Behavioral and Community Health, School of Public Health, University of Maryland, College Park, Maryland ; The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Office of Nutrition Research, Bethesda, Maryland ; Department of International Health, Center for Human Nutrition, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland ; Department of Kinesiology, University of Maryland Eastern Shore, Princess Anne, Maryland ; Department of Pharmacy Administration and Public Health, College of Pharmacy and Health Sciences, St. John's University, Queens, New York ; Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland Y1 - 2016///Spring PY - 2016 DA - Spring 2016 SP - 146 EP - 155 CY - Washington PB - Wiley Subscription Services, Inc. VL - 32 IS - 2 SN - 0890-765X KW - Public Health And Safety KW - Accuracy KW - Research KW - Diseases KW - Adults KW - American Indians KW - Methodology (Data Collection) KW - Climate KW - Methodology (Data Analysis) KW - Prevention KW - Intervention KW - Effectiveness KW - Expenditures KW - Occupations KW - Obesity KW - Physical Fitness KW - Rural Areas KW - Activities KW - American Indian communities KW - American Indian people KW - Chronic diseases KW - Expenditure KW - Indian communities KW - Infrastructure KW - Physical activity KW - Preventive programmes KW - Regional variations KW - Rural communities KW - Time use KW - Uncertainty KW - New Mexico KW - Michigan UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776784158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Rural+Health+%3A+Official+Journal+of+the+American+Rural+Health+Association+and+the+National+Rural+Health+Care+Association&rft.atitle=Self-Reported+Physical+Activity+Among+American+Indian+Adults+From+Two+Diverse+Regions&rft.au=Roberts%2C+Erica+Blue%3BFleischhacker%2C+Sheila%3BPardilla%2C+Marla%3BTreuth%2C+Margarita%3BGadhoke%2C+Preety%3BChristiansen%2C+Karina%3BGittelsohn%2C+Joel&rft.aulast=Roberts&rft.aufirst=Erica&rft.date=2016-04-01&rft.volume=32&rft.issue=2&rft.spage=146&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Rural+Health+%3A+Official+Journal+of+the+American+Rural+Health+Association+and+the+National+Rural+Health+Care+Association&rft.issn=0890765X&rft_id=info:doi/10.1111%2Fjrh.12168 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA); PAIS Index N1 - Copyright - © 2016 National Rural Health Association N1 - Last updated - 2016-05-25 N1 - SubjectsTermNotLitGenreText - Michigan; New Mexico DO - http://dx.doi.org/10.1111/jrh.12168 ER - TY - JOUR T1 - Preparing for future efficacy trials of severe malaria vaccines AN - 1776668101; PQ0002810420 AB - Severe malaria is a major cause of mortality in children, but comprises only a small proportion of Plasmodium falciparum infections in naturally exposed populations. The evaluation of vaccines that prevent severe falciparum disease will require clinical trials whose primary efficacy endpoint will be severe malaria risk during follow-up. Here, we show that such trials are feasible with fewer than 1000 participants in areas with intense malaria transmission during the age interval when severe malaria incidence peaks. JF - Vaccine AU - Goncalves, Bronner P AU - Prevots, DRebecca AU - Kabyemela, Edward AU - Fried, Michal AU - Duffy, Patrick E AD - Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 1865 EP - 1867 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 34 IS - 16 SN - 0264-410X, 0264-410X KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology; Health & Safety Science Abstracts; Immunology Abstracts KW - Severe malaria KW - Vaccine KW - Clinical trial KW - Immunity KW - Sample size KW - Parasites KW - Age KW - Human diseases KW - Disease control KW - Malaria KW - Infection KW - Clinical trials KW - Public health KW - Disease transmission KW - Mortality KW - Plasmodium falciparum KW - Children KW - Health risks KW - Vaccines KW - Mortality causes KW - K 03400:Human Diseases KW - Q1 08485:Species interactions: pests and control KW - Q5 08524:Public health, medicines, dangerous organisms KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776668101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Preparing+for+future+efficacy+trials+of+severe+malaria+vaccines&rft.au=Goncalves%2C+Bronner+P%3BPrevots%2C+DRebecca%3BKabyemela%2C+Edward%3BFried%2C+Michal%3BDuffy%2C+Patrick+E&rft.aulast=Goncalves&rft.aufirst=Bronner&rft.date=2016-04-01&rft.volume=34&rft.issue=16&rft.spage=1865&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2016.02.053 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 15 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Parasites; Human diseases; Disease control; Malaria; Vaccines; Mortality causes; Disease transmission; Public health; Mortality; Age; Children; Infection; Clinical trials; Health risks; Plasmodium falciparum DO - http://dx.doi.org/10.1016/j.vaccine.2016.02.053 ER - TY - JOUR T1 - Biosynthesis of silver nanoparticles using a probiotic Bacillus licheniformis Dahb1 and their antibiofilm activity and toxicity effects in Ceriodaphnia cornuta. AN - 1776093827; 26802520 AB - In the present study, we synthesized and characterized a probiotic Bacillus licheniformis cell free extract (BLCFE) coated silver nanoparticles (BLCFE-AgNPs). These BLCFE-AgNPs were characterized by UV-visible spectrophotometer, XRD, EDX, FTIR, TEM and AFM. A strong surface plasmon resonance centered at 422 nm in UV-visible spectrum indicates the formation of AgNPs. The XRD spectrum of silver nanoparticles exhibited 2θ values corresponding to the silver nanocrystal. TEM and AFM showed the AgNPs were spherical in shape within the range of 18.69-63.42 nm and the presence of silver was confirmed by EDX analysis. Light and Confocal Laser Scanning Microscope (CLSM) images showed a weak adherence and disintegrated biofilm formation of Vibrio parahaemolyticus Dav1 treated with BLCFE-AgNPs compared to control. This result suggests that BLCFE-AgNps may be used for the control of biofilm forming bacterial populations in the biomedical field. In addition, acute toxicity results concluded that BLCFE-AgNPs were less toxic to the fresh water crustacean Ceriodaphnia cornuta (50 μg/ml) when compared to AgNO3 (22 μg/ml). This study also reports a short term analysis (24 h) of uptake and depuration of BLCFE-AgNPs in C. cornuta. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Microbial pathogenesis AU - Shanthi, Sathappan AU - Jayaseelan, Barbanas David AU - Velusamy, Palaniyandi AU - Vijayakumar, Sekar AU - Chih, Cheng Ta AU - Vaseeharan, Baskaralingam AD - Crustacean Molecular Biology and Genomics Lab, Department of Animal Health and Management, Alagappa University, Science Block 4th Floor, Burma Colony, Karaikudi 630004, Tamil Nadu, India. ; Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India. ; Aqua Genetics and Biotechnology Laboratory, Department of Tropical Agriculture and International Cooperation, National Pingtung University of Science and Technology, 1 Hseuh-Fu Rd., Nei-Pu Hsiang, Pingtung 91201, Taiwan. ; Crustacean Molecular Biology and Genomics Lab, Department of Animal Health and Management, Alagappa University, Science Block 4th Floor, Burma Colony, Karaikudi 630004, Tamil Nadu, India. Electronic address: vaseeharanb@gmail.com. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 70 EP - 77 VL - 93 KW - Silver KW - 3M4G523W1G KW - Index Medicus KW - Bacillus licheniformis KW - Vibrio parahaemolyticus KW - Silver nanoparticles KW - Biofilm KW - Ceriodaphnia cornuta KW - Animals KW - Probiotics -- chemistry KW - Probiotics -- metabolism KW - Vibrio parahaemolyticus -- physiology KW - Crustacea -- growth & development KW - Cell-Free System -- metabolism KW - Silver -- toxicity KW - Nanoparticles -- analysis KW - Biofilms -- drug effects KW - Bacillus licheniformis -- chemistry KW - Silver -- metabolism KW - Bacillus licheniformis -- genetics KW - Vibrio parahaemolyticus -- drug effects KW - Nanoparticles -- toxicity KW - Crustacea -- drug effects KW - Cell-Free System -- chemistry KW - Bacillus licheniformis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776093827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbial+pathogenesis&rft.atitle=Biosynthesis+of+silver+nanoparticles+using+a+probiotic+Bacillus+licheniformis+Dahb1+and+their+antibiofilm+activity+and+toxicity+effects+in+Ceriodaphnia+cornuta.&rft.au=Shanthi%2C+Sathappan%3BJayaseelan%2C+Barbanas+David%3BVelusamy%2C+Palaniyandi%3BVijayakumar%2C+Sekar%3BChih%2C+Cheng+Ta%3BVaseeharan%2C+Baskaralingam&rft.aulast=Shanthi&rft.aufirst=Sathappan&rft.date=2016-04-01&rft.volume=93&rft.issue=&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Microbial+pathogenesis&rft.issn=1096-1208&rft_id=info:doi/10.1016%2Fj.micpath.2016.01.014 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-22 N1 - Date created - 2016-03-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.micpath.2016.01.014 ER - TY - JOUR T1 - Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. AN - 1776092632; 26811520 AB - Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues. We conducted a clinical trial of allogeneic T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies that had progressed after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient's alloHSCT donor. Eight of 20 treated patients obtained remission, which included six complete remissions (CRs) and two partial remissions. The response rate was highest for acute lymphoblastic leukemia, with four of five patients obtaining minimal residual disease-negative CR. Responses also occurred in chronic lymphocytic leukemia and lymphoma. The longest ongoing CR was more than 30 months in a patient with chronic lymphocytic leukemia. New-onset acute graft-versus-host disease after CAR T-cell infusion developed in none of the patients. Toxicities included fever, tachycardia, and hypotension. Peak blood CAR T-cell levels were higher in patients who obtained remissions than in those who did not. Programmed cell death protein-1 expression was significantly elevated on CAR T cells after infusion. Presence of blood B cells before CAR T-cell infusion was associated with higher postinfusion CAR T-cell levels. Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT. © 2016 by American Society of Clinical Oncology. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Brudno, Jennifer N AU - Somerville, Robert P T AU - Shi, Victoria AU - Rose, Jeremy J AU - Halverson, David C AU - Fowler, Daniel H AU - Gea-Banacloche, Juan C AU - Pavletic, Steven Z AU - Hickstein, Dennis D AU - Lu, Tangying L AU - Feldman, Steven A AU - Iwamoto, Alexander T AU - Kurlander, Roger AU - Maric, Irina AU - Goy, Andre AU - Hansen, Brenna G AU - Wilder, Jennifer S AU - Blacklock-Schuver, Bazetta AU - Hakim, Frances T AU - Rosenberg, Steven A AU - Gress, Ronald E AU - Kochenderfer, James N AD - Jennifer N. Brudno, Robert P.T. Somerville, Victoria Shi, Jeremy J. Rose, David C. Halverson, Daniel H. Fowler, Juan C. Gea-Banacloche, Steven Z. Pavletic, Dennis D. Hickstein, Tangying L. Lu, Steven A. Feldman, Alexander T. Iwamoto, Brenna G. Hansen, Bazetta Blacklock-Schuver, Frances T. Hakim, Steven A. Rosenberg, Ronald E. Gress, and James N. Kochenderfer, National Cancer Institute; Roger Kurlander and Irina Maric, National Institutes of Health, Bethesda; Jennifer S. Wilder, Frederick National Laboratory for Cancer Research, Frederick, MD; and Andre Goy, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ. ; Jennifer N. Brudno, Robert P.T. Somerville, Victoria Shi, Jeremy J. Rose, David C. Halverson, Daniel H. Fowler, Juan C. Gea-Banacloche, Steven Z. Pavletic, Dennis D. Hickstein, Tangying L. Lu, Steven A. Feldman, Alexander T. Iwamoto, Brenna G. Hansen, Bazetta Blacklock-Schuver, Frances T. Hakim, Steven A. Rosenberg, Ronald E. Gress, and James N. Kochenderfer, National Cancer Institute; Roger Kurlander and Irina Maric, National Institutes of Health, Bethesda; Jennifer S. Wilder, Frederick National Laboratory for Cancer Research, Frederick, MD; and Andre Goy, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ. kochendj@mail.nih.gov. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 1112 EP - 1121 VL - 34 IS - 10 KW - Antigens, CD19 KW - 0 KW - Receptors, Antigen, T-Cell KW - Index Medicus KW - Humans KW - Adult KW - Disease Progression KW - Leukemia, B-Cell -- surgery KW - Aged KW - Middle Aged KW - Transplantation, Homologous KW - Graft vs Host Disease -- etiology KW - Male KW - Female KW - Remission Induction KW - Leukemia, B-Cell -- immunology KW - Antigens, CD19 -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- surgery KW - T-Lymphocytes -- transplantation KW - Leukemia, Lymphocytic, Chronic, B-Cell -- immunology KW - Transplantation Chimera KW - Receptors, Antigen, T-Cell -- metabolism KW - T-Lymphocytes -- immunology KW - Hematopoietic Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776092632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Allogeneic+T+Cells+That+Express+an+Anti-CD19+Chimeric+Antigen+Receptor+Induce+Remissions+of+B-Cell+Malignancies+That+Progress+After+Allogeneic+Hematopoietic+Stem-Cell+Transplantation+Without+Causing+Graft-Versus-Host+Disease.&rft.au=Brudno%2C+Jennifer+N%3BSomerville%2C+Robert+P+T%3BShi%2C+Victoria%3BRose%2C+Jeremy+J%3BHalverson%2C+David+C%3BFowler%2C+Daniel+H%3BGea-Banacloche%2C+Juan+C%3BPavletic%2C+Steven+Z%3BHickstein%2C+Dennis+D%3BLu%2C+Tangying+L%3BFeldman%2C+Steven+A%3BIwamoto%2C+Alexander+T%3BKurlander%2C+Roger%3BMaric%2C+Irina%3BGoy%2C+Andre%3BHansen%2C+Brenna+G%3BWilder%2C+Jennifer+S%3BBlacklock-Schuver%2C+Bazetta%3BHakim%2C+Frances+T%3BRosenberg%2C+Steven+A%3BGress%2C+Ronald+E%3BKochenderfer%2C+James+N&rft.aulast=Brudno&rft.aufirst=Jennifer&rft.date=2016-04-01&rft.volume=34&rft.issue=10&rft.spage=1112&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=1527-7755&rft_id=info:doi/10.1200%2FJCO.2015.64.5929 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-09 N1 - Date created - 2016-03-24 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Blood. 1995 Sep 1;86(5):2041-50 [7655033] Bone Marrow Transplant. 1995 Jun;15(6):825-8 [7581076] J Exp Med. 2005 Oct 3;202(7):907-12 [16203864] Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56 [16338616] J Clin Oncol. 2007 Feb 10;25(5):579-86 [17242396] Best Pract Res Clin Haematol. 2008 Jun;21(2):205-22 [18503987] Blood. 2008 Jun 15;111(12):5446-56 [18216293] Blood. 2008 Dec 1;112(12):4371-83 [19029455] J Clin Oncol. 2009 Jan 20;27(3):426-32 [19064981] J Immunother. 2009 Sep;32(7):689-702 [19561539] Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S138-45 [19857588] Biol Blood Marrow Transplant. 2010 Jul;16(7):871-90 [20399876] Blood. 2010 Nov 11;116(19):3875-86 [20631379] Br J Haematol. 2015 May;169(4):463-78 [25753571] Expert Opin Biol Ther. 2011 Apr;11(4):473-87 [21269237] Nat Immunol. 2011 Jun;12(6):492-9 [21739672] N Engl J Med. 2011 Aug 25;365(8):725-33 [21830940] Blood. 2011 Sep 15;118(11):2951-9 [21734234] Blood. 2012 Mar 22;119(12):2709-20 [22160384] Leukemia. 2012 Jun;26(6):1211-7 [22290066] Cancer J. 2012 Sep-Oct;18(5):457-62 [23006952] PLoS One. 2013;8(3):e57838 [23469246] Tissue Antigens. 2013 Apr;81(4):183-93 [23510414] Sci Transl Med. 2013 Mar 20;5(177):177ra38 [23515080] Nat Rev Clin Oncol. 2013 May;10(5):267-76 [23546520] Blood. 2013 Oct 24;122(17):2965-73 [24030379] Blood. 2013 Dec 12;122(25):4129-39 [24055823] Sci Transl Med. 2014 Feb 19;6(224):224ra25 [24553386] Expert Opin Biol Ther. 2014 Jul;14(7):947-54 [24661086] Blood. 2014 Jul 10;124(2):188-95 [24876563] N Engl J Med. 2014 Oct 16;371(16):1507-17 [25317870] Nature. 2014 Nov 27;515(7528):568-71 [25428505] J Clin Oncol. 2015 Feb 20;33(6):540-9 [25154820] Lancet. 2015 Feb 7;385(9967):517-28 [25319501] Blood. 2003 Feb 15;101(4):1637-44 [12393484] Nature. 1999 Oct 14;401(6754):708-12 [10537110] Blood. 2010 Nov 18;116(20):4099-102 [20668228] Nat Med. 2003 Mar;9(3):279-86 [12579196] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):720-4 [8421711] Blood. 1995 Aug 15;86(4):1261-8 [7632930] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1200/JCO.2015.64.5929 ER - TY - JOUR T1 - Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers. AN - 1776090081; 26764183 AB - A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. JF - Gastroenterology AU - Robles, Ana I AU - Traverso, Giovanni AU - Zhang, Ming AU - Roberts, Nicholas J AU - Khan, Mohammed A AU - Joseph, Christine AU - Lauwers, Gregory Y AU - Selaru, Florin M AU - Popoli, Maria AU - Pittman, Meredith E AU - Ke, Xiquan AU - Hruban, Ralph H AU - Meltzer, Stephen J AU - Kinzler, Kenneth W AU - Vogelstein, Bert AU - Harris, Curtis C AU - Papadopoulos, Nickolas AD - Laboratory of Human Carcinogenesis, National Cancer Institute's Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. ; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. ; Ludwig Center at Johns Hopkins, Baltimore, Maryland. ; Ludwig Center at Johns Hopkins, Baltimore, Maryland; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland. ; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. ; Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland. ; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland. ; Ludwig Center at Johns Hopkins, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. ; Ludwig Center at Johns Hopkins, Baltimore, Maryland; Howard Hughes Medical Institute, Chevy Chase, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: bertvog@gmail.com. ; Laboratory of Human Carcinogenesis, National Cancer Institute's Center for Cancer Research, National Institutes of Health, Bethesda, Maryland. Electronic address: harrisc@mail.nih.gov. ; Ludwig Center at Johns Hopkins, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: npapado1@jhmi.edu. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 931 EP - 943 VL - 150 IS - 4 KW - Biomarkers, Tumor KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Exome KW - Sequencing KW - Crohn’s Disease KW - Ulcerative Colitis KW - Phenotype KW - DNA Copy Number Variations KW - Gene Frequency KW - Humans KW - Genetic Predisposition to Disease KW - Gene Dosage KW - Genome-Wide Association Study KW - Colorectal Neoplasms -- diagnosis KW - Biomarkers, Tumor -- genetics KW - Colitis, Ulcerative -- complications KW - Crohn Disease -- diagnosis KW - DNA Mutational Analysis KW - Colitis, Ulcerative -- diagnosis KW - Crohn Disease -- genetics KW - Colorectal Neoplasms -- genetics KW - Colitis, Ulcerative -- genetics KW - Mutation KW - Crohn Disease -- complications KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776090081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Whole-Exome+Sequencing+Analyses+of+Inflammatory+Bowel+Disease-Associated+Colorectal+Cancers.&rft.au=Robles%2C+Ana+I%3BTraverso%2C+Giovanni%3BZhang%2C+Ming%3BRoberts%2C+Nicholas+J%3BKhan%2C+Mohammed+A%3BJoseph%2C+Christine%3BLauwers%2C+Gregory+Y%3BSelaru%2C+Florin+M%3BPopoli%2C+Maria%3BPittman%2C+Meredith+E%3BKe%2C+Xiquan%3BHruban%2C+Ralph+H%3BMeltzer%2C+Stephen+J%3BKinzler%2C+Kenneth+W%3BVogelstein%2C+Bert%3BHarris%2C+Curtis+C%3BPapadopoulos%2C+Nickolas&rft.aulast=Robles&rft.aufirst=Ana&rft.date=2016-04-01&rft.volume=150&rft.issue=4&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=1528-0012&rft_id=info:doi/10.1053%2Fj.gastro.2015.12.036 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-08 N1 - Date created - 2016-03-26 N1 - Date revised - 2017-01-30 N1 - SuppNotes - Comment In: Gastroenterology. 2016 Apr;150(4):808-10 [26924087] N1 - Last updated - 2017-01-30 DO - http://dx.doi.org/10.1053/j.gastro.2015.12.036 ER - TY - JOUR T1 - Dietary walnut reduces hepatic triglyceride content in high-fat-fed mice via modulation of hepatic fatty acid metabolism and adipose tissue inflammation. AN - 1776086696; 27012628 AB - In this study, we evaluated the protective effects of dietary walnuts on high-fat diet (HFD)-induced fatty liver and studied the underlying mechanisms. Male C57BL/6J mice were fed either a regular rodent chow or HFD (45% energy-derived) with or without walnuts (21.5% energy-derived) for 20weeks. Walnut supplementation did not change HFD-induced increase in body weight or visceral fat mass. However, dietary walnuts significantly decreased the amounts of hepatic triglyceride (TG) observed in HFD-fed mice. The addition of walnuts significantly altered the levels of proteins, involved in the hepatic lipid homeostasis, including AMP-activated protein kinase, fatty acid synthase and peroxisome proliferator-activated receptor-α. Since adipocyte inflammation and apoptosis are reportedly important in regulating hepatic fat accumulation, we also evaluated the protective effects of walnuts on adipose tissue injury. Real-time polymerase chain reaction results revealed that adipose tissues isolated from mice fed the HFD+walnut diets showed significantly decreased levels of macrophage infiltration with suppressed expression of proinflammatory genes compared to those significantly elevated in mice fed HFD alone. These improvements also coincided with reduction of HFD-induced apoptosis of adipocytes by dietary walnuts. However, the supplemented walnuts did not significantly alter HFD-induced peripheral glucose intolerance or insulin resistance despite a trend of improvement. Collectively, these results demonstrate that the protective effects of walnuts against HFD-induced hepatic TG accumulation in mice are mediated, at least partially, by modulating the key proteins in hepatic lipid homeostasis and suppression of the genes related to adipose tissue inflammation and macrophage infiltration as well as prevention of adipocyte apoptosis. Published by Elsevier Inc. JF - The Journal of nutritional biochemistry AU - Choi, Youngshim AU - Abdelmegeed, Mohamed A AU - Akbar, Mohammed AU - Song, Byoung-Joon AD - Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. ; Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. Electronic address: bj.song@nih.gov. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 116 EP - 125 VL - 30 KW - Fatty Acids KW - 0 KW - Triglycerides KW - Index Medicus KW - Walnut KW - Triglyceride KW - High-fat diet KW - Steatosis KW - Liver KW - Adipose tissue KW - Inflammation KW - Animals KW - Mice KW - Adipose Tissue -- metabolism KW - Triglycerides -- metabolism KW - Liver -- metabolism KW - Inflammation -- metabolism KW - Juglans KW - Diet, High-Fat KW - Inflammation -- pathology KW - Fatty Acids -- metabolism KW - Adipose Tissue -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776086696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutritional+biochemistry&rft.atitle=Dietary+walnut+reduces+hepatic+triglyceride+content+in+high-fat-fed+mice+via+modulation+of+hepatic+fatty+acid+metabolism+and+adipose+tissue+inflammation.&rft.au=Choi%2C+Youngshim%3BAbdelmegeed%2C+Mohamed+A%3BAkbar%2C+Mohammed%3BSong%2C+Byoung-Joon&rft.aulast=Choi&rft.aufirst=Youngshim&rft.date=2016-04-01&rft.volume=30&rft.issue=&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutritional+biochemistry&rft.issn=1873-4847&rft_id=info:doi/10.1016%2Fj.jnutbio.2015.12.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-09 N1 - Date created - 2016-03-25 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: JAMA. 2003 Apr 9;289(14):1799-804 [12684358] Int Immunol. 2010 May;22(5):347-52 [20410258] J Gastroenterol Hepatol. 2010 Apr;25(4):772-7 [20492333] Obesity (Silver Spring). 2010 Jun;18(6):1176-82 [19910942] Diabetes. 2010 Dec;59(12):3181-91 [20858684] Nat Rev Immunol. 2011 Feb;11(2):85-97 [21252989] J Nutr. 2011 Apr 1;141(4):603-10 [21346097] Antioxid Redox Signal. 2011 Jun;14(11):2121-35 [21083420] J Nutr Biochem. 2011 Jun;22(6):527-34 [20801629] Science. 2011 Jun 24;332(6037):1519-23 [21700865] Diabetes. 2011 Nov;60(11):2802-9 [22025778] Br J Nutr. 2011 Dec;106(12):1855-63 [21736774] Nutrition. 2012 Jan;28(1):67-75 [21795022] Acta Pharmacol Sin. 2012 Jan;33(1):82-90 [22212431] Cell Metab. 2012 May 2;15(5):570-3 [22560209] Diabetes. 2012 Jul;61(7):1680-90 [22474027] Nat Immunol. 2012 Aug;13(8):707-12 [22814340] J Hepatol. 2012 Oct;57(4):860-6 [22668639] Obesity (Silver Spring). 2012 Oct;20(10):1984-94 [22334255] Br J Nutr. 2012 Nov 28;108(10):1764-72 [22244053] Trends Endocrinol Metab. 2013 Jan;24(1):4-12 [23043895] Mol Nutr Food Res. 2013 Feb;57(2):328-38 [23148048] J Nutr. 2013 Jun;143(6):788-94 [23616506] Obesity (Silver Spring). 2013 Sep;21(9):E396-406 [23696431] Mol Ther. 2013 Oct;21(10):1852-61 [23774795] Can J Physiol Pharmacol. 2013 Nov;91(11):867-72 [24117253] Pharm Res. 2013 Nov;30(11):2940-50 [23783345] Eur J Nutr. 2014;53(2):645-60 [23942585] Inflammation. 2014 Aug;37(4):1297-306 [24639012] Pharm Res. 2015 Apr;32(4):1200-9 [25248334] Food Funct. 2015 May;6(5):1684-91 [25905791] Diabetes. 2003 Jun;52(6):1364-70 [12765945] J Clin Invest. 2003 Dec;112(12):1821-30 [14679177] Hepatology. 2005 Jun;41(6):1313-21 [15915461] J Lipid Res. 2005 Nov;46(11):2347-55 [16150820] J Clin Invest. 2006 Jan;116(1):115-24 [16341265] Endocrinology. 2006 Mar;147(3):1508-16 [16357043] J Clin Invest. 2006 Jun;116(6):1494-505 [16691291] J Nutr Biochem. 2007 Feb;18(2):113-9 [16713233] Am J Clin Nutr. 2007 Feb;85(2):385-91 [17284733] Endocrinology. 2007 Jun;148(6):2753-63 [17347305] Br J Nutr. 2007 Jun;97(6):1144-53 [17381974] J Gastroenterol Hepatol. 2007 Jun;22(6):788-93 [17565631] Diabetes. 2007 Aug;56(8):1960-8 [17620421] J Clin Endocrinol Metab. 2007 Sep;92(9):3490-7 [17595248] Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G894-902 [17702954] Nat Med. 2000 Sep;6(9):998-1003 [10973319] Hepatology. 2001 Dec;34(6):1158-63 [11732005] Diabetes. 2007 Dec;56(12):2910-8 [17848624] Arterioscler Thromb Vasc Biol. 2008 May;28(5):871-7 [18323514] J Lipid Res. 2008 Jul;49(7):1562-8 [18390487] Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1654-9 [18566296] Hepatology. 2008 Sep;48(3):799-807 [18570214] Cell Metab. 2009 May;9(5):407-16 [19416711] Atherosclerosis. 2009 Jun;204(2):e70-6 [18952211] J Nutr. 2009 Aug;139(8):1510-6 [19515743] Pharmacol Ther. 2009 Oct;124(1):31-43 [19563826] J Biol Chem. 2010 Jan 29;285(5):3428-38 [19940134] QJM. 2010 Feb;103(2):71-83 [19914930] Annu Rev Physiol. 2010;72:219-46 [20148674] J Atheroscler Thromb. 2010 Mar 31;17(3):219-28 [20179360] Hepatology. 2010 May;51(5):1593-602 [20222092] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jnutbio.2015.12.005 ER - TY - JOUR T1 - Immunoexpression of Steroid Hormone Receptors and Proliferation Markers in Uterine Leiomyoma and Normal Myometrial Tissues from the Miniature Pig, Sus scrofa. AN - 1775633358; 26692562 AB - Uterine leiomyomas in miniature pet pigs occur similarly to those in women with regard to frequency, age, parity, and cycling. Clinical signs, gross, and histologic features of the porcine tumors closely resemble uterine leiomyomas (fibroids) in women. Although fibroids are hormonally responsive in women, the roles of estrogen and progesterone have not been fully elucidated. In this study, immunohistochemistry was used to assess the expression of the steroid hormone receptors, estrogen receptor alpha (ER-α), estrogen receptor beta (ER-β) and progesterone receptor (PR), and cell proliferation markers, proliferating cell nuclear antigen (PCNA) and Ki-67 in tumor and matched myometrial tissues sampled from miniature pigs. A "quickscore" method was used to determine receptor expression and labeling indices were calculated for the markers. ER-α/β and PR were localized to the nuclei of smooth muscle cells in both tissues. PR expression was intense and diffuse throughout all tissues, with correlation between tumors and matched myometria. Conversely, ER-α expression was variable between the myometrial and tumor tissues, as well as between animals. ER-β expression was low. PCNA and Ki-67 were localized to the nucleus and expression varied among tumors; however, normal tissues were overall negative. These findings support further investigation into the use of the miniature pig as a model of fibroids in women. © The Author(s) 2015. JF - Toxicologic pathology AU - Mozzachio, Kristie AU - Moore, Alicia B AU - Kissling, Grace E AU - Dixon, Darlene AD - Mozzachio Veterinary Services, Hillsborough, North Carolina, USA. ; Molecular Pathogenesis Group, National Toxicology Program Laboratory (NTPL), Division of the NTP, Research Triangle Park, North Carolina, USA. ; Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, North Carolina, USA. ; Molecular Pathogenesis Group, National Toxicology Program Laboratory (NTPL), Division of the NTP, Research Triangle Park, North Carolina, USA dixon@niehs.nih.gov. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 450 EP - 457 VL - 44 IS - 3 KW - Biomarkers KW - 0 KW - Ki-67 Antigen KW - Proliferating Cell Nuclear Antigen KW - Receptors, Estrogen KW - Receptors, Progesterone KW - Index Medicus KW - uterine leiomyoma KW - fibroid KW - miniature pig KW - steroid hormone receptors KW - proliferation markers KW - immunoexpression KW - Swine KW - Animals KW - Receptors, Progesterone -- metabolism KW - Ki-67 Antigen -- analysis KW - Ki-67 Antigen -- metabolism KW - Swine, Miniature KW - Immunohistochemistry KW - Female KW - Receptors, Progesterone -- analysis KW - Leiomyoma -- metabolism KW - Leiomyoma -- pathology KW - Leiomyoma -- veterinary KW - Leiomyoma -- chemistry KW - Proliferating Cell Nuclear Antigen -- analysis KW - Receptors, Estrogen -- analysis KW - Receptors, Estrogen -- metabolism KW - Myometrium -- metabolism KW - Uterine Neoplasms -- pathology KW - Uterine Neoplasms -- chemistry KW - Biomarkers -- analysis KW - Uterine Neoplasms -- veterinary KW - Myometrium -- chemistry KW - Biomarkers -- metabolism KW - Myometrium -- pathology KW - Uterine Neoplasms -- metabolism KW - Proliferating Cell Nuclear Antigen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775633358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Immunoexpression+of+Steroid+Hormone+Receptors+and+Proliferation+Markers+in+Uterine+Leiomyoma+and+Normal+Myometrial+Tissues+from+the+Miniature+Pig%2C+Sus+scrofa.&rft.au=Mozzachio%2C+Kristie%3BMoore%2C+Alicia+B%3BKissling%2C+Grace+E%3BDixon%2C+Darlene&rft.aulast=Mozzachio&rft.aufirst=Kristie&rft.date=2016-04-01&rft.volume=44&rft.issue=3&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=1533-1601&rft_id=info:doi/10.1177%2F0192623315621414 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-23 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Cell Physiol. 2001 Mar;186(3):414-24 [11169981] Med Sci Monit. 2001 Sep-Oct;7(5):908-13 [11535933] Virchows Arch. 2002 Jul;441(1):53-62 [12111201] Toxicol Pathol. 2002 Sep-Oct;30(5):611-6 [12371671] Am J Obstet Gynecol. 2003 Jan;188(1):100-7 [12548202] Environ Health Perspect. 2003 Jun;111(8):1037-54 [12826476] Genes Chromosomes Cancer. 2003 Dec;38(4):349-56 [14566855] ILAR J. 2004;45(2):179-88 [15111737] Toxicol Pathol. 2004 Jul-Aug;32(4):402-7 [15307213] Fertil Steril. 2004 Oct;82 Suppl 3:1244-9 [15474102] Obstet Gynecol. 1980 Jan;55(1):20-4 [7352057] Fertil Steril. 1981 Oct;36(4):433-45 [7026295] Acta Obstet Gynecol Scand. 1985;64(4):307-9 [4024879] Am J Clin Pathol. 1990 Oct;94(4):435-8 [2220671] Am J Pathol. 1995 Jun;146(6):1556-67 [7778693] Biol Reprod. 1995 Apr;52(4):824-32 [7780004] J Clin Pathol. 1995 Sep;48(9):876-8 [7490328] J Clin Invest. 1996 Aug 1;98(3):777-84 [8698870] Epidemiology. 1996 Jul;7(4):440-2 [8793374] Fertil Steril. 2005 Aug;84(2):474-84 [16084893] Am J Obstet Gynecol. 2005 Oct;193(4):1395-403 [16202732] J Formos Med Assoc. 2005 Dec;104(12):920-6 [16607449] Hum Pathol. 2006 Oct;37(10):1350-6 [16949924] Fertil Steril. 2007 Apr;87(4):725-36 [17430732] Mol Med. 2008 May-Jun;14(5-6):264-75 [18231572] Fertil Steril. 2008 Nov;90(5):1878-85 [18166184] Hum Genet. 2009 Apr;125(3):257-63 [19132395] Endocrinology. 2010 Jun;151(6):2433-42 [20375184] Trends Biochem Sci. 2010 Jun;35(6):315-22 [20299225] Cancer Genet Cytogenet. 2010 Oct 1;202(1):11-6 [20804914] Tohoku J Exp Med. 2010 Sep;222(1):55-61 [20814179] Vet Pathol. 2010 Nov;47(6):1071-5 [20817893] Antioxid Redox Signal. 2011 Jan 15;14(2):221-7 [20524847] Hum Reprod Update. 2011 Nov-Dec;17(6):772-90 [21788281] Science. 2011 Oct 14;334(6053):252-5 [21868628] Am J Obstet Gynecol. 2012 Mar;206(3):211.e1-9 [22244472] PLoS One. 2012;7(5):e36935 [22570742] Mol Cell Endocrinol. 2012 Jul 25;358(2):223-31 [21672608] Fertil Steril. 2012 Sep;98(3):741-751.e6 [22633281] Endocr Rev. 2013 Feb;34(1):130-62 [23303565] Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17053-8 [24082114] Hum Reprod Update. 2014 May-Jun;20(3):309-33 [24401287] Biomed Res Int. 2014;2014:521313 [25050358] Curr Opin Obstet Gynecol. 2015 Aug;27(4):276-83 [26107781] Mol Med. 2015;21:242-56 [25879625] Semin Reprod Med. 2015 Sep;33(5):357-65 [26251118] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1177/0192623315621414 ER - TY - JOUR T1 - Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer. AN - 1775632011; 26802155 AB - KRAS mutations in NSCLC are associated with a lack of response to epidermal growth factor receptor inhibitors. Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway. Advanced nonsmall-cell lung cancer (NSCLC) patients failing one to two prior regimens underwent KRAS profiling. KRAS wild-type patients were randomized to erlotinib (150 mg daily) or a combination of selumetinib (150 mg daily) with erlotinib (100 mg daily). KRAS mutant patients were randomized to selumetinib (75 mg b.i.d.) or the combination. The primary end points were progression-free survival (PFS) for the KRAS wild-type cohort and objective response rate (ORR) for the KRAS mutant cohort. Biomarker studies of ERK phosphorylation and immune subsets were carried out. From March 2010 to May 2013, 89 patients were screened; 41 KRAS mutant and 38 KRAS wild-type patients were enrolled. Median PFS in the KRAS wild-type arm was 2.4 months [95% confidence interval (CI) 1.3-3.7] for erlotinib alone and 2.1 months (95% CI 1.8-5.1) for the combination. The ORR in the KRAS mutant group was 0% (95% CI 0.0% to 33.6%) for selumetinib alone and 10% (95% CI 2.1% to 26.3%) for the combination. Combination therapy resulted in increased toxicities, requiring dose reductions (56%) and discontinuation (8%). Programmed cell death-1 expression on regulatory T cells (Tregs), Tim-3 on CD8+ T cells and Th17 levels were associated with PFS and overall survival in patients receiving selumetinib. This study failed to show improvement in ORR or PFS with combination therapy of selumetinib and erlotinib over monotherapy in KRAS mutant and KRAS wild-type advanced NSCLC. The association of immune subsets and immune checkpoint receptor expression with selumetinib may warrant further studies. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Carter, C A AU - Rajan, A AU - Keen, C AU - Szabo, E AU - Khozin, S AU - Thomas, A AU - Brzezniak, C AU - Guha, U AU - Doyle, L A AU - Steinberg, S M AU - Xi, L AU - Raffeld, M AU - Tomita, Y AU - Lee, M J AU - Lee, S AU - Trepel, J B AU - Reckamp, K L AU - Koehler, S AU - Gitlitz, B AU - Salgia, R AU - Gandara, D AU - Vokes, E AU - Giaccone, G AD - John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda. ; Medical Oncology Branch, Center for Cancer Research. ; Lung & Upper Aerodigestive Cancer Research Group Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda. ; Cancer Therapy Evaluation Program, National Institutes of Health, Bethesda. ; Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research. ; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda. ; Department of Hematology and Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte. ; Department of Internal Medicine, University of Southern California, Los Angeles. ; Radiation and Cellular Oncology, University of Chicago, Medicine and Biological Sciences, Chicago. ; Division of Hematology and Oncology, University of California at Davis Cancer Center, Sacramento. ; Medical Oncology Branch, Center for Cancer Research Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA gg496@georgetown.edu. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 693 EP - 699 VL - 27 IS - 4 KW - AZD 6244 KW - 0 KW - Benzimidazoles KW - KRAS protein, human KW - Protein Kinase Inhibitors KW - Erlotinib Hydrochloride KW - DA87705X9K KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - nonsmall-cell lung cancer KW - EGFR KW - KRAS KW - selumetinib KW - MEK KW - erlotinib KW - MAP Kinase Kinase Kinase 1 -- genetics KW - Disease-Free Survival KW - Benzimidazoles -- administration & dosage KW - Aged, 80 and over KW - Humans KW - Protein Kinase Inhibitors -- administration & dosage KW - Adult KW - Aged KW - Middle Aged KW - Mutation KW - Male KW - Female KW - Erlotinib Hydrochloride -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Proto-Oncogene Proteins p21(ras) -- genetics KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775632011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Selumetinib+with+and+without+erlotinib+in+KRAS+mutant+and+KRAS+wild-type+advanced+nonsmall-cell+lung+cancer.&rft.au=Carter%2C+C+A%3BRajan%2C+A%3BKeen%2C+C%3BSzabo%2C+E%3BKhozin%2C+S%3BThomas%2C+A%3BBrzezniak%2C+C%3BGuha%2C+U%3BDoyle%2C+L+A%3BSteinberg%2C+S+M%3BXi%2C+L%3BRaffeld%2C+M%3BTomita%2C+Y%3BLee%2C+M+J%3BLee%2C+S%3BTrepel%2C+J+B%3BReckamp%2C+K+L%3BKoehler%2C+S%3BGitlitz%2C+B%3BSalgia%2C+R%3BGandara%2C+D%3BVokes%2C+E%3BGiaccone%2C+G&rft.aulast=Carter&rft.aufirst=C&rft.date=2016-04-01&rft.volume=27&rft.issue=4&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=1569-8041&rft_id=info:doi/10.1093%2Fannonc%2Fmdw008 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-23 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT01229150; ClinicalTrials.gov N1 - SuppNotes - Cited By: Cancer Cell. 2014 May 12;25(5):697-710 [24746704] J Clin Oncol. 2015 Mar 20;33(9):1000-7 [25667274] Nature. 2006 Jan 19;439(7074):358-62 [16273091] Clin Cancer Res. 2007 Mar 1;13(5):1576-83 [17332304] Clin Cancer Res. 2007 May 15;13(10):2890-6 [17504988] Nature. 2008 Oct 23;455(7216):1069-75 [18948947] Lancet Oncol. 2008 Oct;9(10):962-72 [18804418] Eur J Cancer. 2009 Jan;45(2):228-47 [19097774] Nat Rev Clin Oncol. 2010 Feb;7(2):71-2 [20118973] Clin Cancer Res. 2010 Mar 1;16(5):1613-23 [20179232] Mol Cancer Ther. 2010 Jul;9(7):1985-94 [20587667] J Thorac Oncol. 2010 Oct;5(10):1630-6 [20802351] Clin Adv Hematol Oncol. 2011 Mar;9(3):207-14 [21475126] Nat Rev Drug Discov. 2012 Mar;11(3):215-33 [22301798] Nat Med. 2012 Mar;18(3):378-81 [22327623] Cancer Res. 2012 Jul 1;72(13):3228-37 [22552284] Med Oncol. 2013 Mar;30(1):461 [23335103] Annu Rev Immunol. 2013;31:51-72 [23157435] J Clin Oncol. 2013 Jun 1;31(16):1997-2003 [23610105] Lancet Oncol. 2013 Sep;14(10):981-8 [23883922] CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 [24399786] J Biol Chem. 1995 Jun 23;270(25):14843-6 [7797459] BMJ. 1995 Oct 7;311(7010):889-90 [7580533] Cell. 1998 May 15;93(4):605-15 [9604935] Carcinogenesis. 1999 Aug;20(8):1507-10 [10426799] PLoS Med. 2005 Jan;2(1):e17 [15696205] Clin Cancer Res. 2014 Dec 1;20(23):6034-44 [25294906] N Engl J Med. 2005 Jul 14;353(2):123-32 [16014882] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/annonc/mdw008 ER - TY - JOUR T1 - Liver injury from nonsteroidal anti-inflammatory drugs in the United States. AN - 1775631949; 26601797 AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used and have been associated with hepatotoxicity. Studies of liver injury from NSAIDs have been retrospective and prospective data are lacking. The aim was to report the features and outcomes of the subjects with severe drug-induced liver injury from NSAIDS. The U.S. Drug Induced Liver Injury Network is a prospective registry of idiosyncratic drug hepatotoxicity. All patients are evaluated in a standard fashion and followed up for at least 6 months. Of 1221 Drug Induced Liver Injury Network cases that were adjudicated, 30 cases were attributed to eight different NSAIDs. The mean age was 52 years old, 24 (80%) were women, and 21 (70%) were Caucasian. The mean latency was 67 days. Common signs and symptoms at presentation were nausea (73%), jaundice (67%) and dark urine (67%). Mean peak serum aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase were 898 U/L, 1060 U/L, 12.2 mg/dl and 326 U/L. The most common pattern of injury was hepatocellular (70%) and autoantibodies were detected in 33% of cases. Diclofenac, was the most frequently implicated NSAID (16/30 cases), and characterized by hepatocellular injury. Seventeen cases resulted in hospitalization or prolongation of hospitalization and one patient died from complications of Stevens-Johnson syndrome because of diclofenac. Hepatocellular injury is the most common pattern seen with NSAID hepatotoxicity, and diclofenac is the most frequently implicated agent. Given the number of NSAID alternatives, diclofenac should be reserved for patients who fail other NSAIDs and a high level of suspicion for hepatotoxicity should be maintained. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. JF - Liver international : official journal of the International Association for the Study of the Liver AU - Schmeltzer, Paul A AU - Kosinski, Andrzej S AU - Kleiner, David E AU - Hoofnagle, Jay H AU - Stolz, Andrew AU - Fontana, Robert J AU - Russo, Mark W AU - Drug-Induced Liver Injury Network (DILIN) AD - Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA. ; Duke Clinical Research Institute, Duke University, Durham, NC, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. ; Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA. ; Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA. ; Drug-Induced Liver Injury Network (DILIN) Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 603 EP - 609 VL - 36 IS - 4 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Index Medicus KW - medication KW - nonsteroidal KW - diclofenac KW - hepatotoxicity KW - Young Adult KW - Humans KW - Prognosis KW - Aged KW - Phenotype KW - Registries KW - Prospective Studies KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Middle Aged KW - United States -- epidemiology KW - Time Factors KW - Female KW - Male KW - Chemical and Drug Induced Liver Injury -- mortality KW - Chemical and Drug Induced Liver Injury -- epidemiology KW - Chemical and Drug Induced Liver Injury -- diagnosis KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Chemical and Drug Induced Liver Injury -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775631949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+international+%3A+official+journal+of+the+International+Association+for+the+Study+of+the+Liver&rft.atitle=Liver+injury+from+nonsteroidal+anti-inflammatory+drugs+in+the+United+States.&rft.au=Schmeltzer%2C+Paul+A%3BKosinski%2C+Andrzej+S%3BKleiner%2C+David+E%3BHoofnagle%2C+Jay+H%3BStolz%2C+Andrew%3BFontana%2C+Robert+J%3BRusso%2C+Mark+W%3BDrug-Induced+Liver+Injury+Network+%28DILIN%29&rft.aulast=Schmeltzer&rft.aufirst=Paul&rft.date=2016-04-01&rft.volume=36&rft.issue=4&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Liver+international+%3A+official+journal+of+the+International+Association+for+the+Study+of+the+Liver&rft.issn=1478-3231&rft_id=info:doi/10.1111%2Fliv.13032 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-21 N1 - Date created - 2016-03-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/liv.13032 ER - TY - JOUR T1 - Predictors of Post-Operative Pain Relief in Patients with Chronic Pancreatitis Undergoing the Frey or Whipple Procedure. AN - 1775631906; 26813017 AB - Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (≥5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. A total of 60 patients (age 51.6 years, 53% males) were included in our study, of whom 42 (70%) reported post-operative pain relief over a mean follow-up of 1.1 years. There were 37 (62%) patients with toxic etiology, 36 (60%) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p < 0.01). However, only a toxic etiology was an independent predictor of post-operative pain relief (OR 5.7, 95% CI 1.3, 24.5, p = 0.02). Only a toxic etiology, and not imaging or histopathologic findings, independently predicts post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. JF - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract AU - Sinha, Amitasha AU - Patel, Yuval A AU - Cruise, Michael AU - Matsukuma, Karen AU - Zaheer, Atif AU - Afghani, Elham AU - Yadav, Dhiraj AU - Makary, Martin A AU - Hirose, Kenzo AU - Andersen, Dana K AU - Singh, Vikesh K AD - Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ; Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ; Division of Gastroenterology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ; Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. ; Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. vsingh1@jhmi.edu. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 734 EP - 740 VL - 20 IS - 4 KW - Index Medicus KW - Smoking KW - Alcohol KW - Chronic pancreatitis KW - Post-operative pain relief KW - Pancreas -- pathology KW - Pancreaticoduodenectomy KW - Fibrosis KW - Pancreas -- surgery KW - Humans KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Pain Measurement KW - Pancreatic Ducts -- pathology KW - Adult KW - Dilatation, Pathologic -- complications KW - Middle Aged KW - Female KW - Male KW - Abdominal Pain -- etiology KW - Pancreatitis, Chronic -- etiology KW - Calcinosis -- complications KW - Pancreatitis, Chronic -- surgery KW - Abdominal Pain -- surgery KW - Pancreatitis, Chronic -- pathology KW - Pain, Postoperative -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775631906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+gastrointestinal+surgery+%3A+official+journal+of+the+Society+for+Surgery+of+the+Alimentary+Tract&rft.atitle=Predictors+of+Post-Operative+Pain+Relief+in+Patients+with+Chronic+Pancreatitis+Undergoing+the+Frey+or+Whipple+Procedure.&rft.au=Sinha%2C+Amitasha%3BPatel%2C+Yuval+A%3BCruise%2C+Michael%3BMatsukuma%2C+Karen%3BZaheer%2C+Atif%3BAfghani%2C+Elham%3BYadav%2C+Dhiraj%3BMakary%2C+Martin+A%3BHirose%2C+Kenzo%3BAndersen%2C+Dana+K%3BSingh%2C+Vikesh+K&rft.aulast=Sinha&rft.aufirst=Amitasha&rft.date=2016-04-01&rft.volume=20&rft.issue=4&rft.spage=734&rft.isbn=&rft.btitle=&rft.title=Journal+of+gastrointestinal+surgery+%3A+official+journal+of+the+Society+for+Surgery+of+the+Alimentary+Tract&rft.issn=1873-4626&rft_id=info:doi/10.1007%2Fs11605-016-3081-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-23 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11605-016-3081-7 ER - TY - JOUR T1 - Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies. AN - 1775382814; 27000737 AB - Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative therapy for patients with hemoglobinopathies, mainly severe sickle cell disease (SCD) and thalassemia (TM). However, the applicability of HSCT has been limited mainly by donor availability, with a less than 25%-30% of eligible patients having human leukocyte antigen (HLA)-matched sibling donors. Previous outcomes using alternate donor options have been markedly inferior due to increased regimen-related toxicity, transplant-related mortality, graft failure, and graft-versus-host disease (GVHD). Advances in transplant technology, including high-resolution HLA typing, improved GVHD prophylactic approaches with tolerance induction, and better supportive care over the last decade, are addressing these historical challenges, resulting in increasing donor options. Herein, we review alternate donor HSCT approaches for severe SCD and TM using unrelated donors, umbilical cord blood units, or related haploidentical donors. Though this is an emerging field, early results are promising and in selected patients, this may be the preferred option to mitigate against the age-related morbidity and early mortality associated with these disorders. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Seminars in hematology AU - Alfraih, Feras AU - Aljurf, Mahmoud AU - Fitzhugh, Courtney D AU - Kassim, Adetola A AD - Adult Hematology and Hematopoietic Stem Cell Transplantation, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address: Falfraih@kfshrc.edu.sa. ; Molecular and Clinical Hematology Branch, NHLBI, NIH, Bethesda, MD, USA. ; Division of Hematology and Oncology, Department of Medicine and Vanderbilt- Meharry Center for Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 120 EP - 128 VL - 53 IS - 2 KW - Index Medicus KW - Allogeneic hematopoietic stem cell transplantation KW - Hemoglobinopathies KW - Alternative donor KW - Thalassemia KW - Sickle cell disease KW - Histocompatibility Testing KW - Haploidy KW - Humans KW - Transplantation, Homologous KW - Graft vs Host Disease -- etiology KW - Hematopoietic Stem Cell Transplantation -- adverse effects KW - Hemoglobinopathies -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775382814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+hematology&rft.atitle=Alternative+donor+allogeneic+hematopoietic+cell+transplantation+for+hemoglobinopathies.&rft.au=Alfraih%2C+Feras%3BAljurf%2C+Mahmoud%3BFitzhugh%2C+Courtney+D%3BKassim%2C+Adetola+A&rft.aulast=Alfraih&rft.aufirst=Feras&rft.date=2016-04-01&rft.volume=53&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=1532-8686&rft_id=info:doi/10.1053%2Fj.seminhematol.2016.01.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-12 N1 - Date created - 2016-03-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1053/j.seminhematol.2016.01.001 ER - TY - JOUR T1 - The role of microbiota in cancer therapy. AN - 1775169250; 26820225 AB - The relationship between the host and the commensal microbiota regulates physiological functions including inflammation and immunity and it has been scrutinized in the context of cancer. While viruses and bacterial species have been implicated in oncogenesis, commensal microbes also have a beneficial role in the fight against cancer. Therapy efficacy, including adoptive T cell transfer, alkylating agents and immune checkpoint blockers, relies on immunity that receives its education from the gut microbiota. In cancer therapy with immunostimulating oligonucleotides and platinum salts, the microbiota also modulates the response by priming for the release of pro-inflammatory factors and reactive oxygen species, respectively. This new information offers promising clinical possibilities of modulating cancer therapy and its toxic side effects by targeting the microbiota. Published by Elsevier Ltd. JF - Current opinion in immunology AU - Perez-Chanona, Ernesto AU - Trinchieri, Giorgio AD - Cancer and Inflammation Program, National Cancer Institute, Bethesda, MD 20892, USA; Leidos Biomedical Research, Inc., Frederick, MD 21701, USA. ; Cancer and Inflammation Program, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: trinchig@mail.nih.gov. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 75 EP - 81 VL - 39 KW - Index Medicus KW - Animals KW - Symbiosis KW - Immunity, Innate -- immunology KW - Humans KW - Intestinal Mucosa -- microbiology KW - Neoplasms -- therapy KW - Gastrointestinal Microbiome -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775169250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+immunology&rft.atitle=The+role+of+microbiota+in+cancer+therapy.&rft.au=Perez-Chanona%2C+Ernesto%3BTrinchieri%2C+Giorgio&rft.aulast=Perez-Chanona&rft.aufirst=Ernesto&rft.date=2016-04-01&rft.volume=39&rft.issue=&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+immunology&rft.issn=1879-0372&rft_id=info:doi/10.1016%2Fj.coi.2016.01.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-03 N1 - Date created - 2016-03-21 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nature. 2012 Jun 14;486(7402):207-14 [22699609] Cell Host Microbe. 2011 Oct 20;10(4):324-35 [22018233] Nat Rev Microbiol. 2013 Apr;11(4):227-38 [23435359] Annu Rev Immunol. 2013;31:51-72 [23157435] J Exp Med. 2013 Aug 26;210(9):1695-710 [23897981] Nat Rev Cancer. 2013 Nov;13(11):800-12 [24132111] Science. 2013 Nov 22;342(6161):967-70 [24264989] Science. 2013 Nov 22;342(6161):971-6 [24264990] PLoS One. 2014;9(1):e83744 [24421902] Cell Host Microbe. 2014 Mar 12;15(3):317-28 [24629338] Gastroenterology. 2014 May;146(6):1449-58 [24486050] Nature. 2014 Jun 5;510(7503):152-6 [24739972] Oncology (Williston Park). 2014 Nov;28 Suppl 3:30-8 [25384885] Vaccine. 2014 Nov 12;32(48):6377-89 [24975812] Eur J Immunol. 2015 Jan;45(1):17-31 [25328099] Cancer Cell. 2015 Jan 12;27(1):27-40 [25533336] Lancet Oncol. 2012 Jun;13(6):607-15 [22575588] Cancer Immunol Res. 2015 Feb;3(2):103-9 [25660553] Science. 2015 Apr 3;348(6230):56-61 [25838373] Oncotarget. 2015 Apr 20;6(11):9387-96 [25831236] N Engl J Med. 2015 May 21;372(21):2006-17 [25891304] N Engl J Med. 2015 Jul 2;373(1):23-34 [26027431] Science. 2015 Nov 27;350(6264):1084-9 [26541606] Science. 2015 Nov 27;350(6264):1079-84 [26541610] Cancer Treat Rev. 2016 Jan;42:3-9 [26620820] J Exp Med. 2002 Aug 19;196(4):541-9 [12186845] Oncogene. 2003 Oct 20;22(47):7265-79 [14576837] IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241 [7715068] Cancer Res. 2005 Apr 15;65(8):3437-46 [15833879] J Clin Invest. 2007 Aug;117(8):2197-204 [17657310] J Clin Oncol. 2008 Nov 10;26(32):5233-9 [18809613] Immunity. 2012 Jul 27;37(1):171-86 [22749822] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.coi.2016.01.003 ER - TY - JOUR T1 - Kinase inhibitors and monoclonal antibodies in oncology: clinical implications. AN - 1775166630; 26718105 AB - Molecularly targeted cancer therapies, such as small-molecule kinase inhibitors and monoclonal antibodies, constitute a rapidly growing and an important part of the oncology armamentarium. Unlike conventional (cytotoxic) chemotherapeutics, targeted therapies were designed to disrupt cancer cell pathogenesis at specific biological points essential for the development and progression of the tumour. These agents were developed to disrupt specific targets with the aim of minimizing treatment burden compared with conventional chemotherapy. Nevertheless the increasingly common use of targeted therapies has revealed some unanticipated, often clinically significant toxic effects, as well as compromising effective palliative and end-of-life management approaches. Although patients and clinicians welcome improvements in cancer prognosis, these changes can also impact patient quality-of-life. Therefore, as demand for oncology expertise increases, physicians need to apprise themselves of targeted therapies and their clinical implications, including drug-specific side effects, impact on quality of life, and cost issues, especially in relation to end-of-life care. This Review provides a useful summary and guide for professionals treating patients with malignant diseases. JF - Nature reviews. Clinical oncology AU - Gharwan, Helen AU - Groninger, Hunter AD - Medical Oncology, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 12N226, Bethesda, Maryland 20892-1906, USA. ; Section of Palliative Care, Department of Medicine, MedStar Washington Hospital Center, 110 Irving Street NW, Room 2A-68, Washington, District of Columbia 20008, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 209 EP - 227 VL - 13 IS - 4 KW - Antibodies, Monoclonal KW - 0 KW - Antineoplastic Agents KW - Protein Kinase Inhibitors KW - Index Medicus KW - Humans KW - Disease Management KW - Premedication KW - Drug-Related Side Effects and Adverse Reactions -- diagnosis KW - Drug-Related Side Effects and Adverse Reactions -- classification KW - Molecular Targeted Therapy -- adverse effects KW - Neoplasms -- drug therapy KW - Protein Kinase Inhibitors -- therapeutic use KW - Protein Kinase Inhibitors -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775166630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Clinical+oncology&rft.atitle=Kinase+inhibitors+and+monoclonal+antibodies+in+oncology%3A+clinical+implications.&rft.au=Gharwan%2C+Helen%3BGroninger%2C+Hunter&rft.aulast=Gharwan&rft.aufirst=Helen&rft.date=2016-04-01&rft.volume=13&rft.issue=4&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Clinical+oncology&rft.issn=1759-4782&rft_id=info:doi/10.1038%2Fnrclinonc.2015.213 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-03 N1 - Date created - 2016-03-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/nrclinonc.2015.213 ER - TY - JOUR T1 - Human SR-BI and SR-BII Potentiate Lipopolysaccharide-Induced Inflammation and Acute Liver and Kidney Injury in Mice. AN - 1774533786; 26936883 AB - The class B scavenger receptors BI (SR-BI) and BII (SR-BII) are high-density lipoprotein receptors that recognize various pathogens, including bacteria and their products. It has been reported that SR-BI/II null mice are more sensitive than normal mice to endotoxin-induced inflammation and sepsis. Because the SR-BI/II knockout model demonstrates multiple immune and metabolic disorders, we investigated the role of each receptor in the LPS-induced inflammatory response and tissue damage using transgenic mice with pLiv-11-directed expression of human SR-BI (hSR-BI) or human SR-BII (hSR-BII). At 6 h after i.p. LPS injection, transgenic hSR-BI and hSR-BII mice demonstrated markedly higher serum levels of proinflammatory cytokines and 2- to 3-fold increased expression levels of inflammatory mediators in the liver and kidney, compared with wild-type (WT) mice. LPS-stimulated inducible NO synthase expression was 3- to 6-fold higher in the liver and kidney of both transgenic strains, although serum NO levels were similar in all mice. Despite the lower high-density lipoprotein plasma levels, both transgenic strains responded to LPS by a 5-fold increase of plasma corticosterone levels, which were only moderately lower than in WT animals. LPS treatment resulted in MAPK activation in tissues of all mice; however, the strongest response was detected for hepatic extracellular signal-regulated protein kinase 1 and 2 and kidney JNK of both transgenic mice. Histological examination of hepatic and renal tissue from LPS-challenged mice revealed more injury in hSR-BII, but not hSR-BI, transgenic mice versus WT controls. Our findings demonstrate that hSR-BII, and to a lesser extent hSR-BI, significantly increase LPS-induced inflammation and contribute to LPS-induced tissue injury in the liver and kidney, two major organs susceptible to LPS toxicity. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Baranova, Irina N AU - Souza, Ana C P AU - Bocharov, Alexander V AU - Vishnyakova, Tatyana G AU - Hu, Xuzhen AU - Vaisman, Boris L AU - Amar, Marcelo J AU - Chen, Zhigang AU - Kost, Yana AU - Remaley, Alan T AU - Patterson, Amy P AU - Yuen, Peter S T AU - Star, Robert A AU - Eggerman, Thomas L AD - Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892; ; Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; ; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892; eggermant@niddk.nih.gov abocharov@cc.nih.gov. ; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and. ; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and. ; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892; Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 3135 EP - 3147 VL - 196 IS - 7 KW - Antigens, CD36 KW - 0 KW - Cytokines KW - Inflammation Mediators KW - Lipopolysaccharides KW - Lysosome-Associated Membrane Glycoproteins KW - RNA, Messenger KW - Receptors, Scavenger KW - SCARB2 protein, human KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Abridged Index Medicus KW - Index Medicus KW - Cytokines -- blood KW - Animals KW - Macrophages -- immunology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Gene Expression KW - Disease Models, Animal KW - Inflammation -- genetics KW - Mice KW - Cytokines -- metabolism KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Inflammation Mediators -- metabolism KW - Inflammation Mediators -- blood KW - RNA, Messenger -- metabolism KW - Organ Specificity -- genetics KW - Nitric Oxide Synthase -- genetics KW - Inflammation -- immunology KW - Nitric Oxide Synthase -- metabolism KW - Cell Line KW - Macrophages -- metabolism KW - Inflammation -- pathology KW - Liver Diseases -- immunology KW - Antigens, CD36 -- metabolism KW - Lysosome-Associated Membrane Glycoproteins -- genetics KW - Acute Kidney Injury -- genetics KW - Lipopolysaccharides -- immunology KW - Acute Kidney Injury -- pathology KW - Antigens, CD36 -- genetics KW - Liver Diseases -- pathology KW - Acute Kidney Injury -- immunology KW - Receptors, Scavenger -- metabolism KW - Receptors, Scavenger -- genetics KW - Lysosome-Associated Membrane Glycoproteins -- metabolism KW - Liver Diseases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1774533786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Human+SR-BI+and+SR-BII+Potentiate+Lipopolysaccharide-Induced+Inflammation+and+Acute+Liver+and+Kidney+Injury+in+Mice.&rft.au=Baranova%2C+Irina+N%3BSouza%2C+Ana+C+P%3BBocharov%2C+Alexander+V%3BVishnyakova%2C+Tatyana+G%3BHu%2C+Xuzhen%3BVaisman%2C+Boris+L%3BAmar%2C+Marcelo+J%3BChen%2C+Zhigang%3BKost%2C+Yana%3BRemaley%2C+Alan+T%3BPatterson%2C+Amy+P%3BYuen%2C+Peter+S+T%3BStar%2C+Robert+A%3BEggerman%2C+Thomas+L&rft.aulast=Baranova&rft.aufirst=Irina&rft.date=2016-04-01&rft.volume=196&rft.issue=7&rft.spage=3135&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=1550-6606&rft_id=info:doi/10.4049%2Fjimmunol.1501709 LA - 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Last updated - 2017-01-19 DO - http://dx.doi.org/10.4049/jimmunol.1501709 ER - TY - JOUR T1 - Anti-Helicobacter pylori Antibody Profiles in Epstein-Barr virus (EBV)-Positive and EBV-Negative Gastric Cancer. AN - 1773232893; 26251258 AB - Helicobacter pylori is the primary cause of gastric cancer, but about 9% of cases harbor Epstein-Barr virus (EBV) in the tumor cells. There is limited evidence on the possible interaction or antagonism between these infectious agents in gastric carcinogenesis. We compared H. pylori serologic profiles of EBV-positive (n = 58) and EBV-negative (n = 111) noncardia gastric cancer patients from the United States National Cancer Institute's International EBV-Gastric Cancer Consortium. EBV positivity of tumors was assessed by in situ hybridization. Serum levels of 15 antibodies to immunogenic proteins of H. pylori (Cad, CagA, Cagδ, CagM, Catalase, GroEL, HcpC, HP0231, HP0305, HpaA, HyuA, NapA, Omp, UreA, VacA) were assessed using bead-based multiplex serology. Logistic regression models were used to adjust odds ratios (OR) for country, age, sex, and year of diagnosis. Seropositivity to individual proteins ranged up to 90% overall. Antibodies to Catalase were borderline associated with tumor EBV positivity (adjusted OR = 3.15, p = .0024, Bonferroni corrected p = .036). Distributions of other antibodies did not vary by tumor EBV status. Similarity of host-response indicates the essential etiological role of H. pylori in EBV-positive gastric cancer. © 2015 John Wiley & Sons Ltd. JF - Helicobacter AU - Camargo, M Constanza AU - Kim, Kyoung-Mee AU - Matsuo, Keitaro AU - Torres, Javier AU - Liao, Linda M AU - Morgan, Douglas R AU - Michel, Angelika AU - Waterboer, Tim AU - Zabaleta, Jovanny AU - Dominguez, Ricardo L AU - Yatabe, Yasushi AU - Kim, Sung AU - Rocha-Guevara, Erick R AU - Lissowska, Jolanta AU - Pawlita, Michael AU - Rabkin, Charles S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA. ; Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. ; Unidad de Investigación en Enfermedades Infecciosas, UMAE Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, México City, México. ; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA. ; Division of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DFKZ), Heidelberg, Germany. ; Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. ; Department of Medicine, Western Regional Hospital, Santa Rosa de Copan, Honduras. ; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan. ; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Hospital de Oncología, CMN SXXI, Instituto Mexicano del Seguro Social, México City, México. ; Division of Cancer Epidemiology and Prevention, M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 153 EP - 157 VL - 21 IS - 2 KW - Antibodies, Bacterial KW - 0 KW - Index Medicus KW - gastric cancer KW - Interaction KW - Helicobacter pylori KW - Epstein-Barr virus KW - serology KW - United States KW - Humans KW - Helicobacter Infections -- complications KW - Aged KW - Middle Aged KW - Male KW - Female KW - Stomach Neoplasms -- pathology KW - Helicobacter pylori -- immunology KW - Antibodies, Bacterial -- blood KW - Stomach Neoplasms -- virology KW - Herpesvirus 4, Human -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773232893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Helicobacter&rft.atitle=Anti-Helicobacter+pylori+Antibody+Profiles+in+Epstein-Barr+virus+%28EBV%29-Positive+and+EBV-Negative+Gastric+Cancer.&rft.au=Camargo%2C+M+Constanza%3BKim%2C+Kyoung-Mee%3BMatsuo%2C+Keitaro%3BTorres%2C+Javier%3BLiao%2C+Linda+M%3BMorgan%2C+Douglas+R%3BMichel%2C+Angelika%3BWaterboer%2C+Tim%3BZabaleta%2C+Jovanny%3BDominguez%2C+Ricardo+L%3BYatabe%2C+Yasushi%3BKim%2C+Sung%3BRocha-Guevara%2C+Erick+R%3BLissowska%2C+Jolanta%3BPawlita%2C+Michael%3BRabkin%2C+Charles+S&rft.aulast=Camargo&rft.aufirst=M&rft.date=2016-04-01&rft.volume=21&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Helicobacter&rft.issn=1523-5378&rft_id=info:doi/10.1111%2Fhel.12249 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-13 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/hel.12249 ER - TY - JOUR T1 - Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons. AN - 1773232287; 26906474 AB - Fluorine and chlorine are metabolically stable, but generally less active replacements for a nitro group at the 3-position of indenoisoquinoline topoisomerase IB (Top1) poisons. A number of strategies were employed in the present investigation to enhance the Top1 inhibitory potencies and cancer cell growth inhibitory activities of halogenated indenoisoquinolines. In several cases, the new compounds' activities were found to rival or surpass those of similarly substituted 3-nitroindenoisoquinolines, and several unusually potent analogs were discovered through testing in human cancer cell cultures. A hydroxyethylaminopropyl side chain on the lactam nitrogen of two halogenated indenoisoquinoline Top1 inhibitors was found to also impart inhibitory activity against tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes that participate in the repair of DNA damage induced by Top1 poisons. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Bioorganic & medicinal chemistry AU - Beck, Daniel E AU - Lv, Wei AU - Abdelmalak, Monica AU - Plescia, Caroline B AU - Agama, Keli AU - Marchand, Christophe AU - Pommier, Yves AU - Cushman, Mark AD - Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and the Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. ; Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 21892, United States. ; Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and the Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. Electronic address: cushman@purdue.edu. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 1469 EP - 1479 VL - 24 IS - 7 KW - Indenes KW - 0 KW - Isoquinolines KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Tyrosyl DNA phosphodiesterase 2 KW - Tyrosyl DNA phosphodiesterase 1 KW - Cytotoxicity KW - Anticancer KW - Indenoisoquinoline KW - Topoisomerase I KW - Molecular Structure KW - Models, Molecular KW - Dose-Response Relationship, Drug KW - Humans KW - Structure-Activity Relationship KW - Topoisomerase I Inhibitors -- pharmacology KW - Indenes -- chemical synthesis KW - Isoquinolines -- pharmacology KW - Isoquinolines -- chemistry KW - Indenes -- pharmacology KW - Topoisomerase I Inhibitors -- chemistry KW - Indenes -- chemistry KW - Isoquinolines -- chemical synthesis KW - DNA Topoisomerases, Type I -- metabolism KW - Topoisomerase I Inhibitors -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773232287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=Synthesis+and+biological+evaluation+of+new+fluorinated+and+chlorinated+indenoisoquinoline+topoisomerase+I+poisons.&rft.au=Beck%2C+Daniel+E%3BLv%2C+Wei%3BAbdelmalak%2C+Monica%3BPlescia%2C+Caroline+B%3BAgama%2C+Keli%3BMarchand%2C+Christophe%3BPommier%2C+Yves%3BCushman%2C+Mark&rft.aulast=Beck&rft.aufirst=Daniel&rft.date=2016-04-01&rft.volume=24&rft.issue=7&rft.spage=1469&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry&rft.issn=1464-3391&rft_id=info:doi/10.1016%2Fj.bmc.2016.02.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-08 N1 - Date created - 2016-03-13 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Med Chem. 2000 Oct 5;43(20):3688-98 [11020283] J Med Chem. 2015 May 14;58(9):3997-4015 [25909279] Proteins. 2003 Sep 1;52(4):609-23 [12910460] Cancer Res. 2003 Nov 1;63(21):7428-35 [14612542] Bioorg Med Chem. 2004 Apr 1;12(7):1585-604 [15028252] Bioorg Med Chem Lett. 2004 Jul 16;14(14):3659-63 [15203138] J Med Chem. 2004 Nov 4;47(23):5651-61 [15509164] Science. 1998 Mar 6;279(5356):1504-13 [9488644] Science. 1998 Mar 6;279(5356):1534-41 [9488652] Mol Pharmacol. 2005 Feb;67(2):523-30 [15531731] J Med Chem. 2005 Apr 7;48(7):2336-45 [15801827] Nat Rev Cancer. 2006 Oct;6(10):789-802 [16990856] Nat Rev Cancer. 2006 Oct;6(10):813-23 [16990858] J Med Chem. 2006 Oct 19;49(21):6283-9 [17034134] J Med Chem. 2007 Sep 6;50(18):4419-30 [17696418] Cancer Res. 2007 Nov 1;67(21):10397-405 [17974983] Nat Protoc. 2008;3(11):1736-50 [18927559] Mol Cancer Ther. 2009 Jan;8(1):240-8 [19139134] Chem Rev. 2009 Jul;109(7):2894-902 [19476377] Mol Cancer Ther. 2010 May;9(5):1451-60 [20442306] Prog Med Chem. 2011;50:1-47 [21315927] J Med Chem. 2011 Jul 28;54(14):4937-53 [21710981] J Med Chem. 2012 May 10;55(9):4457-78 [22536944] J Biol Chem. 2012 Aug 31;287(36):30842-52 [22822062] Nucleic Acids Res. 2012 Sep 1;40(17):8371-80 [22740648] J Med Chem. 2012 Dec 27;55(24):10844-62 [23215354] ACS Chem Biol. 2013 Jan 18;8(1):82-95 [23259582] J Med Chem. 2013 Aug 22;56(16):6352-70 [23859074] J Med Chem. 2014 Feb 27;57(4):1495-512 [24517248] J Med Chem. 2014 May 22;57(10):4324-36 [24800942] DNA Repair (Amst). 2014 Jul;19:114-29 [24856239] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92 [12426403] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bmc.2016.02.015 ER - TY - JOUR T1 - A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer. AN - 1772833237; 26666244 AB - KRAS mutations are clinically important predictors of resistance to EGFR-directed therapies in colorectal cancer (CRC). Oncogenic activation of the RAS/RAF/MEK/ERK signaling cascade mediates proliferation independent of growth factor signaling. We hypothesized that targeting MEK with selumetinib could overcome resistance to cetuximab in KRAS mutant CRC. A phase I study (NCT01287130) was undertaken to determine the tolerability, and pharmacokinetic profiles of the combination of selumetinib and cetuximab, with an expanded cohort in KRAS-mutant CRC. 15 patients were treated in the dose escalation cohort and 18 patients were treated in the expansion cohort. Two dose-limiting toxicities were observed. One grade 3 acneiform rash and one grade 4 hypomagnesemia occurred. The most common grade 1 and 2 adverse events included rash, nausea/vomiting, diarrhea, and fatigue. The maximum tolerated dose was established at selumetinib 75 mg p.o. BID and cetuximab 250 mg/m(2) weekly following a 400 mg/m(2) load. Best clinical response in the dose escalation group included 1 unconfirmed partial response in a patient with CRC and stable disease (SD) in 5 patients (1 squamous cell carcinoma of the tonsil, 1 non-small cell lung cancer, and 3 CRC), and in the KRAS-mutant CRC dose expansion cohort, of the 14 patients who were evaluable for response, 5 patients had SD and 9 patients had progressive disease. The combination of selumetinib and cetuximab is safe and well tolerated. Minimal anti-tumor activity was observed in KRAS-mutant refractory metastatic CRC. Further investigations might be warranted in other cancer subtypes. JF - Investigational new drugs AU - Deming, Dustin A AU - Cavalcante, Ludmila L AU - Lubner, Sam J AU - Mulkerin, Daniel L AU - LoConte, Noelle K AU - Eickhoff, Jens C AU - Kolesar, Jill M AU - Fioravanti, Suzanne AU - Greten, Tim F AU - Compton, Kathryn AU - Doyle, Austin G AU - Wilding, George AU - Duffy, Austin AU - Liu, Glenn AD - University of Wisconsin-Madison Carbone Cancer Center, 600 Highland Avenue, K6/544 CSC, Madison, WI, 53792, USA. ddeming@medicine.wisc.edu. ; University of Wisconsin-Madison Carbone Cancer Center, 600 Highland Avenue, K6/544 CSC, Madison, WI, 53792, USA. ; National Cancer Institute/Medical Oncology Branch, Bethesda, MD, USA. ; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 168 EP - 175 VL - 34 IS - 2 KW - AZD 6244 KW - 0 KW - Benzimidazoles KW - KRAS protein, human KW - Protein Kinase Inhibitors KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Cetuximab KW - PQX0D8J21J KW - Index Medicus KW - Phase I KW - KRAS KW - AZD6244 KW - Selumetinib KW - Colon cancer KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Aged, 80 and over KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Maximum Tolerated Dose KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Male KW - Cetuximab -- pharmacology KW - Protein Kinase Inhibitors -- pharmacology KW - Benzimidazoles -- adverse effects KW - Benzimidazoles -- pharmacology KW - Benzimidazoles -- therapeutic use KW - Colorectal Neoplasms -- genetics KW - Benzimidazoles -- pharmacokinetics KW - Colorectal Neoplasms -- drug therapy KW - Mitogen-Activated Protein Kinase Kinases -- metabolism KW - Cetuximab -- adverse effects KW - Protein Kinase Inhibitors -- therapeutic use KW - Mutation -- genetics KW - Colorectal Neoplasms -- blood KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - Proto-Oncogene Proteins p21(ras) -- genetics KW - Cetuximab -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1772833237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=A+phase+I+study+of+selumetinib+%28AZD6244%2FARRY-142866%29%2C+a+MEK1%2F2+inhibitor%2C+in+combination+with+cetuximab+in+refractory+solid+tumors+and+KRAS+mutant+colorectal+cancer.&rft.au=Deming%2C+Dustin+A%3BCavalcante%2C+Ludmila+L%3BLubner%2C+Sam+J%3BMulkerin%2C+Daniel+L%3BLoConte%2C+Noelle+K%3BEickhoff%2C+Jens+C%3BKolesar%2C+Jill+M%3BFioravanti%2C+Suzanne%3BGreten%2C+Tim+F%3BCompton%2C+Kathryn%3BDoyle%2C+Austin+G%3BWilding%2C+George%3BDuffy%2C+Austin%3BLiu%2C+Glenn&rft.aulast=Deming&rft.aufirst=Dustin&rft.date=2016-04-01&rft.volume=34&rft.issue=2&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=1573-0646&rft_id=info:doi/10.1007%2Fs10637-015-0314-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-11 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT01287130; ClinicalTrials.gov N1 - SuppNotes - Cited By: Cell Growth Differ. 2001 Aug;12(8):397-408 [11504705] Clin Cancer Res. 2007 Mar 1;13(5):1576-83 [17332304] Cancer Res. 2007 Mar 15;67(6):2643-8 [17363584] Mol Cancer Ther. 2007 Aug;6(8):2209-19 [17699718] N Engl J Med. 2008 Mar 13;358(11):1160-74 [18337605] J Clin Oncol. 2008 May 1;26(13):2139-46 [18390968] Br J Cancer. 2011 Mar 1;104(5):856-62 [21285991] J Clin Oncol. 2008 Dec 10;26(35):5705-12 [19001320] Eur J Cancer. 2009 Jan;45(2):228-47 [19097774] Br J Cancer. 2009 Aug 4;101(3):465-72 [19603024] Am J Health Syst Pharm. 2010 Feb 1;67(3):223-6 [20101065] Clin Cancer Res. 2010 Mar 1;16(5):1613-23 [20179232] N Engl J Med. 2008 Oct 23;359(17):1757-65 [18946061] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10637-015-0314-7 ER - TY - JOUR T1 - Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats. AN - 1772833017; 26728879 AB - D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2C7-IT to support an initial Food and Drug Administration Investigational New Drug application. After the optimization of the formulation and administration, two cohorts (an acute and chronic cohort necropsied on study days 5 and 34) of Sprague-Dawley (SD) rats (four groups of 5 males and 5 females) were infused with the D2C7-IT formulation at total doses of 0, 0.05, 0.1, 0.4 μg (the acute cohort) and 0, 0.05, 0.1, 0.35 μg (the chronic cohort) for approximately 72 h by intracerebral convection-enhanced delivery using osmotic pumps. Mortality was observed in the 0.40 μg (5/10 rats) and 0.35 μg (4/10 rats) high-dose groups of each cohort. Body weight loss and abnormal behavior were only revealed in the rats treated with high doses of D2C7-IT. No dose-related effects were observed in clinical laboratory tests in either cohort. A gross pathologic examination of systemic tissues from the high-dose and control groups in both cohorts exhibited no dose-related or drug-related pathologic findings. Brain histopathology revealed the frequent occurrence of dose-related encephalomalacia, edema, and demyelination in the high-dose groups of both cohorts. In this study, the maximum tolerated dose of D2C7-IT was determined to be between 0.10 and 0.35 μg, and the no-observed-adverse-effect-level was 0.05 μg in SD rats. Both parameters were utilized to design the Phase I/II D2C7-IT clinical trial. JF - Investigational new drugs AU - Bao, Xuhui AU - Chandramohan, Vidyalakshmi AU - Reynolds, Randall P AU - Norton, John N AU - Wetsel, William C AU - Rodriguiz, Ramona M AU - Aryal, Dipendra K AU - McLendon, Roger E AU - Levin, Edward D AU - Petry, Neil A AU - Zalutsky, Michael R AU - Burnett, Bruce K AU - Kuan, Chien-Tsun AU - Pastan, Ira H AU - Bigner, Darell D AD - Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, 177 MSRB-1, 203 Research Drive, Box 3156, Durham, NC, USA. ; Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC, USA. ; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. ; Department of Radiology, Duke University Medical Center, Durham, NC, USA. ; Duke Translational Medicine Institute, Regulatory Affairs Office, Durham, NC, USA. ; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, 177 MSRB-1, 203 Research Drive, Box 3156, Durham, NC, USA. darell.bigner@duke.edu. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 149 EP - 158 VL - 34 IS - 2 KW - D2C7-(scdsFv)-PE38KDEL KW - 0 KW - Immunoconjugates KW - Immunotoxins KW - Single-Chain Antibodies KW - Index Medicus KW - Rat KW - Toxicity KW - Convection-enhanced delivery KW - Immunotoxin KW - Animals KW - Rats, Sprague-Dawley KW - Brain -- pathology KW - Brain -- drug effects KW - Inhibitory Concentration 50 KW - Male KW - Female KW - Injections, Intraventricular KW - Convection KW - Drug Delivery Systems KW - Single-Chain Antibodies -- administration & dosage KW - Immunotoxins -- toxicity KW - Single-Chain Antibodies -- toxicity KW - Immunoconjugates -- administration & dosage KW - Immunotoxins -- administration & dosage KW - Immunoconjugates -- toxicity KW - Drug Evaluation, Preclinical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1772833017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Preclinical+toxicity+evaluation+of+a+novel+immunotoxin%2C+D2C7-%28scdsFv%29-PE38KDEL%2C+administered+via+intracerebral+convection-enhanced+delivery+in+rats.&rft.au=Bao%2C+Xuhui%3BChandramohan%2C+Vidyalakshmi%3BReynolds%2C+Randall+P%3BNorton%2C+John+N%3BWetsel%2C+William+C%3BRodriguiz%2C+Ramona+M%3BAryal%2C+Dipendra+K%3BMcLendon%2C+Roger+E%3BLevin%2C+Edward+D%3BPetry%2C+Neil+A%3BZalutsky%2C+Michael+R%3BBurnett%2C+Bruce+K%3BKuan%2C+Chien-Tsun%3BPastan%2C+Ira+H%3BBigner%2C+Darell+D&rft.aulast=Bao&rft.aufirst=Xuhui&rft.date=2016-04-01&rft.volume=34&rft.issue=2&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=1573-0646&rft_id=info:doi/10.1007%2Fs10637-015-0318-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-11 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cancer Res. 2000 Mar 1;60(5):1383-7 [10728703] Neuro Oncol. 2014 Oct;16 Suppl 4:iv1-63 [25304271] Virchows Arch B Cell Pathol Incl Mol Pathol. 1980;35(1):19-32 [6111154] J Neuroimmunol. 1989 Dec;25(2-3):185-93 [2584396] Eur J Cancer. 1992;28(1):11-7 [1567659] Crit Rev Oncol Hematol. 1995 Jul;19(3):183-232 [7612182] Nat Rev Cancer. 2006 Jul;6(7):559-65 [16794638] Neurosurg Focus. 2007;22(5):E5 [17613236] Neuro Oncol. 2008 Jun;10(3):320-9 [18403491] N Engl J Med. 2008 Jul 31;359(5):492-507 [18669428] J Neurooncol. 2010 May;98(1):1-7 [19898744] Methods Mol Biol. 2011;686:447-63 [21082387] Neurosurgery. 2011 Sep;69(3):668-76 [21430586] J Neurosurg. 2011 Sep;115(3):463-4; discussion 465-6 [21619413] Toxins (Basel). 2010 Nov;2(11):2519-83 [22069564] Clin Dev Immunol. 2012;2012:480429 [22400035] Clin Dev Immunol. 2012;2012:980250 [22474489] Curr Drug Discov Technol. 2012 Dec;9(4):305-10 [22339074] Clin Cancer Res. 2013 Sep 1;19(17):4717-27 [23857604] MAbs. 2013 Sep-Oct;5(5):748-62 [23924792] Stroke. 1978 May-Jun;9(3):249-54 [644623] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10637-015-0318-3 ER - TY - JOUR T1 - Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. AN - 1772830779; 26690555 AB - The diagnosis of drug-induced liver injury is hindered by the limited utility of clinical chemistries. We have shown that hepatotoxicants can produce peripheral blood transcriptome "signatures" (PBTS) in rodents and humans. In this study, 42 adults were treated with acetaminophen (APAP; 1 g every 6 hours) for seven days, followed by three days of placebo. Eleven subjects received only placebo. After five days, 12 subjects (30%) had increases in serum alanine aminotransferase (ALT) levels ("responders"). PBTS of 707 and 760 genes, respectively, could distinguish responders and nonresponders from placebos. Functional analysis of the responder PBTS revealed increased expression of genes involved in TH2-mediated and innate immune responses, whereas the nonresponders demonstrated increased gene expression consistent with a tolerogenic immune response. Taken together, these observations suggest that the clinical subjects with transient increases in serum ALT failed to maintain or intensify a hepatic tolerogenic immune response. © 2015 American Society for Clinical Pharmacology and Therapeutics. JF - Clinical pharmacology and therapeutics AU - Fannin, R D AU - Gerrish, K AU - Sieber, S O AU - Bushel, P R AU - Watkins, P B AU - Paules, R S AD - National Institute of Environmental Health Sciences, Molecular Genomics Core, National Institute of Health, Research Triangle Park, North Carolina, USA. ; National Institute of Environmental Health Sciences, Biostatistics and Computational Biology Branch, National Institute of Health, Research Triangle Park, North Carolina, USA. ; Hamner - University of North Carolina Institute for Drug Safety Sciences, Research Triangle Park, North Carolina, USA. ; National Institute of Environmental Health Sciences, National Toxicology Program, Biomolecular Screening Branch, National Institute of Health, Research Triangle Park, North Carolina, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 432 EP - 441 VL - 99 IS - 4 KW - Analgesics, Non-Narcotic KW - 0 KW - Genetic Markers KW - RNA, Messenger KW - Acetaminophen KW - 362O9ITL9D KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Drug Administration Schedule KW - Double-Blind Method KW - Immunity, Innate -- drug effects KW - Humans KW - Principal Component Analysis KW - Predictive Value of Tests KW - Immunity, Innate -- genetics KW - Th2 Cells -- drug effects KW - Up-Regulation KW - Th2 Cells -- immunology KW - Time Factors KW - Chemical and Drug Induced Liver Injury -- blood KW - Drug Monitoring -- methods KW - Acetaminophen -- administration & dosage KW - Chemical and Drug Induced Liver Injury -- diagnosis KW - Chemical and Drug Induced Liver Injury -- genetics KW - Acetaminophen -- adverse effects KW - Analgesics, Non-Narcotic -- administration & dosage KW - Chemical and Drug Induced Liver Injury -- enzymology KW - Chemical and Drug Induced Liver Injury -- immunology KW - Analgesics, Non-Narcotic -- adverse effects KW - Gene Expression Profiling KW - Alanine Transaminase -- blood KW - RNA, Messenger -- blood KW - Transcriptome -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1772830779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Blood+transcript+immune+signatures+distinguish+a+subset+of+people+with+elevated+serum+ALT+from+others+given+acetaminophen.&rft.au=Fannin%2C+R+D%3BGerrish%2C+K%3BSieber%2C+S+O%3BBushel%2C+P+R%3BWatkins%2C+P+B%3BPaules%2C+R+S&rft.aulast=Fannin&rft.aufirst=R&rft.date=2016-04-01&rft.volume=99&rft.issue=4&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=1532-6535&rft_id=info:doi/10.1002%2Fcpt.328 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-18 N1 - Date created - 2016-03-10 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: PLoS One. 2012;7(9):e44880 [23028657] Hepatology. 2012 Aug;56(2):735-46 [22334567] Nat Rev Immunol. 2013 Apr;13(4):227-42 [23470321] J Hepatol. 2013 Sep;59(3):528-35 [23665041] Anal Chem. 2013 Dec 3;85(23):11326-34 [24127682] Drug Metab Dispos. 2014 Jan;42(1):28-32 [24104197] Toxicol Appl Pharmacol. 2014 Mar 1;275(2):122-33 [24440789] Br J Clin Pharmacol. 2014 May;77(5):904-5 [23879521] Liver Int. 2014 Mar;34(3):367-78 [24118944] Ann Intern Med. 2002 Dec 17;137(12):947-54 [12484709] Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 [16199517] Pharmacoepidemiol Drug Saf. 2006 Apr;15(4):241-3 [16552790] Blood. 2006 Jul 1;108(1):218-27 [16527888] Chem Res Toxicol. 2007 Feb;20(2):208-16 [17305405] Blood. 2007 Jul 1;110(1):220-7 [17356132] Toxicol Sci. 2007 Sep;99(1):326-37 [17562736] Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18211-6 [17984051] J Hepatol. 2008 Jun;48(6):952-61 [18395288] J Immunol. 2008 Jul 1;181(1):225-34 [18566388] Genome Biol. 2008;9(6):R100 [18570634] J Immunol. 2008 Sep 1;181(5):3285-90 [18714000] Blood. 2008 Oct 15;112(8):3283-92 [18664628] Hepatology. 2008 Nov;48(5):1680-9 [18853438] J Clin Invest. 2009 Feb;119(2):305-14 [19164858] J Immunol. 2009 Feb 15;182(4):1901-11 [19201843] J Clin Invest. 2009 Feb;119(2):246-9 [19244605] J Immunol. 2009 Aug 15;183(4):2232-41 [19635906] Genome Res. 2009 Sep;19(9):1507-15 [19416960] Cell Mol Biol Lett. 2009;14(4):587-608 [19554266] Hepatology. 2010 Jan;51(1):227-36 [19918972] Cytometry A. 2010 Apr;77(4):328-37 [20140969] Clin Pharmacol Ther. 2010 Jul;88(1):45-51 [20182423] J Immunol. 2010 Jul 15;185(2):1037-44 [20554958] Nat Genet. 2010 Aug;42(8):711-4 [20639878] Nat Rev Immunol. 2010 Nov;10(11):753-66 [20972472] Nat Immunol. 2011 Apr;12(4):295-303 [21358638] Nat Rev Gastroenterol Hepatol. 2011 Apr;8(4):202-11 [21386809] Nat Rev Immunol. 2011 Nov;11(11):723-37 [21997792] Hepatology. 2011 Sep 2;54(3):959-68 [21574173] Drug Metab Rev. 2012 Feb;44(1):107-15 [22235834] Sci Signal. 2012 Jan 17;5(207):ra5 [22253262] Blood. 2012 Mar 1;119(9):2003-12 [22238324] Toxicol Appl Pharmacol. 2012 Mar 15;259(3):320-8 [22285215] Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5010-5 [22403066] Toxicol Appl Pharmacol. 2012 Jul 15;262(2):139-48 [22575169] Int Immunol. 2013 Mar;25(3):171-82 [23125331] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cpt.328 ER - TY - JOUR T1 - UGT1A1 genotype-dependent dose adjustment of belinostat in patients with advanced cancers using population pharmacokinetic modeling and simulation. AN - 1772147118; 26637161 AB - Belinostat is a second-generation zinc-binding histone deacetylase inhibitor that is approved for peripheral T-cell lymphoma and is currently being studied in small cell lung cancer and other advanced carcinomas as a 48-hour continuous intravenous infusion. Belinostat is predominantly metabolized by UGT1A1, which is polymorphic. Preliminary analyses revealed a difference in belinostat clearance based on UGT1A1 genotype. A 2-compartment population pharmacokinetic (PK) model was developed and validated that incorporated the UGT1A1 genotype, albumin, and creatinine clearance on the clearance parameter; body weight was a significant covariate on volume. Simulated doses of 600 and 400 mg/m(2) /24 h given to patients considered extensive or impaired metabolizers, respectively, provided equivalent AUCs. This model and subsequent simulations supported additional PK/toxicity and pharmacogenomics/toxicity analyses to suggest a UGT1A1 genotype-based dose adjustment to normalize belinostat exposure and allow for more tolerable therapy. In addition, global protein lysine acetylation was modeled with PK and demonstrated a reversible belinostat exposure/response relationship, consistent with previous reports. © 2015, The American College of Clinical Pharmacology. JF - Journal of clinical pharmacology AU - Peer, Cody J AU - Goey, Andrew K L AU - Sissung, Tristan M AU - Erlich, Sheryl AU - Lee, Min-Jung AU - Tomita, Yusuke AU - Trepel, Jane B AU - Piekarz, Richard AU - Balasubramaniam, Sanjeeve AU - Bates, Susan E AU - Figg, William D AD - Clinical Pharmacology Program, National Cancer Institute, NIH, Bethesda, MD, USA. ; Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, USA. ; Cancer Therapy Evaluation Program, National Cancer Institute, NIH, Bethesda, MD, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 450 EP - 460 VL - 56 IS - 4 KW - Albumins KW - 0 KW - Antineoplastic Agents KW - Hydroxamic Acids KW - Sulfonamides KW - Creatinine KW - AYI8EX34EU KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - belinostat KW - F4H96P17NZ KW - Index Medicus KW - pharmacometrics KW - oncology KW - pharmacogenetics KW - clinical pharmacology KW - pharmacokinetics KW - population KW - Genotype KW - Albumins -- metabolism KW - Creatinine -- metabolism KW - Kinetics KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Pharmacogenetics -- methods KW - Models, Biological KW - Male KW - Female KW - Sulfonamides -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Glucuronosyltransferase -- genetics KW - Hydroxamic Acids -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Hydroxamic Acids -- pharmacokinetics KW - Sulfonamides -- administration & dosage KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1772147118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=UGT1A1+genotype-dependent+dose+adjustment+of+belinostat+in+patients+with+advanced+cancers+using+population+pharmacokinetic+modeling+and+simulation.&rft.au=Peer%2C+Cody+J%3BGoey%2C+Andrew+K+L%3BSissung%2C+Tristan+M%3BErlich%2C+Sheryl%3BLee%2C+Min-Jung%3BTomita%2C+Yusuke%3BTrepel%2C+Jane+B%3BPiekarz%2C+Richard%3BBalasubramaniam%2C+Sanjeeve%3BBates%2C+Susan+E%3BFigg%2C+William+D&rft.aulast=Peer&rft.aufirst=Cody&rft.date=2016-04-01&rft.volume=56&rft.issue=4&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=1552-4604&rft_id=info:doi/10.1002%2Fjcph.627 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-09 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/jcph.627 ER - TY - JOUR T1 - Feasibility of radiolabeled small molecule permeability as a quantitative measure of microbicide candidate toxicity. AN - 1771452152; 26772905 AB - To determine the feasibility of using quantitative changes in vaginal permeability to small molecules as a measure of candidate microbicide toxicity. Controlled, open-labeled, prospective study. Seven healthy women received a single vaginal dose of hydroxyethylcellulose gel (HEC), nonoxynol-9 (N-9) or K-Y Jelly. Each gel was radiolabeled with a small molecule ((99m)Tc-DTPA) followed by 12-h blood and urine collection. Pharmacokinetic (PK) parameters of (99m)Tc-DTPA were calculated to compare the impact of each gel on vaginal permeability. Each woman served as her own control. The Friedman test with post hoc Wilcoxon test was used to detect differences among the gels. Vaginal permeability of (99m)Tc-DTPA was highest for the N-9 radiolabel. N-9 plasma area under the concentration curve was 2.7-fold higher (p=.04), and peak concentration was threefold higher (p=.04) compared to HEC. There were no significant PK parameter differences between HEC and K-Y Jelly or between N-9 and K-Y Jelly. Cumulative dose-adjusted median (interquartile range) 12-h timed urine gamma activity was 66.70 × 10(-4)μCi (27.90-152.00) following HEC dosing, 103.00 × 10(-4)μCi (98.20-684.00) following N-9 gel dosing and 20.30 × 10(-4)μCi (11.10-55.90) following K-Y gel dosing. The differences between urine HEC and K-Y Jelly (p=.047) and between N-9 and K-Y Jelly (p=.016) were statistically significant. It is feasible to measure differences in vaginal permeability among vaginal gels using a radiolabeled small molecule, though there are permeability differences that require a nuanced understanding of gel composition to interpret the results. Establishing the safety of both vehicle and active pharmaceutical ingredient is an essential task in microbicide development, to be determined as soon as possible. This study suggests that a combination of microbicide toxicity assessments, that is, cervicovaginal permeability, inspection and histopathology, may need to be studied simultaneously. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Contraception AU - Coleman, Jenell S AU - Fuchs, Edward AU - Aung, Wutyi S AU - Marzinke, Mark A AU - Bakshi, Rahul P AU - Spiegel, Hans M L AU - Robinson, Jennifer AU - Hendrix, Craig W AD - Johns Hopkins University School of Medicine, Department of Gynecology & Obstetrics; Johns Hopkins University School of Medicine Division of Clinical Pharmacology, Department of Medicine. Electronic address: colemanj@jhmi.edu. ; Johns Hopkins University School of Medicine Division of Clinical Pharmacology, Department of Medicine. ; Johns Hopkins University School of Medicine Division of Clinical Pharmacology, Department of Medicine; Johns Hopkins University School of Medicine, Department of Pathology. ; HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. ; Johns Hopkins University School of Medicine, Department of Gynecology & Obstetrics; Johns Hopkins University School of Medicine Division of Clinical Pharmacology, Department of Medicine. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 331 EP - 336 VL - 93 IS - 4 KW - Anti-Infective Agents KW - 0 KW - Gels KW - K-Y jelly KW - Phosphates KW - Propylene Glycols KW - Vaginal Creams, Foams, and Jellies KW - Nonoxynol KW - 26027-38-3 KW - Cellulose KW - 9004-34-6 KW - hydroxyethylcellulose KW - 9004-62-0 KW - Glycerol KW - PDC6A3C0OX KW - Technetium Tc 99m Pentetate KW - VW78417PU1 KW - Index Medicus KW - Permeability KW - Microbicide KW - Spermicide KW - N-9 KW - HIV KW - Phosphates -- pharmacokinetics KW - Nonoxynol -- administration & dosage KW - Glycerol -- pharmacokinetics KW - Humans KW - Cellulose -- administration & dosage KW - Propylene Glycols -- administration & dosage KW - Cellulose -- analogs & derivatives KW - Glycerol -- administration & dosage KW - Prospective Studies KW - Nonoxynol -- pharmacokinetics KW - Cellulose -- pharmacokinetics KW - Adult KW - HIV Infections -- prevention & control KW - Technetium Tc 99m Pentetate -- pharmacokinetics KW - Propylene Glycols -- pharmacokinetics KW - Vaginal Creams, Foams, and Jellies -- pharmacokinetics KW - Middle Aged KW - Adolescent KW - Vaginal Creams, Foams, and Jellies -- chemistry KW - Phosphates -- administration & dosage KW - Female KW - Cell Membrane Permeability KW - Vagina -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1771452152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Contraception&rft.atitle=Feasibility+of+radiolabeled+small+molecule+permeability+as+a+quantitative+measure+of+microbicide+candidate+toxicity.&rft.au=Coleman%2C+Jenell+S%3BFuchs%2C+Edward%3BAung%2C+Wutyi+S%3BMarzinke%2C+Mark+A%3BBakshi%2C+Rahul+P%3BSpiegel%2C+Hans+M+L%3BRobinson%2C+Jennifer%3BHendrix%2C+Craig+W&rft.aulast=Coleman&rft.aufirst=Jenell&rft.date=2016-04-01&rft.volume=93&rft.issue=4&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Contraception&rft.issn=1879-0518&rft_id=info:doi/10.1016%2Fj.contraception.2016.01.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-07 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: AIDS Res Hum Retroviruses. 2015 Nov;31(11):1089-97 [26066390] AIDS Res Hum Retroviruses. 2015 Nov;31(11):1109-15 [26077739] J Biomed Opt. 2013 Apr;18(4):046010 [23588808] AIDS Res Hum Retroviruses. 2011 Sep;27(9):1019-24 [21309617] J Infect Dis. 2007 Mar 1;195(5):703-10 [17262713] Sex Transm Dis. 2008 Mar;35(3):269-75 [18091028] Science. 2010 Sep 3;329(5996):1168-74 [20643915] Nat Rev Immunol. 2005 Oct;5(10):783-92 [16200081] Arzneimittelforschung. 1998 May;48(5):512-7 [9638320] J Nucl Med. 1972 Jan;13(1):107-10 [5007959] Lancet. 2002 Sep 28;360(9338):971-7 [12383665] Sex Transm Dis. 2013 Nov;40(11):854-9 [24113407] AIDS Res Hum Retroviruses. 2013 Nov;29(11):1487-95 [23885722] N Engl J Med. 2015 Feb 5;372(6):509-18 [25651245] Int J Pharm. 2003 Aug 11;261(1-2):147-52 [12878403] Arch Oral Biol. 2004 May;49(5):387-92 [15041486] Antimicrob Agents Chemother. 2004 May;48(5):1837-47 [15105142] AAPS PharmSciTech. 2004 Mar 12;5(1):E17 [15198538] Contraception. 2004 Aug;70(2):107-10 [15288213] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.contraception.2016.01.002 ER - TY - JOUR T1 - Identification of compounds that modulate retinol signaling using a cell-based qHTS assay. AN - 1770888668; 26820057 AB - In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling. Copyright © 2016 Elsevier Ltd. All rights reserved. JF - Toxicology in vitro : an international journal published in association with BIBRA AU - Chen, Yanling AU - Sakamuru, Srilatha AU - Huang, Ruili AU - Reese, David H AU - Xia, Menghang AD - Division of Molecular Biology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD 20708, United States. Electronic address: yanling.chen@fda.hhs.gov. ; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, United States. ; Division of Molecular Biology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD 20708, United States. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 287 EP - 296 VL - 32 KW - Vitamin A KW - 11103-57-4 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - LOPAC KW - Developmental toxicant KW - High-throughput screening KW - Tox21 KW - Stem cell KW - Retinol signaling KW - Animals KW - Genes, Reporter KW - Mice KW - Response Elements KW - Luciferases -- genetics KW - Signal Transduction KW - Cell Line KW - Vitamin A -- agonists KW - High-Throughput Screening Assays KW - Vitamin A -- antagonists & inhibitors KW - Vitamin A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770888668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+in+vitro+%3A+an+international+journal+published+in+association+with+BIBRA&rft.atitle=Identification+of+compounds+that+modulate+retinol+signaling+using+a+cell-based+qHTS+assay.&rft.au=Chen%2C+Yanling%3BSakamuru%2C+Srilatha%3BHuang%2C+Ruili%3BReese%2C+David+H%3BXia%2C+Menghang&rft.aulast=Chen&rft.aufirst=Yanling&rft.date=2016-04-01&rft.volume=32&rft.issue=&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Toxicology+in+vitro+%3A+an+international+journal+published+in+association+with+BIBRA&rft.issn=1879-3177&rft_id=info:doi/10.1016%2Fj.tiv.2016.01.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-05 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Annu Rev Pharmacol Toxicol. 1999;39:399-430 [10331090] Cancer Res. 1999 Jun 1;59(11):2566-9 [10363974] Dev Biol. 1999 Sep 15;213(2):390-404 [10479456] J Cell Sci. 2004 Nov 15;117(Pt 24):5731-7 [15522889] Neurotoxicology. 2005 Aug;26(4):531-45 [16112319] Nat Genet. 2005 Oct;37(10):1035-7 [16155570] Trends Biochem Sci. 2006 May;31(5):268-75 [16603362] Leukemia. 2006 Jun;20(6):941-51 [16617325] Apoptosis. 2006 Jul;11(7):1101-9 [16699956] Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11473-8 [16864780] Cell. 2006 Aug 25;126(4):663-76 [16904174] Mol Cell Endocrinol. 2007 Jan 29;264(1-2):74-81 [17101211] Biochem Pharmacol. 2007 Aug 15;74(4):601-11 [17601492] Cancer Res. 2007 Dec 1;67(23):11386-92 [18056466] Cell. 2008 Feb 8;132(3):344-62 [18267068] Stem Cells. 2008 Jul;26(7):1858-64 [18436859] Cell. 2008 Sep 19;134(6):921-31 [18805086] Blood. 2008 Nov 1;112(9):3762-71 [18495959] J Cell Biochem. 2009 Mar 1;106(4):682-92 [19160421] Physiol Rev. 2000 Jul;80(3):1021-54 [10893430] Cell Growth Differ. 2001 Apr;12(4):193-200 [11331248] Expert Opin Pharmacother. 2001 Mar;2(3):491-505 [11336601] Annu Rev Nutr. 2001;21:167-92 [11375434] Dev Biol. 2001 Sep 1;237(1):107-15 [11518509] Biochem J. 2002 Feb 1;361(Pt 3):621-7 [11802792] Biochim Biophys Acta. 2002 Apr 1;1596(1):156-62 [11983430] J Lipid Res. 2002 Nov;43(11):1773-808 [12401878] Cardiovasc Res. 2003 May 1;58(2):292-302 [12757864] Cell Res. 2003 Dec;13(6):429-42 [14728799] Cell Stem Cell. 2013 Jun 6;12(6):713-26 [23602540] Drug Discov Today. 2013 Aug;18(15-16):716-23 [23732176] FASEB J. 1996 Jul;10(9):940-54 [8801176] Cancer Res. 1998 Jul 15;58(14):3163-72 [9679985] Nat Med. 2009 Apr;15(4):401-9 [19252500] Nucl Recept Signal. 2009;7:e002 [19381305] Environ Health Perspect. 2009 May;117(5):685-95 [19479008] Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8912-7 [19447925] Biochemistry. 2009 Nov 3;48(43):10267-74 [19772353] Trends Pharmacol Sci. 2010 Jan;31(1):36-45 [19896224] Mol Cancer. 2010;9:15 [20102612] Oncogene. 2010 Feb 25;29(8):1135-44 [19935721] Cancer Res. 2010 Mar 15;70(6):2516-27 [20215516] Cell Signal. 2010 Aug;22(8):1175-84 [20206686] Environ Health Perspect. 2011 Aug;119(8):1142-8 [21543282] Hum Reprod Update. 2011 Sep-Oct;17(5):589-604 [21747128] J Cell Biochem. 2011 Oct;112(10):2865-72 [21618588] Biochim Biophys Acta. 2012 Jan;1821(1):152-67 [21621639] Biochemistry. 2012 Feb 28;51(8):1730-9 [22304499] Physiol Genomics. 2012 May 1;44(9):495-503 [22433785] J Biol Chem. 2012 May 18;287(21):17530-45 [22474287] J Bone Miner Metab. 2013 Jan;31(1):53-63 [23014973] Br J Pharmacol. 2013 Mar;168(5):1201-14 [23062100] Toxicol In Vitro. 2014 Mar;28(2):282-91 [24287113] J Biol Chem. 2014 Jan 10;289(2):1142-50 [24265316] Cell. 2014 Mar 27;157(1):255-66 [24679540] Pharmacol Biochem Behav. 2014 May;120:117-23 [24582848] PLoS One. 2014;9(5):e96512 [24788806] Cancer Lett. 2014 Jul 10;349(1):8-14 [24732808] Sci Rep. 2014;4:5664 [25012808] Ann Hematol. 2014 Sep;93(9):1621-3 [24399307] Dev Growth Differ. 2014 Sep;56(7):518-25 [25212816] Biochim Biophys Acta. 2015 Jan;1851(1):66-75 [24768681] Environ Health Perspect. 2015 Jan;123(1):49-56 [25302578] Nat Rev Mol Cell Biol. 2015 Feb;16(2):110-23 [25560970] Cell Mol Life Sci. 2015 Apr;72(8):1559-76 [25558812] Cell. 2004 Feb 20;116(4):499-509 [14980218] J Am Acad Dermatol. 2004 Jun;50(6):900-6 [15153892] Cancer Res. 1973 Dec;33(12):3231-8 [4357355] Fed Proc. 1976 May 1;35(6):1332-8 [770206] J Cell Biol. 1982 Aug;94(2):253-62 [7107698] J Cell Physiol. 1992 May;151(2):239-48 [1572900] J Biol Chem. 1993 Jan 5;268(1):591-600 [8380169] Leuk Res. 1994 Apr;18(4):299-304 [8170172] Nature. 1994 Oct 6;371(6497):528-31 [7935766] Cell Mol Biol Res. 1994;40(4):297-312 [7866431] J Nutr. 1995 Oct;125(10):2483-92 [7562082] Birth Defects Res B Dev Reprod Toxicol. 2013 Jun;98(3):276-82 [23696197] Chem Pharm Bull (Tokyo). 1999 Dec;47(12):1778-86 [10748721] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.tiv.2016.01.011 ER - TY - JOUR T1 - Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Proposed DSM-5 Diagnosis. AN - 1770862834; 26202432 AB - Over the past 40 years, a significant body of animal and human research has documented the teratogenic effects of prenatal alcohol exposure (PAE). Neurobehavioral Disorder associated with PAE is proposed as a new clarifying term, intended to encompass the neurodevelopmental and mental health symptoms associated with PAE. Defining this disorder is a necessary step to adequately characterize these symptoms and allow clinical assessment not possible using existing physically-based diagnostic schemes. Without appropriate diagnostic guidelines, affected individuals are frequently misdiagnosed and treated inappropriately (often to their considerable detriment) by mental health, educational, and criminal justice systems. Three core areas of deficits identified from the available research, including neurocognitive, self-regulation, and adaptive functioning impairments, are discussed and information regarding associated features and disorders, prevalence, course, familial patterns, differential diagnosis, and treatment of the proposed disorder are also provided. JF - Child psychiatry and human development AU - Kable, Julie A AU - O'Connor, Mary J AU - Olson, Heather Carmichael AU - Paley, Blair AU - Mattson, Sarah N AU - Anderson, Sally M AU - Riley, Edward P AD - Departments of Psychiatry and Behavioral Sciences and Pediatrics, Emory University School of Medicine, Atlanta, GA, 30329, USA. jkabl01@emory.edu. ; Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA. ; Department of Psychology, Center for Behavioral Teratology, San Diego State University, San Diego, CA, 92120, USA. ; National Institute on Alcohol Abuse and Alcoholism, Bethesda, MA, USA. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 335 EP - 346 VL - 47 IS - 2 KW - Index Medicus KW - Prenatal alcohol exposure KW - ND-PAE KW - Psychiatric diagnosis KW - Fetal alcohol spectrum disorders KW - Humans KW - Fetal Alcohol Spectrum Disorders -- physiopathology KW - Neurodevelopmental Disorders -- etiology KW - Neurodevelopmental Disorders -- diagnosis KW - Neurodevelopmental Disorders -- physiopathology KW - Diagnostic and Statistical Manual of Mental Disorders KW - Fetal Alcohol Spectrum Disorders -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770862834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+psychiatry+and+human+development&rft.atitle=Neurobehavioral+Disorder+Associated+with+Prenatal+Alcohol+Exposure+%28ND-PAE%29%3A+Proposed+DSM-5+Diagnosis.&rft.au=Kable%2C+Julie+A%3BO%27Connor%2C+Mary+J%3BOlson%2C+Heather+Carmichael%3BPaley%2C+Blair%3BMattson%2C+Sarah+N%3BAnderson%2C+Sally+M%3BRiley%2C+Edward+P&rft.aulast=Kable&rft.aufirst=Julie&rft.date=2016-04-01&rft.volume=47&rft.issue=2&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Child+psychiatry+and+human+development&rft.issn=1573-3327&rft_id=info:doi/10.1007%2Fs10578-015-0566-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s10578-015-0566-7 ER - TY - JOUR T1 - An acute, epitope-specific modification in the dopamine transporter associated with methamphetamine-induced neurotoxicity. AN - 1767074703; 26799527 AB - Preclinical studies demonstrate that repeated, high-dose methamphetamine administrations rapidly decrease plasmalemmal dopamine uptake, which may contribute to aberrant dopamine accumulation, reactive species generation, and long-term dopaminergic deficits. The present study extends these findings by demonstrating a heretofore unreported, epitope-specific modification in the dopamine transporter caused by a methamphetamine regimen that induces these deficits. Specifically, repeated, high-dose methamphetamine injections (4 × 10 mg/kg/injection, 2-h intervals) rapidly decreased immunohistochemical detection of striatal dopamine transporter as assessed 1 h after the final methamphetamine exposure. In contrast, neither a single high dose (1 × 10 mg/kg) nor repeated injections of a lower dose (4 × 2 mg/kg/injection) induced this change. The high-dose regimen-induced alteration was only detected using antibodies directed against the N-terminus. Immunohistochemical staining using antibodies directed against the C-terminus did not reveal any changes. The high-dose regimen also did not alter dopamine transporter expression as assessed using [(125) I]RTI-55 autoradiography. These data suggest that the repeated, high-dose methamphetamine regimen alters the N-terminus of the dopamine transporter. Further, these data may be predictive of persistent dopamine deficits caused by the stimulant. Future studies of the signaling cascades involved should provide novel insight into potential mechanisms underlying the physiological and pathophysiological regulation of the dopamine transporter. © 2016 Wiley Periodicals, Inc. JF - Synapse (New York, N.Y.) AU - Fricks-Gleason, Ashley N AU - German, Christopher L AU - Hoonakker, Amanda J AU - Friend, Danielle M AU - Ganesh, Kamala K AU - Carver, Aaron S AU - Hanson, Glen R AU - Fleckenstein, Annette E AU - Keefe, Kristen A AD - Department of Psychology and Neuroscience, Regis University, Denver, Colorado, 80221. ; School of Dentistry, University of Utah, Salt Lake City, Utah, 84108. ; Eating and Addiction Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, 20892. ; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, 84112. ; Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, Utah, 84112. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 139 EP - 146 VL - 70 IS - 4 KW - Dopamine Agents KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Epitopes KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - toxicity KW - immunohistochemistry KW - striatum KW - rodent KW - N-terminus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Corpus Striatum -- metabolism KW - Molecular Sequence Data KW - Corpus Striatum -- drug effects KW - Amino Acid Sequence KW - Protein Binding KW - Protein Domains KW - Male KW - Epitopes -- metabolism KW - Dopamine Agents -- toxicity KW - Methamphetamine -- administration & dosage KW - Dopamine Plasma Membrane Transport Proteins -- chemistry KW - Dopamine Agents -- pharmacology KW - Methamphetamine -- pharmacology KW - Dopamine Plasma Membrane Transport Proteins -- metabolism KW - Methamphetamine -- toxicity KW - Dopamine Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767074703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=An+acute%2C+epitope-specific+modification+in+the+dopamine+transporter+associated+with+methamphetamine-induced+neurotoxicity.&rft.au=Fricks-Gleason%2C+Ashley+N%3BGerman%2C+Christopher+L%3BHoonakker%2C+Amanda+J%3BFriend%2C+Danielle+M%3BGanesh%2C+Kamala+K%3BCarver%2C+Aaron+S%3BHanson%2C+Glen+R%3BFleckenstein%2C+Annette+E%3BKeefe%2C+Kristen+A&rft.aulast=Fricks-Gleason&rft.aufirst=Ashley&rft.date=2016-04-01&rft.volume=70&rft.issue=4&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=1098-2396&rft_id=info:doi/10.1002%2Fsyn.21891 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-02-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/syn.21891 ER - TY - JOUR T1 - Immunogold electron microscopy and confocal analyses reveal distinctive patterns of histone H3 phosphorylation during mitosis in MCF-7 cells. AN - 1765115514; 26799600 AB - Histone phosphorylation has a profound impact on epigenetic regulation of gene expression, chromosome condensation and segregation, and maintenance of genome integrity. Histone H3 Serine 10 is evolutionally conserved and heavily phosphorylated during mitosis. To examine Histone H3 Serine 10 phosphorylation (H3S10ph) dynamics in mitosis, we applied immunogold labeling and confocal microscopy to visualize H3S10ph expression in MCF-7 cells. Confocal observations showed that MCF-7 cells had abundant H3S10ph expression in prophase and metaphase. In anaphase, the H3S10ph expression was significantly decreased and displayed only sparsely localized staining that mainly associated with the chromatid tips. We showed that immunogold bead density distribution followed the H3S10ph expression patterns observed in confocal analysis. At a higher magnification in metaphase, the immunogold beads were readily visible and the bead distribution along the condensed chromosomes was distinctive, indicating the specificity and reliability of the immunogold staining procedure. In anaphase, the beads were found to distribute focally in specific regions of chromatids, reinforcing the confocal observations of differential H3 phosphorylation. To our knowledge, this is the first report to show the specific H3S10ph expression with an immunogold technique and transmission electron microscopy. Additionally, with confocal microscopy, we analyzed H3S10ph expression in an immortalized cell line derived from benign uterine smooth muscle tumor cells. H3S10ph epitope was expressed more abundantly during anaphase in the benign tumor cells, and there was no dramatic differential expression within the condensed chromatid clusters as observed in MCF-7 cells. The differences in H3S10ph expression pattern and dynamics may contribute to the differential proliferative potential between benign tumor cells and MCF-7 cells. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Genes, chromosomes & cancer AU - Yan, Yitang AU - Cummings, Connie A AU - Sutton, Deloris AU - Yu, Linda AU - Castro, Lysandra AU - Moore, Alicia B AU - Gao, Xiaohua AU - Dixon, Darlene AD - National Toxicology Program Laboratory (NTPL), Molecular Pathogenesis Group, Division of the NTP (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, 27709. ; Cellular and Molecular Pathology Branch, Pathology Support Group, DNTP, NIEHS, NIH, Research Triangle Park, NC, 27709. Y1 - 2016/04// PY - 2016 DA - April 2016 SP - 397 EP - 406 VL - 55 IS - 4 KW - Chromatin KW - 0 KW - Epitopes KW - Histones KW - Serine KW - 452VLY9402 KW - Index Medicus KW - Chromatin -- metabolism KW - Phosphorylation KW - Humans KW - MCF-7 Cells KW - Cell Proliferation KW - Epitopes -- biosynthesis KW - Microscopy, Electron, Transmission -- methods KW - Mitosis KW - Microscopy, Immunoelectron -- methods KW - Histones -- metabolism KW - Microscopy, Confocal -- methods KW - Serine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1765115514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Immunogold+electron+microscopy+and+confocal+analyses+reveal+distinctive+patterns+of+histone+H3+phosphorylation+during+mitosis+in+MCF-7+cells.&rft.au=Yan%2C+Yitang%3BCummings%2C+Connie+A%3BSutton%2C+Deloris%3BYu%2C+Linda%3BCastro%2C+Lysandra%3BMoore%2C+Alicia+B%3BGao%2C+Xiaohua%3BDixon%2C+Darlene&rft.aulast=Yan&rft.aufirst=Yitang&rft.date=2016-04-01&rft.volume=55&rft.issue=4&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=1098-2264&rft_id=info:doi/10.1002%2Fgcc.22343 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-26 N1 - Date created - 2016-02-11 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Oncogene. 2002 May 9;21(20):3103-11 [12082625] Lab Invest. 2002 Jun;82(6):719-28 [12065682] J Biol Chem. 2003 Mar 21;278(12):10588-93 [12529330] Cell. 1999 Apr 2;97(1):99-109 [10199406] Cancer Res. 2005 Jul 1;65(13):5818-27 [15994958] Toxicology. 1999 Aug 31;136(2-3):79-88 [10514001] EMBO J. 1999 Sep 1;18(17):4779-93 [10469656] Mol Carcinog. 2006 Jun;45(6):416-21 [16637065] Subcell Biochem. 2007;41:319-36 [17484134] Cancer Res. 2008 Apr 1;68(7):2538-47 [18381464] Carcinogenesis. 2008 Jun;29(6):1276-81 [18375956] Toxicol Appl Pharmacol. 2009 Dec 15;241(3):275-82 [19716834] Science. 2010 Aug 6;329(5992):689-93 [20616235] Dev Biol. 2010 Nov 15;347(2):348-59 [20832397] Mod Pathol. 2013 Sep;26(9):1153-60 [23558574] Biochem Soc Trans. 2013 Dec;41(6):1761-5 [24256288] Carcinogenesis. 2014 Jun;35(6):1228-37 [24398671] Appl Immunohistochem Mol Morphol. 2015 Nov-Dec;23(10):689-95 [25611243] J Biol Chem. 2000 Jul 14;275(28):20980-4 [10806218] Oncogene. 2001 May 28;20(24):3021-7 [11420717] Cancer Res. 2002 Sep 15;62(18):5168-77 [12234980] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/gcc.22343 ER - TY - JOUR T1 - A case-control study of occupational sunlight exposure and renal cancer risk. AN - 1760909253; 26505275 AB - Epidemiological evidence of a relationship between vitamin D and kidney cancer risk has been inconsistent despite experimental data indicating that vitamin D and its metabolites may inhibit carcinogenesis. Previously we reported an inverse association between renal cell carcinoma (RCC) risk and occupational ultraviolet (UV) exposure among European men. In this study, we examined the association between occupational UV exposure and RCC risk among US residents and investigated whether this association varied by race and sex. Lifetime occupational data for 1,217 RCC cases and 1,235 controls in a population-based case-control study, conducted from 2002 to 2007, were assessed for occupational UV exposure. We evaluated exposure metrics in quartiles based on control exposure levels and calculated associations between RCC risk and occupational UV exposure using unconditional logistic regression adjusted for sex, race, body mass index, smoking, hypertension, center, education, family history of cancer and dietary vitamin D intake. A general pattern of decreasing RCC risk with increasing UV exposure was observed. Cases had significantly lower cumulative occupational UV exposure than controls (fourth quartile vs. first: odds ratio = 0.74 [95% confidence interval = 0.56-0.99], p-trend = 0.03). Similar results were observed for other UV exposure metrics. The association with occupational UV exposure was stronger for women than for men, but did not differ by race. Our findings suggest an inverse association between occupational UV exposure and RCC, particularly among women. Given the sex finding discrepancies in this study versus our previous study, additional research is need to clarify whether the protective effects of occupational UV exposure and RCC risk are real. © 2015 UICC. JF - International journal of cancer AU - Karami, Sara AU - Colt, Joanne S AU - Stewart, Patricia A AU - Schwartz, Kendra AU - Davis, Faith G AU - Ruterbusch, Julie J AU - Chow, Wong-Ho AU - Wacholder, Sholom AU - Graubard, Barry I AU - Purdue, Mark P AU - Moore, Lee E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD. ; Stewart Exposure Assessments, LLC, Arlington, VA. ; Karmanos Cancer Institute, Wayne State University, Detroit, MI. ; University of Illinois, Chicago, IL. Y1 - 2016/04/01/ PY - 2016 DA - 2016 Apr 01 SP - 1626 EP - 1633 VL - 138 IS - 7 KW - Index Medicus KW - occupational UV KW - sunlight KW - race KW - kidney cancer KW - Young Adult KW - Odds Ratio KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Sunlight -- adverse effects KW - Occupational Exposure -- adverse effects KW - Kidney Neoplasms -- epidemiology KW - Carcinoma, Renal Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760909253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=A+case-control+study+of+occupational+sunlight+exposure+and+renal+cancer+risk.&rft.au=Karami%2C+Sara%3BColt%2C+Joanne+S%3BStewart%2C+Patricia+A%3BSchwartz%2C+Kendra%3BDavis%2C+Faith+G%3BRuterbusch%2C+Julie+J%3BChow%2C+Wong-Ho%3BWacholder%2C+Sholom%3BGraubard%2C+Barry+I%3BPurdue%2C+Mark+P%3BMoore%2C+Lee+E&rft.aulast=Karami&rft.aufirst=Sara&rft.date=2016-04-01&rft.volume=138&rft.issue=7&rft.spage=1626&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.29902 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-09 N1 - Date created - 2016-01-22 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Epidemiology. 2001 Sep;12(5):552-7 [11505175] CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 [24399786] Nutr Rev. 2003 Mar;61(3):107-13 [12723644] Recent Results Cancer Res. 2003;164:371-7 [12899536] Eur J Clin Nutr. 2003 Oct;57(10):1222-9 [14506481] Stat Methods Med Res. 1996 Sep;5(3):283-310 [8931197] Am J Clin Nutr. 1999 May;69(5):842-56 [10232622] CMAJ. 2005 Jul 5;173(1):15-6; author reply 17 [15997024] Photochem Photobiol. 2005 Jul-Aug;81(4):736-49 [15819599] BMC Cancer. 2006;6:264 [17096841] Horm Metab Res. 2007 Feb;39(2):85-95 [17326004] Eur J Cancer. 2007 Jul;43(11):1701-12 [17540555] Cancer Lett. 2008 Mar 18;261(2):127-36 [18267352] Cancer. 2010 Apr 15;116(8):2001-10 [20213683] Nat Rev Urol. 2010 May;7(5):245-57 [20448658] Am J Epidemiol. 2010 Jul 1;172(1):47-57 [20562187] Epidemiology. 2011 Nov;22(6):797-804 [21881515] Curr Osteoporos Rep. 2012 Mar;10(1):4-15 [22249582] Arch Biochem Biophys. 2012 Jul 1;523(1):107-14 [22085499] Int J Cancer. 2012 Sep 15;131(6):E1015-23 [22539073] J Intern Med. 2002 Aug;252(2):178-9; author reply 179-80 [12190894] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.29902 ER - TY - JOUR T1 - Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations. AN - 1777983865; 27029323 AB - DNA topoisomerase I (Top1) is a DNA unwinding protein and the specific target of the camptothecin class of chemotherapeutic drugs. One of these, irinotecan, acting through its active metabolite SN-38, is used in the treatment of metastatic colorectal cancer. However, resistance to irinotecan represents a major clinical problem. Since molecular alterations in Top1 may result in resistance to irinotecan, we characterized Top1 in three human colon cancer cell lines with acquired resistance to SN-38. Three SN-38 resistant (20-67 fold increased resistance) cell lines were generated and compared to wild-type parental cells with regards to: TOP1 gene copy number and gene sequence, Top1 expression (mRNA and protein), Top1 enzymatic activity in the absence and presence of drug, and Top1-DNA cleavage complexes in drug treated cells. TOP1 mutations were validated by PCR using mutant specific primers. Furthermore, cross-resistance to two indenoisoquinoline Top1-targeting drugs (NSC 725776 and NSC 743400) and two Top2-targeting drugs (epirubicin and etoposide) was investigated. Two of three SN-38 resistant cell lines carried TOP1 gene copy number aberrations: A TOP1 gene copy gain and a loss of chromosome 20, respectively. One resistant cell line harbored a pair of yet unreported TOP1 mutations (R364K and G717R) in close proximity to the drug binding site. Mutant TOP1 was expressed at a markedly higher level than wild-type TOP1. None or very small reductions were observed in Top1 expression or Top1 activity in the absence of drug. In all three SN-38 resistant cell lines Top1 activity was maintained in the presence of high concentrations of SN-38. None or only partial cross-resistance were observed for etoposide and epirubicin, respectively. SN-38 resistant cells with wild-type TOP1 remained sensitive to NSC 743400, while cells with mutant TOP1 was fully cross-resistant to both indenoisoquinolines. Top1-DNA cleavage complex formation following drug treatment supported the other findings. This study adds to the growing knowledge about resistance mechanisms for Top1-targeting chemotherapeutic drugs. Importantly, two yet unreported TOP1 mutations were identified, and it was underlined that cross-resistance to the new indenoisoquinoline drugs depends on the specific underlying molecular mechanism of resistance to SN-38. JF - Journal of experimental & clinical cancer research : CR AU - Jensen, Niels Frank AU - Agama, Keli AU - Roy, Amit AU - Smith, David Hersi AU - Pfister, Thomas D AU - Rømer, Maria Unni AU - Zhang, Hong-Liang AU - Doroshow, James H AU - Knudsen, Birgitta R AU - Stenvang, Jan AU - Brünner, Nils AU - Pommier, Yves AD - Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Section for Molecular Disease Biology, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. ; National Institutes of Health, National Cancer Institute, Center for Cancer Research, Laboratory of Molecular Pharmacology, 37 Convent Drive, Building 37, Room 5068, Bethesda, MD, 20892-4255, USA. ; Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, DK-8000, Aarhus C, Denmark. ; Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. ; Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Section for Molecular Disease Biology, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. stenvang@sund.ku.dk. Y1 - 2016/03/31/ PY - 2016 DA - 2016 Mar 31 SP - 56 VL - 35 KW - 7-nitro-1H-indole-2-carboxylic acid (4-(1-(guanidinohydrazone)ethyl)phenyl)amide KW - 0 KW - Benzodioxoles KW - Guanidines KW - Hydrazones KW - Isoquinolines KW - NSC 725776 KW - irinotecan KW - 0H43101T0J KW - Epirubicin KW - 3Z8479ZZ5X KW - Etoposide KW - 6PLQ3CP4P3 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - TOP1 protein, human KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - SN-38 KW - TOP1 KW - Resistance KW - Irinotecan KW - Colon cancer KW - DNA topoisomerase I KW - Mutation KW - Etoposide -- pharmacology KW - Chromosome Deletion KW - Humans KW - Cell Line, Tumor KW - HCT116 Cells KW - Binding Sites KW - Guanidines -- pharmacology KW - Isoquinolines -- pharmacology KW - Epirubicin -- pharmacology KW - Hydrazones -- pharmacology KW - HT29 Cells KW - Gene Dosage KW - Benzodioxoles -- pharmacology KW - Colonic Neoplasms -- genetics KW - Camptothecin -- pharmacology KW - Camptothecin -- analogs & derivatives KW - Drug Resistance, Neoplasm KW - Colonic Neoplasms -- metabolism KW - DNA Topoisomerases, Type I -- genetics KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777983865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Characterization+of+DNA+topoisomerase+I+in+three+SN-38+resistant+human+colon+cancer+cell+lines+reveals+a+new+pair+of+resistance-associated+mutations.&rft.au=Jensen%2C+Niels+Frank%3BAgama%2C+Keli%3BRoy%2C+Amit%3BSmith%2C+David+Hersi%3BPfister%2C+Thomas+D%3BR%C3%B8mer%2C+Maria+Unni%3BZhang%2C+Hong-Liang%3BDoroshow%2C+James+H%3BKnudsen%2C+Birgitta+R%3BStenvang%2C+Jan%3BBr%C3%BCnner%2C+Nils%3BPommier%2C+Yves&rft.aulast=Jensen&rft.aufirst=Niels&rft.date=2016-03-31&rft.volume=35&rft.issue=&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=1756-9966&rft_id=info:doi/10.1186%2Fs13046-016-0335-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-31 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cancer Res. 2001 Mar 1;61(5):1964-9 [11280753] Annu Rev Biochem. 2001;70:369-413 [11395412] J Biol Chem. 2002 Feb 8;277(6):3813-22 [11733535] Lung Cancer. 2002 Mar;35(3):299-304 [11844605] Lancet. 2003 Jun 28;361(9376):2235-42 [12842380] J Clin Oncol. 2004 Jan 15;22(2):229-37 [14657227] J Mol Biol. 2004 Jun 11;339(4):773-84 [15165849] Int J Cancer. 2004 Aug 20;111(2):252-8 [15197779] J Natl Cancer Inst. 2004 Oct 6;96(19):1420-5 [15467030] Cancer Res. 1988 Apr 1;48(7):1722-6 [2832051] Proc Natl Acad Sci U S A. 1988 Oct;85(20):7501-5 [2845409] Cancer Res. 1989 Sep 15;49(18):5016-22 [2548707] Cancer Res. 1990 Nov 1;50(21):6925-30 [2170010] Cancer Res. 1990 Dec 15;50(24):7962-5 [2174738] Biochem Biophys Res Commun. 1992 Oct 30;188(2):571-7 [1332703] Biochem Pharmacol. 1993 Jan 26;45(2):339-48 [8382060] Ann Oncol. 1993 May;4(5):359-69 [8353070] Cancer Res. 1993 Sep 15;53(18):4343-8 [8395982] J Biol Chem. 1994 Jan 28;269(4):2433-9 [8300570] Cancer Res. 1994 Jun 15;54(12):3248-52 [8205547] Anticancer Drugs. 1994 Dec;5(6):645-9 [7888702] J Biol Chem. 1995 Mar 17;270(11):6141-8 [7890748] Br J Cancer. 1995 Aug;72(2):399-404 [7640225] Br J Cancer. 1996 Aug;74(4):508-12 [8761363] Oncol Res. 1996;8(7-8):295-301 [8938793] Int J Cancer. 1997 Jan 27;70(3):335-40 [9033637] Cancer Res. 1997 Apr 15;57(8):1516-22 [9108454] Biochem Pharmacol. 1997 Apr 4;53(7):1019-27 [9174116] J Clin Oncol. 2005 Aug 1;23(22):4866-75 [15939922] Mol Cancer Ther. 2006 Mar;5(3):502-8 [16546964] Int J Cancer. 2006 Nov 15;119(10):2435-42 [16894565] Curr Med Chem. 2006;13(27):3291-305 [17168852] J Biol Chem. 2007 Mar 30;282(13):9855-64 [17276985] Lancet. 2007 Jul 14;370(9582):135-42 [17630036] Lancet. 2007 Jul 14;370(9582):143-52 [17630037] Cancer Res. 2007 Sep 15;67(18):8752-61 [17875716] Cancer Res. 2007 Nov 1;67(21):10397-405 [17974983] J Biol Chem. 2008 Feb 8;283(6):3305-15 [18056711] Biochem Pharmacol. 2008 Mar 15;75(6):1262-71 [18061144] J Clin Oncol. 2008 Jun 1;26(16):2690-8 [18509181] Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9053-8 [18574145] Nucleic Acids Res. 2008 Oct;36(17):5635-44 [18772225] Pharmacogenomics. 2008 Oct;9(10):1459-66 [18855534] Chem Biol. 2010 May 28;17(5):421-33 [20534341] Ann Oncol. 2010 May;21 Suppl 5:v93-7 [20555112] Mol Cancer Ther. 2009 May;8(5):1008-14 [19383846] Biochemistry. 2011 Feb 8;50(5):704-14 [21182307] Mol Cancer. 2011;10:64 [21619602] Br J Pharmacol. 2011 Dec;164(7):1767-79 [21175590] Mol Pharm. 2011 Dec 5;8(6):1996-2011 [21770407] Scand J Gastroenterol. 2012 Jan;47(1):68-79 [22171973] Scand J Gastroenterol. 2012 Mar;47(3):340-55 [22181013] Scand J Gastroenterol. 2012 Mar;47(3):296-314 [22242568] J Med Chem. 2012 Dec 27;55(24):10844-62 [23215354] PLoS One. 2012;7(12):e50494 [23284638] ACS Chem Biol. 2013 Jan 18;8(1):82-95 [23259582] PLoS One. 2013;8(4):e60613 [23577133] Mol Cancer. 2013;12(1):100 [24004603] Mol Oncol. 2015 Jun;9(6):1169-85 [25759163] ACS Nano. 2009 Jan 27;3(1):223-33 [19206270] Nat Rev Cancer. 2009 May;9(5):338-50 [19377506] Eur J Cancer. 2009 Jul;45(11):1935-49 [19473832] Mol Cancer Ther. 2009 Jul;8(7):1878-84 [19584232] ACS Nano. 2009 Dec 22;3(12):4043-54 [19950974] Mol Pharmacol. 1999 Dec;56(6):1105-15 [10570037] J Biol Chem. 2000 May 19;275(20):15246-53 [10809761] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13046-016-0335-x ER - TY - JOUR T1 - Relationship between ambient ultraviolet radiation and Hodgkin lymphoma subtypes in the United States AN - 1805497970; PQ0002933296 AB - Background: There are few modifiable risk factors for Hodgkin lymphoma (HL), the most common cancer among young adults in Western populations. Some studies have found a reduced risk with exposure to ultraviolet radiation (UVR), but findings have been inconsistent and limited to HL as a group or the most common subtypes. Methods: We evaluated UVR and incidence of HL subtypes using data from 15 population-based cancer registries in the United States from 2001 to 2010 (n=20 021). Ground-based ambient UVR estimates were linked to county of diagnosis. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression models adjusted for age, sex, race/ethnicity, diagnosis year, and registry. Results: Hodgkin lymphoma incidence was lower in the highest UVR quintile for nodular sclerosis (IRR=0.84, 95% CI=0.75-0.96, P-trend<0.01), mixed cellularity/lymphocyte-depleted (IRR=0.66, 95% CI=0.51-0.86, P-trend=0.11), lymphocyte-rich (IRR=0.71, 95% CI=0.57-0.88, P-trend<0.01), and nodular lymphocyte predominant HL (IRR=0.74, 95% CI=0.56-0.97, P-trend<0.01), but 'not otherwise specified' HL (IRR=1.19, 95% CI=0.96-1.47, P-trend=0.11). Conclusions: This is the largest study of UVR and HL subtypes covering a wide range of UVR levels; however, we lack information on personal UVR and other individual risk factors. These findings support an inverse association between UVR and HL. JF - British Journal of Cancer AU - Bowen, Emily M AU - Pfeiffer, Ruth M AU - Linet, Martha S AU - Liu, Wayne T AU - Weisenburger, Dennis D AU - Freedman, D Michal AU - Cahoon, Elizabeth K AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, 9609 Medical Center Drive, Rockville, MD 20850, USA Y1 - 2016/03/29/ PY - 2016 DA - 2016 Mar 29 SP - 826 EP - 831 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 114 IS - 7 SN - 0007-0920, 0007-0920 KW - Toxicology Abstracts KW - Hodgkin's disease KW - U.V. radiation KW - Data processing KW - Risk factors KW - Regression analysis KW - Sclerosis KW - Lymphocytes KW - Cancer KW - Ethnic groups KW - X 24390:Radioactive Materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1805497970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=Relationship+between+ambient+ultraviolet+radiation+and+Hodgkin+lymphoma+subtypes+in+the+United+States&rft.au=Bowen%2C+Emily+M%3BPfeiffer%2C+Ruth+M%3BLinet%2C+Martha+S%3BLiu%2C+Wayne+T%3BWeisenburger%2C+Dennis+D%3BFreedman%2C+D+Michal%3BCahoon%2C+Elizabeth+K&rft.aulast=Bowen&rft.aufirst=Emily&rft.date=2016-03-29&rft.volume=114&rft.issue=7&rft.spage=826&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/10.1038%2Fbjc.2015.383 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Data processing; U.V. radiation; Hodgkin's disease; Risk factors; Regression analysis; Sclerosis; Lymphocytes; Ethnic groups; Cancer DO - http://dx.doi.org/10.1038/bjc.2015.383 ER - TY - JOUR T1 - Structural Insights into the Activation of Human Relaxin Family Peptide Receptor 1 by Small-Molecule Agonists. AN - 1777078721; 26866459 AB - The GPCR relaxin family peptide receptor 1 (RXFP1) mediates the action of relaxin peptide hormone, including its tissue remodeling and antifibrotic effects. The peptide has a short half-life in plasma, limiting its therapeutic utility. However, small-molecule agonists of human RXFP1 can overcome this limitation and may provide a useful therapeutic approach, especially for chronic diseases such as heart failure and fibrosis. The first small-molecule agonists of RXFP1 were recently identified from a high-throughput screening, using a homogeneous cell-based cAMP assay. Optimization of the hit compounds resulted in a series of highly potent and RXFP1 selective agonists with low cytotoxicity, and excellent in vitro ADME and pharmacokinetic properties. Here, we undertook extensive site-directed mutagenesis studies in combination with computational modeling analysis to probe the molecular basis of the small-molecule binding to RXFP1. The results showed that the agonists bind to an allosteric site of RXFP1 in a manner that closely interacts with the seventh transmembrane domain (TM7) and the third extracellular loop (ECL3). Several residues were determined to play an important role in the agonist binding and receptor activation, including a hydrophobic region at TM7 consisting of W664, F668, and L670. The G659/T660 motif within ECL3 is crucial to the observed species selectivity of the agonists for RXFP1. The receptor binding and activation effects by the small molecule ML290 were compared with the cognate ligand, relaxin, providing valuable insights on the structural basis and molecular mechanism of receptor activation and selectivity for RXFP1. JF - Biochemistry AU - Hu, Xin AU - Myhr, Courtney AU - Huang, Zaohua AU - Xiao, Jingbo AU - Barnaeva, Elena AU - Ho, Brian A AU - Agoulnik, Irina U AU - Ferrer, Marc AU - Marugan, Juan J AU - Southall, Noel AU - Agoulnik, Alexander I AD - NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health , 9800 Medical Center Drive, Rockville, Maryland 20850, United States. Y1 - 2016/03/29/ PY - 2016 DA - 2016 Mar 29 SP - 1772 EP - 1783 VL - 55 IS - 12 KW - RXFP1 protein, human KW - 0 KW - Receptors, G-Protein-Coupled KW - Receptors, Peptide KW - Relaxin KW - 9002-69-1 KW - Index Medicus KW - Swine KW - Rats KW - Protein Binding -- physiology KW - Animals KW - Protein Structure, Secondary KW - Macaca KW - Humans KW - HEK293 Cells KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Protein Structure, Tertiary KW - Relaxin -- metabolism KW - Receptors, Peptide -- chemistry KW - Receptors, Peptide -- metabolism KW - Receptors, G-Protein-Coupled -- agonists KW - Receptors, G-Protein-Coupled -- chemistry KW - Receptors, G-Protein-Coupled -- metabolism KW - Relaxin -- pharmacology KW - Receptors, Peptide -- agonists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1777078721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Structural+Insights+into+the+Activation+of+Human+Relaxin+Family+Peptide+Receptor+1+by+Small-Molecule+Agonists.&rft.au=Hu%2C+Xin%3BMyhr%2C+Courtney%3BHuang%2C+Zaohua%3BXiao%2C+Jingbo%3BBarnaeva%2C+Elena%3BHo%2C+Brian+A%3BAgoulnik%2C+Irina+U%3BFerrer%2C+Marc%3BMarugan%2C+Juan+J%3BSouthall%2C+Noel%3BAgoulnik%2C+Alexander+I&rft.aulast=Hu&rft.aufirst=Xin&rft.date=2016-03-29&rft.volume=55&rft.issue=12&rft.spage=1772&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=1520-4995&rft_id=info:doi/10.1021%2Facs.biochem.5b01195 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-18 N1 - Date created - 2016-03-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.biochem.5b01195 ER - TY - JOUR T1 - UCP3 is associated with Hax-1 in mitochondria in the presence of calcium ion. AN - 1774158514; 26915802 AB - Uncoupling protein 3 (UCP3) is known to regulate energy dissipation, proton leakage, fatty acid oxidation, and oxidative stress. To identify the putative protein regulators of UCP3, we performed yeast two-hybrid screens. Here we report that UCP3 interacted with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that was localized in the mitochondria, and is involved in cellular responses to Ca(2+). The hydrophilic sequences within loop 2, and the matrix-localized hydrophilic domain of mouse UCP3, were necessary for binding to Hax-1 at the C-terminal domain, adjacent to the mitochondrial inner membrane. Interestingly, interaction of these proteins occurred in a calcium-dependent manner. Moreover, the NMR spectrum of the C-terminal domain of Hax-1 was dramatically changed by removal of Ca(2+), suggesting that the C-terminal domain of Hax-1 underwent a Ca(2+)-induced conformational change. In the Ca(2+)-free state, the C-terminal Hax-1 tended to unfold, suggesting that Ca(2+) binding may induce protein folding of the Hax-1 C-terminus. These results suggested that the UCP3-Hax-1 complex may regulate mitochondrial functional changes caused by mitochondrial Ca(2+). Copyright © 2016 Elsevier Inc. All rights reserved. JF - Biochemical and biophysical research communications AU - Hirasaka, Katsuya AU - Mills, Edward M AU - Haruna, Marie AU - Bando, Aki AU - Ikeda, Chika AU - Abe, Tomoki AU - Kohno, Shohei AU - Nowinski, Sara M AU - Lago, Cory U AU - Akagi, Ken-Ichi AU - Tochio, Hidehito AU - Ohno, Ayako AU - Teshima-Kondo, Shigetada AU - Okumura, Yuushi AU - Nikawa, Takeshi AD - Graduate School of Fisheries and Environmental Sciences, Nagasaki University, Nagasaki, Japan; Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima, Tokushima, Japan. Electronic address: hirasaka@nagasaki-u.ac.jp. ; Division of Pharmacology/Toxicology, University of Texas at Austin, Austin, TX, USA. ; Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima, Tokushima, Japan. ; Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. ; Section of Laboratory Equipment, National Institute of Biomedical Innovation, Osaka, Japan. ; Graduate School of Engineering, Kyoto University, Kyoto, Japan. ; Department of Nutrition and Health, Sagami Woman's University, Kanagawa, Japan. Y1 - 2016/03/25/ PY - 2016 DA - 2016 Mar 25 SP - 108 EP - 113 VL - 472 IS - 1 KW - Hs1bp1 protein, mouse KW - 0 KW - Ion Channels KW - Mitochondrial Proteins KW - Proteins KW - Recombinant Fusion Proteins KW - UCP3 protein, human KW - Ucp3 protein, mouse KW - Uncoupling Protein 3 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Folding KW - Mitochondria KW - Calcium ion KW - Uncoupling protein 3 KW - Recombinant Fusion Proteins -- metabolism KW - Animals KW - Models, Molecular KW - Nuclear Magnetic Resonance, Biomolecular KW - Humans KW - HEK293 Cells KW - Two-Hybrid System Techniques KW - Recombinant Fusion Proteins -- genetics KW - Mice KW - Protein Interaction Domains and Motifs KW - Recombinant Fusion Proteins -- chemistry KW - Protein Conformation KW - Mitochondrial Membranes -- metabolism KW - Calcium -- metabolism KW - Ion Channels -- chemistry KW - Proteins -- chemistry KW - Mitochondrial Proteins -- genetics KW - Mitochondria -- metabolism KW - Mitochondrial Proteins -- metabolism KW - Mitochondrial Proteins -- chemistry KW - Ion Channels -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1774158514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=UCP3+is+associated+with+Hax-1+in+mitochondria+in+the+presence+of+calcium+ion.&rft.au=Hirasaka%2C+Katsuya%3BMills%2C+Edward+M%3BHaruna%2C+Marie%3BBando%2C+Aki%3BIkeda%2C+Chika%3BAbe%2C+Tomoki%3BKohno%2C+Shohei%3BNowinski%2C+Sara+M%3BLago%2C+Cory+U%3BAkagi%2C+Ken-Ichi%3BTochio%2C+Hidehito%3BOhno%2C+Ayako%3BTeshima-Kondo%2C+Shigetada%3BOkumura%2C+Yuushi%3BNikawa%2C+Takeshi&rft.aulast=Hirasaka&rft.aufirst=Katsuya&rft.date=2016-03-25&rft.volume=472&rft.issue=1&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=1090-2104&rft_id=info:doi/10.1016%2Fj.bbrc.2016.02.075 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-02 N1 - Date created - 2016-03-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.bbrc.2016.02.075 ER - TY - JOUR T1 - Tracking matrix effects in the analysis of DNA adducts of polycyclic aromatic hydrocarbons. AN - 1772837155; 26607319 AB - LC-MS using electrospray ionization is currently the method of choice in bio-organic analysis covering a wide range of applications in a broad spectrum of biological media. The technique is noted for its high sensitivity but one major limitation that hinders achievement of its optimal sensitivity is the signal suppression due to matrix inferences introduced by the presence of co-extracted compounds during the sample preparation procedure. The analysis of DNA adducts of common environmental carcinogens is particularly sensitive to such matrix effects as sample preparation is a multistep process which involves "contamination" of the sample due to the addition of enzymes and other reagents for digestion of the DNA in order to isolate the analyte(s). This problem is further exacerbated by the need to reach low levels of quantitation (LOQ in the ppb level) while also working with limited (2-5 μg) quantities of sample. We report here on the systematic investigation of ion signal suppression contributed by each individual step involved in the sample preparation associated with the analysis of DNA adducts of polycyclic aromatic hydrocarbon (PAH) using as model analyte BaP-dG, the deoxyguanosine (dG) adduct of benzo[a]pyrene (BaP). The individual matrix contribution of each one of these sources to analyte signal was systematically addressed as were any interactive effects. The information was used to develop a validated analytical protocol for the target biomarker at levels typically encountered in vivo using as little as 2 μg of DNA and applied to a dose response study using a metabolically competent cell line. Copyright © 2015 Elsevier B.V. All rights reserved. JF - Journal of chromatography. A AU - Klaene, Joshua J AU - Flarakos, Caroline AU - Glick, James AU - Barret, Jennifer T AU - Zarbl, Helmut AU - Vouros, Paul AD - Department of Chemistry and Chemical Biology and Barnett Institute, Northeastern University, Boston, MA 02115, USA. ; Graduate School of Biomedical Sciences, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. ; Graduate School of Biomedical Sciences, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; NIEHS Center for Environmental Exposures and Disease, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. ; Department of Chemistry and Chemical Biology and Barnett Institute, Northeastern University, Boston, MA 02115, USA. Electronic address: p.vouros@neu.edu. Y1 - 2016/03/25/ PY - 2016 DA - 2016 Mar 25 SP - 112 EP - 123 VL - 1439 KW - Carcinogens, Environmental KW - 0 KW - DNA Adducts KW - Polycyclic Aromatic Hydrocarbons KW - benzo(a)pyrene-DNA adduct KW - Benzo(a)pyrene KW - 3417WMA06D KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - 7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine KW - 62698-04-8 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Benzo[a]pyrene KW - DNA adducts KW - Polycyclic aromatic hydrocarbons KW - Matrix effects KW - Ion suppression KW - Benzo(a)pyrene -- pharmacology KW - Mass Spectrometry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analysis KW - Cells, Cultured KW - Benzo(a)pyrene -- analysis KW - Humans KW - Chromatography, Liquid KW - Deoxyguanosine -- analysis KW - Deoxyguanosine -- analogs & derivatives KW - DNA Adducts -- pharmacology KW - DNA Adducts -- analysis KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Carcinogens, Environmental -- analysis KW - Carcinogens, Environmental -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1772837155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chromatography.+A&rft.atitle=Tracking+matrix+effects+in+the+analysis+of+DNA+adducts+of+polycyclic+aromatic+hydrocarbons.&rft.au=Klaene%2C+Joshua+J%3BFlarakos%2C+Caroline%3BGlick%2C+James%3BBarret%2C+Jennifer+T%3BZarbl%2C+Helmut%3BVouros%2C+Paul&rft.aulast=Klaene&rft.aufirst=Joshua&rft.date=2016-03-25&rft.volume=1439&rft.issue=&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+A&rft.issn=1873-3778&rft_id=info:doi/10.1016%2Fj.chroma.2015.10.057 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-24 N1 - Date created - 2016-03-12 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Oncotarget. 2015 Jan 20;6(2):836-45 [25596734] Cancer Lett. 2013 Jun 28;334(1):10-9 [22960573] Cancer Res. 2002 Jan 1;62(1):105-12 [11782366] Drug Metab Dispos. 2001 Sep;29(9):1176-82 [11502724] Talanta. 2013 Sep 30;114:25-31 [23953436] Environ Health Perspect. 2002 Jun;110 Suppl 3:451-88 [12060843] J Toxicol Environ Health A. 2002 Jun 28;65(12):853-67 [12079611] Mutat Res. 2003 Jan;543(1):17-30 [12510015] Anal Chem. 2003 Jul 1;75(13):3019-30 [12964746] Anal Bioanal Chem. 2004 Feb;378(4):883-97 [14647953] IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-1438 [15285078] Proc Natl Acad Sci U S A. 1978 Nov;75(11):5358-61 [281685] Nature. 1983 Jun 9-15;303(5917):468-72 [6304528] Mutagenesis. 1986 May;1(3):201-6 [3331660] Methods Enzymol. 1990;193:782-90 [1706062] Physiol Chem Phys Med NMR. 1993;25(2):125-35 [8378439] Environ Health Perspect. 1993 Oct;101 Suppl 3:145-50 [8143607] Chem Res Toxicol. 1995 Dec;8(8):1005-13 [8605282] Anal Chem. 1997 Dec 1;69(23):4885-93 [9406535] Food Chem Toxicol. 1999 Feb-Mar;37(2-3):125-34 [10227736] Chem Res Toxicol. 1999 Jul;12(7):623-9 [10409402] Anal Chem. 2006 Feb 1;78(3):743-52 [16448047] Chem Res Toxicol. 2006 Jun;19(6):868-78 [16780367] Anal Chem. 2007 Dec 15;79(24):9302-9 [17997523] Electrophoresis. 2008 May;29(9):1836-43 [18393343] Methods Mol Biol. 2009;544:3-15 [19488689] J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 15;877(22):2104-12 [19535305] J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Aug 1;877(23):2198-207 [19179125] Anal Chem. 2009 Nov 1;81(21):8818-25 [19807107] J Chromatogr A. 2010 Jun 18;1217(25):4135-43 [19932483] J Chromatogr A. 2010 Jun 18;1217(25):3929-37 [20004403] Anal Chem. 2010 Aug 1;82(15):6704-11 [20617825] Carcinogenesis. 2010 Nov;31(11):1999-2003 [20810543] IARC Monogr Eval Carcinog Risks Hum. 2010;92:1-853 [21141735] Mass Spectrom Rev. 2011 May-Jun;30(3):491-509 [21500246] Cancer Res. 2011 Jun 1;71(11):3904-11 [21487034] Rapid Commun Mass Spectrom. 2013 Jul 15;27(13):1473-80 [23722681] Chem Res Toxicol. 2013 Oct 21;26(10):1486-97 [23937706] Exp Hematol. 2015 Mar;43(3):223-8 [25461252] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.chroma.2015.10.057 ER - TY - JOUR T1 - Isoquinoline-1,3-diones as Selective Inhibitors of Tyrosyl DNA Phosphodiesterase II (TDP2). AN - 1776093292; 26910725 AB - Tyrosyl DNA phosphodiesterase II (TDP2) is a recently discovered enzyme that specifically repairs DNA damages induced by topoisomerase II (Top2) poisons and causes resistance to these drugs. Inhibiting TDP2 is expected to enhance the efficacy of clinically important Top2-targeting anticancer drugs. However, TDP2 as a therapeutic target remains poorly understood. We report herein the discovery of isoquinoline-1,3-dione as a viable chemotype for selectively inhibiting TDP2. The initial hit compound 43 was identified by screening our in-house collection of synthetic compounds. Further structure-activity relationship (SAR) studies identified numerous analogues inhibiting TDP2 in low micromolar range without appreciable inhibition against the homologous TDP1 at the highest testing concentration (111 μM). The best compound 64 inhibited recombinant TDP2 with an IC50 of 1.9 μM. The discovery of this chemotype may provide a platform toward understanding TDP2 as a drug target. JF - Journal of medicinal chemistry AU - Kankanala, Jayakanth AU - Marchand, Christophe AU - Abdelmalak, Monica AU - Aihara, Hideki AU - Pommier, Yves AU - Wang, Zhengqiang AD - Center for Drug Design, Academic Health Center, University of Minnesota , Minneapolis, Minnesota 55455, United States. ; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States. ; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota , Minneapolis, Minnesota 55455, United States. Y1 - 2016/03/24/ PY - 2016 DA - 2016 Mar 24 SP - 2734 EP - 2746 VL - 59 IS - 6 KW - Antineoplastic Agents KW - 0 KW - Isoquinolines KW - Recombinant Proteins KW - Topoisomerase II Inhibitors KW - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - TDP2 protein, mouse KW - Index Medicus KW - High-Throughput Screening Assays KW - Animals KW - Models, Molecular KW - DNA Damage KW - Mice KW - Substrate Specificity KW - Drug Design KW - Antineoplastic Agents -- pharmacology KW - Topoisomerase II Inhibitors -- pharmacology KW - Structure-Activity Relationship KW - Isoquinolines -- pharmacology KW - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins -- antagonists & inhibitors KW - Isoquinolines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776093292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Isoquinoline-1%2C3-diones+as+Selective+Inhibitors+of+Tyrosyl+DNA+Phosphodiesterase+II+%28TDP2%29.&rft.au=Kankanala%2C+Jayakanth%3BMarchand%2C+Christophe%3BAbdelmalak%2C+Monica%3BAihara%2C+Hideki%3BPommier%2C+Yves%3BWang%2C+Zhengqiang&rft.aulast=Kankanala&rft.aufirst=Jayakanth&rft.date=2016-03-24&rft.volume=59&rft.issue=6&rft.spage=2734&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=1520-4804&rft_id=info:doi/10.1021%2Facs.jmedchem.5b01973 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-23 N1 - Date created - 2016-03-24 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jmedchem.5b01973 ER - TY - JOUR T1 - Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice. AN - 1770889316; 26873546 AB - Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F1 mice given a weekly intravenous dose of 3mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before each weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Vijay, Vikrant AU - Moland, Carrie L AU - Han, Tao AU - Fuscoe, James C AU - Lee, Taewon AU - Herman, Eugene H AU - Jenkins, G Ronald AU - Lewis, Sherry M AU - Cummings, Connie A AU - Gao, Yuan AU - Cao, Zhijun AU - Yu, Li-Rong AU - Desai, Varsha G AD - Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; Department of Mathematics, Korea University, Sejong, Republic of Korea. ; Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734, United States. ; Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; UltraPath Imaging, 2228 Page Road, Durham, NC 27703, United States. ; Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. ; Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States. Electronic address: varsha.desai@fda.hhs.gov. Y1 - 2016/03/15/ PY - 2016 DA - 2016 Mar 15 SP - 68 EP - 84 VL - 295 KW - Antineoplastic Agents KW - 0 KW - Biomarkers KW - Cardiotonic Agents KW - Troponin T KW - Dexrazoxane KW - 048L81261F KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Mitochondria KW - Cardiotoxicity KW - Real-Time Polymerase Chain Reaction KW - Microscopy, Electron, Transmission KW - Gene Ontology KW - Animals KW - Dose-Response Relationship, Drug KW - Gene Expression KW - Energy Metabolism -- genetics KW - Troponin T -- biosynthesis KW - Mice KW - Male KW - Doxorubicin -- pharmacology KW - Dexrazoxane -- pharmacology KW - Mitochondria, Heart -- drug effects KW - Cardiotonic Agents -- pharmacology KW - Mitochondria, Heart -- genetics KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770889316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Early+transcriptional+changes+in+cardiac+mitochondria+during+chronic+doxorubicin+exposure+and+mitigation+by+dexrazoxane+in+mice.&rft.au=Vijay%2C+Vikrant%3BMoland%2C+Carrie+L%3BHan%2C+Tao%3BFuscoe%2C+James+C%3BLee%2C+Taewon%3BHerman%2C+Eugene+H%3BJenkins%2C+G+Ronald%3BLewis%2C+Sherry+M%3BCummings%2C+Connie+A%3BGao%2C+Yuan%3BCao%2C+Zhijun%3BYu%2C+Li-Rong%3BDesai%2C+Varsha+G&rft.aulast=Vijay&rft.aufirst=Vikrant&rft.date=2016-03-15&rft.volume=295&rft.issue=&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2016.02.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-19 N1 - Date created - 2016-03-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.taap.2016.02.003 ER - TY - JOUR T1 - Characterization of neuropathology in the HIV-1 transgenic rat at different ages. AN - 1770881657; 26943969 AB - The transgenic HIV-1 rat (Tg) is a commonly used neuroHIV model with documented neurologic/behavioral deficits. Using immunofluorescent staining of the Tg brain, we found astrocytic dysfunction/damage, as well as dopaminergic neuronal loss/dysfunction, both of which worsening significantly in the striatum with age. We saw mild microglial activation in young Tg brains, but this decreased with age. There were no differences in neurogenesis potential suggesting a neurodegenerative rather than a neurodevelopmental process. Gp120 CSF levels exceeded serum gp120 levels in some animals, suggesting local viral protein production in the brain. Further probing of the pathophysiology underlying astrocytic injury in this model is warranted. Published by Elsevier B.V. JF - Journal of neuroimmunology AU - Reid, William C AU - Ibrahim, Wael G AU - Kim, Saejeong J AU - Denaro, Frank AU - Casas, Rafael AU - Lee, Dianne E AU - Maric, Dragan AU - Hammoud, Dima A AD - Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA. ; Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA. ; Department of Biology, Morgan State University, Baltimore, MD, USA. ; Division of Intermural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA. ; Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA. Electronic address: hammoudd@cc.nih.gov. Y1 - 2016/03/15/ PY - 2016 DA - 2016 Mar 15 SP - 116 EP - 125 VL - 292 KW - Aif1 protein, rat KW - 0 KW - Antigens, CD11b KW - Calcium-Binding Proteins KW - Glial Fibrillary Acidic Protein KW - HIV Envelope Protein gp120 KW - Microfilament Proteins KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Index Medicus KW - HIV-1 transgenic rat KW - Neurotoxicity KW - Viral proteins KW - Astrocytic loss KW - Neuro-HIV KW - Neuropathology KW - Animals KW - HIV-1 -- genetics KW - Tyrosine 3-Monooxygenase -- metabolism KW - Rats, Transgenic KW - Microfilament Proteins -- metabolism KW - Antigens, CD11b -- genetics KW - Antigens, CD11b -- metabolism KW - Humans KW - Glial Fibrillary Acidic Protein -- metabolism KW - HIV Envelope Protein gp120 -- genetics KW - Glial Fibrillary Acidic Protein -- genetics KW - Rats KW - Tyrosine 3-Monooxygenase -- genetics KW - HIV-1 -- pathogenicity KW - HIV Envelope Protein gp120 -- cerebrospinal fluid KW - Case-Control Studies KW - Enzyme-Linked Immunosorbent Assay KW - Calcium-Binding Proteins -- metabolism KW - Male KW - Gene Expression Regulation, Viral -- physiology KW - AIDS-Associated Nephropathy -- metabolism KW - AIDS-Associated Nephropathy -- virology KW - Brain -- pathology KW - AIDS-Associated Nephropathy -- pathology KW - Aging -- pathology KW - Brain -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770881657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroimmunology&rft.atitle=Characterization+of+neuropathology+in+the+HIV-1+transgenic+rat+at+different+ages.&rft.au=Reid%2C+William+C%3BIbrahim%2C+Wael+G%3BKim%2C+Saejeong+J%3BDenaro%2C+Frank%3BCasas%2C+Rafael%3BLee%2C+Dianne+E%3BMaric%2C+Dragan%3BHammoud%2C+Dima+A&rft.aulast=Reid&rft.aufirst=William&rft.date=2016-03-15&rft.volume=292&rft.issue=&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=1872-8421&rft_id=info:doi/10.1016%2Fj.jneuroim.2016.01.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-12 N1 - Date created - 2016-03-05 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):487-95 [23242157] J Neuroimmune Pharmacol. 2013 Sep;8(4):988-97 [23690140] J Neurovirol. 2013 Oct;19(5):418-31 [23982957] J Neuroimmune Pharmacol. 2013 Dec;8(5):1224-38 [23702663] Biochem Biophys Res Commun. 2014 Feb 21;444(4):531-6 [24472536] J Neuroinflammation. 2014;11:53 [24655810] Mol Neurodegener. 2014;9:26 [24980976] J Neuroimmune Pharmacol. 2014 Sep;9(4):508-21 [24764039] PLoS One. 2014;9(8):e105256 [25127062] PLoS One. 2014;9(8):e105752 [25144656] Mol Imaging. 2014;13. doi: 10.2310/7290.2014.00031 [25248756] PLoS One. 2014;9(10):e108399 [25271421] J Neurovirol. 2014 Oct;20(5):474-84 [24970236] Mol Neurodegener. 2014;9:58 [25523827] Cell Cycle. 2015;14(5):712-20 [25590687] Curr HIV Res. 2015;13(1):21-42 [25613135] Curr HIV Res. 2015;13(1):80-7 [25760043] Brain Behav Immun. 2015 Aug;48:336-49 [25733103] Behav Pharmacol. 2015 Dec;26(8 Spec No):720-32 [26397758] Am J Respir Cell Mol Biol. 2016 Apr;54(4):461-8 [26291195] J Virol. 2000 Nov;74(21):9868-77 [11024113] Neurochem Res. 2000 Oct;25(9-10):1439-51 [11059815] Nat Neurosci. 2001 Jul;4(7):702-10 [11426226] Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9271-6 [11481487] Microbes Infect. 2002 Mar;4(3):301-8 [11909740] Glia. 2002 Nov;40(2):164-74 [12379904] J Neurovirol. 2003 Apr;9(2):205-21 [12707851] Virology. 2003 Jul 20;312(1):60-73 [12890621] J Virol. 2003 Nov;77(21):11745-53 [14557659] BMC Pharmacol. 2003 Aug 28;3:11 [12943556] J Neurochem. 2004 Feb;88(4):844-56 [14756805] J Neurovirol. 2004;10 Suppl 1:25-32 [14982736] Neurochem Int. 2004 Dec;45(7):1113-23 [15337311] FASEB J. 1991 Jul;5(10):2391-7 [2065887] J Leukoc Biol. 1994 Sep;56(3):389-98 [8083614] J Histochem Cytochem. 1996 Oct;44(10):1167-71 [8813082] Brain Pathol. 1996 Jan;6(1):1-15 [8866743] Vet Pathol. 2005 Nov;42(6):753-73 [16301571] J Neuroimmune Pharmacol. 2007 Dec;2(4):319-28 [18040850] Am J Respir Cell Mol Biol. 2008 Aug;39(2):218-26 [18314538] Neuroimage. 2008 Aug 15;42(2):869-78 [18579413] J Neurovirol. 2009 Jan;15(1):14-24 [19085205] J Neuroimmune Pharmacol. 2009 Sep;4(3):309-16 [19444617] J Neuroimmune Pharmacol. 2009 Dec;4(4):430-47 [19768553] J Neuroimmunol. 2010 Jan 25;218(1-2):94-101 [19913921] J Neuroimmune Pharmacol. 2010 Mar;5(1):44-62 [19697136] J Neurovirol. 2009 Sep;15(5-6):360-70 [20175693] J Neurovirol. 2009 Sep;15(5-6):401-10 [20175694] J Neurovirol. 2010 Feb;16(1):33-40 [20113193] J Neurovirol. 2010 Mar;16(2):168-73 [20337512] Ann Neurol. 2010 Jun;67(6):699-714 [20517932] FASEB J. 2010 Jun;24(6):1799-812 [20097875] J Neurovirol. 2009 May;15(3):257-74 [19499455] J Neuroinflammation. 2010;7:64 [20937161] Am J Pathol. 2010 Dec;177(6):2938-49 [21088215] J Neurovirol. 2011 Feb;17(1):26-40 [21165787] J Cereb Blood Flow Metab. 2011 Feb;31(2):486-93 [20664612] J Neurosci. 2011 Mar 2;31(9):3148-57 [21368026] Pharmacol Biochem Behav. 2011 Jun;98(4):587-97 [21420997] Immunol Invest. 2011;40(5):498-522 [21425908] Cell Tissue Res. 2011 Jul;345(1):1-19 [21647561] Retrovirology. 2011;8:65 [21835012] Neurotox Res. 2012 Jan;21(1):79-89 [21948112] Neurobiol Dis. 2012 Feb;45(2):657-70 [22036626] Cell Mol Immunol. 2012 May;9(3):237-44 [22504952] J Neuroimmunol. 2012 Jun 15;247(1-2):16-24 [22503372] Curr HIV Res. 2012 Jul;10(5):369-83 [22591361] Curr HIV Res. 2012 Jul;10(5):415-24 [22591365] Curr HIV Res. 2012 Jul;10(5):463-8 [22591370] AIDS. 2012 Nov 13;26(17):2135-44 [22824628] Virology. 2013 Jan 5;435(1):14-28 [23217612] Exp Neurol. 2013 Jan;239:139-47 [23063600] Mol Cell Neurosci. 2013 May;54:22-9 [23267846] Neurology. 2013 Apr 9;80(15):1415-23 [23486877] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.jneuroim.2016.01.022 ER - TY - JOUR T1 - Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products. AN - 1765918438; 26802282 AB - Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco-specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. JF - Toxicology letters AU - Song, Min-Ae AU - Marian, Catalin AU - Brasky, Theodore M AU - Reisinger, Sarah AU - Djordjevic, Mirjana AU - Shields, Peter G AD - Division of Epidemiology, The Ohio State University, The College of Public Health, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH, USA. ; Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH, USA; Biochemistry and Pharmacology Department, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania. ; Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH, USA. ; Tobacco Control Research Branch, National Cancer Institute, Rockville, MD, USA. ; Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH, USA. Electronic address: peter.shields@osumc.edu. Y1 - 2016/03/14/ PY - 2016 DA - 2016 Mar 14 SP - 68 EP - 77 VL - 245 KW - Carcinogens KW - 0 KW - Nitrosamines KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Smokeless tobacco KW - TSNAs KW - Cancer risk KW - Moist snuff KW - Animals KW - Dose-Response Relationship, Drug KW - Hydrogen-Ion Concentration KW - Humans KW - Principal Component Analysis KW - Nicotine -- analysis KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Nitrosamines -- analysis KW - Risk Assessment KW - Carcinogens -- toxicity KW - Tobacco, Smokeless -- analysis KW - Tobacco, Smokeless -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1765918438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Chemical+and+toxicological+characteristics+of+conventional+and+low-TSNA+moist+snuff+tobacco+products.&rft.au=Song%2C+Min-Ae%3BMarian%2C+Catalin%3BBrasky%2C+Theodore+M%3BReisinger%2C+Sarah%3BDjordjevic%2C+Mirjana%3BShields%2C+Peter+G&rft.aulast=Song&rft.aufirst=Min-Ae&rft.date=2016-03-14&rft.volume=245&rft.issue=&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=1879-3169&rft_id=info:doi/10.1016%2Fj.toxlet.2016.01.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-29 N1 - Date created - 2016-02-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.toxlet.2016.01.012 ER - TY - JOUR T1 - Dysregulation of microRNA biogenesis in cancer: the impact of mutant p53 on Drosha complex activity. AN - 1773428652; 26971015 AB - A widespread decrease of mature microRNAs is often observed in human malignancies giving them potential to act as tumor suppressors. Thus, microRNAs may be potential targets for cancer therapy. The global miRNA deregulation is often the result of defects in the miRNA biogenesis pathway, such as genomic mutation or aberrant expression/localization of enzymes and cofactors responsible of miRNA maturation. Alterations in the miRNA biogenesis machinery impact on the establishment and development of cancer programs. Accumulation of pri-microRNAs and corresponding depletion of mature microRNAs occurs in human cancers compared to normal tissues, strongly indicating an impairment of crucial steps in microRNA biogenesis. In agreement, inhibition of microRNA biogenesis, by depletion of Dicer1 and Drosha, tends to enhance tumorigenesis in vivo. The p53 tumor suppressor gene, TP53, is mutated in half of human tumors resulting in an oncogene with Gain-Of-Function activities. In this review we discuss recent studies that have underlined a role of mutant p53 (mutp53) on the global regulation of miRNA biogenesis in cancer. In particular we describe how a new transcriptionally independent function of mutant p53 in miRNA maturation, through a mechanism by which this oncogene is able to interfere with the Drosha processing machinery, generally inhibits miRNA processing in cancer and consequently impacts on carcinogenesis. JF - Journal of experimental & clinical cancer research : CR AU - Gurtner, Aymone AU - Falcone, Emmanuela AU - Garibaldi, Francesca AU - Piaggio, Giulia AD - Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, 00144, Rome, Italy. ; Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, 00144, Rome, Italy. garibaldi@ifo.it. Y1 - 2016/03/12/ PY - 2016 DA - 2016 Mar 12 SP - 45 VL - 35 KW - MicroRNAs KW - 0 KW - TP53 protein, human KW - Tumor Suppressor Protein p53 KW - DROSHA protein, human KW - EC 3.1.26.3 KW - Ribonuclease III KW - Index Medicus KW - p72 KW - mutp53 KW - miRNA KW - Microprocessor complex KW - Biogenesis KW - p68 KW - Drosha KW - Gene Expression Regulation, Neoplastic KW - Humans KW - Gene Regulatory Networks KW - Mutation KW - Signal Transduction KW - MicroRNAs -- genetics KW - Ribonuclease III -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773428652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Dysregulation+of+microRNA+biogenesis+in+cancer%3A+the+impact+of+mutant+p53+on+Drosha+complex+activity.&rft.au=Gurtner%2C+Aymone%3BFalcone%2C+Emmanuela%3BGaribaldi%2C+Francesca%3BPiaggio%2C+Giulia&rft.aulast=Gurtner&rft.aufirst=Aymone&rft.date=2016-03-12&rft.volume=35&rft.issue=&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=1756-9966&rft_id=info:doi/10.1186%2Fs13046-016-0319-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-13 N1 - Date created - 2016-03-14 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nat Rev Cancer. 2011 Sep;11(9):644-56 [21822212] PLoS One. 2011;6(8):e23787 [21901135] Nat Commun. 2011;2:513 [22027593] Oncotarget. 2012 Jan;3(1):9-21 [22308266] Nature. 2012 Feb 16;482(7385):347-55 [22337054] EMBO Mol Med. 2012 Mar;4(3):143-59 [22351564] J Cell Biol. 2012 Apr 16;197(2):201-8 [22492723] Cell Death Differ. 2012 Jun;19(6):1038-48 [22193543] Oncogene. 2012 Sep 20;31(38):4196-206 [22231442] FEBS Lett. 2012 Sep 21;586(19):3508-21 [22958893] Mol Oncol. 2012 Dec;6(6):590-610 [23102669] Oncogene. 2013 Jan 3;32(1):61-9 [22330136] Cancer Lett. 2013 Feb 28;329(2):164-73 [23142219] Sci Signal. 2013 Mar 12;6(266):ra16 [23482664] Cell Death Dis. 2013;4:e574 [23559009] Oncogene. 2013 Jun 13;32(24):2992-3000 [22797073] Oncogene. 2013 Jul 4;32(27):3286-95 [22847613] J Clin Invest. 2013 Jun;123(6):2703-18 [23728176] Cell Death Differ. 2003 Apr;10(4):431-42 [12719720] Nature. 2003 Sep 25;425(6956):415-9 [14508493] Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004 [14973191] Nucleic Acids Res. 2004;32(16):4776-85 [15356295] EMBO J. 2004 Oct 13;23(20):4051-60 [15372072] Nature. 2004 Nov 11;432(7014):235-40 [15531877] Nucleic Acids Res. 2005;33(8):2697-706 [15891114] Nature. 2005 Jun 9;435(7043):828-33 [15944707] Nature. 2005 Jun 9;435(7043):834-8 [15944708] N Engl J Med. 2005 Oct 27;353(17):1793-801 [16251535] EMBO J. 2006 Feb 8;25(3):522-32 [16424907] Cancer Cell. 2006 Mar;9(3):189-98 [16530703] Cell. 2006 Jun 2;125(5):887-901 [16751099] Genes Dev. 2006 Aug 15;20(16):2202-7 [16882971] Nat Struct Mol Biol. 2006 Dec;13(12):1097-101 [17099701] Science. 2007 Mar 16;315(5818):1576-9 [17322030] Nat Genet. 2007 May;39(5):673-7 [17401365] Expert Opin Biol Ther. 2007 Jul;7(7):1009-19 [17665990] Annu Rev Cell Dev Biol. 2007;23:175-205 [17506695] Nature. 2008 Jul 3;454(7200):56-61 [18548003] Mol Cell. 2008 Nov 7;32(3):383-93 [18995836] Cell. 2009 Jan 23;136(2):215-33 [19167326] Biol Rev Camb Philos Soc. 2009 Feb;84(1):55-71 [19046400] Nat Genet. 2009 Mar;41(3):365-70 [19219043] Cell Cycle. 2009 Mar 1;8(5):712-5 [19221490] Nat Cell Biol. 2009 Mar;11(3):228-34 [19255566] Nature. 2009 Jul 23;460(7254):529-33 [19626115] Cell. 2009 Jul 23;138(2):328-39 [19632182] Cell. 2009 Jul 23;138(2):340-51 [19632183] Science. 2009 Aug 21;325(5943):965 [19556464] Cell. 2009 Aug 21;138(4):696-708 [19703396] Nat Rev Genet. 2009 Oct;10(10):704-14 [19763153] Nat Rev Cancer. 2009 Nov;9(11):831-41 [19776746] Genes Dev. 2009 Dec 15;23(24):2806-11 [20008931] Cancer Res. 2010 Apr 1;70(7):2675-85 [20233879] J Biol Chem. 2010 May 7;285(19):14160-9 [20223820] Genes Dev. 2010 May 15;24(10):992-1009 [20413612] PLoS One. 2010;5(6):e11166 [20567512] Nat Rev Genet. 2010 Sep;11(9):597-610 [20661255] Cancer Cell. 2010 Oct 19;18(4):303-15 [20951941] Cell Cycle. 2010 Apr 1;9(7):1354-9 [20305372] Mol Cell. 2011 Feb 18;41(4):371-83 [21329876] Future Oncol. 2011 Feb;7(2):239-51 [21345143] Clin Sci (Lond). 2011 Aug;121(4):141-58 [21526983] FEBS Lett. 2011 May 6;585(9):1322-30 [21482222] Cancer Res. 2013 Oct 1;73(19):5936-48 [23928990] Cancer Res. 2013 Oct 1;73(19):6046-55 [23950210] EMBO J. 2013 Dec 11;32(24):3192-205 [24219989] Gastroenterology. 2014 Jan;146(1):278-90 [24120475] J Exp Clin Cancer Res. 2013;32:96 [24261995] Cancer Lett. 2014 Mar 28;344(2):166-73 [24262661] Cell. 2014 Feb 27;156(5):893-906 [24581491] Oncogene. 2014 Mar 20;33(12):1601-8 [23584479] Cancer Cell. 2014 Mar 17;25(3):304-17 [24651012] J Dermatol Sci. 2014 May;74(2):142-9 [24548601] Mol Cancer Res. 2014 May;12(5):639-53 [24526064] Hum Mutat. 2014 Jun;35(6):715-27 [24415648] FEBS J. 2014 Jul;281(13):2937-44 [24814047] Nat Rev Mol Cell Biol. 2014 Aug;15(8):509-24 [25027649] J Exp Clin Cancer Res. 2014;33:67 [25107371] Cell Rep. 2014 Sep 11;8(5):1447-60 [25176654] Int J Cancer. 2015 Feb 15;136(4):761-70 [24975878] Cancer Biol Ther. 2014;15(11):1444-55 [25482951] Cancer Cell. 2015 Feb 9;27(2):286-97 [25670082] Cancer Cell. 2015 Feb 9;27(2):298-311 [25670083] Oncogene. 2015 Feb 26;34(9):1094-104 [24662829] J Biol Chem. 2015 Mar 6;290(10):6215-25 [25616665] J Exp Clin Cancer Res. 2014;33:64 [25150365] Oncogene. 2015 May 7;34(19):2493-504 [24998848] Cancer Gene Ther. 2015 Oct;22(10):475-80 [26384136] J Exp Clin Cancer Res. 2015;34:128 [26503703] Oncotarget. 2015 Dec 29;6(42):44660-74 [26587974] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13046-016-0319-x ER - TY - JOUR T1 - The Gq signalling pathway inhibits brown and beige adipose tissue. AN - 1772145832; 26955961 AB - Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes. Expression of a constitutively active Gq protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of Gq in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that Gq signalling regulates brown/beige adipocytes and inhibition of Gq signalling may be a novel therapeutic approach to combat obesity. JF - Nature communications AU - Klepac, Katarina AU - Kilić, Ana AU - Gnad, Thorsten AU - Brown, Loren M AU - Herrmann, Beate AU - Wilderman, Andrea AU - Balkow, Aileen AU - Glöde, Anja AU - Simon, Katharina AU - Lidell, Martin E AU - Betz, Matthias J AU - Enerbäck, Sven AU - Wess, Jürgen AU - Freichel, Marc AU - Blüher, Matthias AU - König, Gabi AU - Kostenis, Evi AU - Insel, Paul A AU - Pfeifer, Alexander AD - Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany. ; Department of Pharmacology, University of California, San Diego, California 92093, USA. ; Research Training Group 1873, University of Bonn, 53127 Bonn, Germany. ; Department of Medical and Clinical Genetics, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-405 30, Sweden. ; Molecular Signalling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. ; Institute of Pharmacology, University of Heidelberg, D-69120 Heidelberg, Germany. ; Department of Medicine, University of Leipzig, 04103 Leipzig, Germany. ; Institute of Pharmaceutical Biology, University of Bonn, D-53115 Bonn, Germany. Y1 - 2016/03/09/ PY - 2016 DA - 2016 Mar 09 SP - 10895 VL - 7 KW - Ion Channels KW - 0 KW - Mitochondrial Proteins KW - UCP1 protein, human KW - Ucp1 protein, mouse KW - Uncoupling Protein 1 KW - GTP-Binding Protein alpha Subunits, Gq-G11 KW - EC 3.6.5.1 KW - Index Medicus KW - Animals KW - Adipocytes, Brown -- enzymology KW - Humans KW - Cell Differentiation KW - Mitochondrial Proteins -- genetics KW - Mice KW - Ion Channels -- metabolism KW - Adipogenesis KW - Adipocytes, Brown -- cytology KW - Adipocytes, White -- enzymology KW - Mitochondrial Proteins -- metabolism KW - Ion Channels -- genetics KW - Adipocytes, White -- cytology KW - Adipose Tissue, White -- enzymology KW - GTP-Binding Protein alpha Subunits, Gq-G11 -- metabolism KW - Adipose Tissue, Brown -- enzymology KW - GTP-Binding Protein alpha Subunits, Gq-G11 -- genetics KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1772145832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=The+Gq+signalling+pathway+inhibits+brown+and+beige+adipose+tissue.&rft.au=Klepac%2C+Katarina%3BKili%C4%87%2C+Ana%3BGnad%2C+Thorsten%3BBrown%2C+Loren+M%3BHerrmann%2C+Beate%3BWilderman%2C+Andrea%3BBalkow%2C+Aileen%3BGl%C3%B6de%2C+Anja%3BSimon%2C+Katharina%3BLidell%2C+Martin+E%3BBetz%2C+Matthias+J%3BEnerb%C3%A4ck%2C+Sven%3BWess%2C+J%C3%BCrgen%3BFreichel%2C+Marc%3BBl%C3%BCher%2C+Matthias%3BK%C3%B6nig%2C+Gabi%3BKostenis%2C+Evi%3BInsel%2C+Paul+A%3BPfeifer%2C+Alexander&rft.aulast=Klepac&rft.aufirst=Katarina&rft.date=2016-03-09&rft.volume=7&rft.issue=&rft.spage=10895&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms10895 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-20 N1 - Date created - 2016-03-09 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nat Biotechnol. 2010 Sep;28(9):943-9 [20711173] J Clin Invest. 2016 Jan;126(1):40-9 [26595811] Can J Physiol Pharmacol. 2003 Jun;81(6):503-10 [12839262] Physiol Rev. 2004 Jan;84(1):277-359 [14715917] Mol Cell Biol. 1992 Oct;12(10):4687-93 [1328859] Am J Physiol. 1992 Sep;263(3 Pt 1):E500-6 [1415530] J Biol Chem. 1995 Oct 20;270(42):24631-4 [7559569] Eur J Pharmacol. 1995 Sep 15;291(1):33-41 [8549645] Transgenic Res. 2004 Dec;13(6):513-22 [15672832] Physiol Rev. 2005 Oct;85(4):1159-204 [16183910] Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5163-8 [17360345] Acta Physiol (Oxf). 2007 May;190(1):9-19 [17428228] Nat Methods. 2008 Aug;5(8):673-8 [18668035] Cell. 2008 Oct 31;135(3):561-71 [18984166] N Engl J Med. 2009 Apr 9;360(15):1500-8 [19357405] N Engl J Med. 2009 Apr 9;360(15):1518-25 [19357407] Stem Cells. 2009 Nov;27(11):2753-60 [19697348] Sci Signal. 2009;2(99):ra78 [19952371] Mol Cell Endocrinol. 2010 Mar 25;316(2):129-39 [19723556] Cell Metab. 2010 Apr 7;11(4):253-6 [20374956] Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E506-15 [20570822] Trends Pharmacol Sci. 2011 Apr;32(4):213-8 [21414670] Am J Physiol Endocrinol Metab. 2009 Nov;297(5):E977-86 [19458063] Cell Metab. 2012 Apr 4;15(4):480-91 [22482730] Sci Signal. 2012 Aug 28;5(239):ra62 [22932701] Life Sci. 2012 Oct 15;91(13-14):507-16 [22483688] Nucleic Acids Res. 2013 Jan;41(Database issue):D1083-8 [23087376] Acta Biochim Pol. 2012;59(4):515-29 [23251911] Nat Commun. 2013;4:1769 [23612310] J Clin Endocrinol Metab. 2013 Oct;98(10):4097-104 [23744406] Nat Med. 2013 Oct;19(10):1252-63 [24100998] Exp Cell Res. 2013 Oct 15;319(17):2718-27 [23948306] Cell. 2014 Jan 16;156(1-2):20-44 [24439368] Annu Rev Physiol. 2014;76:225-49 [24188710] Am J Physiol Regul Integr Comp Physiol. 2014 Apr 15;306(8):R596-606 [24523340] J Clin Invest. 2014 May;124(5):2099-112 [24713652] Nature. 2014 Dec 18;516(7531):395-9 [25317558] Annu Rev Pharmacol Toxicol. 2015;55:207-27 [25149919] Cell. 2015 Jan 15;160(1-2):105-18 [25579684] Pharmacol Ther. 2015 Feb;146:61-93 [25242198] Nat Commun. 2015;6:7235 [26011238] Mol Pharmacol. 2015 Jul;88(1):181-7 [25737495] Nat Med. 2015 Jul;21(7):760-8 [26076036] Nat Commun. 2015;6:10156 [26658454] Science. 2002 May 31;296(5573):1636-9 [12040175] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms10895 ER - TY - JOUR T1 - Inhibition of RPE65 Retinol Isomerase Activity by Inhibitors of Lipid Metabolism. AN - 1770878363; 26719343 AB - RPE65 is the isomerase catalyzing conversion of all-trans-retinyl ester (atRE) into 11-cis-retinol in the retinal visual cycle. Crystal structures of RPE65 and site-directed mutagenesis reveal aspects of its catalytic mechanism, especially retinyl moiety isomerization, but other aspects remain to be determined. To investigate potential interactions between RPE65 and lipid metabolism enzymes, HEK293-F cells were transfected with expression vectors for visual cycle proteins and co-transfected with either fatty acyl:CoA ligases (ACSLs) 1, 3, or 6 or the SLC27A family fatty acyl-CoA synthase FATP2/SLCA27A2 to test their effect on isomerase activity. These experiments showed that RPE65 activity was reduced by co-expression of ACSLs or FATP2. Surprisingly, however, in attempting to relieve the ACSL-mediated inhibition, we discovered that triacsin C, an inhibitor of ACSLs, also potently inhibited RPE65 isomerase activity in cellulo. We found triacsin C to be a competitive inhibitor of RPE65 (IC50 = 500 nm). We confirmed that triacsin C competes directly with atRE by incubating membranes prepared from chicken RPE65-transfected cells with liposomes containing 0-1 μM atRE. Other inhibitors of ACSLs had modest inhibitory effects compared with triascin C. In conclusion, we have identified an inhibitor of ACSLs as a potent inhibitor of RPE65 that competes with the atRE substrate of RPE65 for binding. Triacsin C, with an alkenyl chain resembling but not identical to either acyl or retinyl chains, may compete with binding of the acyl moiety of atRE via the alkenyl moiety. Its inhibitory effect, however, may reside in its nitrosohydrazone/triazene moiety. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Eroglu, Abdulkerim AU - Gentleman, Susan AU - Poliakov, Eugenia AU - Redmond, T Michael AD - From the Laboratory of Retinal Cell & Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. ; From the Laboratory of Retinal Cell & Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892 redmondd@helix.nih.gov. Y1 - 2016/03/04/ PY - 2016 DA - 2016 Mar 04 SP - 4966 EP - 4973 VL - 291 IS - 10 KW - Enzyme Inhibitors KW - 0 KW - Triazenes KW - triacsin C KW - 6M6D4602I5 KW - retinoid isomerohydrolase KW - EC 3.1.1.64 KW - cis-trans-Isomerases KW - EC 5.2.- KW - Coenzyme A Ligases KW - EC 6.2.1.- KW - Index Medicus KW - liposome KW - vision KW - retinoid KW - retinal metabolism KW - visual cycle KW - RPE65 KW - fatty acyl:CoA ligase KW - enzyme inhibitor KW - Animals KW - Chickens KW - Humans KW - HEK293 Cells KW - Molecular Sequence Data KW - Coenzyme A Ligases -- antagonists & inhibitors KW - Amino Acid Sequence KW - Protein Binding KW - Binding Sites KW - cis-trans-Isomerases -- antagonists & inhibitors KW - Triazenes -- pharmacology KW - cis-trans-Isomerases -- genetics KW - cis-trans-Isomerases -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - cis-trans-Isomerases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770878363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Inhibition+of+RPE65+Retinol+Isomerase+Activity+by+Inhibitors+of+Lipid+Metabolism.&rft.au=Eroglu%2C+Abdulkerim%3BGentleman%2C+Susan%3BPoliakov%2C+Eugenia%3BRedmond%2C+T+Michael&rft.aulast=Eroglu&rft.aufirst=Abdulkerim&rft.date=2016-03-04&rft.volume=291&rft.issue=10&rft.spage=4966&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/10.1074%2Fjbc.M115.685651 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-03 N1 - Date created - 2016-03-05 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Biol Chem. 2003 Oct 31;278(44):43008-13 [12937175] Nat Chem Biol. 2015 Jun;11(6):409-15 [25894083] Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-63 [15272157] Biochem J. 1974 Jan;137(1):143-4 [4206907] Prostaglandins. 1981 Feb;21(2):333-43 [6784192] J Antibiot (Tokyo). 1982 Feb;35(2):151-6 [6804425] J Antibiot (Tokyo). 1982 Feb;35(2):157-63 [6804426] Biochim Biophys Acta. 1984 Feb 9;792(2):214-26 [6696931] J Antibiot (Tokyo). 1986 Sep;39(9):1211-8 [3781919] Prostaglandins. 1987 Apr;33(4):603-15 [3110863] Biochim Biophys Acta. 1987 Oct 17;921(3):595-8 [3117118] J Chromatogr. 1988 Apr 22;438(2):383-92 [3384888] J Biol Chem. 1995 Aug 25;270(34):20090-7 [7650027] Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8162-7 [15917330] Cell. 2005 Aug 12;122(3):449-59 [16096063] J Clin Invest. 2015 Jul 1;125(7):2781-94 [26075817] FEBS J. 2009 Jun;276(11):3020-30 [19490105] Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17325-30 [19805034] J Comput Chem. 2010 Jan 30;31(2):455-61 [19499576] J Biol Chem. 2010 Jan 15;285(3):1919-27 [19920137] J Lipid Res. 2010 Feb;51(2):247-61 [19666736] J Biol Chem. 2010 Jun 11;285(24):18759-68 [20356843] Biochemistry. 2011 Aug 16;50(32):6739-41 [21736383] Eur J Med Chem. 2012 Apr;50:311-8 [22365411] J Biol Chem. 2012 Aug 31;287(36):30552-9 [22745121] Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):E2747-56 [23012475] PLoS One. 2012;7(11):e49975 [23209628] J Neurosci. 2013 Feb 13;33(7):3178-89 [23407971] J Biochem Mol Toxicol. 2004;18(2):100-6 [15122652] Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12413-8 [16116091] Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13658-63 [16150724] J Biol Chem. 2008 Mar 28;283(13):8110-7 [18216020] J Antibiot (Tokyo). 2008 May;61(5):318-21 [18653998] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1074/jbc.M115.685651 ER - TY - JOUR T1 - Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas. AN - 1784745672; 26890396 AB - Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs. JF - Epigenetics AU - Kleb, Brittany AU - Estécio, Marcos R H AU - Zhang, Jiexin AU - Tzelepi, Vassiliki AU - Chung, Woonbok AU - Jelinek, Jaroslav AU - Navone, Nora M AU - Tahir, Salahaldin AU - Marquez, Victor E AU - Issa, Jean-Pierre AU - Maity, Sankar AU - Aparicio, Ana AD - a Department of Genitourinary Medical Oncology Unit 1374 , The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas. ; b Department of Epigenetics and Molecular Carcinogenesis , Unit 0081, The University of Texas, MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas. ; c Department of Bioinformatics and Computational Biology , Unit 1410, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas. ; d Department of Pathology , University of Patras, Panepistimioupoli Patron , Greece. ; e Fels Institute of Cancer Research and Molecular Biology, Temple University , 3307 N Broad Street, Philadelphia , PA. ; f Department of Genitourinary Medical Oncology , Unit 1374, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas. ; g Center for Cancer Research, National Cancer Institute, Building 376 Frederick , MD. Y1 - 2016/03/03/ PY - 2016 DA - 2016 Mar 03 SP - 184 EP - 193 VL - 11 IS - 3 KW - Index Medicus KW - histone methylation KW - Androgen receptor KW - neuroendocrine KW - xenograft KW - epigenetics KW - EZH2 KW - DNA methylation KW - small-cell prostate carcinoma KW - prostate cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1784745672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epigenetics&rft.atitle=Differentially+methylated+genes+and+androgen+receptor+re-expression+in+small+cell+prostate+carcinomas.&rft.au=Kleb%2C+Brittany%3BEst%C3%A9cio%2C+Marcos+R+H%3BZhang%2C+Jiexin%3BTzelepi%2C+Vassiliki%3BChung%2C+Woonbok%3BJelinek%2C+Jaroslav%3BNavone%2C+Nora+M%3BTahir%2C+Salahaldin%3BMarquez%2C+Victor+E%3BIssa%2C+Jean-Pierre%3BMaity%2C+Sankar%3BAparicio%2C+Ana&rft.aulast=Kleb&rft.aufirst=Brittany&rft.date=2016-03-03&rft.volume=11&rft.issue=3&rft.spage=184&rft.isbn=&rft.btitle=&rft.title=Epigenetics&rft.issn=1559-2308&rft_id=info:doi/10.1080%2F15592294.2016.1146851 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-04-26 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Clin Cancer Res. 2016 Mar 15;22(6):1520-30 [26546618] Nucleic Acids Res. 2002 Feb 15;30(4):e15 [11842121] Nature. 2002 Oct 10;419(6907):624-9 [12374981] Prostate. 2003 Apr 1;55(1):55-64 [12640661] Biotechniques. 2003 Jul;35(1):146-50 [12866414] Methods Mol Med. 2004;88:121-32 [14634223] Cancer Res. 2004 Mar 15;64(6):1975-86 [15026333] Cancer. 1987 Mar 1;59(5):977-82 [2434204] Urology. 1992 May;39(5):411-6 [1315995] Cancer Res. 1999 Sep 15;59(18):4535-41 [10493502] Genes Dev. 2007 May 1;21(9):1050-63 [17437993] J Cell Physiol. 2007 Nov;213(2):384-90 [17708532] Int J Urol. 2001 Aug;8(8):431-6; discussion 437 [11555007] Oncogene. 2007 Sep 13;26(42):6238-43 [17369840] Genome Res. 2007 Oct;17(10):1529-36 [17785535] Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18654-9 [18003927] Oncogene. 2008 Jan 24;27(5):596-603 [17700537] J Clin Invest. 2008 Aug;118(8):2697-710 [18618013] Nature. 2008 Aug 7;454(7205):766-70 [18600261] Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12182-7 [18723679] Nat Genet. 2009 Feb;41(2):178-86 [19151715] Cell. 2009 Jul 23;138(2):245-56 [19632176] Nat Rev Genet. 2009 Nov;10(11):805-11 [19789556] Cold Spring Harb Protoc. 2009 Feb;2009(2):pdb.prot5138 [20147068] N Engl J Med. 2010 Aug 26;363(9):809-19 [20818844] Prostate. 2011 Jun 1;71(8):846-56 [21456067] Clin Cancer Res. 2012 Feb 1;18(3):666-77 [22156612] J Pathol. 2012 Jul;227(3):286-97 [22553170] Cancer J. 2013 Jan-Feb;19(1):43-9 [23337756] Clin Cancer Res. 2013 Jul 1;19(13):3621-30 [23649003] J Clin Oncol. 2013 Aug 1;31(22):2791-8 [23816964] Oncol Rep. 2014 Jan;31(1):34-40 [24173286] J Clin Oncol. 2002 Jul 15;20(14):3072-80 [12118020] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1080/15592294.2016.1146851 ER - TY - JOUR T1 - Discovery and Characterization of a Biologically Active Non-ATP-Competitive p38 MAP Kinase Inhibitor AN - 1846403747; PQ0003824698 AB - Mitogen-activated protein kinase (MAPK) p38 is part of a broad and ubiquitously expressed family of MAPKs whose activity is responsible for mediating an intracellular response to extracellular stimuli through a phosphorylation cascade. p38 is central to this signaling node and is activated by upstream kinases while being responsible for activating downstream kinases and transcription factors via phosphorylation. Dysregulated p38 activity is associated with numerous autoimmune disorders and has been implicated in the progression of several types of cancer. A number of p38 inhibitors have been tested in clinical trials, with none receiving regulatory approval. One characteristic shared by all of the compounds that failed clinical trials is that they are all adenosine triphosphate (ATP)-competitive p38 inhibitors. Seeing this lack of mechanistic diversity as an opportunity, we screened ~32,000 substances in search of novel p38 inhibitors. Among the inhibitors discovered is a compound that is both non-ATP competitive and biologically active in cell-based models for p38 activity. This is the first reported discovery of a non-ATP-competitive p38 inhibitor that is active in cells and, as such, may enable new pharmacophore designs for both therapeutic and basic research to better understand and exploit non-ATP-competitive inhibitors of p38 activity. JF - Journal of Biomolecular Screening AU - Wilson, Brice AP AU - Alam, Muhammad S AU - Guszczynski, Tad AU - Jakob, Michal AU - Shenoy, Shilpa R AU - Mitchell, Carter A AU - Goncharova, Ekaterina I AU - Evans, Jason R AU - Wipf, Peter AU - Liu, Gang AU - Ashwell, Jonathan D AU - O'Keefe, Barry R AD - 1 .Molecular Targets Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA, okeefeba@mail.nih.gov Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 277 EP - 289 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 21 IS - 3 SN - 1087-0571, 1087-0571 KW - Biotechnology and Bioengineering Abstracts KW - high throughput KW - p38 KW - non-ATP competitive KW - enzyme kinetics KW - Intracellular signalling KW - MAP kinase KW - Phosphorylation KW - Transcription factors KW - Autoimmune diseases KW - ATP KW - Nodes KW - Clinical trials KW - pharmacophores KW - Cancer KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846403747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomolecular+Screening&rft.atitle=Discovery+and+Characterization+of+a+Biologically+Active+Non-ATP-Competitive+p38+MAP+Kinase+Inhibitor&rft.au=Wilson%2C+Brice+AP%3BAlam%2C+Muhammad+S%3BGuszczynski%2C+Tad%3BJakob%2C+Michal%3BShenoy%2C+Shilpa+R%3BMitchell%2C+Carter+A%3BGoncharova%2C+Ekaterina+I%3BEvans%2C+Jason+R%3BWipf%2C+Peter%3BLiu%2C+Gang%3BAshwell%2C+Jonathan+D%3BO%27Keefe%2C+Barry+R&rft.aulast=Wilson&rft.aufirst=Brice&rft.date=2016-03-01&rft.volume=21&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+Screening&rft.issn=10870571&rft_id=info:doi/10.1177%2F1087057115615518 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Number of references - 35 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Intracellular signalling; MAP kinase; Phosphorylation; Transcription factors; Autoimmune diseases; ATP; Nodes; Clinical trials; Cancer; pharmacophores DO - http://dx.doi.org/10.1177/1087057115615518 ER - TY - JOUR T1 - Genome-wide footprinting: ready for prime time? AN - 1846398721; PQ0003819210 AB - High-throughput sequencing technologies have allowed many gene locus-level molecular biology assays to become genome-wide profiling methods. DNA-cleaving enzymes such as DNase I have been used to probe accessible chromatin. The accessible regions contain functional regulatory sites, including promoters, insulators and enhancers. Deep sequencing of DNase-seq libraries and computational analysis of the cut profiles have been used to infer protein occupancy in the genome at the nucleotide level, a method introduced as 'digital genomic footprinting'. The approach has been proposed as an attractive alternative to the analysis of transcription factors (TFs) by chromatin immunoprecipitation followed by sequencing (ChIP-seq), and in theory it should overcome antibody issues, poor resolution and batch effects. Recent reports point to limitations of the DNase-based genomic footprinting approach and call into question the scope of detectable protein occupancy, especially for TFs with short-lived chromatin binding. The genomics community is grappling with issues concerning the utility of genomic footprinting and is reassessing the proposed approaches in terms of robust deliverables. Here we summarize the consensus as well as different views emerging from recent reports, and we describe the remaining issues and hurdles for genomic footprinting. JF - Nature Methods AU - Sung, Myong-Hee AU - Baek, Songjoon AU - Hager, Gordon L AD - Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 222 EP - 228 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 13 IS - 3 SN - 1548-7091, 1548-7091 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Chromatin KW - Footprinting KW - Nucleotide sequence KW - DNA probes KW - Immunoprecipitation KW - Enzymes KW - Computer applications KW - Nucleotides KW - Promoters KW - Enhancers KW - Antibodies KW - Reviews KW - Transcription factors KW - Deoxyribonuclease KW - genomics KW - G 07720:Immunogenetics KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846398721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Methods&rft.atitle=Genome-wide+footprinting%3A+ready+for+prime+time%3F&rft.au=Sung%2C+Myong-Hee%3BBaek%2C+Songjoon%3BHager%2C+Gordon+L&rft.aulast=Sung&rft.aufirst=Myong-Hee&rft.date=2016-03-01&rft.volume=13&rft.issue=3&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Nature+Methods&rft.issn=15487091&rft_id=info:doi/10.1038%2Fnmeth.3766 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - Footprinting; Chromatin; DNA probes; Nucleotide sequence; Immunoprecipitation; Enzymes; Computer applications; Nucleotides; Enhancers; Promoters; Antibodies; Transcription factors; Reviews; Deoxyribonuclease; genomics DO - http://dx.doi.org/10.1038/nmeth.3766 ER - TY - JOUR T1 - Genomic Test Results and the Courtroom: The Roles of Experts and Expert Testimony AN - 1839206373 AB - The rapid advancement from single-gene testing to whole genome sequencing has significantly broadened the type and amount of information available to researchers, physicians, patients, and the public in general. Much debate has ensued about whether genomic test results should be reported to research participants, patients and consumers, and at what stage we can be sure that existing evidence justifies their use in clinical settings. Courts and judges evaluating the utility of these results will not be immune to this uncertainty. As scholars increasingly explore the duty of care standards related to reporting genomic test results, it is timely to provide a framework for understanding how uncertainty about genetic and genomic tests influences evidentiary considerations in the court room. Here, we explore the subtleties and nuances of interpreting genetic data in an environment of substantial discord related to the value that individuals should place on genetic and genomic tests. In conjunction, we discuss the roles courts should play in qualifying experts, expert testimony, and genetic and genomic tests given the intricate and complex nature of genetic and genomic information. JF - The Journal of Law, Medicine & Ethics AU - Ramos, Edward AU - Callier, Shawneequa L AU - Swann, Peter B AU - Harvey, Hosea H AD - Edward Ramos, Ph.D., is a Program Director at the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. Shawneequa L. Callier, J.D., M.A., is an Assistant Professor in the Department of Clinical Research and Leadership at the George Washington University School of Medicine and Health Sciences. Peter B. Swann, J.D., is Judge, Division One, Arizona Court of Appeals. Hosea H. Harvey, J.D., Ph.D., is Associate Professor of Law and Temple University Beasley School of Law. ; Edward Ramos, Ph.D., is a Program Director at the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. Shawneequa L. Callier, J.D., M.A., is an Assistant Professor in the Department of Clinical Research and Leadership at the George Washington University School of Medicine and Health Sciences. Peter B. Swann, J.D., is Judge, Division One, Arizona Court of Appeals. Hosea H. Harvey, J.D., Ph.D., is Associate Professor of Law and Temple University Beasley School of Law. Y1 - 2016/03// PY - 2016 DA - Mar 2016 SP - 205 EP - 215 CY - Boston PB - SAGE PUBLICATIONS, INC. VL - 44 IS - 1 SN - 1073-1105 KW - Medical Sciences KW - Testimony KW - Experts KW - Natural Environment KW - Consumers KW - Judges KW - Intellectuals KW - Patients KW - Standards KW - Courts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1839206373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apais&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Law%2C+Medicine+%26+Ethics&rft.atitle=Genomic+Test+Results+and+the+Courtroom%3A+The+Roles+of+Experts+and+Expert+Testimony&rft.au=Ramos%2C+Edward%3BCallier%2C+Shawneequa+L%3BSwann%2C+Peter+B%3BHarvey%2C+Hosea+H&rft.aulast=Ramos&rft.aufirst=Edward&rft.date=2016-03-01&rft.volume=44&rft.issue=1&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Law%2C+Medicine+%26+Ethics&rft.issn=10731105&rft_id=info:doi/10.1177%2F1073110516644211 LA - English DB - PAIS Index N1 - Copyright - © 2016 American Society of Law, Medicine & Ethics N1 - Last updated - 2017-01-24 DO - http://dx.doi.org/10.1177/1073110516644211 ER - TY - JOUR T1 - Blood gene expression profiling of an early acetaminophen response. AN - 1826655669; 26927286 AB - Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.The Pharmacogenomics Journal advance online publication, 1 March 2016; doi:10.1038/tpj.2016.8. JF - The pharmacogenomics journal AU - Bushel, P R AU - Fannin, R D AU - Gerrish, K AU - Watkins, P B AU - Paules, R S AD - Microarray and Genome Informatics Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; Molecular Genomics Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. ; The Hamner Institute for Health Sciences, Research Triangle Park, NC, USA. Y1 - 2016/03/01/ PY - 2016 DA - 2016 Mar 01 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1826655669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+pharmacogenomics+journal&rft.atitle=Blood+gene+expression+profiling+of+an+early+acetaminophen+response.&rft.au=Bushel%2C+P+R%3BFannin%2C+R+D%3BGerrish%2C+K%3BWatkins%2C+P+B%3BPaules%2C+R+S&rft.aulast=Bushel&rft.aufirst=P&rft.date=2016-03-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=The+pharmacogenomics+journal&rft.issn=1473-1150&rft_id=info:doi/10.1038%2Ftpj.2016.8 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-03-01 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/tpj.2016.8 ER - TY - JOUR T1 - The Effects of Genetic Background of Mouse Models of Cancer: Friend or Foe? AN - 1808741238; PQ0003355112 AB - Over the past century, mice have been selectively bred to give rise to the strains used in biomedical research today. Mouse models of cancer allow researchers to control variables of diet, environment, and genetic heterogeneity to better dissect the role of these factors in cancer in humans. Because of the important role of genetic background in cancer, the strain of the mouse can introduce confounding results in studies of mouse models if not properly controlled. Conversely, genetic variation between strains can also provide important new insights into cancer mechanisms. Here, the sources of genetic heterogeneity in mouse models are reviewed, with an explanation of how heterogeneity modifies cancer phenotypes. JF - Cold Spring Harbor Protocols AU - Reilly, Karlyne M AD - Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702, reillyk@mail.nih.gov Y1 - 2016/03// PY - 2016 DA - March 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States IS - 3 SN - 1940-3402, 1940-3402 KW - Biotechnology and Bioengineering Abstracts KW - Diets KW - Reviews KW - Animal models KW - Genetic diversity KW - Cancer KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808741238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Protocols&rft.atitle=The+Effects+of+Genetic+Background+of+Mouse+Models+of+Cancer%3A+Friend+or+Foe%3F&rft.au=Reilly%2C+Karlyne+M&rft.aulast=Reilly&rft.aufirst=Karlyne&rft.date=2016-03-01&rft.volume=&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Protocols&rft.issn=19403402&rft_id=info:doi/10.1101%2Fpdb.top076273 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Diets; Reviews; Animal models; Genetic diversity; Cancer DO - http://dx.doi.org/10.1101/pdb.top076273 ER - TY - JOUR T1 - Using the Collaborative Cross to Study the Role of Genetic Diversity in Cancer-Related Phenotypes AN - 1808740551; PQ0003355123 AB - Human populations are genetically diverse and often a single mouse model can only represent a small subset of the human population. Studying genetic diversity directly can improve the predictive value of mouse models of cancer biology and research on the effects of carcinogens and therapeutics in humans. The collaborative cross is a panel of inbred mouse lines that captures 90% of the genetic diversity of the Mus musculus strain and can help identify regions of the genome that are responsible for variation in cancer phenotypes across the population. The appropriate procedure will depend on the mouse model used; here, three mouse cross designs are described as examples. JF - Cold Spring Harbor Protocols AU - Reilly, Karlyne M AD - Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702, reillyk@mail.nih.gov Y1 - 2016/03// PY - 2016 DA - March 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States IS - 3 SN - 1940-3402, 1940-3402 KW - Biotechnology and Bioengineering Abstracts KW - Genomes KW - Population genetics KW - Animal models KW - Genetic diversity KW - Inbreeding KW - Carcinogens KW - Mus musculus KW - Cancer KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808740551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Protocols&rft.atitle=Using+the+Collaborative+Cross+to+Study+the+Role+of+Genetic+Diversity+in+Cancer-Related+Phenotypes&rft.au=Reilly%2C+Karlyne+M&rft.aulast=Reilly&rft.aufirst=Karlyne&rft.date=2016-03-01&rft.volume=&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Protocols&rft.issn=19403402&rft_id=info:doi/10.1101%2Fpdb.prot079178 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Genomes; Population genetics; Animal models; Genetic diversity; Inbreeding; Carcinogens; Cancer; Mus musculus DO - http://dx.doi.org/10.1101/pdb.prot079178 ER - TY - JOUR T1 - Controlling Genetic Background in Crosses of Mouse Models of Cancer AN - 1808739317; PQ0003355122 AB - The design of a mouse cross can affect the distribution of variation in the control and experimental groups. Often, the goal of a study involving mouse cancer models is to determine the effect of a gene or intervention of interest in different mouse groups without the confounding effects of strain background differences. The appropriate procedure for controlling genetic background will depend on the mouse model employed; two examples are provided here. The first example describes a simple model in which a single-mutant allele is followed in crosses on an inbred strain background. The second example describes a more complex cross in which the model is homozygous for a floxed allele of the gene of interest and carries a tissue-specific Cre transgene. JF - Cold Spring Harbor Protocols AU - Reilly, Karlyne M AD - Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702, reillyk@mail.nih.gov Y1 - 2016/03// PY - 2016 DA - March 2016 PB - Cold Spring Harbor Laboratory Press, Fulfillment & Distribution Dept. Woodbury NY 11797-2924 United States IS - 3 SN - 1940-3402, 1940-3402 KW - Biotechnology and Bioengineering Abstracts KW - Transgenes KW - Animal models KW - Inbreeding KW - Cancer KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1808739317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cold+Spring+Harbor+Protocols&rft.atitle=Controlling+Genetic+Background+in+Crosses+of+Mouse+Models+of+Cancer&rft.au=Reilly%2C+Karlyne+M&rft.aulast=Reilly&rft.aufirst=Karlyne&rft.date=2016-03-01&rft.volume=&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cold+Spring+Harbor+Protocols&rft.issn=19403402&rft_id=info:doi/10.1101%2Fpdb.prot079160 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-07-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Transgenes; Animal models; Inbreeding; Cancer DO - http://dx.doi.org/10.1101/pdb.prot079160 ER - TY - JOUR T1 - Chromatin looping as a target for altering erythroid gene expression AN - 1794499907; PQ0003149832 AB - The beta -hemoglobinopathies are the most common monogenic disorders in humans, with symptoms arising after birth when the fetal gamma -globin genes are silenced and the adult beta -globin gene is activated. There is a growing appreciation that genome organization and the folding of chromosomes are key determinants of gene transcription. Underlying this function is the activity of transcriptional enhancers that increase the transcription of target genes over long linear distances. To accomplish this, enhancers engage in close physical contact with target promoters through chromosome folding or looping that is orchestrated by protein complexes that bind to both sites and stabilize their interaction. We find that enhancer activity can be redirected with concomitant changes in gene transcription. Both targeting the beta -globin locus control region (LCR) to the gamma -globin gene in adult erythroid cells by tethering and epigenetic unmasking of a silenced gamma -globin gene lead to increased frequency of LCR/ gamma -globin contacts and reduced LCR/ beta -globin contacts. The outcome of these manipulations is robust, pancellular gamma -globin transcription activation with a concomitant reduction in beta -globin transcription. These examples show that chromosome looping may be considered a therapeutic target for gene activation in beta -thalassemia and sickle cell disease. JF - Annals of the New York Academy of Sciences AU - Krivega, Ivan AU - Dean, Ann AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 31 EP - 39 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1368 IS - 1 SN - 0077-8923, 0077-8923 KW - Genetics Abstracts; Environment Abstracts KW - Genomes KW - Chromatin KW - Erythroid cells KW - Transcription KW - Fetuses KW - Gene expression KW - Birth KW - Promoters KW - Enhancers KW - Chromosomes KW - Protein folding KW - epigenetics KW - Proteins KW - Sickle cell disease KW - Transcription activation KW - Gene silencing KW - G 07730:Development & Cell Cycle KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1794499907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Chromatin+looping+as+a+target+for+altering+erythroid+gene+expression&rft.au=Krivega%2C+Ivan%3BDean%2C+Ann&rft.aulast=Krivega&rft.aufirst=Ivan&rft.date=2016-03-01&rft.volume=1368&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fnyas.13012 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-06-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Genomes; Chromatin; Erythroid cells; Transcription; Fetuses; Birth; Gene expression; Enhancers; Promoters; Chromosomes; Protein folding; epigenetics; Sickle cell disease; Transcription activation; Gene silencing; Proteins DO - http://dx.doi.org/10.1111/nyas.13012 ER - TY - JOUR T1 - Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity AN - 1785247151; PQ0002918466 AB - Due to the increasing prevalence of neurological disorders and the large number of untested compounds in the environment, there is a need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect neurological development. Herein, we report on a library of 80 compounds screened for their ability to inhibit neurite outgrowth, a process by which compounds may elicit developmental neurotoxicity, in a high-throughput, high-content assay using human neurons derived from induced pluripotent stem cells (iPSC). The library contains a diverse set of compounds including those that have been known to be associated with developmental neurotoxicity (DNT) and/or neurotoxicity (NT), environmental compounds with unknown neurotoxic potential (e.g., polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs)), as well as compounds with no documented neurotoxic potential. Neurons were treated for 72h across a 6-point concentration range (0.3-100 mu M) in 384-well plates. Effects on neurite outgrowth were assessed by quantifying total outgrowth, branches, and processes. We also assessed the number ofviable cells per well. Concentration-response profiles were evaluated using a Hill model to derive benchmark concentration (BMC) values. Assay performance was evaluated using positive and negative controls and test replicates. Compounds were ranked by activity and selectivity (i.e., specific effects on neurite outgrowth in the absence of concomitant cytotoxicity) and repeat studies were conducted to confirm selectivity. Among the 80 compounds tested, 38 compounds were active, of which 16 selectively inhibited neurite outgrowth. Of these 16 compounds, 12 were known to cause DNT/NT and the remaining 4 compounds included 3 PAHs and 1 FR. In independent repeat studies, 14/16 selective compounds were reproducibly active in the assay, of which only 6 were selective for inhibition of neurite outgrowth. These 6 compounds were previously shown in the literature to be neurotoxic. These studies shed light on the current status of human iPSCs in DNT/NT screening and their utility in identifying, ranking, and prioritizing compounds with DNT/NT potential for further in vivo testing. JF - Neurotoxicology AU - Ryan, Kristen R AU - Sirenko, Oksana AU - Parham, Fred AU - Hsieh, Jui-Hua AU - Cromwell, Evan F AU - Tice, Raymond R AU - Behl, Mamta AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 271 EP - 281 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 53 SN - 0161-813X, 0161-813X KW - Environment Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - Neurite outgrowth KW - High-throughput screening KW - High-content screening KW - Human iPSC KW - Benchmark concentration KW - Chemicals KW - Polycyclic aromatic hydrocarbons KW - Neurological diseases KW - Inhibitory postsynaptic potentials KW - Fire retardant chemicals KW - Stem cells KW - Cytotoxicity KW - Neurons KW - Neurotoxicity KW - Bone mineral content KW - Axonogenesis KW - Fire retardants KW - Human factors KW - Benchmarks KW - Hills KW - N3 11028:Neuropharmacology & toxicology KW - X 24350:Industrial Chemicals KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785247151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Neurite+outgrowth+in+human+induced+pluripotent+stem+cell-derived+neurons+as+a+high-throughput+screen+for+developmental+neurotoxicity+or+neurotoxicity&rft.au=Ryan%2C+Kristen+R%3BSirenko%2C+Oksana%3BParham%2C+Fred%3BHsieh%2C+Jui-Hua%3BCromwell%2C+Evan+F%3BTice%2C+Raymond+R%3BBehl%2C+Mamta&rft.aulast=Ryan&rft.aufirst=Kristen&rft.date=2016-03-01&rft.volume=53&rft.issue=&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/10.1016%2Fj.neuro.2016.02.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Polycyclic aromatic hydrocarbons; Cytotoxicity; Stem cells; Neurological diseases; Neurons; Inhibitory postsynaptic potentials; Neurotoxicity; Bone mineral content; Axonogenesis; Fire retardant chemicals; Chemicals; Human factors; Fire retardants; Benchmarks; Hills DO - http://dx.doi.org/10.1016/j.neuro.2016.02.003 ER - TY - JOUR T1 - Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study AN - 1785235855; PQ0002896145 AB - High-dose ionizing radiation is associated with circulatory disease. Risks from lower-dose fractionated exposures, such as from diagnostic radiation procedures, remain unclear. In this study we aimed to ascertain the relationship between fractionated low-to-medium dose radiation exposure and circulatory disease mortality in a cohort of 13,568 tuberculosis patients in Massachusetts, some with fluoroscopy screenings, between 1916 and 1961 and follow-up until the end of 2002. Analysis of mortality was in relation to cumulative thyroid (cerebrovascular) or lung (all other circulatory disease) radiation dose via Poisson regression. Over the full dose range, there was no overall radiation-related excess risk of death from circulatory disease (n = 3221; excess relative risk/Gy -0.023; 95 % CI -0.067, 0.028; p = 0.3574). Risk was somewhat elevated in hypertensive heart disease (n = 89; excess relative risk/Gy 0.357; 95 % CI -0.043, 1.030, p = 0.0907) and slightly decreased in ischemic heart disease (n = 1950; excess relative risk/Gy -0.077; 95 % CI -0.130, -0.012; p = 0.0211). However, under 0.5 Gy, there was a borderline significant increasing trend for all circulatory disease (excess relative risk/Gy 0.345; 95 % CI -0.032, 0.764; p = 0.0743) and for ischemic heart disease (excess relative risk/Gy 0.465; 95 % CI, -0.032, 1.034, p = 0.0682). Pneumolobectomy increased radiation-associated risk (excess relative risk/Gy 0.252; 95 % CI 0.024, 0.579). Fractionation of dose did not modify excess risk. In summary, we found no evidence of radiation-associated excess circulatory death risk overall, but there are indications of excess circulatory death risk at lower doses (<0.5 Gy). Although consistent with other radiation-exposed groups, the indications of higher risk at lower doses are unusual and should be confirmed against other data. JF - European Journal of Epidemiology AU - Little, Mark P AU - Zablotska, Lydia B AU - Brenner, Alina V AU - Lipshultz, Steven E AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, 20892-9778, USA, mark.little@nih.gov Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 287 EP - 309 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 31 IS - 3 SN - 0393-2990, 0393-2990 KW - Microbiology Abstracts B: Bacteriology; Health & Safety Science Abstracts KW - Risk assessment KW - Mortality KW - USA, Massachusetts KW - Data processing KW - Mycobacterium KW - Thyroid KW - Ischemia KW - Radiation KW - Fractionation KW - Lung KW - Risk factors KW - Ionizing radiation KW - Tuberculosis KW - fluoroscopy KW - Heart diseases KW - H 8000:Radiation Safety/Electrical Safety KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785235855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Epidemiology&rft.atitle=Circulatory+disease+mortality+in+the+Massachusetts+tuberculosis+fluoroscopy+cohort+study&rft.au=Little%2C+Mark+P%3BZablotska%2C+Lydia+B%3BBrenner%2C+Alina+V%3BLipshultz%2C+Steven+E&rft.aulast=Little&rft.aufirst=Mark&rft.date=2016-03-01&rft.volume=31&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Epidemiology&rft.issn=03932990&rft_id=info:doi/10.1007%2Fs10654-015-0075-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 58 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Risk assessment; Mortality; Data processing; Ionizing radiation; Risk factors; Thyroid; fluoroscopy; Tuberculosis; Ischemia; Heart diseases; Fractionation; Radiation; Lung; Mycobacterium; USA, Massachusetts DO - http://dx.doi.org/10.1007/s10654-015-0075-9 ER - TY - JOUR T1 - Tuberculosis control AN - 1785234074; PQ0002810179 JF - Lancet AU - Godfrey, Catherine AU - Andersen, Janet AU - Mngqibisa, Rosie AU - Scott, Lesley E AU - Conradie, Francesca AD - National Institutes of Health, Bethesda, MD, USA Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 1157 EP - 1158 PB - Elsevier B.V., Radarweg 29 Amsterdam 1043 NX Netherlands VL - 387 IS - 10024 SN - 0140-6736, 0140-6736 KW - Microbiology Abstracts B: Bacteriology KW - Mycobacterium KW - Tuberculosis KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785234074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet&rft.atitle=Tuberculosis+control&rft.au=Godfrey%2C+Catherine%3BAndersen%2C+Janet%3BMngqibisa%2C+Rosie%3BScott%2C+Lesley+E%3BConradie%2C+Francesca&rft.aulast=Godfrey&rft.aufirst=Catherine&rft.date=2016-03-01&rft.volume=387&rft.issue=10024&rft.spage=1157&rft.isbn=&rft.btitle=&rft.title=Lancet&rft.issn=01406736&rft_id=info:doi/10.1016%2FS0140-6736%2816%2900706-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Number of references - 4 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Tuberculosis; Mycobacterium DO - http://dx.doi.org/10.1016/S0140-6736(16)00706-6 ER - TY - JOUR T1 - Global Mortality Impact of the 1957-1959 Influenza Pandemic AN - 1780527142; PQ0002893209 AB - Background.Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics. Methods.We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas. We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic. Results.The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2-2.6 cases/10 000 population) on average during 1957-1959. Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively. Excess mortality was delayed by 1-2 years in 18 countries (46%). Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality. Development indicators were moderate predictors of excess mortality, explaining 35%-77% of the variance. Overall, we attribute 1.1 million excess deaths (95% CI, .7 million-1.5 million excess deaths) globally to the 1957-1959 pandemic. Conclusions.The global mortality rate of the 1957-1959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic. The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic. JF - Journal of Infectious Diseases AU - Viboud, Cecile AU - Simonsen, Lone AU - Fuentes, Rodrigo AU - Flores, Jose AU - Miller, Mark A AU - Chowell, Gerardo AD - Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, viboudc@mail.nih.gov Y1 - 2016/03/01/ PY - 2016 DA - 2016 Mar 01 SP - 738 EP - 745 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 5 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - mortality rates KW - pandemic influenza KW - historical studies KW - vital statistics KW - severity KW - models KW - global disease burden KW - development indicators KW - health indicators KW - pandemic planning KW - Historical account KW - Mortality KW - Statistics KW - Respiration KW - Latin America KW - Elderly KW - Children KW - Vaccination KW - Influenza KW - pandemics KW - Infectious diseases KW - ANE, Europe KW - Background levels KW - Geriatrics KW - Vaccines KW - Young adults KW - H 1000:Occupational Safety and Health KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780527142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Global+Mortality+Impact+of+the+1957-1959+Influenza+Pandemic&rft.au=Viboud%2C+Cecile%3BSimonsen%2C+Lone%3BFuentes%2C+Rodrigo%3BFlores%2C+Jose%3BMiller%2C+Mark+A%3BChowell%2C+Gerardo&rft.aulast=Viboud&rft.aufirst=Cecile&rft.date=2016-03-01&rft.volume=213&rft.issue=5&rft.spage=738&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiv534 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Influenza; Mortality; pandemics; Statistics; Respiration; Background levels; Geriatrics; Children; Vaccination; Historical account; Infectious diseases; Elderly; Young adults; Vaccines; ANE, Europe; Latin America DO - http://dx.doi.org/10.1093/infdis/jiv534 ER - TY - JOUR T1 - Concise Review: Progress and Challenges in Using Human Stem Cells for Biological and Therapeutics Discovery: Neuropsychiatric Disorders AN - 1780523197; PQ0002836451 AB - Abstract In facing the daunting challenge of using human embryonic and induced pluripotent stem cells to study complex neural circuit disorders such as schizophrenia, mood and anxiety disorders, and autism spectrum disorders, a 2012 National Institute of Mental Health workshop produced a set of recommendations to advance basic research and engage industry in cell-based studies of neuropsychiatric disorders. This review describes progress in meeting these recommendations, including the development of novel tools, strides in recapitulating relevant cell and tissue types, insights into the genetic basis of these disorders that permit integration of risk-associated gene regulatory networks with cell/circuit phenotypes, and promising findings of patient-control differences using cell-based assays. However, numerous challenges are still being addressed, requiring further technological development, approaches to resolve disease heterogeneity, and collaborative structures for investigators of different disciplines. Additionally, since data obtained so far is on small sample sizes, replication in larger sample sets is needed. A number of individual success stories point to a path forward in developing assays to translate discovery science to therapeutics development. Stem Cells 2016; 34:523-536 JF - Stem Cells AU - Panchision, David M AD - Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 523 EP - 536 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 34 IS - 3 SN - 1066-5099, 1066-5099 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Data processing KW - Anxiety KW - Conferences KW - Replication KW - Neural networks KW - Circuits KW - Drug development KW - Mood KW - Schizophrenia KW - Integration KW - Mental disorders KW - Stem cells KW - Reviews KW - Embryos KW - Autism KW - N3 11023:Neurogenetics KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780523197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Concise+Review%3A+Progress+and+Challenges+in+Using+Human+Stem+Cells+for+Biological+and+Therapeutics+Discovery%3A+Neuropsychiatric+Disorders&rft.au=Panchision%2C+David+M&rft.aulast=Panchision&rft.aufirst=David&rft.date=2016-03-01&rft.volume=34&rft.issue=3&rft.spage=523&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/10.1002%2Fstem.2295 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Data processing; Conferences; Anxiety; Neural networks; Replication; Drug development; Circuits; Schizophrenia; Mood; Integration; Stem cells; Mental disorders; Reviews; Embryos; Autism DO - http://dx.doi.org/10.1002/stem.2295 ER - TY - JOUR T1 - Assessment of drone-based surface flow observations AN - 1780502979; PQ0002835896 AB - Remote surface flow observations are crucial for improving the comprehension of hydrological phenomena. A recent advancement in remote hydrological measurements involves the use of drones for generating surface flow-velocity field maps through large-scale particle image velocimetry (LSPIV). In this work, we perform a comparative analysis of drone-based LSPIV with fixed implementations. Quantitative indices are introduced to test the efficiency of the techniques with regards to measurement accuracy, sensitivity to the transit of tracers, and platform mobility. Experimental findings support drone-based observations in outdoor settings. Specifically, measurements from the aerial platform are more sensitive to the transit of tracers and closer to benchmark values than traditional LSPIV implementations. Future work should aim at improving the stability of the aerial platform and mitigating the effects of tracer scarcity. JF - Hydrological Processes AU - Tauro, Flavia AU - Petroselli, Andrea AU - Arcangeletti, Ettore AD - Dipartimento per l'Innovazione nei sistemi Biologici, Agroalimentari e Forestali, University of Tuscia, Viterbo, 01100, Italy. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 1114 EP - 1130 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 30 IS - 7 SN - 0885-6087, 0885-6087 KW - Environment Abstracts; ASFA 2: Ocean Technology Policy & Non-Living Resources; Aqualine Abstracts; Water Resources Abstracts KW - Testing Procedures KW - Sensitivity KW - Surface Flow KW - Mitigation KW - Mobility KW - Particulates KW - Maps KW - Current observations KW - Tracers KW - Assessments KW - Scarcity KW - Benchmarks KW - AQ 00001:Water Resources and Supplies KW - Q2 09283:Soil mechanics KW - SW 0810:General KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780502979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hydrological+Processes&rft.atitle=Assessment+of+drone-based+surface+flow+observations&rft.au=Tauro%2C+Flavia%3BPetroselli%2C+Andrea%3BArcangeletti%2C+Ettore&rft.aulast=Tauro&rft.aufirst=Flavia&rft.date=2016-03-01&rft.volume=30&rft.issue=7&rft.spage=1114&rft.isbn=&rft.btitle=&rft.title=Hydrological+Processes&rft.issn=08856087&rft_id=info:doi/10.1002%2Fhyp.10698 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Current observations; Sensitivity; Tracers; Mitigation; Mobility; Scarcity; Particulates; Benchmarks; Testing Procedures; Surface Flow; Assessments; Maps DO - http://dx.doi.org/10.1002/hyp.10698 ER - TY - JOUR T1 - Kinetics of Genetic Variation of the Mycoplasma genitalium MG192 Gene in Experimentally Infected Chimpanzees AN - 1776665887; PQ0002745132 AB - Mycoplasma genitalium, a human pathogen associated with sexually transmitted diseases, is capable of causing chronic infections, though mechanisms for persistence remain unclear. Previous studies have found that variation of the MgPa operon occurs by recombination of repetitive chromosomal sequences (known as MgPars) into the MG191 and MG192 genes carried on this operon, which may lead to antigenic variation and immune evasion. In this study, we determined the kinetics of MG192 sequence variation during the course of experimental infection using archived specimens from two chimpanzees infected with M. genitalium strain G37. The highly variable region of MG192 was amplified by PCR from M. genitalium isolates obtained at various time points postinfection (p.i.). Sequence analysis revealed that MG192 sequence variation began at 5 weeks p.i. With the progression of infection, sequence changes accumulated throughout the MG192 variable region. The presence of MG192 variants at specific time points was confirmed by variant-specific PCR assays and sequence analysis of single-colony cloned M. genitalium organisms. MG192 nucleotide sequence variation correlated with estimated recombination events, predicted amino acid changes, and time of seroconversion, a finding consistent with immune selection of MG192 variants. In addition, we provided evidence that MG192 sequence variation occurred during the process of M. genitalium single-colony cloning. Such spontaneous variation suggests that some MG192 variation is independent of immune selection but may form the basis for subsequent immune selection. JF - Infection and Immunity AU - Ma, Liang AU - Jensen, Joergen S AU - Mancuso, Miriam AU - Myers, Leann AU - Martin, David H AD - << + $0, liang.ma@nih.gov. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 747 EP - 753 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 84 IS - 3 SN - 0019-9567, 0019-9567 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Experimental infection KW - Sexually-transmitted diseases KW - Mycoplasma genitalium KW - Nucleotide sequence KW - Genetic diversity KW - Pathogens KW - Pan troglodytes KW - Recombination KW - Kinetics KW - Chronic infection KW - Seroconversion KW - Polymerase chain reaction KW - Operons KW - Amino acid sequence KW - Variable region KW - J 02350:Immunology KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776665887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Kinetics+of+Genetic+Variation+of+the+Mycoplasma+genitalium+MG192+Gene+in+Experimentally+Infected+Chimpanzees&rft.au=Ma%2C+Liang%3BJensen%2C+Joergen+S%3BMancuso%2C+Miriam%3BMyers%2C+Leann%3BMartin%2C+David+H&rft.aulast=Ma&rft.aufirst=Liang&rft.date=2016-03-01&rft.volume=84&rft.issue=3&rft.spage=747&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.01162-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 24 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Experimental infection; Sexually-transmitted diseases; Nucleotide sequence; Genetic diversity; Pathogens; Recombination; Kinetics; Chronic infection; Polymerase chain reaction; Seroconversion; Operons; Variable region; Amino acid sequence; Mycoplasma genitalium; Pan troglodytes DO - http://dx.doi.org/10.1128/IAI.01162-15 ER - TY - JOUR T1 - Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study AN - 1776663806; PQ0002694450 AB - Background Artemisinin resistance in Plasmodium falciparum threatens to reduce the efficacy of artemisinin combination therapies (ACTs), thus compromising global efforts to eliminate malaria. Recent treatment failures with dihydroartemisinin-piperaquine, the current first-line ACT in Cambodia, suggest that piperaquine resistance may be emerging in this country. We explored the relation between artemisinin resistance and dihydroartemisinin-piperaquine failures, and sought to confirm the presence of piperaquine-resistant P falciparum infections in Cambodia. Methods In this prospective cohort study, we enrolled patients aged 2-65 years with uncomplicated P falciparum malaria in three Cambodian provinces: Pursat, Preah Vihear, and Ratanakiri. Participants were given standard 3-day courses of dihydroartemisinin-piperaquine. Peripheral blood parasite densities were measured until parasites cleared and then weekly to 63 days. The primary outcome was recrudescent P falciparum parasitaemia within 63 days. We measured piperaquine plasma concentrations at baseline, 7 days, and day of recrudescence. We assessed phenotypic and genotypic markers of drug resistance in parasite isolates. The study is registered with ClinicalTrials.gov, number NCT01736319. Findings Between Sept 4, 2012, and Dec 31, 2013, we enrolled 241 participants. In Pursat, where artemisinin resistance is entrenched, 37 (46%) of 81 patients had parasite recrudescence. In Preah Vihear, where artemisinin resistance is emerging, ten (16%) of 63 patients had recrudescence and in Ratanakiri, where artemisinin resistance is rare, one (2%) of 60 patients did. Patients with recrudescent P falciparum infections were more likely to have detectable piperaquine plasma concentrations at baseline compared with non-recrudescent patients, but did not differ significantly in age, initial parasite density, or piperaquine plasma concentrations at 7 days. Recrudescent parasites had a higher prevalence of kelch13 mutations, higher piperaquine 50% inhibitory concentration (IC50) values, and lower mefloquine IC50 values; none had multiple pfmdr1 copies, a genetic marker of mefloquine resistance. Interpretation Dihydroartemisinin-piperaquine failures are caused by both artemisinin and piperaquine resistance, and commonly occur in places where dihydroartemisinin-piperaquine has been used in the private sector. In Cambodia, artesunate plus mefloquine may be a viable option to treat dihydroartemisinin-piperaquine failures, and a more effective first-line ACT in areas where dihydroartemisinin-piperaquine failures are common. The use of single low-dose primaquine to eliminate circulating gametocytes is needed in areas where artemisinin and ACT resistance is prevalent. Funding National Institute of Allergy and Infectious Diseases. JF - Lancet Infectious Diseases AU - Amaratunga, Chanaki AU - Lim, Pharath AU - Suon, Seila AU - Sreng, Sokunthea AU - Mao, Sivanna AU - Sopha, Chantha AU - Sam, Baramey AU - Dek, Dalin AU - Try, Vorleak AU - Amato, Roberto AU - Blessborn, Daniel AU - Song, Lijiang AU - Tullo, Gregory S AU - Fay, Michael P AU - Anderson, Jennifer M AU - Tarning, Joel AU - Fairhurst, Rick M AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 357 EP - 365 PB - Elsevier B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands VL - 16 IS - 3 SN - 1473-3099, 1473-3099 KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Parasites KW - Age KW - Human diseases KW - Primaquine KW - Drug resistance KW - Disease control KW - Malaria KW - Infection KW - Public health KW - Hypersensitivity KW - Serological studies KW - Infectious diseases KW - Mefloquine KW - artesunate KW - Gametocytes KW - Peripheral blood KW - Plasmodium falciparum KW - Endoparasites KW - Blood KW - Cambodia KW - Genetic markers KW - artemisinin KW - Mutation KW - K 03410:Animal Diseases KW - Q1 08604:Stock assessment and management KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776663806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+Infectious+Diseases&rft.atitle=Dihydroartemisinin-piperaquine+resistance+in+Plasmodium+falciparum+malaria+in+Cambodia%3A+a+multisite+prospective+cohort+study&rft.au=Amaratunga%2C+Chanaki%3BLim%2C+Pharath%3BSuon%2C+Seila%3BSreng%2C+Sokunthea%3BMao%2C+Sivanna%3BSopha%2C+Chantha%3BSam%2C+Baramey%3BDek%2C+Dalin%3BTry%2C+Vorleak%3BAmato%2C+Roberto%3BBlessborn%2C+Daniel%3BSong%2C+Lijiang%3BTullo%2C+Gregory+S%3BFay%2C+Michael+P%3BAnderson%2C+Jennifer+M%3BTarning%2C+Joel%3BFairhurst%2C+Rick+M&rft.aulast=Amaratunga&rft.aufirst=Chanaki&rft.date=2016-03-01&rft.volume=16&rft.issue=3&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Lancet+Infectious+Diseases&rft.issn=14733099&rft_id=info:doi/10.1016%2FS1473-3099%2815%2900487-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 41 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Blood; Parasites; Serological studies; Human diseases; Infectious diseases; Disease control; Malaria; Endoparasites; Public health; Age; Primaquine; Gametocytes; Drug resistance; Peripheral blood; Infection; Hypersensitivity; Genetic markers; artemisinin; Mefloquine; artesunate; Mutation; Plasmodium falciparum; Cambodia DO - http://dx.doi.org/10.1016/S1473-3099(15)00487-9 ER - TY - JOUR T1 - Post-treatment with cocaine- and amphetamine-regulated transcript enhances infarct resolution, reinnervation, and angiogenesis in stroke rats - an MRI study AN - 1776655272; PQ0002807251 AB - Recent studies have shown that post-treatment with cocaine- and amphetamine-regulated transcript (CART) has neuroregenerative effects in animal models of stroke. The purpose of this study was to characterize CART-mediated neuronal and vascular repairments using non-invasive MRI techniques. Adult male rats were subjected to a 90 min middle cerebral artery occlusion (MCAo). Animals were separated into two groups with similar infarction sizes, measured by T sub(2)-weighted MRI on Day 2 after MCAo, and were treated with CART or vehicle intranasally from Day 3 to Day 12. Diffusion tensor imaging was used to examine changes in plasticity of white matter elements. Susceptibility-weighted imaging (SWI) was used to measure angiogenesis. Post-treatment with CART significantly increased fractional anisotropy (FA) in lesioned cortex on Days 10 and 25 post stroke. A significant correlation between the behavioral recovery in body asymmetry and the change in FA was shown, suggesting that behavioral recovery was associated with reinnervation to the lesioned hemisphere. CART also increased the intensity of SWI and the immunoreactivity of the vascular marker alpha-smooth muscle actin in lesioned cortex. Together, our data support a non-invasive treatment strategy for stroke through angiogenesis and reinnervation by CART. Treatment with cocaine- and amphetamine-regulated transcript (CART) significantly increased fractional anisotropy (FA) in lesioned cortex on Days 10 and 25 post stroke. We found a significant correlation between the change in FA and behavioral recovery in the CART-treated animals. CART also increased the intensity of SWI and the immunoreactivity of the vascular marker alpha -smooth muscle actin in lesioned cortex. Together, our data support a non-invasive treatment strategy for stroke through angiogenesis and reinnervation by CART. JF - NMR in Biomedicine AU - Liu, H-S AU - Shen, H AU - Luo, Y AU - Hoffer, B J AU - Wang, Y AU - Yang, Y AD - Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 361 EP - 370 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 29 IS - 3 SN - 0952-3480, 0952-3480 KW - Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - Hemispheric laterality KW - Data processing KW - Anisotropy KW - Magnetic resonance imaging KW - Stroke KW - Muscles KW - Angiogenesis KW - Substantia alba KW - Ischemia KW - Cortex KW - Plasticity (behavioral) KW - Immunoreactivity KW - Asymmetry KW - Actin KW - Reinnervation KW - Cerebral blood flow KW - Cerebral infarction KW - Cocaine- and amphetamine-regulated transcript protein KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776655272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NMR+in+Biomedicine&rft.atitle=Post-treatment+with+cocaine-+and+amphetamine-regulated+transcript+enhances+infarct+resolution%2C+reinnervation%2C+and+angiogenesis+in+stroke+rats+-+an+MRI+study&rft.au=Liu%2C+H-S%3BShen%2C+H%3BLuo%2C+Y%3BHoffer%2C+B+J%3BWang%2C+Y%3BYang%2C+Y&rft.aulast=Liu&rft.aufirst=H-S&rft.date=2016-03-01&rft.volume=29&rft.issue=3&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=NMR+in+Biomedicine&rft.issn=09523480&rft_id=info:doi/10.1002%2Fnbm.3461 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Hemispheric laterality; Neuroimaging; Anisotropy; Data processing; Stroke; Magnetic resonance imaging; Angiogenesis; Muscles; Substantia alba; Ischemia; Cortex; Plasticity (behavioral); Asymmetry; Immunoreactivity; Actin; Reinnervation; Cerebral blood flow; Cocaine- and amphetamine-regulated transcript protein; Cerebral infarction DO - http://dx.doi.org/10.1002/nbm.3461 ER - TY - JOUR T1 - super(13)C MRS of human brain at 7 Tesla using [2- super(13)C]glucose infusion and low power broadband stochastic proton decoupling AN - 1776655220; PQ0002805670 AB - Purpose Carbon-13 ( super(13)C) MR spectroscopy (MRS) of the human brain at 7 Tesla (T) may pose patient safety issues due to high radiofrequency (RF) power deposition for proton decoupling. The purpose of present work is to study the feasibility of in vivo super(13)C MRS of human brain at 7 T using broadband low RF power proton decoupling. Methods Carboxylic/amide super(13)C MRS of human brain by broadband stochastic proton decoupling was demonstrated on a 7 T scanner. RF safety was evaluated using the finite-difference time-domain method. super(13)C signal enhancement by nuclear Overhauser effect (NOE) and proton decoupling was evaluated in both phantoms and in vivo. Results At 7 T, the peak amplitude of carboxylic/amide super(13)C signals was increased by a factor of greater than 4 due to the combined effects of NOE and proton decoupling. The 7 T super(13)C MRS technique used decoupling power and average transmit power of less than 35 watts (W) and 3.6 W, respectively. Conclusion In vivo super(13)C MRS studies of human brain can be performed at 7 T, well below the RF safety threshold, by detecting carboxylic/amide carbons with broadband stochastic proton decoupling. Magn Reson Med 75:954-961, 2016. JF - Magnetic Resonance in Medicine AU - Li, Shizhe AU - An, Li AU - Yu, Shao AU - Ferraris Araneta, Maria AU - Johnson, Christopher S AU - Wang, Shumin AU - Shen, Jun AD - Magnetic Resonance Spectroscopy Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 954 EP - 961 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 75 IS - 3 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Carbon KW - Protons KW - Magnetic resonance spectroscopy KW - Brain KW - N.M.R. KW - Nuclear Overhauser effect KW - Stochasticity KW - amides KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776655220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=super%2813%29C+MRS+of+human+brain+at+7+Tesla+using+%5B2-+super%2813%29C%5Dglucose+infusion+and+low+power+broadband+stochastic+proton+decoupling&rft.au=Li%2C+Shizhe%3BAn%2C+Li%3BYu%2C+Shao%3BFerraris+Araneta%2C+Maria%3BJohnson%2C+Christopher+S%3BWang%2C+Shumin%3BShen%2C+Jun&rft.aulast=Li&rft.aufirst=Shizhe&rft.date=2016-03-01&rft.volume=75&rft.issue=3&rft.spage=954&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.25721 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Carbon; Protons; Magnetic resonance spectroscopy; Brain; N.M.R.; Nuclear Overhauser effect; amides; Stochasticity DO - http://dx.doi.org/10.1002/mrm.25721 ER - TY - JOUR T1 - Surface-Exposed Lipoproteins: An Emerging Secretion Phenomenon in Gram-Negative Bacteria AN - 1776654404; PQ0002699242 AB - Bacterial lipoproteins are hydrophilic proteins that are anchored to a cell membrane by N-terminally linked fatty acids. It is widely believed that nearly all lipoproteins produced by Gram-negative bacteria are either retained in the inner membrane (IM) or transferred to the inner leaflet of the outer membrane (OM). Lipoproteins that are exposed on the cell surface have also been reported but are generally considered to be rare. Results from a variety of recent studies, however, now suggest that the prevalence of surface-exposed lipoproteins has been underestimated. In this review we describe the evidence that the surface exposure of lipoproteins in Gram-negative bacteria is a widespread phenomenon and discuss possible mechanisms by which these proteins might be transported across the OM. JF - Trends in Microbiology AU - Wilson, Marlena M AU - Bernstein, Harris D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 198 EP - 208 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 24 IS - 3 SN - 0966-842X, 0966-842X KW - Microbiology Abstracts B: Bacteriology KW - Gram-negative bacteria KW - lipoproteins KW - outer membrane KW - protein secretion KW - protein translocation KW - Bacteria KW - Cell surface KW - Cell membranes KW - Reviews KW - Inner membranes KW - Secretion KW - Lipoproteins KW - Outer membranes KW - Fatty acids KW - J 02330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776654404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=Surface-Exposed+Lipoproteins%3A+An+Emerging+Secretion+Phenomenon+in+Gram-Negative+Bacteria&rft.au=Wilson%2C+Marlena+M%3BBernstein%2C+Harris+D&rft.aulast=Wilson&rft.aufirst=Marlena&rft.date=2016-03-01&rft.volume=24&rft.issue=3&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2Fj.tim.2015.11.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Cell surface; Cell membranes; Secretion; Inner membranes; Reviews; Gram-negative bacteria; Outer membranes; Lipoproteins; Fatty acids; Bacteria DO - http://dx.doi.org/10.1016/j.tim.2015.11.006 ER - TY - JOUR T1 - A genetic perspective on granulomatous diseases with an emphasis on mycobacterial infections AN - 1776645681; PQ0002813907 AB - Identification of the genetic factors predisposing to mycobacterial infections has been a subject of intense research activities. Current knowledge of the genetic and immunological basis of susceptibility to mycobacteria largely comes from natural human and experimental models of Bacille Calmette Guerin (BCG) and nontuberculous mycobacterial infections. These observations support the central role of the IL-12/IFN- gamma pathway in controlling mycobacterial infection. In this review, we discuss the knowledge that associates both simple and complex inheritance with susceptibility to mycobacterial diseases. We place a special emphasis on monogenic disorders, since these clearly pinpoint pathways and can adduce mechanism. We also describe the clinical, immunological, and pathological features that may steer clinical investigation in the appropriate directions. JF - Seminars in Immunopathology AU - Wu, Un-In AU - Holland, Steven M AD - Division of Infectious Diseases, National Taiwan University Hospital, Taipei, Taiwan, smh@nih.gov Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 199 EP - 212 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 38 IS - 2 SN - 1863-2297, 1863-2297 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - gamma -Interferon KW - Interleukin 12 KW - Genetic factors KW - Heredity KW - Mycobacterium KW - BCG KW - Infection KW - Models KW - J 02350:Immunology KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776645681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+Immunopathology&rft.atitle=A+genetic+perspective+on+granulomatous+diseases+with+an+emphasis+on+mycobacterial+infections&rft.au=Wu%2C+Un-In%3BHolland%2C+Steven+M&rft.aulast=Wu&rft.aufirst=Un-In&rft.date=2016-03-01&rft.volume=38&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Seminars+in+Immunopathology&rft.issn=18632297&rft_id=info:doi/10.1007%2Fs00281-015-0552-y LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 117 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Interleukin 12; gamma -Interferon; Genetic factors; Heredity; BCG; Infection; Models; Mycobacterium DO - http://dx.doi.org/10.1007/s00281-015-0552-y ER - TY - JOUR T1 - Systematic review of interventions to reduce problematic alcohol use in men who have sex with men AN - 1775309841 AB - Issues Rates of heavy drinking, alcohol problems and alcohol-related disorders are high among men who have sex with men (MSM) and are an important public health issue. Associations between heavy drinking and human immunodeficiency virus (HIV) acquisition among MSM also suggest that drinking may have more severe and chronic consequences for this population relative to others. Consequently, effective interventions to reduce heavy drinking and alcohol-related risk factors among MSM are needed. Approach We conducted a systematic review of randomised controlled trials of interventions to reduce heavy drinking and/or alcohol-related problems among MSM. We searched five electronic databases, screened 3722 records and identified 5 studies involving 1022 participants that satisfied inclusion criteria, which included having: (i) incorporated a comparison condition; (ii) randomised participants to groups; and (iii) reported quantitative outcomes. Key Findings The methodological quality of studies varied, and meta-analysis was not conducted because of heterogeneity in intervention approaches and outcomes. Studies provided preliminary support for the use of motivational interviewing/motivational enhancement-based interventions (MI) and hybrid MI and cognitive behavioural therapy treatments for heavy drinking among MSM over no treatment. Perhaps the most important conclusion of this review, however, is that well-designed, theoretically informed research focused on establishing the efficacy of interventions for hazardous drinking and alcohol use disorders among MSM is alarmingly scarce. Conclusions Effective interventions to reduce hazardous drinking among MSM and prevent key alcohol-related outcomes, including risk for HIV transmission and health problems among HIV-positive MSM, are needed to mitigate health disparities in this population. [Wray TB, Grin B, Dorfman L, Glynn TR, Kahler CW, Marshall BDL, van den Berg JJ, Zaller ND, Bryant KJ, Operario D. Systematic review of interventions to reduce problematic alcohol use in men who have sex with men. Drug Alcohol Rev 2016;35:148-57] JF - Drug and Alcohol Review AU - Wray, Tyler B AU - Grin, Benjamin AU - Dorfman, Leah AU - Glynn, Tiffany R AU - Kahler, Christopher W AU - Marshall, Brandon D L AU - Berg, Jacob J AU - Zaller, Nickolas D AU - Bryant, Kendall J AU - Operario, Don AD - Department of Behavioral and Social Sciences and Center for Alcohol and Addictions Studies, Brown University School of Public Health, Providence, USA ; Department of Epidemiology, Brown University School of Public Health, Providence, USA ; Division of Infectious Diseases, The Miriam Hospital, The Warren Alpert School of Brown University, Providence, USA ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, USA Y1 - 2016/03// PY - 2016 DA - Mar 2016 SP - 148 EP - 157 CY - Surry Hills PB - Wiley Subscription Services, Inc. VL - 35 IS - 2 SN - 0959-5236 KW - Education KW - Alcohol related KW - Alcohol related disorders KW - Alcohol related problems KW - Binge drinking KW - Cognitive behaviour therapy KW - Cognitive-Behavioural factors KW - Databases KW - Efficacy KW - Health inequalities KW - Health problems KW - Heavy drinking KW - Heterogeneity KW - HIV KW - Homosexuals KW - Immune disorders KW - Interventions KW - Interviewing KW - Men KW - Motivational interviewing KW - Problem drinking KW - Public health KW - Risk factors KW - Risk reduction KW - Substance abuse KW - Substance abuse disorders KW - Systematic reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1775309841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Review&rft.atitle=Systematic+review+of+interventions+to+reduce+problematic+alcohol+use+in+men+who+have+sex+with+men&rft.au=Wray%2C+Tyler+B%3BGrin%2C+Benjamin%3BDorfman%2C+Leah%3BGlynn%2C+Tiffany+R%3BKahler%2C+Christopher+W%3BMarshall%2C+Brandon+D+L%3BBerg%2C+Jacob+J%3BZaller%2C+Nickolas+D%3BBryant%2C+Kendall+J%3BOperario%2C+Don&rft.aulast=Wray&rft.aufirst=Tyler&rft.date=2016-03-01&rft.volume=35&rft.issue=2&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Review&rft.issn=09595236&rft_id=info:doi/10.1111%2Fdar.12271 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - Copyright © 2016 Australasian Professional Society on Alcohol and other Drugs N1 - Last updated - 2016-10-06 DO - http://dx.doi.org/10.1111/dar.12271 ER - TY - JOUR T1 - Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery AN - 1773826408; PQ0002717335 AB - The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. JF - Vaccine AU - Ford, Andrew Q AU - Touchette, Nancy AU - Hall, BFenton AU - Hwang, Angela AU - Hombach, Joachim AD - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 1489 EP - 1495 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 34 IS - 13 SN - 0264-410X, 0264-410X KW - Health & Safety Science Abstracts; Immunology Abstracts KW - GVIRF KW - GVAP KW - Stakeholders KW - Infectious diseases KW - Vaccines KW - Allergies KW - Immunization KW - Research programs KW - Public health KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773826408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Global+Vaccine+and+Immunization+Research+Forum%3A+Opportunities+and+challenges+in+vaccine+discovery%2C+development%2C+and+delivery&rft.au=Ford%2C+Andrew+Q%3BTouchette%2C+Nancy%3BHall%2C+BFenton%3BHwang%2C+Angela%3BHombach%2C+Joachim&rft.aulast=Ford&rft.aufirst=Andrew&rft.date=2016-03-01&rft.volume=34&rft.issue=13&rft.spage=1489&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2015.11.038 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 18 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Stakeholders; Infectious diseases; Vaccines; Allergies; Research programs; Immunization; Public health DO - http://dx.doi.org/10.1016/j.vaccine.2015.11.038 ER - TY - JOUR T1 - Spinal and Bulbar Muscular Atrophy Overview. AN - 1773807279; 26547319 AB - Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by an expanded repeat in the androgen receptor gene. The mutant protein is toxic to motor neurons and muscle. The toxicity is ligand-dependent and likely involves aberrant interaction of the mutant androgen receptor with other nuclear factors leading to transcriptional dysregulation. Various therapeutic strategies have been effective in transgenic animal models, and the challenge now is to translate these strategies into safe and effective treatment in patients. JF - Journal of molecular neuroscience : MN AU - Fischbeck, Kenneth H AD - Neurogenetics Branch, National Institute for Neurological Disorders and Stroke, National Institutes of Health, 35-2A1000, 35 Convent Dr., Bethesda, MD, 20892-3705, USA. kf@ninds.nih.gov. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 317 EP - 320 VL - 58 IS - 3 KW - Receptors, Androgen KW - 0 KW - Index Medicus KW - Androgen receptor KW - Polyglutamine KW - Spinal and bulbar muscular atrophy KW - Motor Neurons -- metabolism KW - Motor Neurons -- physiology KW - Humans KW - Bulbo-Spinal Atrophy, X-Linked -- genetics KW - Receptors, Androgen -- genetics KW - Receptors, Androgen -- metabolism KW - Bulbo-Spinal Atrophy, X-Linked -- physiopathology KW - Bulbo-Spinal Atrophy, X-Linked -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773807279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+neuroscience+%3A+MN&rft.atitle=Spinal+and+Bulbar+Muscular+Atrophy+Overview.&rft.au=Fischbeck%2C+Kenneth+H&rft.aulast=Fischbeck&rft.aufirst=Kenneth&rft.date=2016-03-01&rft.volume=58&rft.issue=3&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=1559-1166&rft_id=info:doi/10.1007%2Fs12031-015-0674-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s12031-015-0674-7 ER - TY - JOUR T1 - In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22. AN - 1770884854; 26810398 AB - In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 μM FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 μM was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after β-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the same metabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after β-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake. JF - The AAPS journal AU - Diao, Xingxing AU - Scheidweiler, Karl B AU - Wohlfarth, Ariane AU - Pang, Shaokun AU - Kronstrand, Robert AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, Maryland, 21224, USA. ; Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 58758, Linköping, Sweden. ; SCIEX, Redwood City, California, 94404, USA. ; Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Blvd, Suite 200 Room 05A721, Baltimore, Maryland, 21224, USA. mhuestis@intra.nida.nih.gov. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 455 EP - 464 VL - 18 IS - 2 KW - Cannabinoids KW - 0 KW - Plant Preparations KW - Index Medicus KW - hepatocyte metabolism KW - synthetic cannabinoid KW - FDU-PB-22 KW - FUB-PB-22 KW - high-resolution mass spectrometry KW - Hepatocytes -- drug effects KW - Microsomes, Liver -- metabolism KW - Humans KW - Microsomes, Liver -- drug effects KW - Hepatocytes -- metabolism KW - Plant Preparations -- chemistry KW - Cannabinoids -- urine KW - Cannabinoids -- chemistry KW - Plant Preparations -- urine KW - Plant Preparations -- pharmacology KW - Cannabinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770884854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+AAPS+journal&rft.atitle=In+Vitro+and+In+Vivo+Human+Metabolism+of+Synthetic+Cannabinoids+FDU-PB-22+and+FUB-PB-22.&rft.au=Diao%2C+Xingxing%3BScheidweiler%2C+Karl+B%3BWohlfarth%2C+Ariane%3BPang%2C+Shaokun%3BKronstrand%2C+Robert%3BHuestis%2C+Marilyn+A&rft.aulast=Diao&rft.aufirst=Xingxing&rft.date=2016-03-01&rft.volume=18&rft.issue=2&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=The+AAPS+journal&rft.issn=1550-7416&rft_id=info:doi/10.1208%2Fs12248-016-9867-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-05 N1 - Date revised - 2017-01-27 N1 - SuppNotes - Cited By: Drug Metab Dispos. 2012 Oct;40(10):2009-20 [22822035] Am J Emerg Med. 2012 Sep;30(7):1320.e5-7 [21802885] Hum Exp Toxicol. 2012 Oct;31(10):1006-11 [22859662] Drug Metab Dispos. 2012 Nov;40(11):2174-84 [22904561] Addiction. 2013 Mar;108(3):534-44 [22971158] Br J Pharmacol. 2013 Apr;168(7):1687-706 [23126373] Clin Chem. 2013 Nov;59(11):1638-48 [24014837] Anal Bioanal Chem. 2014 Feb;406(6):1763-80 [24518903] Drug Metab Dispos. 2014 Apr;42(4):774-81 [24468743] Drug Test Anal. 2012 Oct;4(10):745-53 [23042760] Forensic Sci Int. 2014 Nov;244:263-75 [25305529] Anal Bioanal Chem. 2015 Jan;407(3):883-97 [25224637] Drug Test Anal. 2015 Mar;7(3):199-206 [24802286] AAPS J. 2015 May;17(3):660-77 [25721194] Drug Test Anal. 2015 Jul;7(7):565-76 [25346527] Acta Pharmacol Sin. 2015 Dec;36(12):1520-7 [26567730] Bioanalysis. 2016;8(1):65-82 [26648097] Clin Chem. 2016 Jan;62(1):157-69 [26430074] Nat Prod Rep. 1999 Dec;16(6):697-709 [10641323] Life Sci. 2004 Jan 23;74(10):1307-15 [14697412] Pharm Res. 1997 Feb;14(2):152-5 [9090701] Chem Biol Interact. 1999 Jun 1;121(1):117-23 [10418974] Br J Pharmacol. 2006 Jan;147 Suppl 1:S163-71 [16402100] Pharmacol Rep. 2006 Jul-Aug;58(4):453-72 [16963792] Chem Biol Interact. 2007 May 20;168(1):2-15 [17208208] Assay Drug Dev Technol. 2008 Feb;6(1):121-9 [18336089] Aktuelle Urol. 2010 Jan;41 Suppl 1:S34-40 [20094950] Drug Metab Dispos. 2012 Mar;40(3):556-67 [22184458] Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 3;39(2):234-43 [22561602] N1 - Last updated - 2017-01-28 DO - http://dx.doi.org/10.1208/s12248-016-9867-4 ER - TY - JOUR T1 - Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss. AN - 1770221608; 26161573 AB - Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: -0.5 days (95% CI: -0.9, -0.1), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: -0.8 days (95% CI: -1.2, -0.4), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.02), p = 0.001]. BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle-specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. JF - Environmental health perspectives AU - Jukic, Anne Marie AU - Calafat, Antonia M AU - McConnaughey, D Robert AU - Longnecker, Matthew P AU - Hoppin, Jane A AU - Weinberg, Clarice R AU - Wilcox, Allen J AU - Baird, Donna D AD - Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Durham, North Carolina, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 321 EP - 328 VL - 124 IS - 3 KW - Benzhydryl Compounds KW - 0 KW - Environmental Pollutants KW - Phenols KW - Phthalic Acids KW - bisphenol A KW - MLT3645I99 KW - Index Medicus KW - Pregnancy Trimester, First KW - Humans KW - Adult KW - Female KW - Pregnancy KW - Environmental Pollutants -- toxicity KW - Phenols -- toxicity KW - Environmental Pollutants -- urine KW - Follicular Phase -- drug effects KW - Phthalic Acids -- urine KW - Phthalic Acids -- toxicity KW - Benzhydryl Compounds -- urine KW - Benzhydryl Compounds -- toxicity KW - Abortion, Spontaneous -- chemically induced KW - Abortion, Spontaneous -- urine KW - Luteal Phase -- drug effects KW - Phenols -- urine KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770221608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Urinary+Concentrations+of+Phthalate+Metabolites+and+Bisphenol+A+and+Associations+with+Follicular-Phase+Length%2C+Luteal-Phase+Length%2C+Fecundability%2C+and+Early+Pregnancy+Loss.&rft.au=Jukic%2C+Anne+Marie%3BCalafat%2C+Antonia+M%3BMcConnaughey%2C+D+Robert%3BLongnecker%2C+Matthew+P%3BHoppin%2C+Jane+A%3BWeinberg%2C+Clarice+R%3BWilcox%2C+Allen+J%3BBaird%2C+Donna+D&rft.aulast=Jukic&rft.aufirst=Anne&rft.date=2016-03-01&rft.volume=124&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1408164 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-02 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Environ Res. 2011 Jul;111(5):718-26 [21349512] Neurotoxicol Teratol. 2011 Sep-Oct;33(5):558-66 [21854843] Environ Sci Technol. 2012 Jan 3;46(1):477-85 [22085025] Occup Environ Med. 2005 Nov;62(11):806-18 [16234408] Toxicol Sci. 2006 Sep;93(1):189-95 [16763070] Reprod Toxicol. 2007 Feb;23(2):138-44 [17070006] J Womens Health (Larchmt). 2007 Nov;16(9):1340-7 [18001191] J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Dec 1;860(1):106-12 [17997365] Trends Genet. 2008 Feb;24(2):86-93 [18192063] Mutat Res. 2008 Mar 12;651(1-2):71-81 [18093867] Environ Res. 2008 Oct;108(2):260-7 [18774129] Reprod Toxicol. 2008 Oct;26(2):94-9 [18638542] Biol Reprod. 2009 May;80(5):1066-71 [19164168] Toxicol Lett. 2009 Aug 25;189(1):14-20 [19410640] Fertil Steril. 1999 Jan;71(1):40-9 [9935114] Am J Epidemiol. 1999 Mar 15;149(6):550-7 [10084244] Mol Hum Reprod. 2005 Jun;11(6):389-96 [15879462] Anal Chem. 2005 Aug 15;77(16):5407-13 [16097788] Environ Res. 2009 Aug;109(6):734-7 [19463991] Int J Hyg Environ Health. 2009 Sep;212(5):481-91 [19394271] J Expo Sci Environ Epidemiol. 2010 Mar;20(2):169-75 [19277068] Int J Androl. 2010 Apr;33(2):385-93 [20002217] Reprod Toxicol. 2010 Nov;30(3):393-400 [20599497] Environ Health Perspect. 2012 Mar;120(3):458-63 [22113848] Environ Health Perspect. 2012 May;120(5):739-45 [22262702] Hum Reprod. 2012 Dec;27(12):3583-92 [23014629] Crit Rev Toxicol. 2013 Mar;43(3):200-19 [23405971] Toxicol Appl Pharmacol. 2013 Apr 1;268(1):47-54 [23360888] Int J Hyg Environ Health. 2013 Nov;216(6):735-42 [23474103] Environ Health Perspect. 2014 Mar;122(3):235-41 [24425099] Environ Health Perspect. 2014 May;122(5):521-8 [24577876] Fertil Steril. 2014 May;101(5):1359-66 [24534276] Environ Sci Technol. 2014 Jun 17;48(12):7018-25 [24845688] Environ Health Perspect. 2015 Jul;123(7):705-11 [25782115] Reprod Toxicol. 2001 Jan-Feb;15(1):71-4 [11137380] Epidemiology. 2002 Nov;13(6):675-84 [12410009] Curr Biol. 2003 Apr 1;13(7):546-53 [12676084] Am J Epidemiol. 1986 Sep;124(3):470-80 [3740046] N Engl J Med. 1988 Jul 28;319(4):189-94 [3393170] Lancet. 1988 Dec 24-31;2(8626-8627):1453-6 [2904572] Am J Epidemiol. 1989 May;129(5):1072-8 [2705427] Epidemiology. 1990 Sep;1(5):382-5 [2078614] Stat Med. 1991 Feb;10(2):255-66 [2052803] Epidemiology. 1994 Sep;5(5):484-9 [7986861] N Engl J Med. 1995 Dec 7;333(23):1517-21 [7477165] Environ Health Perspect. 1997 Feb;105 Suppl 1:249-50 [9114309] Int J Cancer. 1998 Jan 19;75(2):290-4 [9462721] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1408164 ER - TY - JOUR T1 - Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice. AN - 1770221561; 26295903 AB - Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear. We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood. Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood. Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance. Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice. JF - Environmental health perspectives AU - Rodriguez, Karina F AU - Ungewitter, Erica K AU - Crespo-Mejias, Yasmin AU - Liu, Chang AU - Nicol, Barbara AU - Kissling, Grace E AU - Yao, Humphrey Hung-Chang AD - Reproductive Developmental Biology Group, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 336 EP - 343 VL - 124 IS - 3 KW - Arsenites KW - 0 KW - Blood Glucose KW - Drinking Water KW - Environmental Pollutants KW - Gonadotropins KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - Index Medicus KW - Vagina -- drug effects KW - Animals KW - Vagina -- physiology KW - Prenatal Exposure Delayed Effects -- metabolism KW - Blood Glucose -- metabolism KW - Drinking Water -- chemistry KW - Mice KW - Estrous Cycle -- drug effects KW - Pregnancy KW - Gonadotropins -- blood KW - Adipose Tissue -- drug effects KW - Prenatal Exposure Delayed Effects -- physiopathology KW - Female KW - Fertility -- drug effects KW - Sexual Maturation -- drug effects KW - Environmental Pollutants -- toxicity KW - Reproduction -- drug effects KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770221561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Effects+of+in+Utero+Exposure+to+Arsenic+during+the+Second+Half+of+Gestation+on+Reproductive+End+Points+and+Metabolic+Parameters+in+Female+CD-1+Mice.&rft.au=Rodriguez%2C+Karina+F%3BUngewitter%2C+Erica+K%3BCrespo-Mejias%2C+Yasmin%3BLiu%2C+Chang%3BNicol%2C+Barbara%3BKissling%2C+Grace+E%3BYao%2C+Humphrey+Hung-Chang&rft.aulast=Rodriguez&rft.aufirst=Karina&rft.date=2016-03-01&rft.volume=124&rft.issue=3&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1509703 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-02 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 2011 Feb 15;251(1):59-69 [21134390] Arch Toxicol. 2011 Jun;85(6):653-61 [20978746] Environ Health Perspect. 2013 Aug;121(8):971-7 [23757598] Environ Health Perspect. 2011 Aug;119(8):1104-9 [21592922] Cells Tissues Organs. 2011;194(2-4):261-7 [21555858] Toxicol Appl Pharmacol. 2011 Oct 15;256(2):146-53 [21851829] Exp Toxicol Pathol. 2012 Jan;64(1-2):25-30 [20580540] PLoS One. 2012;7(5):e38249 [22693606] Curr Diabetes Rev. 2012 May;8(3):155-61 [22497653] Environ Health. 2012;11:38 [22676249] Environ Health Perspect. 2012 Oct;120(10):1353-61 [22672778] Environ Health Perspect. 2013 Feb;121(2):244-50 [23221970] Int J Epidemiol. 2013 Aug;42(4):1077-86 [24062297] Toxicol Lett. 2014 Jan 3;224(1):130-40 [24157283] Ann Intern Med. 2013 Nov 19;159(10):649-59 [24061511] JAMA Intern Med. 2014 Feb 1;174(2):298 [24493600] Biol Reprod. 2014 Feb;90(2):24 [24337314] Reprod Toxicol. 2014 Apr;44:41-9 [24090629] Arch Toxicol. 2014 Aug;88(8):1619-29 [25005685] Cancer Epidemiol Biomarkers Prev. 2014 Aug;23(8):1529-38 [24859871] Mol Endocrinol. 2014 Aug;28(8):1329-36 [24992182] Environ Health Perspect. 2014 Oct;122(10):1059-65 [24927198] Sci Rep. 2014;4:6894 [25367288] PLoS One. 2015;10(3):e0119784 [25768847] Int J Obes (Lond). 2015 Apr;39(4):702-11 [25091727] BMJ. 1999 Nov 27;319(7222):1403-7 [10574856] Environ Health Perspect. 2000 Sep;108(9):847-51 [11017889] Toxicol Lett. 2003 Jan 31;137(1-2):3-13 [12505428] Toxicol Appl Pharmacol. 2003 Jan 1;186(1):7-17 [12583988] Carcinogenesis. 2004 Jan;25(1):133-41 [14514661] Toxicology. 2004 May 20;198(1-3):31-8 [15138027] Biol Reprod. 1983 Nov;29(4):924-31 [6640041] J Epidemiol Community Health. 1989 Sep;43(3):237-40 [2607302] Biol Reprod. 1993 Mar;48(3):669-73 [8452942] Endocrinology. 1997 Aug;138(8):3540-7 [9231809] Diabet Med. 1998 Mar;15(3):220-7 [9545123] Teratology. 1999 Jul;60(1):13-21 [10413334] Toxicol Sci. 1999 Sep;51(1):98-107 [10496681] Toxicol Appl Pharmacol. 2005 Feb 15;203(1):53-61 [15694464] Cancer Res. 2006 Feb 1;66(3):1337-45 [16452187] Toxicology. 2006 Jul 5;224(1-2):147-55 [16753250] Toxicol Appl Pharmacol. 2007 May 1;220(3):284-91 [17350061] Int J Obes (Lond). 2007 Jun;31(6):1023-9 [17299386] Toxicol Appl Pharmacol. 2007 Aug 1;222(3):271-80 [17306315] JAMA. 2008 Aug 20;300(7):814-22 [18714061] Toxicol Appl Pharmacol. 2009 Aug 15;239(1):29-36 [19446573] Pharmacol Biochem Behav. 2010 Apr;95(2):249-57 [20138905] Reprod Toxicol. 2010 Jun;29(3):279-85 [20025959] Int J Toxicol. 2010 May-Jun;29(3):291-6 [20448261] Ann N Y Acad Sci. 2010 Sep;1205:148-55 [20840267] Toxicol Sci. 2010 Oct;117(2):404-17 [20667999] Trends Endocrinol Metab. 2010 Nov;21(11):643-51 [20846876] Pharmacol Ther. 2013 Mar;137(3):331-40 [23178510] BMC Pharmacol Toxicol. 2013;14:13 [23419080] Comment In: Environ Health Perspect. 2016 Mar;124(3):A46-7 [26930461] Environ Health Perspect. 2016 Mar;124(3):A46 [26930347] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1509703 ER - TY - JOUR T1 - Environmental Pollution: An Under-recognized Threat to Children's Health, Especially in Low- and Middle-Income Countries. AN - 1770221406; 26930243 AB - Exposures to environmental pollutants during windows of developmental vulnerability in early life can cause disease and death in infancy and childhood as well as chronic, non-communicable diseases that may manifest at any point across the life span. Patterns of pollution and pollution-related disease change as countries move through economic development. Environmental pollution is now recognized as a major cause of morbidity and mortality in low- and middle-income countries (LMICs). According to the World Health Organization, pollution is responsible for 8.9 million deaths around the world each year; of these, 94% (8.4 million) are in LMICs. Toxic chemical pollution is growing into a major threat to children's health in LMICs. The disease and disability caused by environmental pollution have great economic costs, and these costs can undercut trajectories of national development. To combat pollution, improved programs of public health and environmental protection are needed in countries at every level of development. Pollution control strategies and technologies that have been developed in high-income countries must now be transferred to LMICs to assist these emerging economies to avoid the mistakes of the past. A new international clearinghouse is needed to define and track the health effects of pollution, quantify the economic costs of these effects, and direct much needed attention to environmental pollution as a risk factor for disease. JF - Environmental health perspectives AU - Suk, William A AU - Ahanchian, Hamid AU - Asante, Kwadwo Ansong AU - Carpenter, David O AU - Diaz-Barriga, Fernando AU - Ha, Eun-Hee AU - Huo, Xia AU - King, Malcolm AU - Ruchirawat, Mathuros AU - da Silva, Emerson R AU - Sly, Leith AU - Sly, Peter D AU - Stein, Renato T AU - van den Berg, Martin AU - Zar, Heather AU - Landrigan, Philip J AD - Hazardous Substances Research Branch, Superfund Research Program, National Institute for Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - A41 EP - A45 VL - 124 IS - 3 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - World Health Organization KW - Chronic Disease -- prevention & control KW - Risk Factors KW - Humans KW - Child KW - Environmental Exposure -- prevention & control KW - Morbidity KW - Environmental Pollution -- prevention & control KW - Child Health KW - Developing Countries KW - Environmental Pollutants -- adverse effects KW - Environmental Pollution -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1770221406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Environmental+Pollution%3A+An+Under-recognized+Threat+to+Children%27s+Health%2C+Especially+in+Low-+and+Middle-Income+Countries.&rft.au=Suk%2C+William+A%3BAhanchian%2C+Hamid%3BAsante%2C+Kwadwo+Ansong%3BCarpenter%2C+David+O%3BDiaz-Barriga%2C+Fernando%3BHa%2C+Eun-Hee%3BHuo%2C+Xia%3BKing%2C+Malcolm%3BRuchirawat%2C+Mathuros%3Bda+Silva%2C+Emerson+R%3BSly%2C+Leith%3BSly%2C+Peter+D%3BStein%2C+Renato+T%3Bvan+den+Berg%2C+Martin%3BZar%2C+Heather%3BLandrigan%2C+Philip+J&rft.aulast=Suk&rft.aufirst=William&rft.date=2016-03-01&rft.volume=124&rft.issue=3&rft.spage=A41&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1510517 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-03-02 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Am Coll Cardiol. 2000 Dec;36(7):2348-50 [11127483] Public Health Rep. 2000 Nov-Dec;115(6):521-9 [11354334] Environ Health Perspect. 2002 May;110(5):487-500 [12003752] Environ Health Perspect. 2002 Jun;110(6):563-9 [12055046] Pediatrics. 2002 Aug;110(2 Pt 1):315-22 [12165584] Environ Health Perspect. 2003 Aug;111(10):1340-7 [12896856] Br Med Bull. 2003;68:1-24 [14757707] N Engl J Med. 2004 Sep 9;351(11):1057-67 [15356303] Int J Epidemiol. 2004 Oct;33(5):1132-7 [15218010] J Am Acad Child Psychiatry. 1982 Mar;21(2):144-52 [7069080] Annu Rev Public Health. 1981;2:277-98 [7348554] N Engl J Med. 1996 Sep 12;335(11):783-9 [8703183] Environ Health Perspect. 1998 Jun;106 Suppl 3:875-80 [9646051] J Am Coll Nutr. 2004 Dec;23(6 Suppl):588S-595S [15640511] MMWR Morb Mortal Wkly Rep. 2006 Jan 6;54(51):1301-5 [16397457] Diabetes Care. 2007 Mar;30(3):622-8 [17327331] JAMA. 2008 Sep 17;300(11):1303-10 [18799442] Environ Toxicol Chem. 2013 Jan;32(1):32-48 [23136056] Lancet Oncol. 2013 Apr;14(4):287-8 [23499544] ILAR J. 2012;53(3-4):289-305 [23744968] PLoS One. 2013;8(9):e72788 [24023773] Vital Health Stat 3. 2012 Nov;(35):1-58 [24252609] Lancet Neurol. 2014 Mar;13(3):330-8 [24556010] MMWR Surveill Summ. 2014 Mar 28;63(2):1-21 [24670961] Endocr Rev. 2014 Aug;35(4):557-601 [24483949] Hormones (Athens). 2010 Jul-Sep;9(3):206-17 [20688618] Sci Am. 2010 Nov;303(5):92 [21033292] Environ Health Perspect. 2011 Mar;119(3):319-25 [21362590] Health Aff (Millwood). 2011 May;30(5):863-70 [21543421] Health Aff (Millwood). 2011 May;30(5):842-50 [21543423] Environ Health Perspect. 2011 Aug;119(8):1189-95 [21507776] Environ Health Perspect. 2011 Aug;119(8):1196-201 [21507777] Environ Health Perspect. 2012 Jan;120(1):38-43 [22222676] Environ Int. 2012 Apr;40:170-8 [21835469] JAMA. 2012 Sep 19;308(11):1113-21 [22990270] Environ Health Perspect. 2012 Oct;120(10):1353-61 [22672778] Environ Health Perspect. 2012 Nov;120(11):1527-31 [22949133] Mt Sinai J Med. 2012 Nov-Dec;79(6):632-40 [23239202] Lancet. 2012 Dec 15;380(9859):2055-8 [23245598] Lancet. 2012 Dec 15;380(9859):2095-128 [23245604] Lancet. 2012 Dec 15;380(9859):2224-60 [23245609] Lancet Glob Health. 2013 Dec;1(6):e350-61 [25104600] Lancet Glob Health. 2014 Mar;2(3):e129-30 [25102838] Environ Health Perspect. 2014 Sep;122(9):906-11 [24911630] Int J Hyg Environ Health. 2014 Nov;217(8):819-29 [24948353] Sci Total Environ. 2014 Nov 1;497-498:97-105 [25127444] Am J Epidemiol. 2014 Nov 15;180(10):968-77 [25324558] Ann Glob Health. 2014 Jul-Aug;80(4):257-62 [25459326] Ann Glob Health. 2014 Jul-Aug;80(4):286-95 [25459330] Environ Health Perspect. 2015 Mar;123(3):201-9 [25499717] World Hosp Health Serv. 2014;50(4):35-40 [25985560] JAMA. 2015 Jun 16;313(23):2319-20 [25996138] Lancet. 2015 Oct 10;386(10002):1429-31 [26466029] Lancet. 2015 Nov 28;386(10009):2145-91 [26321261] CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30 [26742998] Environ Health Perspect. 2016 May;124(5):550-5 [26418733] Environ Int. 2009 Aug;35(6):971-86 [19375165] Environ Health Perspect. 2009 Dec;117(12):1945-52 [20049216] Environ Health Perspect. 2010 Apr;118(4):565-71 [20106747] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1510517 ER - TY - JOUR T1 - UGT genotyping in belinostat dosing. AN - 1769983968; 26773202 AB - Certain genetic polymorphisms of UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) can reduce gene expression (*28, *60, *93) or activity (*6), thereby altering the pharmacokinetics, pharmacodynamics, and the risk of toxicities of UGT1A1 substrates, of which irinotecan is a widely-described example. This review presents an overview of the clinical effects of UGT1A1 polymorphisms on the pharmacology of UGT1A1 substrates, with a special focus on the novel histone deacetylase inhibitor belinostat. Belinostat, approved for the treatment of peripheral T-cell lymphoma, is primarily glucuronidated by UGT1A1. Recent preclinical and clinical data showed that UGT1A1*28 was associated with reduced glucuronidation in human liver microsomes, while in a retrospective analysis of a Phase I trial with patients receiving belinostat UGT1A1*60 was predominantly associated with increased belinostat plasma concentrations. Furthermore, both UGT1A1*28 and *60 variants were associated with increased incidence of thrombocytopenia and neutropenia. Using population pharmacokinetic analysis a 33% dose reduction has been proposed for patients carrying UGT1A1 variant alleles. Clinical effects of this genotype-based dosing recommendation is currently prospectively being investigated. Overall, the data suggest that UGT1A1 genotyping is useful for improving belinostat therapy. Published by Elsevier Ltd. JF - Pharmacological research AU - Goey, Andrew K L AU - Figg, William D AD - Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: andrew.goey@nih.gov. ; Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: figgw@helix.nih.gov. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 22 EP - 27 VL - 105 KW - Antineoplastic Agents KW - 0 KW - Histone Deacetylase Inhibitors KW - Hydroxamic Acids KW - Sulfonamides KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - belinostat KW - F4H96P17NZ KW - Index Medicus KW - Belinostat KW - Pharmacogenomics KW - Polymorphisms KW - UGT1A1 KW - Pharmacokinetics KW - Pharmacodynamics KW - Genotyping Techniques KW - Animals KW - Lymphoma, T-Cell, Peripheral -- genetics KW - Humans KW - Lymphoma, T-Cell, Peripheral -- drug therapy KW - Pharmacogenetics KW - Lymphoma, T-Cell, Peripheral -- metabolism KW - Glucuronosyltransferase -- genetics KW - Hydroxamic Acids -- therapeutic use KW - Histone Deacetylase Inhibitors -- pharmacology KW - Antineoplastic Agents -- administration & dosage KW - Polymorphism, Genetic KW - Antineoplastic Agents -- pharmacokinetics KW - Histone Deacetylase Inhibitors -- pharmacokinetics KW - Glucuronosyltransferase -- metabolism KW - Sulfonamides -- administration & dosage KW - Sulfonamides -- therapeutic use KW - Sulfonamides -- metabolism KW - Hydroxamic Acids -- administration & dosage KW - Histone Deacetylase Inhibitors -- therapeutic use KW - Histone Deacetylase Inhibitors -- administration & dosage KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Hydroxamic Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1769983968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=UGT+genotyping+in+belinostat+dosing.&rft.au=Goey%2C+Andrew+K+L%3BFigg%2C+William+D&rft.aulast=Goey&rft.aufirst=Andrew+K&rft.date=2016-03-01&rft.volume=105&rft.issue=&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=1096-1186&rft_id=info:doi/10.1016%2Fj.phrs.2016.01.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-11 N1 - Date created - 2016-03-01 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Clin Cancer Res. 2012 Apr 1;18(7):2099-107 [22307138] Br J Clin Pharmacol. 2009 Apr;67(4):437-44 [19371317] Biochem Biophys Res Commun. 2002 Mar 29;292(2):492-7 [11906189] Pharmacogenetics. 2002 Dec;12(9):725-33 [12464801] Drug Metab Dispos. 2003 May;31(5):589-95 [12695347] Blood. 2004 Jan 1;103(1):67-72 [12969965] Pharmacogenomics J. 2004;4(1):49-53 [14647407] J Clin Oncol. 2004 Apr 15;22(8):1382-8 [15007088] Clin Pharmacol Ther. 2004 Jun;75(6):501-15 [15179405] Pharmacogenetics. 1999 Oct;9(5):591-9 [10591539] J Natl Cancer Inst. 2000 Aug 2;92(15):1210-6 [10922406] J Biol Chem. 2000 Nov 17;275(46):36164-71 [10748067] Biochim Biophys Acta. 1998 Apr 28;1406(3):267-73 [9630669] Hepatology. 2001 May;33(5):1232-8 [11343253] J Clin Oncol. 2009 Apr 20;27(12):2091-6 [19188670] Int J Clin Oncol. 2009 Apr;14(2):136-42 [19390945] Clin Pharmacol Ther. 2009 Jun;85(6):623-7 [19279563] J Clin Oncol. 2009 May 20;27(15):2457-65 [19364970] N Engl J Med. 2009 Sep 3;361(10):947-57 [19692680] J Clin Oncol. 2010 Feb 10;28(5):866-71 [20038727] Cancer Chemother Pharmacol. 2013 Jun;71(6):1609-17 [23595344] Lancet Oncol. 2013 Jul;14(8):777-86 [23782814] Clin Pharmacokinet. 2013 Sep;52(9):713-25 [23677771] Invest New Drugs. 2013 Dec;31(6):1559-67 [24114122] Pharmacogenet Genomics. 2014 Mar;24(3):177-83 [24492252] Lancet Oncol. 2014 Jul;15(8):852-61 [24882434] J Clin Oncol. 2014 Aug 1;32(22):2328-34 [24958824] Clin Cancer Res. 2014 Nov 1;20(21):5392-402 [25189481] Lancet Oncol. 2015 Feb;16(2):141-51 [25589191] Drug Metab Pharmacokinet. 2014;29(6):449-54 [24898899] J Clin Pharmacol. 2016 Apr;56(4):461-73 [26313268] J Clin Pharmacol. 2016 Apr;56(4):450-60 [26637161] Br J Cancer. 2010 Apr 27;102(9):1371-7 [20389299] Lancet Oncol. 2010 Jun;11(6):521-9 [20493771] Clin Cancer Res. 2010 Aug 1;16(15):3832-42 [20562211] Clin Pharmacol Ther. 2011 May;89(5):662-73 [21412232] Br J Cancer. 2011 Jun 28;105(1):53-7 [21654688] Cancer Sci. 2011 Oct;102(10):1868-73 [21740478] J Biol Chem. 1991 Jan 15;266(2):1043-7 [1898728] N Engl J Med. 1995 Nov 2;333(18):1171-5 [7565971] Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8170-4 [9653159] Mol Pharmacol. 1998 Oct;54(4):647-54 [9765507] Biochem Mol Biol Int. 1998 Sep;46(1):21-6 [9784835] Pediatrics. 1999 Jun;103(6 Pt 1):1224-7 [10353933] Hum Mutat. 2005 Mar;25(3):325 [15712364] Pharmacogenet Genomics. 2005 Oct;15(10):677-85 [16141793] Pharmacogenet Genomics. 2006 May;16(5):321-9 [16609363] Hepatology. 2006 Nov;44(5):1324-32 [17058217] Eur J Cancer. 2007 Jan;43(1):55-63 [17095207] Pharmacogenet Genomics. 2007 Jul;17(7):497-504 [17558305] J Natl Cancer Inst. 2007 Sep 5;99(17):1290-5 [17728214] Leukemia. 2007 Nov;21(11):2311-5 [17611564] PLoS One. 2013;8(1):e54522 [23382909] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.phrs.2016.01.002 ER - TY - JOUR T1 - Alcoholic beverages, obesity, physical activity and other nutritional factors, and cancer risk: A review of the evidence. AN - 1768564593; 26811140 AB - Prevention is a priority in the fight against cancers, especially nutritional prevention. To update the levels of evidence of relationships between 10 nutritional factors and cancer risk, the scientific literature published from 2006 to 2014 was reviewed by an expert group. Data from 133 meta-analyses, pooled analyses or intervention trials were examined. Nearly 150 relationships between nutritional factors and cancer at various sites were evaluated. According to the evidence graded as convincing or probable, these factors were divided in two groups. Factors which increase the risk of cancer are alcoholic beverages, overweight and obesity, red meat and processed meat, salt and salted foods and beta-carotene supplements. Factors which decrease the risk of cancer are physical activity, fruits and vegetables, dietary fiber, dairy products and breastfeeding. Three main nutritional objectives should be attained to improve cancer prevention: to reduce alcoholic beverages consumption, to have a balanced and diversified diet and to be physically active. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. JF - Critical reviews in oncology/hematology AU - Latino-Martel, Paule AU - Cottet, Vanessa AU - Druesne-Pecollo, Nathalie AU - Pierre, Fabrice H F AU - Touillaud, Marina AU - Touvier, Mathilde AU - Vasson, Marie-Paule AU - Deschasaux, Mélanie AU - Le Merdy, Julie AU - Barrandon, Emilie AU - Ancellin, Raphaëlle AD - Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), Inserm U1153, Inra U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France; French Network on Nutrition and Cancer Research (NACRe Network), France(1). Electronic address: paule.martel@jouy.inra.fr. ; French Network on Nutrition and Cancer Research (NACRe Network), France(1); University Hospital of Dijon, Inserm U866, Digestive Cancer Registry of Burgundy, University of Burgundy, Dijon, France. ; Sorbonne Paris Cité Epidemiology and Statistics Research Centre (CRESS), Inserm U1153, Inra U1125, Cnam, Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France; French Network on Nutrition and Cancer Research (NACRe Network), France(1). ; French Network on Nutrition and Cancer Research (NACRe Network), France(1); UMR 1331 Toxalim, Inra, INP, UPS, Team 9 "Prevention, Promotion of Carcinogenesis by Food", Toulouse, France. ; French Network on Nutrition and Cancer Research (NACRe Network), France(1); Cancer and Environment Department, Léon-Bérard Cancer Centre, Lyon, France. ; French Network on Nutrition and Cancer Research (NACRe Network), France(1); Clermont Université, Université d'Auvergne, UFR Pharmacie; Inra, UMR 1019, CRNH Auvergne; Centre Jean-Perrin, CHU Gabriel-Montpied, Unité de Nutrition, Clermont-Ferrand, France. ; French National Cancer Institute, Department of Prevention, Boulogne-Billancourt, France. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 308 EP - 323 VL - 99 KW - Index Medicus KW - Breastfeeding KW - Obesity KW - Alcohol KW - Prevention KW - Beta-carotene supplements KW - Physical activity KW - Diet KW - Cancer KW - Humans KW - Motor Activity KW - Alcoholic Beverages -- adverse effects KW - Neoplasms -- prevention & control KW - Exercise KW - Obesity -- physiopathology KW - Neoplasms -- etiology KW - Obesity -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768564593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oncology%2Fhematology&rft.atitle=Alcoholic+beverages%2C+obesity%2C+physical+activity+and+other+nutritional+factors%2C+and+cancer+risk%3A+A+review+of+the+evidence.&rft.au=Latino-Martel%2C+Paule%3BCottet%2C+Vanessa%3BDruesne-Pecollo%2C+Nathalie%3BPierre%2C+Fabrice+H+F%3BTouillaud%2C+Marina%3BTouvier%2C+Mathilde%3BVasson%2C+Marie-Paule%3BDeschasaux%2C+M%C3%A9lanie%3BLe+Merdy%2C+Julie%3BBarrandon%2C+Emilie%3BAncellin%2C+Rapha%C3%ABlle&rft.aulast=Latino-Martel&rft.aufirst=Paule&rft.date=2016-03-01&rft.volume=99&rft.issue=&rft.spage=308&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncology%2Fhematology&rft.issn=1879-0461&rft_id=info:doi/10.1016%2Fj.critrevonc.2016.01.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-18 N1 - Date created - 2016-02-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.critrevonc.2016.01.002 ER - TY - JOUR T1 - Comparison of toxicity following different conditioning regimens (busulfan/melphalan and carboplatin/etoposide/melphalan) for advanced stage neuroblastoma: Experience of two transplant centers. AN - 1768558443; 26614402 AB - The outcome for advanced neuroblastoma has improved with combined modality therapy: induction chemotherapy, surgery, and consolidation with high-dose chemotherapy/autologous HSCT, followed by local radiation, cisretinoic acid, and recently antibody therapy. In the United States, the most common conditioning regimen is CEM, while in Europe/Middle East, Bu/Mel has been widely used; it remains unclear which regimen has the best outcome. Assess renal, hepatic, and infectious toxicity through Day+100 in 2 different regimens. Retrospective comparison between CEM-DFCHCC Boston and Bu/Mel- CCHE-57357. Thirty-five patients, median age 4, in Boston (2007-2011) and 38 patients, median age 3, in Cairo (2009-2011). Renal toxicity; creatinine was significantly higher in CEM than Bu/Mel: 57% (median day+90) vs. 29% (median>day+100), p = 0.004. One CEM patient died from renal dialysis at day+19. Hepatic toxicity was significantly higher in CEM than Bu/Mel: 80% (median day+26) vs. 58% (median day+60), p = 0.04. In infectious complications with CEM 14%, bacteremia (n = 4) and fungemia (n = 1), 3 had culture-negative sepsis requiring vasopressors. With Bu/Mel 18%, bacteremia (n = 7), none required pressors, p = 0.4. Bu/Mel was associated with less acute hepatic and renal toxicity and thus may be preferable for preserving organ functions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. JF - Pediatric transplantation AU - Elborai, Yasser AU - Hafez, Hanafy AU - Moussa, Emad A AU - Hammad, Mahmoud AU - Hussein, Hany AU - Lehmann, Leslie AU - Elhaddad, Alaa AD - Pediatric Oncology Department, National Cancer Institute (NCI), Cairo University, Cairo, Egypt. ; Pediatric Oncology and Bone Marrow Transplant Department, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt. ; Pediatric Stem Cell Transplantation Unit, Dana Farber/Children's Hospital Cancer Care Center, Boston, MA, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 284 EP - 289 VL - 20 IS - 2 KW - Antineoplastic Agents KW - 0 KW - Etoposide KW - 6PLQ3CP4P3 KW - Carboplatin KW - BG3F62OND5 KW - Busulfan KW - G1LN9045DK KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - carboplatin KW - renal toxicity KW - autologous hematopoietic stem cell transplantation (HSCT) KW - busulfan/melphalan (Bu/Mel) KW - melphalan (CEM) KW - neuroblastoma KW - etoposide KW - Infant KW - Egypt KW - Antineoplastic Agents -- administration & dosage KW - Humans KW - Treatment Outcome KW - Retrospective Studies KW - Infant, Newborn KW - Child KW - Boston KW - Adolescent KW - Child, Preschool KW - Busulfan -- administration & dosage KW - Brain Neoplasms -- therapy KW - Neuroblastoma -- therapy KW - Brain Neoplasms -- drug therapy KW - Neuroblastoma -- drug therapy KW - Etoposide -- administration & dosage KW - Melphalan -- administration & dosage KW - Transplantation Conditioning -- methods KW - Carboplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768558443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+transplantation&rft.atitle=Comparison+of+toxicity+following+different+conditioning+regimens+%28busulfan%2Fmelphalan+and+carboplatin%2Fetoposide%2Fmelphalan%29+for+advanced+stage+neuroblastoma%3A+Experience+of+two+transplant+centers.&rft.au=Elborai%2C+Yasser%3BHafez%2C+Hanafy%3BMoussa%2C+Emad+A%3BHammad%2C+Mahmoud%3BHussein%2C+Hany%3BLehmann%2C+Leslie%3BElhaddad%2C+Alaa&rft.aulast=Elborai&rft.aufirst=Yasser&rft.date=2016-03-01&rft.volume=20&rft.issue=2&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=Pediatric+transplantation&rft.issn=1399-3046&rft_id=info:doi/10.1111%2Fpetr.12638 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-30 N1 - Date created - 2016-02-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/petr.12638 ER - TY - JOUR T1 - Technetium Tc 99m sulfur colloid phenotypic probe for the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin in women with ovarian cancer. AN - 1768556812; 26822231 AB - Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells. We investigated TSC as a phenotypic probe of PLD pharmacokinetics and pharmacodynamics in women with epithelial ovarian cancer. TSC 10 mCi IVP was administered and followed by dynamic planar and SPECT/CT imaging and blood pharmacokinetics sampling. PLD 30-40 mg/m(2) IV was administered with or without carboplatin, followed by plasma pharmacokinetics sampling. There was a linear relationship between TSC clearance and encapsulated doxorubicin clearance (R(2) = 0.61, p = 0.02), particularly in patients receiving PLD alone (R(2) = 0.81, p = 0.04). There was a positive relationship (ρ = 0.81, p = 0.01) between maximum grade palmar-plantar erythrodysesthesia toxicity developed and estimated encapsulated doxorubicin concentration in hands. TSC is a phenotypic probe for PLD pharmacokinetics and pharmacodynamics and may be used to individualize PLD therapy in ovarian cancer and for other nanoparticles in development. JF - Cancer chemotherapy and pharmacology AU - Giovinazzo, Hugh AU - Kumar, Parag AU - Sheikh, Arif AU - Brooks, Kristina M AU - Ivanovic, Marija AU - Walsh, Mark AU - Caron, Whitney P AU - Kowalsky, Richard J AU - Song, Gina AU - Whitlow, Ann AU - Clarke-Pearson, Daniel L AU - Brewster, Wendy R AU - Van Le, Linda AU - Zamboni, Beth A AU - Bae-Jump, Victoria AU - Gehrig, Paola A AU - Zamboni, William C AD - Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill-Eshelman School of Pharmacy, 120 Mason Farm Road, Suite 1013, CB 7361, Chapel Hill, NC, 27599-7361, USA. ; UNC School of Medicine, 321 S. Columbia St., Chapel Hill, NC, 27599, USA. ; Clinical Pharmacokinetics Research Laboratory, National Institutes of Health, Clinical Center Pharmacy Department, 10 Center Drive Bldg. 10, 1C-240G, Bethesda, MD, 20892, USA. ; Department of Mathematics, Carlow University, Pittsburgh, PA, USA. ; Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill-Eshelman School of Pharmacy, 120 Mason Farm Road, Suite 1013, CB 7361, Chapel Hill, NC, 27599-7361, USA. zamboni@email.unc.edu. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 565 EP - 573 VL - 77 IS - 3 KW - Antibiotics, Antineoplastic KW - 0 KW - Radiopharmaceuticals KW - liposomal doxorubicin KW - Polyethylene Glycols KW - 30IQX730WE KW - Technetium Tc 99m Sulfur Colloid KW - 556Q0P6PB1 KW - Doxorubicin KW - 80168379AG KW - Carboplatin KW - BG3F62OND5 KW - Index Medicus KW - TSC KW - Ovarian cancer KW - Phenotypic probe KW - Liposomes KW - Pharmacokinetics KW - Pharmacodynamics KW - PEGylated liposomal doxorubicin KW - Tomography, X-Ray Computed -- methods KW - Tomography, Emission-Computed, Single-Photon -- methods KW - Hand-Foot Syndrome -- etiology KW - Humans KW - Polyethylene Glycols -- pharmacokinetics KW - Aged KW - Polyethylene Glycols -- adverse effects KW - Polyethylene Glycols -- administration & dosage KW - Carboplatin -- administration & dosage KW - Phenotype KW - Adult KW - Middle Aged KW - Female KW - Doxorubicin -- pharmacokinetics KW - Doxorubicin -- analogs & derivatives KW - Doxorubicin -- adverse effects KW - Antibiotics, Antineoplastic -- administration & dosage KW - Radiopharmaceuticals -- administration & dosage KW - Neoplasms, Glandular and Epithelial -- drug therapy KW - Technetium Tc 99m Sulfur Colloid -- administration & dosage KW - Ovarian Neoplasms -- pathology KW - Doxorubicin -- administration & dosage KW - Antibiotics, Antineoplastic -- pharmacokinetics KW - Ovarian Neoplasms -- drug therapy KW - Antibiotics, Antineoplastic -- adverse effects KW - Neoplasms, Glandular and Epithelial -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768556812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Technetium+Tc+99m+sulfur+colloid+phenotypic+probe+for+the+pharmacokinetics+and+pharmacodynamics+of+PEGylated+liposomal+doxorubicin+in+women+with+ovarian+cancer.&rft.au=Giovinazzo%2C+Hugh%3BKumar%2C+Parag%3BSheikh%2C+Arif%3BBrooks%2C+Kristina+M%3BIvanovic%2C+Marija%3BWalsh%2C+Mark%3BCaron%2C+Whitney+P%3BKowalsky%2C+Richard+J%3BSong%2C+Gina%3BWhitlow%2C+Ann%3BClarke-Pearson%2C+Daniel+L%3BBrewster%2C+Wendy+R%3BVan+Le%2C+Linda%3BZamboni%2C+Beth+A%3BBae-Jump%2C+Victoria%3BGehrig%2C+Paola+A%3BZamboni%2C+William+C&rft.aulast=Giovinazzo&rft.aufirst=Hugh&rft.date=2016-03-01&rft.volume=77&rft.issue=3&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=1432-0843&rft_id=info:doi/10.1007%2Fs00280-015-2945-y LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-26 N1 - Date created - 2016-02-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00280-015-2945-y ER - TY - JOUR T1 - Methamphetamine induces a rapid increase of intracellular Ca(++) levels in neurons overexpressing GCaMP5. AN - 1768556573; 25377775 AB - In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular Ca(++) (Ca(++) i) signals were examined in real time in primary cortical neurons overexpressing an intracellular Ca(++) probe, GCaMP5, by adeno-associated viral (AAV) serotype 1. Binding of Ca(++) to GCaMP increased green fluorescence intensity in cells. Both Meth and Glu induced a rapid increase in Ca(++) i, which was blocked by MK801, suggesting that Meth enhanced Ca(++) i through Glu receptor in neurons. The Meth-mediated Ca(++) signal was also blocked by Mg(++) , low Ca(++) or the L-type Ca(++) channel inhibitor nifedipine. The ryanodine receptor inhibitor dantrolene did not alter the initial Ca(++) influx but partially reduced the peak of Ca(++) i. These data suggest that Meth enhanced Ca(++) influx through membrane Ca(++) channels, which then triggered the release of Ca(++) from the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the parietal cortex of adult rats. Administration of Meth enhanced fluorescence in the ipsilateral cortex. Using immunohistochemistry, Meth-induced green fluorescence was found in the NeuN-containing cells in the cortex, suggesting that Meth increased Ca(++) in neurons in vivo. In conclusion, we have used in vitro and in vivo techniques to demonstrate a rapid increase of Ca(++) i by Meth in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral responses and neurotoxicity through Ca(++) i, modulation of Ca(++) i may be useful to reduce Meth-related reactions. © 2014 Society for the Study of Addiction. JF - Addiction biology AU - Yu, Seong-Jin AU - Wu, Kou-Jen AU - Bae, Eun K AU - Hsu, Man-Jung AU - Richie, Christopher T AU - Harvey, Brandon K AU - Wang, Yun AD - Center for Neuropsychiatric Research, National Health Research Institutes, Taiwan. ; National Institute on Drug Abuse, NIH, Baltimore, MD, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 255 EP - 266 VL - 21 IS - 2 KW - Calcium Channel Blockers KW - 0 KW - Calcium Channels KW - Calcium-Binding Proteins KW - Calmodulin KW - Dopamine Agents KW - Excitatory Amino Acid Antagonists KW - Indicators and Reagents KW - Muscle Relaxants, Central KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Glutamic Acid KW - 3KX376GY7L KW - Methamphetamine KW - 44RAL3456C KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Dantrolene KW - F64QU97QCR KW - Nifedipine KW - I9ZF7L6G2L KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - magnesium KW - methamphetamine KW - glutamate KW - Calmodulin -- metabolism KW - Animals KW - Analysis of Variance KW - Cerebral Cortex -- drug effects KW - Dantrolene -- pharmacology KW - Indicators and Reagents -- pharmacology KW - Muscle Relaxants, Central -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Nifedipine -- pharmacology KW - Rats, Sprague-Dawley KW - Calcium Channel Blockers -- pharmacology KW - Cells, Cultured KW - Calcium Channels -- drug effects KW - Signal Transduction -- drug effects KW - Calcium-Binding Proteins -- metabolism KW - Green Fluorescent Proteins -- metabolism KW - Male KW - Female KW - Calcium -- metabolism KW - Methamphetamine -- pharmacokinetics KW - Neurons -- metabolism KW - Dopamine Agents -- pharmacology KW - Glutamic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768556573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+biology&rft.atitle=Methamphetamine+induces+a+rapid+increase+of+intracellular+Ca%28%2B%2B%29+levels+in+neurons+overexpressing+GCaMP5.&rft.au=Yu%2C+Seong-Jin%3BWu%2C+Kou-Jen%3BBae%2C+Eun+K%3BHsu%2C+Man-Jung%3BRichie%2C+Christopher+T%3BHarvey%2C+Brandon+K%3BWang%2C+Yun&rft.aulast=Yu&rft.aufirst=Seong-Jin&rft.date=2016-03-01&rft.volume=21&rft.issue=2&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Addiction+biology&rft.issn=1369-1600&rft_id=info:doi/10.1111%2Fadb.12193 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-20 N1 - Date created - 2016-02-25 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/adb.12193 ER - TY - JOUR T1 - Effects of the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) on cocaine versus food choice and extended-access cocaine intake in rhesus monkeys. AN - 1768555074; 25581305 AB - The dynorphin/kappa opioid receptor (KOR) system has been implicated as one potential neurobiological modulator of the abuse-related effects of cocaine and as a potential target for medications development. This study determined effects of the KOR antagonist nor-binaltorphimine (nor-BNI) on cocaine self-administration under a novel procedure that featured two daily components: (1) a 2-hour 'choice' component (9:00-11:00 am) when monkeys could choose between food pellets and cocaine injections (0-0.1 mg/kg per injection, intravenous) and (2) a 20-hour 'extended-access' component (noon to 8:00 am) when cocaine (0.1 mg/kg per injection) was available under a fixed-ratio schedule to promote high daily cocaine intakes. Rhesus monkeys (n = 4) were given 14 days of exposure to the choice + extended-access procedure then treated with nor-BNI (3.2 or 10.0 mg/kg, intramuscular), and cocaine choice and extended-access cocaine intake were evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained both a dose-dependent increase in cocaine choice during choice components and a high level of cocaine intake during extended-access components. Neither 3.2 nor 10 mg/kg nor-BNI significantly altered cocaine choice or extended-access cocaine intake. In two additional monkeys, nor-BNI also had no effect on cocaine choice or extended-access cocaine intake when it was administered at the beginning of exposure to the extended-access components. Overall, these results do not support a major role for the dynorphin/KOR system in modulating cocaine self-administration under these conditions in non-human primates nor do they support the clinical utility of KOR antagonists as a pharmacotherapeutic strategy for cocaine addiction. © 2015 Society for the Study of Addiction. JF - Addiction biology AU - Hutsell, Blake A AU - Cheng, Kejun AU - Rice, Kenner C AU - Negus, Sidney Stevens AU - Banks, Matthew L AD - Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA. ; Chemical Biology Branch, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 360 EP - 373 VL - 21 IS - 2 KW - Narcotic Antagonists KW - 0 KW - Receptors, Opioid, kappa KW - norbinaltorphimine KW - 36OOQ86QM1 KW - Naltrexone KW - 5S6W795CQM KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - rhesus monkey KW - nor-binaltorphimine KW - choice KW - cocaine KW - Addiction KW - kappa opioid receptor KW - Drug-Seeking Behavior -- drug effects KW - Animals KW - Analysis of Variance KW - Self Administration KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Conditioning, Operant KW - Macaca mulatta KW - Male KW - Naltrexone -- analogs & derivatives KW - Naltrexone -- pharmacology KW - Cocaine -- pharmacology KW - Narcotic Antagonists -- pharmacology KW - Food Preferences -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768555074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+biology&rft.atitle=Effects+of+the+kappa+opioid+receptor+antagonist+nor-binaltorphimine+%28nor-BNI%29+on+cocaine+versus+food+choice+and+extended-access+cocaine+intake+in+rhesus+monkeys.&rft.au=Hutsell%2C+Blake+A%3BCheng%2C+Kejun%3BRice%2C+Kenner+C%3BNegus%2C+Sidney+Stevens%3BBanks%2C+Matthew+L&rft.aulast=Hutsell&rft.aufirst=Blake&rft.date=2016-03-01&rft.volume=21&rft.issue=2&rft.spage=360&rft.isbn=&rft.btitle=&rft.title=Addiction+biology&rft.issn=1369-1600&rft_id=info:doi/10.1111%2Fadb.12206 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-20 N1 - Date created - 2016-02-25 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Neuropsychopharmacology. 2003 May;28(5):919-31 [12637948] Behav Pharmacol. 2011 Dec;22(8):824-36 [22015808] Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):189-93 [22015480] Addict Biol. 2012 Mar;17(2):378-91 [21955224] Sci Transl Med. 2012 Aug 8;4(146):146ra110 [22875830] Trends Neurosci. 2012 Oct;35(10):587-96 [22709632] Neuropsychopharmacology. 2012 Nov;37(12):2605-14 [22871910] Neuropsychopharmacology. 2013 Feb;38(3):395-404 [22968813] J Pharmacol Exp Ther. 2013 Feb;344(2):329-38 [23211363] Cold Spring Harb Perspect Med. 2013 Feb;3(2):a012005 [23293139] J Exp Anal Behav. 2013 Mar;99(2):211-33 [23319458] Drug Alcohol Depend. 2013 Aug 1;131(3):204-13 [23726979] Neuropsychopharmacology. 2013 Dec;38(13):2698-707 [23893022] Psychopharmacology (Berl). 2014 Jul;231(14):2751-8 [24481567] Brain Res. 2003 Aug 22;982(1):38-44 [12915238] Psychopharmacology (Berl). 2004 Apr;172(4):422-9 [14712335] Psychopharmacology (Berl). 2004 Nov;176(2):204-13 [15112031] Pharmacol Rev. 1975 Sep;27(3):343-55 [817306] Drug Alcohol Depend. 1981 Aug;8(1):69-78 [7297414] Am J Psychiatry. 1990 Jun;147(6):719-24 [2343913] Psychopharmacology (Berl). 1991;105(2):169-74 [1796123] Behav Pharmacol. 2000 Feb;11(1):87-91 [10821213] Brain Res. 2002 Jan 11;924(2):141-50 [11750899] Neuropsychopharmacology. 2002 Jul;27(1):35-46 [12062905] Synapse. 1991 Sep;9(1):60-5 [1796352] Brain Res. 1992 Oct 16;593(2):314-8 [1450939] Synapse. 1993 Apr;13(4):357-69 [7683144] Synapse. 1993 Jun;14(2):169-77 [8101394] J Pharmacol Exp Ther. 1993 Nov;267(2):896-903 [8246165] J Pharmacol Exp Ther. 1993 Dec;267(3):1269-76 [8263790] Eur J Pharmacol. 1994 May 2;256(3):335-8 [7913893] Neurosci Lett. 1994 Nov 7;181(1-2):57-60 [7898771] Brain Res Bull. 1995;37(5):523-7 [7633900] Brain Res. 1995 May 29;681(1-2):147-52 [7552272] Neuropsychopharmacology. 1996 Jun;14(6):375-424 [8726752] Brain Res Mol Brain Res. 1996 May;38(1):71-6 [8737669] Nature. 1997 Apr 24;386(6627):830-3 [9126741] J Pharmacol Exp Ther. 1997 Jul;282(1):44-55 [9223538] J Pharmacol Exp Ther. 1998 May;285(2):595-601 [9580603] J Pharmacol Exp Ther. 1998 Jul;286(1):362-75 [9655881] Psychopharmacology (Berl). 1999 Mar;143(1):102-10 [10227086] Eur J Pharmacol. 2005 Dec 5;526(1-3):9-20 [16263108] J Pharmacol Exp Ther. 2006 Jan;316(1):440-7 [16223871] PLoS One. 2007;2(8):e698 [17668074] Addiction. 2007 Dec;102(12):1888-9 [18031424] Psychopharmacology (Berl). 2008 Jan;196(1):63-70 [17899019] Drug Alcohol Depend. 2008 Jul 1;96(1-2):1-15 [18436394] Neuropharmacology. 2008 Jul;55(1):41-6 [18538358] Psychopharmacology (Berl). 2008 Aug;199(3):403-19 [18283437] Psychopharmacology (Berl). 2009 Jun;204(3):523-9 [19221719] Psychopharmacology (Berl). 2009 Aug;205(2):237-47 [19365621] Psychopharmacology (Berl). 2009 Sep;205(4):565-75 [19484223] Am J Psychiatry. 2009 Oct;166(10):1170-7 [19723785] Neuropsychopharmacology. 2010 Jan;35(2):493-504 [19776729] Psychopharmacology (Berl). 2010 Jun;210(2):121-35 [20352414] PLoS Biol. 2010;8(6):e1000412 [20613859] PLoS One. 2010;5(7):e11592 [20676364] Am J Psychiatry. 2011 Jun;168(6):634-41 [21406463] Eur J Neurosci. 2003 May;17(10):2212-8 [12786988] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/adb.12206 ER - TY - JOUR T1 - Crystal structures of MBP fusion proteins. AN - 1767624429; 26682969 AB - Although chaperone-assisted protein crystallization remains a comparatively rare undertaking, the number of crystal structures of polypeptides fused to maltose-binding protein (MBP) that have been deposited in the Protein Data Bank (PDB) has grown dramatically during the past decade. Altogether, 102 fusion protein structures were detected by Basic Local Alignment Search Tool (BLAST) analysis. Collectively, these structures comprise a range of sizes, space groups, and resolutions that are typical of the PDB as a whole. While most of these MBP fusion proteins were equipped with short inter-domain linkers to increase their rigidity, fusion proteins with long linkers have also been crystallized. In some cases, surface entropy reduction mutations in MBP appear to have facilitated the formation of crystals. A comparison of the structures of fused and unfused proteins, where both are available, reveals that MBP-mediated structural distortions are very rare. © 2016 The Protein Society. JF - Protein science : a publication of the Protein Society AU - Waugh, David S AD - Protein Engineering Section, Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Frederick, Maryland, 21702-1201. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 559 EP - 571 VL - 25 IS - 3 KW - Maltose-Binding Proteins KW - 0 KW - Molecular Chaperones KW - Peptides KW - Recombinant Fusion Proteins KW - Index Medicus KW - chaperone-assisted crystallization KW - MBP fusion protein KW - crystallization chaperone KW - maltose-binding protein KW - crystallization tag KW - surface entropy reduction mutagenesis KW - Animals KW - Molecular Chaperones -- genetics KW - Molecular Chaperones -- chemistry KW - Molecular Chaperones -- isolation & purification KW - Models, Molecular KW - Humans KW - Crystallography -- methods KW - Cloning, Molecular -- methods KW - Amino Acid Sequence KW - Mutation KW - Entropy KW - Protein Conformation KW - Maltose-Binding Proteins -- genetics KW - Recombinant Fusion Proteins -- isolation & purification KW - Recombinant Fusion Proteins -- genetics KW - Maltose-Binding Proteins -- chemistry KW - Crystallization -- methods KW - Peptides -- chemistry KW - Maltose-Binding Proteins -- isolation & purification KW - Peptides -- genetics KW - Peptides -- isolation & purification KW - Recombinant Fusion Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767624429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Crystal+structures+of+MBP+fusion+proteins.&rft.au=Waugh%2C+David+S&rft.aulast=Waugh&rft.aufirst=David&rft.date=2016-03-01&rft.volume=25&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=1469-896X&rft_id=info:doi/10.1002%2Fpro.2863 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-02-22 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited 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AN - 1767624306; 26643807 AB - We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab for recurrent malignant gliomas and explored serologic correlates. We enrolled 81 patients with glioblastomas (GBM, n = 40) and anaplastic gliomas (AG, n = 41). Patients received enzastaurin as a loading dose of 1125 mg, followed by 500 or 875 mg daily for patients on non-enzyme-inducing or enzyme-inducing antiepileptics, respectively. Patients received bevacizumab 10 mg/kg intravenously biweekly. Clinical evaluations were repeated every 4 weeks. Magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median overall survival was 7.5 and 12.4 months for glioblastomas and anaplastic glioma cohorts, with median progression-free survivals of 2.0 and 4.4 months, respectively. Of GBM patients, 3/40 (7.5 %) were not evaluable, while 8/37 (22 %) had partial or complete response and 20/37 (54 %) had stable disease for 2+ months. Of the 39 evaluable AG patients, 18 (46 %) had an objective response, and 16 (41 %) had stable disease for 2+ months. The most common grade 3+ toxicities were lymphopenia (15 %), hypophosphatemia (8.8 %) and thrombotic events (7.5 %). Two (2.5 %) GBM patients died suddenly; another death (1.3 %) occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did not correlate with treatment response. A minimally important improvement in health-related quality of life was self-reported in 7-9/24 (29.2-37.5 %). Early response based on Levin criteria was significantly associated with significantly longer progression free survival for glioblastomas. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy. JF - Journal of neuro-oncology AU - Odia, Yazmin AU - Iwamoto, Fabio M AU - Moustakas, Argirios AU - Fraum, Tyler J AU - Salgado, Carlos A AU - Li, Aiguo AU - Kreisl, Teri N AU - Sul, Joohee AU - Butman, John A AU - Fine, Howard A AD - Neuro-Oncology Division, Neurological Institute of New York, Columbia University College of Physicians and Surgeons, 710 West 168th Street, 9th Floor, NI 9-017, New York, NY, 10032, USA. yo2240@cumc.columbia.edu. ; Neuro-Oncology Division, Neurological Institute of New York, Columbia University College of Physicians and Surgeons, 710 West 168th Street, 9th Floor, NI 9-017, New York, NY, 10032, USA. ; University of Vermont Medical Center, 89 South Williams Street, Burlington, VT, 05401, USA. ; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, 510 S. Kingshighway Blvd., Saint Louis, MO, 63110, USA. ; University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD, 21201, USA. ; Center for Cancer Research, National Cancer Institute, Building 37, Room 1142, Bethesda, MD, 20892, USA. ; Federal Drug Administration, 10903 New Hampshire Ave, Bldg WO22 Rm 2331, Silver Spring, MD, 20993, USA. ; Department of Radiology, National Institutes of Health Clinical Center, Building 10, Clinical Center 10 Center Drive, MSC 1074, Bethesda, MD, 20892, USA. ; Division of Neuro-Oncology, Director of the Brain Tumor Center, New York-Presbyterian Hospital/Weill Cornell Medical Center, 1305 York Avenue, 9th Floor, New York, NY, 10021, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 127 EP - 135 VL - 127 IS - 1 KW - Indoles KW - 0 KW - Bevacizumab KW - 2S9ZZM9Q9V KW - Glycogen Synthase Kinase 3 KW - EC 2.7.11.26 KW - enzastaurin KW - UC96G28EQF KW - Index Medicus KW - Glioblastoma KW - Trial KW - Enzastaurin KW - Glioma KW - Neoplasm Staging KW - Humans KW - Prognosis KW - Quality of Life KW - Aged KW - Survival Rate KW - Adult KW - Indoles -- administration & dosage KW - Follow-Up Studies KW - Glycogen Synthase Kinase 3 -- metabolism KW - Middle Aged KW - Bevacizumab -- administration & dosage KW - Leukocytes, Mononuclear -- drug effects KW - Female KW - Male KW - Brain Neoplasms -- pathology KW - Glioma -- pathology KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Neoplasm Recurrence, Local -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Neoplasm Recurrence, Local -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767624306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuro-oncology&rft.atitle=A+phase+II+trial+of+enzastaurin+%28LY317615%29+in+combination+with+bevacizumab+in+adults+with+recurrent+malignant+gliomas.&rft.au=Odia%2C+Yazmin%3BIwamoto%2C+Fabio+M%3BMoustakas%2C+Argirios%3BFraum%2C+Tyler+J%3BSalgado%2C+Carlos+A%3BLi%2C+Aiguo%3BKreisl%2C+Teri+N%3BSul%2C+Joohee%3BButman%2C+John+A%3BFine%2C+Howard+A&rft.aulast=Odia&rft.aufirst=Yazmin&rft.date=2016-03-01&rft.volume=127&rft.issue=1&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuro-oncology&rft.issn=1573-7373&rft_id=info:doi/10.1007%2Fs11060-015-2020-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-02-22 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT00586508; ClinicalTrials.gov N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11060-015-2020-x ER - TY - JOUR T1 - Evaluation of pedometry as a patient-centered outcome in patients undergoing hematopoietic cell transplant (HCT): a comparison of pedometry and patient reports of symptoms, health, and quality of life. AN - 1767071526; 26577763 AB - We evaluated pedometry as a novel patient-centered outcome because it enables passive continuous assessment of activity and may provide information about the consequences of symptomatic toxicity complementary to self-report. Adult patients undergoing hematopoietic cell transplant (HCT) wore pedometers and completed PRO assessments during transplant hospitalization (4 weeks) and 4 weeks post-discharge. Patient reports of symptomatic treatment toxicities (single items from PRO-CTCAE, http://healthcaredelivery.cancer.gov/pro-ctcae ) and symptoms, physical health, mental health, and quality of life (PROMIS(®) Global-10, http://nih.promis.org ), assessed weekly with 7-day recall on Likert scales, were compared individually with pedometry data, summarized as average daily steps per week, using linear mixed models. Thirty-two patients [mean age 55 (SD = 14), 63 % male, 84 % white, 56 % autologous, 43 % allogeneic] completed a mean 4.6 (SD = 1.5, range 1-8) evaluable assessments. Regression model coefficients (β) indicated within-person decrements in average daily steps were associated with increases in pain (β = -852; 852 fewer steps per unit increase in pain score, p < 0.001), fatigue (β = -886, p < 0.001), vomiting (β = -518, p < 0.01), shaking/chills (β = -587, p < 0.01), diarrhea (β = -719, p < 0.001), shortness of breath (β = -1018, p < 0.05), reduction in carrying out social activities (β = 705, p < 0.01) or physical activities (β = 618, p < 0.01), and global physical health (β = 101, p < 0.001), but not global mental health or quality of life. In this small sample of HCT recipients, more severe symptoms, impaired physical health, and restrictions in the performance of usual daily activities were associated with statistically significant decrements in objectively measured daily steps. Pedometry may be a valuable outcome measure and validation anchor in clinical research. JF - Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation AU - Bennett, Antonia V AU - Reeve, Bryce B AU - Basch, Ethan M AU - Mitchell, Sandra A AU - Meeneghan, Mathew AU - Battaglini, Claudio L AU - Smith-Ryan, Abbie E AU - Phillips, Brett AU - Shea, Thomas C AU - Wood, William A AD - Department of Health Policy and Management, University of North Carolina at Chapel Hill, Campus Box 7411, Chapel Hill, NC, 27599, USA. avbenn@unc.edu. ; Department of Health Policy and Management, University of North Carolina at Chapel Hill, Campus Box 7411, Chapel Hill, NC, 27599, USA. ; Department of Medicine, University of North Carolina at Chapel Hill, Campus Box 7305, Chapel Hill, NC, 27599, USA. ; Division of Cancer Control and Population Sciences, Outcomes Research Branch, National Cancer Institute, 9609 Medical Center Drive, East Tower, Room 3-448, Rockville, MD, 20850, USA. ; Department of Exercise and Sports Science, University of North Carolina at Chapel Hill, Campus Box 8700, Chapel Hill, NC, 27599, USA. ; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Campus Box 7295, Chapel Hill, NC, 27599, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 535 EP - 546 VL - 25 IS - 3 KW - Index Medicus KW - Hematopoietic cell transplant KW - Pedometry KW - Oncology KW - Validation KW - PROMIS Global-10 KW - PRO-CTCAE KW - Fitbit KW - Young Adult KW - Self Report KW - Cross-Sectional Studies KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Male KW - Female KW - Health Status Indicators KW - Motor Activity KW - Hematopoietic Stem Cell Transplantation -- psychology KW - Accelerometry KW - Quality of Life KW - Activities of Daily Living KW - Patient Outcome Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767071526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Quality+of+life+research+%3A+an+international+journal+of+quality+of+life+aspects+of+treatment%2C+care+and+rehabilitation&rft.atitle=Evaluation+of+pedometry+as+a+patient-centered+outcome+in+patients+undergoing+hematopoietic+cell+transplant+%28HCT%29%3A+a+comparison+of+pedometry+and+patient+reports+of+symptoms%2C+health%2C+and+quality+of+life.&rft.au=Bennett%2C+Antonia+V%3BReeve%2C+Bryce+B%3BBasch%2C+Ethan+M%3BMitchell%2C+Sandra+A%3BMeeneghan%2C+Mathew%3BBattaglini%2C+Claudio+L%3BSmith-Ryan%2C+Abbie+E%3BPhillips%2C+Brett%3BShea%2C+Thomas+C%3BWood%2C+William+A&rft.aulast=Bennett&rft.aufirst=Antonia&rft.date=2016-03-01&rft.volume=25&rft.issue=3&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Quality+of+life+research+%3A+an+international+journal+of+quality+of+life+aspects+of+treatment%2C+care+and+rehabilitation&rft.issn=1573-2649&rft_id=info:doi/10.1007%2Fs11136-015-1179-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-06 N1 - Date created - 2016-02-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11136-015-1179-0 ER - TY - JOUR T1 - Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration. AN - 1767068928; 26851651 AB - Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze(®) (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)μg/L for cocaine and 248 (96.9-953)μg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)μg/L and 360 (77.2-836)μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. Published by Elsevier Ireland Ltd. JF - Forensic science international AU - Ellefsen, Kayla N AU - Concheiro, Marta AU - Pirard, Sandrine AU - Gorelick, David A AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD. ; Currently at Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY. ; Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD. ; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD. ; Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD. Electronic address: mhuestis@intra.nida.nih.gov. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 95 EP - 101 VL - 260 KW - Narcotics KW - 0 KW - benzoylecgonine KW - 5353I8I6YS KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - StatSure Saliva Sampler™ KW - Oral-Eze(®) KW - Benzoylecgonine KW - Oral Fluid KW - Pharmacokinetics KW - Injections, Intravenous KW - Half-Life KW - Substance Abuse Detection -- instrumentation KW - Humans KW - Adult KW - Gas Chromatography-Mass Spectrometry KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Cocaine -- analysis KW - Cocaine -- analogs & derivatives KW - Saliva -- chemistry KW - Narcotics -- pharmacokinetics KW - Narcotics -- administration & dosage KW - Cocaine -- pharmacokinetics KW - Cocaine -- administration & dosage KW - Narcotics -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767068928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Forensic+science+international&rft.atitle=Oral+fluid+cocaine+and+benzoylecgonine+concentrations+following+controlled+intravenous+cocaine+administration.&rft.au=Ellefsen%2C+Kayla+N%3BConcheiro%2C+Marta%3BPirard%2C+Sandrine%3BGorelick%2C+David+A%3BHuestis%2C+Marilyn+A&rft.aulast=Ellefsen&rft.aufirst=Kayla&rft.date=2016-03-01&rft.volume=260&rft.issue=&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Forensic+science+international&rft.issn=1872-6283&rft_id=info:doi/10.1016%2Fj.forsciint.2016.01.013 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-06 N1 - Date created - 2016-02-20 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Clin Chem. 2014 Feb;60(2):307-22 [24153253] Drug Test Anal. 2014 May;6(5):461-71 [24039237] Drug Test Anal. 2015 Feb;7(2):114-20 [24995604] Bioanalysis. 2015;7(16):2041-56 [26327184] J Clin Pharmacol. 2015 Dec;55(12):1332-43 [26032168] J Anal Toxicol. 2000 Oct;24(7):458-66 [11043647] Ther Drug Monit. 2008 Apr;30(2):203-6 [18367981] J Anal Toxicol. 2006 Sep;30(7):458-62 [16959139] Forensic Sci Int. 2005 Sep 10;152(2-3):149-55 [15978340] Forensic Sci Int. 2005 Jun 10;150(2-3):143-50 [15944054] J Anal Toxicol. 1997 Oct;21(6):465-75 [9323527] J Anal Toxicol. 1995 Oct;19(6):359-74 [8926729] Clin Chem. 1994 Jul;40(7 Pt 1):1299-305 [8013103] J Anal Toxicol. 1993 Oct;17(6):338-41 [8271779] J Anal Toxicol. 1988 Jul-Aug;12(4):200-6 [3184889] J Anal Toxicol. 2000 Oct;24(7):467-77 [11043648] Traffic Inj Prev. 2014;15(2):111-8 [24345011] J Anal Toxicol. 1987 Jan-Feb;11(1):36-8 [3821076] J Anal Toxicol. 2013 Sep;37(7):452-74 [23934984] Clin Chem. 2012 Jul;58(7):1101-9 [22532594] Clin Chem. 2011 Jun;57(6):805-10 [21350039] Ther Drug Monit. 2010 Oct;32(5):628-37 [20814350] Clin Chem. 2009 Nov;55(11):1910-31 [19745062] Ther Drug Monit. 2009 Aug;31(4):511-9 [19571773] Addiction. 2008 Aug;103(8):1258-68 [18855814] J Anal Toxicol. 2008 Jul-Aug;32(6):393-401 [18652744] J Anal Toxicol. 2013 Oct;37(8):552-8 [23943437] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.forsciint.2016.01.013 ER - TY - JOUR T1 - Phase II study of everolimus in refractory testicular germ cell tumors. AN - 1767068656; 26612480 AB - Testicular germ cell tumors (TGCTs) represent a highly curable disease; however, a small proportion of patients develop disease recurrence. Loss of the tumor-suppressor gene phosphatase and tensin homolog marks the transition from intratubular germ cell neoplasia to invasive GCT and is correlated with disease progression. Inactivation of phosphatase and tensin homolog is associated with deregulation of the PI3K/Akt pathway and increased mammalian target of rapamycin signaling. This study aimed to determine the efficacy and toxicity of a mammalian target of rapamycin inhibitor, everolimus, in patients with refractory TGCTs. From December 2011 to February 2015, 15 patients with refractory GCTs were enrolled in the phase II study. All patients were pretreated with at least 2 cisplatin-based therapies; 4 tumors (26.7%) were absolutely refractory to cisplatin and 9 patients (60.0%) had visceral nonpulmonary metastases. Everolimus was administered at a dose of 10mg daily until progression or unacceptable toxicity. The primary end point was the objective response rate, according to Response Evaluation Criteria in Solid Tumors. No objective response was observed, but 6 patients (40.0%) achieved 12-week progression-free survival. During a median follow-up period of 3.6 months (range: 1-35.1mo), all patients experienced disease progression and 11 patients (80.0%) died. Median progression-free survival was 1.7 months (95% CI: 1.1-4.0mo) and median overall survival was 3.6 months (95% CI: 2.0-11.0mo). This study failed to achieve its primary end point and our data suggest limited efficacy of everolimus against unselected heavily pretreated refractory TGCTs. Everolimus showed limited efficacy in unselected heavily pretreated refractory TGCTs. Prolonged disease stabilization could be achieved in selected patients. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Urologic oncology AU - Mego, Michal AU - Svetlovska, Daniela AU - Miskovska, Vera AU - Obertova, Jana AU - Palacka, Patrik AU - Rajec, Jan AU - Sycova-Mila, Zuzana AU - Chovanec, Michal AU - Rejlekova, Katarina AU - Zuzák, Peter AU - Ondrus, Dalibor AU - Spanik, Stanislav AU - Reckova, Maria AU - Mardiak, Jozef AD - 2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia; Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia. Electronic address: misomego@gmail.com. ; 2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia; Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia. ; 1st Department of Oncology, Faculty of Medicine, Comenius University, St. Elisabeth Cancer Institute, Bratislava, Slovakia; Department of Medical Oncology, St. Elizabeth Cancer Institute, Bratislava, Slovakia. ; 2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia. ; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia. ; Department of Medical Oncology, St. Elizabeth Cancer Institute, Bratislava, Slovakia. ; 2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 122.e17 EP - 22 VL - 34 IS - 3 KW - Antineoplastic Agents KW - 0 KW - Everolimus KW - 9HW64Q8G6G KW - Index Medicus KW - Testicular germ cell tumors KW - Refractory KW - PTEN KW - mTOR inhibition KW - Young Adult KW - Survival Rate KW - Neoplasm Staging KW - Humans KW - Adult KW - Prognosis KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Testicular Neoplasms -- drug therapy KW - Neoplasm Recurrence, Local -- drug therapy KW - Testicular Neoplasms -- pathology KW - Salvage Therapy KW - Everolimus -- therapeutic use KW - Neoplasms, Germ Cell and Embryonal -- pathology KW - Neoplasms, Germ Cell and Embryonal -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Neoplasm Recurrence, Local -- pathology KW - Drug Resistance, Neoplasm -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767068656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urologic+oncology&rft.atitle=Phase+II+study+of+everolimus+in+refractory+testicular+germ+cell+tumors.&rft.au=Mego%2C+Michal%3BSvetlovska%2C+Daniela%3BMiskovska%2C+Vera%3BObertova%2C+Jana%3BPalacka%2C+Patrik%3BRajec%2C+Jan%3BSycova-Mila%2C+Zuzana%3BChovanec%2C+Michal%3BRejlekova%2C+Katarina%3BZuz%C3%A1k%2C+Peter%3BOndrus%2C+Dalibor%3BSpanik%2C+Stanislav%3BReckova%2C+Maria%3BMardiak%2C+Jozef&rft.aulast=Mego&rft.aufirst=Michal&rft.date=2016-03-01&rft.volume=34&rft.issue=3&rft.spage=122.e17&rft.isbn=&rft.btitle=&rft.title=Urologic+oncology&rft.issn=1873-2496&rft_id=info:doi/10.1016%2Fj.urolonc.2015.10.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-02-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.urolonc.2015.10.010 ER - TY - JOUR T1 - Urinary concentrations of PAH and VOC metabolites in marijuana users. AN - 1765579922; 26690539 AB - Marijuana is seeing increased therapeutic use, and is the world's third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p<0.05). Urinary thiocyanate (p<0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p<0.001) and acrylamide (p<0.001), were significantly higher in recent marijuana users than in nonusers. We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. Published by Elsevier Ltd. JF - Environment international AU - Wei, Binnian AU - Alwis, K Udeni AU - Li, Zheng AU - Wang, Lanqing AU - Valentin-Blasini, Liza AU - Sosnoff, Connie S AU - Xia, Yang AU - Conway, Kevin P AU - Blount, Benjamin C AD - Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, United States. Electronic address: bwei@cdc.gov. ; Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, United States. ; Division of Epidemiology, Services and Prevention Research at the National Institutes of Health, United States. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 1 EP - 8 VL - 88 KW - Biomarkers KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Tobacco Smoke Pollution KW - Volatile Organic Compounds KW - Index Medicus KW - VOCs KW - PAHs KW - Secondhand smoke KW - Environmental tobacco smoke (ETS) KW - Biomonitoring KW - Cannabis smoke KW - Young Adult KW - Humans KW - Adult KW - Tobacco Smoke Pollution -- adverse effects KW - Case-Control Studies KW - Biomarkers -- urine KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Marijuana Smoking -- urine KW - Marijuana Smoking -- adverse effects KW - Volatile Organic Compounds -- urine KW - Cannabis -- adverse effects KW - Polycyclic Aromatic Hydrocarbons -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1765579922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environment+international&rft.atitle=Urinary+concentrations+of+PAH+and+VOC+metabolites+in+marijuana+users.&rft.au=Wei%2C+Binnian%3BAlwis%2C+K+Udeni%3BLi%2C+Zheng%3BWang%2C+Lanqing%3BValentin-Blasini%2C+Liza%3BSosnoff%2C+Connie+S%3BXia%2C+Yang%3BConway%2C+Kevin+P%3BBlount%2C+Benjamin+C&rft.aulast=Wei&rft.aufirst=Binnian&rft.date=2016-03-01&rft.volume=88&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Environment+international&rft.issn=1873-6750&rft_id=info:doi/10.1016%2Fj.envint.2015.12.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-12 N1 - Date created - 2016-02-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.envint.2015.12.003 ER - TY - JOUR T1 - Immunogenicity of therapeutic recombinant immunotoxins. AN - 1765117163; 26864110 AB - Recombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38-kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less-immunogenic RITs by identifying and removing T- and B-cell epitopes to hide the RIT from the immune system. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. JF - Immunological reviews AU - Mazor, Ronit AU - Onda, Masanori AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 152 EP - 164 VL - 270 IS - 1 KW - Antibodies, Monoclonal, Humanized KW - 0 KW - Antibodies, Neutralizing KW - Antigens KW - Bacterial Toxins KW - Epitopes, B-Lymphocyte KW - Epitopes, T-Lymphocyte KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunosuppressive Agents KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Polyethylene Glycols KW - 30IQX730WE KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - neutralizing antibodies KW - mesothelin KW - anti-drug antibodies KW - immunotherapy KW - mesothelioma KW - Animals KW - Virulence Factors -- chemistry KW - Immunotherapy KW - Humans KW - Epitopes, T-Lymphocyte -- immunology KW - Neoplasms -- therapy KW - Drug Administration Routes KW - ADP Ribose Transferases -- genetics KW - Bacterial Toxins -- genetics KW - ADP Ribose Transferases -- chemistry KW - Antibodies, Monoclonal, Humanized -- therapeutic use KW - Antibodies, Monoclonal, Humanized -- immunology KW - Antibodies, Neutralizing -- immunology KW - Immunoglobulin Fragments -- immunology KW - Immunosuppressive Agents -- therapeutic use KW - Antigens -- immunology KW - Sequence Deletion KW - Neoplasms -- immunology KW - Immunosuppressive Agents -- administration & dosage KW - Exotoxins -- genetics KW - ADP Ribose Transferases -- immunology KW - Genetic Engineering KW - Clinical Trials as Topic KW - Antibody Formation KW - Virulence Factors -- genetics KW - Mice KW - Exotoxins -- chemistry KW - Bacterial Toxins -- immunology KW - Exotoxins -- immunology KW - Virulence Factors -- immunology KW - Immunoglobulin Fragments -- therapeutic use KW - Drug Therapy, Combination KW - Bacterial Toxins -- chemistry KW - Epitopes, B-Lymphocyte -- immunology KW - Epitope Mapping KW - Immunotoxins -- chemistry KW - Immunotoxins -- immunology KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- genetics KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1765117163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunological+reviews&rft.atitle=Immunogenicity+of+therapeutic+recombinant+immunotoxins.&rft.au=Mazor%2C+Ronit%3BOnda%2C+Masanori%3BPastan%2C+Ira&rft.aulast=Mazor&rft.aufirst=Ronit&rft.date=2016-03-01&rft.volume=270&rft.issue=1&rft.spage=152&rft.isbn=&rft.btitle=&rft.title=Immunological+reviews&rft.issn=1600-065X&rft_id=info:doi/10.1111%2Fimr.12390 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-04 N1 - Date created - 2016-02-11 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Immunol. 2002 Mar 1;168(5):2530-7 [11859148] Clin Cancer Res. 2002 Oct;8(10):3092-9 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17;109(29):11782-7 [22753489] Hematology Am Soc Hematol Educ Program. 2012;2012:660-6 [23233649] Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):E3597-603 [23213206] Blood. 2001 Dec 1;98(12):3241-8 [11719360] N Engl J Med. 2002 Feb 14;346(7):469-75 [11844847] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/imr.12390 ER - TY - JOUR T1 - Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation. AN - 1764338977; 26769917 AB - 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(-)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(-)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(-)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(-)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(-)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. U.S. Government work not protected by U.S. copyright. JF - The Journal of pharmacology and experimental therapeutics AU - Gannon, Brenda M AU - Williamson, Adrian AU - Suzuki, Masaki AU - Rice, Kenner C AU - Fantegrossi, William E AD - Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.). ; Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.) WEFantegrossi@uams.edu. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 615 EP - 623 VL - 356 IS - 3 KW - 3,4-methylenedioxypyrovalerone KW - 0 KW - Benzodioxoles KW - Designer Drugs KW - Pyrrolidines KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Mice KW - Male KW - Discrimination Learning -- drug effects KW - Body Temperature Regulation -- drug effects KW - Discrimination Learning -- physiology KW - Designer Drugs -- pharmacology KW - Pyrrolidines -- chemistry KW - Body Temperature Regulation -- physiology KW - Pyrrolidines -- pharmacology KW - Motor Activity -- physiology KW - Motor Activity -- drug effects KW - Benzodioxoles -- pharmacology KW - Benzodioxoles -- chemistry KW - Designer Drugs -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1764338977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Stereoselective+Effects+of+Abused+%22Bath+Salt%22+Constituent+3%2C4-Methylenedioxypyrovalerone+in+Mice%3A+Drug+Discrimination%2C+Locomotor+Activity%2C+and+Thermoregulation.&rft.au=Gannon%2C+Brenda+M%3BWilliamson%2C+Adrian%3BSuzuki%2C+Masaki%3BRice%2C+Kenner+C%3BFantegrossi%2C+William+E&rft.aulast=Gannon&rft.aufirst=Brenda&rft.date=2016-03-01&rft.volume=356&rft.issue=3&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=1521-0103&rft_id=info:doi/10.1124%2Fjpet.115.229500 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-22 N1 - Date created - 2016-02-09 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Drug Alcohol Depend. 2012 Nov 1;126(1-2):168-75 [22664136] Rapid Commun Mass Spectrom. 2012 Dec 15;26(23):2665-72 [23124656] Br J Pharmacol. 2013 Jan;168(2):458-70 [22897747] J Anal Toxicol. 2013 Mar;37(2):64-73 [23316030] Neuropsychopharmacology. 2013 Mar;38(4):552-62 [23072836] Neuropsychopharmacology. 2013 Mar;38(4):563-73 [23212455] Neuropharmacology. 2013 Aug;71:130-40 [23597511] Behav Pharmacol. 2013 Sep;24(5-6):437-47 [23839026] Forensic Sci Int. 2013 Dec 10;233(1-3):416-22 [24314548] Chirality. 2015 Apr;27(4):287-93 [25727807] ACS Chem Neurosci. 2015 May 20;6(5):771-7 [25688761] Psychopharmacology (Berl). 2001 Dec;159(1):58-63 [11797070] J Pharmacol Exp Ther. 1973 Oct;187(1):27-33 [4795731] Pharmacol Biochem Behav. 1984 Jul;21(1):1-3 [6463083] Pharmacol Biochem Behav. 1984 Dec;21(6):895-901 [6522418] Pharmacol Biochem Behav. 1986 May;24(5):1161-5 [3725823] Chirality. 1993;5(7):495-500 [8240925] Pharmacol Biochem Behav. 1995 Apr;50(4):601-6 [7617707] J Pharmacol Exp Ther. 1996 Nov;279(2):1043-52 [8930215] Mol Pharmacol. 2008 Mar;73(3):813-23 [17978168] J Pharmacol Exp Ther. 2009 Jun;329(3):1006-15 [19276400] J Pharmacol Exp Ther. 2009 Nov;331(2):717-23 [19684254] Neuropsychopharmacology. 2012 Apr;37(5):1192-203 [22169943] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/jpet.115.229500 ER - TY - JOUR T1 - Maintenance Therapy in Colorectal Cancer: Moving the Artillery Down While Keeping an Eye on the Enemy. AN - 1763707661; 26421728 AB - The survival improvement in metastatic colorectal cancer, achieved with more intensive chemotherapy regimens, has recently led clinicians to question the optimal duration of therapies and to consider the role of maintenance. Indeed, patients whose disease is controlled after induction chemotherapy may benefit from continuing a less intensive regimen in order to reinforce the results achieved with up-front treatment. In addition, the more favorable toxicity profile of maintenance approaches would ensure a better quality of life. After discussing the rationale and the difference of pursuing a maintenance strategy with chemotherapeutic and/or biologic agents, we present significant available data from the literature and comment on the current implications and future directions of maintenance therapy. The current roles of depotentiated treatment schedules, antiangiogenic compounds, epidermal growth factor receptor inhibitors, and novel targeted therapies are also reviewed. Finally, we address elements that may foster clinical and social debate on this topic, suggesting potential aspects that need to be further investigated. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Clinical colorectal cancer AU - Aprile, Giuseppe AU - Giuliani, Francesco AU - Lutrino, Stefania Eufemia AU - Fontanella, Caterina AU - Bonotto, Marta AU - Rihawi, Karim AU - Fasola, Gianpiero AD - Department of Oncology, University Hospital, Udine, Italy. Electronic address: aprile.giuseppe@aoud.sanita.fvg.it. ; Department of Medical Oncology, National Cancer Institute "G. Paolo II", Bari, Italy. ; Department of Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy. ; Department of Oncology, University Hospital, Udine, Italy. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 7 EP - 15 VL - 15 IS - 1 KW - Angiogenesis Inhibitors KW - 0 KW - MGN1703 KW - Organoplatinum Compounds KW - oxaliplatin KW - 04ZR38536J KW - irinotecan KW - 0H43101T0J KW - Bevacizumab KW - 2S9ZZM9Q9V KW - DNA KW - 9007-49-2 KW - Erlotinib Hydrochloride KW - DA87705X9K KW - Fluorouracil KW - U3P01618RT KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Erlotinib KW - Efatutazone KW - Colorectal cancer KW - Treatment duration KW - EGFR inhibitors KW - Maintenance KW - Fluorouracil -- administration & dosage KW - Erlotinib Hydrochloride -- administration & dosage KW - Organoplatinum Compounds -- administration & dosage KW - DNA -- administration & dosage KW - Induction Chemotherapy KW - Humans KW - Camptothecin -- analogs & derivatives KW - Quality of Life KW - Bevacizumab -- administration & dosage KW - Camptothecin -- administration & dosage KW - Angiogenesis Inhibitors -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Colorectal Neoplasms -- drug therapy KW - Maintenance Chemotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1763707661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+colorectal+cancer&rft.atitle=Maintenance+Therapy+in+Colorectal+Cancer%3A+Moving+the+Artillery+Down+While+Keeping+an+Eye+on+the+Enemy.&rft.au=Aprile%2C+Giuseppe%3BGiuliani%2C+Francesco%3BLutrino%2C+Stefania+Eufemia%3BFontanella%2C+Caterina%3BBonotto%2C+Marta%3BRihawi%2C+Karim%3BFasola%2C+Gianpiero&rft.aulast=Aprile&rft.aufirst=Giuseppe&rft.date=2016-03-01&rft.volume=15&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Clinical+colorectal+cancer&rft.issn=1938-0674&rft_id=info:doi/10.1016%2Fj.clcc.2015.08.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-01 N1 - Date created - 2016-02-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.clcc.2015.08.002 ER - TY - JOUR T1 - National Cancer Institute-supported chemotherapy-induced peripheral neuropathy trials: outcomes and lessons. AN - 1761462923; 26686859 AB - Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional--yet unsubstantiated--practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Majithia, Neil AU - Temkin, Sarah M AU - Ruddy, Kathryn J AU - Beutler, Andreas S AU - Hershman, Dawn L AU - Loprinzi, Charles L AD - Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. majithia.neil@mayo.edu. ; Community Oncology and Prevention Trials Research Group, Division of Cancer Prevention, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA. ; Department of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. ; Department of Medicine, Department of Epidemiology, Mailman School of Public Health, Columbia University College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, Columbia University, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, 161 Fort Washington Ave #1068, New York, NY, 10032, USA. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 1439 EP - 1447 VL - 24 IS - 3 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Peripheral neuropathy KW - Chemotherapy KW - Clinical trials KW - Cancer KW - United States KW - National Cancer Institute (U.S.) KW - Humans KW - Treatment Outcome KW - Antineoplastic Agents -- therapeutic use KW - Peripheral Nervous System Diseases -- chemically induced KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761462923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=National+Cancer+Institute-supported+chemotherapy-induced+peripheral+neuropathy+trials%3A+outcomes+and+lessons.&rft.au=Majithia%2C+Neil%3BTemkin%2C+Sarah+M%3BRuddy%2C+Kathryn+J%3BBeutler%2C+Andreas+S%3BHershman%2C+Dawn+L%3BLoprinzi%2C+Charles+L&rft.aulast=Majithia&rft.aufirst=Neil&rft.date=2016-03-01&rft.volume=24&rft.issue=3&rft.spage=1439&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=1433-7339&rft_id=info:doi/10.1007%2Fs00520-015-3063-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-21 N1 - Date created - 2016-01-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00520-015-3063-4 ER - TY - JOUR T1 - Risk-Based Therapy for Localized Osteosarcoma. AN - 1760915488; 26501936 AB - The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival. Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m(2) on day -4, cyclophosphamide 2,000 mg/m(2) on days -3, and -2 followed by stem cell infusion. Fifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths. Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival. © 2015 Wiley Periodicals, Inc. JF - Pediatric blood & cancer AU - Venkatramani, Rajkumar AU - Murray, Jeffrey AU - Helman, Lee AU - Meyer, William AU - Hicks, M John AU - Krance, Robert AU - Lau, Ching AU - Jo, Eunji AU - Chintagumpala, Murali AD - Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas. ; Cook Children's Medical Center, Fort Worth, Texas. ; National Institutes of Health Clinical Center, Pediatric Oncology Branch, Bethesda, Maryland. ; Department of Pediatrics, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma. ; Department of Pathology and Immunology and Department of Pediatrics, Baylor College of Medicine, Houston, Texas. ; Biostatistics and Informatics Shared Resource, The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 412 EP - 417 VL - 63 IS - 3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Cisplatin KW - Q20Q21Q62J KW - Melphalan KW - Q41OR9510P KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - stem cell transplantation KW - high-dose chemotherapy KW - necrosis KW - clinical trials KW - osteosarcoma KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Doxorubicin -- administration & dosage KW - Cisplatin -- administration & dosage KW - Femoral Neoplasms -- drug therapy KW - Femoral Neoplasms -- therapy KW - Treatment Outcome KW - Adolescent KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Stem Cell Transplantation KW - Methotrexate -- administration & dosage KW - Chemotherapy, Adjuvant KW - Female KW - Male KW - Osteosarcoma -- mortality KW - Osteosarcoma -- drug therapy KW - Bone Neoplasms -- drug therapy KW - Bone Neoplasms -- mortality KW - Bone Neoplasms -- therapy KW - Osteosarcoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760915488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+blood+%26+cancer&rft.atitle=Risk-Based+Therapy+for+Localized+Osteosarcoma.&rft.au=Venkatramani%2C+Rajkumar%3BMurray%2C+Jeffrey%3BHelman%2C+Lee%3BMeyer%2C+William%3BHicks%2C+M+John%3BKrance%2C+Robert%3BLau%2C+Ching%3BJo%2C+Eunji%3BChintagumpala%2C+Murali&rft.aulast=Venkatramani&rft.aufirst=Rajkumar&rft.date=2016-03-01&rft.volume=63&rft.issue=3&rft.spage=412&rft.isbn=&rft.btitle=&rft.title=Pediatric+blood+%26+cancer&rft.issn=1545-5017&rft_id=info:doi/10.1002%2Fpbc.25808 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-13 N1 - Date created - 2016-01-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/pbc.25808 ER - TY - JOUR T1 - Food preparation methods, drinking water source, and esophageal squamous cell carcinoma in the high-risk area of Golestan, Northeast Iran. AN - 1760909453; 25851181 AB - Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders. JF - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) AU - Golozar, Asieh AU - Etemadi, Arash AU - Kamangar, Farin AU - Fazeltabar Malekshah, Akbar AU - Islami, Farhad AU - Nasrollahzadeh, Dariush AU - Abedi-Ardekani, Behnoosh AU - Khoshnia, Masoud AU - Pourshams, Akram AU - Semnani, Shahriar AU - Marjani, Haji Amin AU - Shakeri, Ramin AU - Sotoudeh, Masoud AU - Brennan, Paul AU - Taylor, Philip AU - Boffetta, Paolo AU - Abnet, Christian AU - Dawsey, Sanford AU - Malekzadeh, Reza AD - aDigestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran bGolestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran cDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda dDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health eSchool of Community Health and Policy, Morgan State University, Baltimore, Maryland fThe Tisch Cancer Institute and Institute for Translational Epidemiology, Mount Sinai School of Medicine, New York, New York, USA gMedical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden hGenetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 123 EP - 129 VL - 25 IS - 2 KW - Drinking Water KW - 0 KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Iran -- epidemiology KW - Prognosis KW - Aged KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Male KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- epidemiology KW - Meat -- adverse effects KW - Cooking -- methods KW - Feeding Behavior KW - Esophageal Neoplasms -- etiology KW - Drinking Water -- adverse effects KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760909453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.atitle=Food+preparation+methods%2C+drinking+water+source%2C+and+esophageal+squamous+cell+carcinoma+in+the+high-risk+area+of+Golestan%2C+Northeast+Iran.&rft.au=Golozar%2C+Asieh%3BEtemadi%2C+Arash%3BKamangar%2C+Farin%3BFazeltabar+Malekshah%2C+Akbar%3BIslami%2C+Farhad%3BNasrollahzadeh%2C+Dariush%3BAbedi-Ardekani%2C+Behnoosh%3BKhoshnia%2C+Masoud%3BPourshams%2C+Akram%3BSemnani%2C+Shahriar%3BMarjani%2C+Haji+Amin%3BShakeri%2C+Ramin%3BSotoudeh%2C+Masoud%3BBrennan%2C+Paul%3BTaylor%2C+Philip%3BBoffetta%2C+Paolo%3BAbnet%2C+Christian%3BDawsey%2C+Sanford%3BMalekzadeh%2C+Reza&rft.aulast=Golozar&rft.aufirst=Asieh&rft.date=2016-03-01&rft.volume=25&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.issn=1473-5709&rft_id=info:doi/10.1097%2FCEJ.0000000000000156 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-25 N1 - Date created - 2016-01-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1097/CEJ.0000000000000156 ER - TY - JOUR T1 - Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study. AN - 1760882489; 26413860 AB - Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults. © 2015 UICC. JF - International journal of cancer AU - Izano, Monika AU - Wei, Esther K AU - Tai, Caroline AU - Swede, Helen AU - Gregorich, Steven AU - Harris, Tamara B AU - Klepin, Heidi AU - Satterfield, Suzanne AU - Murphy, Rachel AU - Newman, Anne B AU - Rubin, Susan M AU - Braithwaite, Dejana AU - Health ABC study AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA. ; California Pacific Medical Center Research Institute, San Francisco, CA. ; Department of Community Medicine & Health Care, University of Connecticut Health Center, Farmington, CT. ; Division of General Internal Medicine, University of California, San Francisco, CA. ; National Institutes of Health, National Institute on Aging, National Institutes of Health, Bethesda, MD. ; Wake Forest School of Medicine, Winston-Salem, NC. ; Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN. ; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PN. ; Health ABC study Y1 - 2016/03/01/ PY - 2016 DA - 2016 Mar 01 SP - 1118 EP - 1128 VL - 138 IS - 5 KW - Interleukin-6 KW - 0 KW - Tumor Necrosis Factor-alpha KW - C-Reactive Protein KW - 9007-41-4 KW - Index Medicus KW - inflammatory markers KW - incidence KW - colorectal cancer KW - cohort study KW - Humans KW - Aging KW - Aged KW - Body Composition KW - C-Reactive Protein -- analysis KW - Interleukin-6 -- blood KW - Risk KW - Prospective Studies KW - Tumor Necrosis Factor-alpha -- blood KW - Chronic Disease KW - Female KW - Male KW - Proportional Hazards Models KW - Colorectal Neoplasms -- etiology KW - Inflammation -- complications KW - Obesity -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760882489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Chronic+inflammation+and+risk+of+colorectal+and+other+obesity-related+cancers%3A+The+health%2C+aging+and+body+composition+study.&rft.au=Izano%2C+Monika%3BWei%2C+Esther+K%3BTai%2C+Caroline%3BSwede%2C+Helen%3BGregorich%2C+Steven%3BHarris%2C+Tamara+B%3BKlepin%2C+Heidi%3BSatterfield%2C+Suzanne%3BMurphy%2C+Rachel%3BNewman%2C+Anne+B%3BRubin%2C+Susan+M%3BBraithwaite%2C+Dejana%3BHealth+ABC+study&rft.aulast=Izano&rft.aufirst=Monika&rft.date=2016-03-01&rft.volume=138&rft.issue=5&rft.spage=1118&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=1097-0215&rft_id=info:doi/10.1002%2Fijc.29868 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-01 N1 - Date created - 2016-01-15 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/ijc.29868 ER - TY - JOUR T1 - Human CD34(+) progenitor hematopoiesis in liquid culture for in vitro assessment of drug-induced myelotoxicity. AN - 1752354936; 26616282 AB - Utilization of validated CFU-GM assays for myelotoxicity screening is hampered by its labor-intensive and low-throughput nature. Herein, we transformed the defined CFU-GM assay conditions and IC90 endpoint into a higher throughput format. Human CD34(+) hematopoietic progenitors were cultured in a 96-well plate for 14 days with the same cytokine (rhGM-CSF) used in the CFU-GM assay. Expansion and differentiation toward myeloid lineages were manifested by characteristic changes in nuclear and cytoplasmic morphology and by temporal expression patterns of CD34, CD11b and CD13 markers. Inhibition of CD34(+) cell myelopoiesis by 12 anticancer drugs known to induce myelotoxicity in the clinic was quantifiable using either general cytotoxicity endpoints (cell growth area or total nucleus count) or lineage specific readouts (count of cells expressing CD11b and/or CD13). The IC50 and IC90 values derived from the concentration-response curves of 14-day drug exposure in CD34(+) cell culture were highly correlated with those from the international validation study of the CFU-GM assay, demonstrating capability to assess general cytotoxicity, cell proliferation and myelopoiesis simultaneously. These results suggest that this human CD34(+) hematopoietic progenitor cell assay can be used as a direct replacement for the validated, low throughput CFU-GM assay, and could expand application of in vitro myelotoxicity testing. Copyright © 2015 Elsevier B.V. All rights reserved. JF - Toxicology in vitro : an international journal published in association with BIBRA AU - Guo, Liang AU - Hamre, John AU - Davis, Myrtle AU - Parchment, Ralph E AD - Laboratory of Investigative Toxicology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: liang.guo@fnlcr.nih.gov. ; Laboratory of Investigative Toxicology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: john.hamre@fnlcr.nih.gov. ; Laboratory of Investigative Toxicology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: davismillinm@mail.nih.gov. ; Laboratory of Investigative Toxicology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: parchmentr@mail.nih.gov. Y1 - 2016/03// PY - 2016 DA - March 2016 SP - 103 EP - 113 VL - 31 KW - Antigens, CD11b KW - 0 KW - Antigens, CD34 KW - Antineoplastic Agents KW - ITGAM protein, human KW - Antigens, CD13 KW - EC 3.4.11.2 KW - Index Medicus KW - High content analysis (HCA) KW - FACS analysis KW - High throughput screening (HTS) KW - Microplate culture KW - Hematotoxicity KW - CD11b/CD13 KW - CD34(+) progenitors KW - Cell Proliferation -- drug effects KW - Granulocyte-Macrophage Progenitor Cells KW - Cell Survival -- drug effects KW - Antigens, CD13 -- metabolism KW - Cells, Cultured KW - Antigens, CD11b -- metabolism KW - Humans KW - Cell Culture Techniques KW - Hematopoiesis KW - Myeloid Progenitor Cells -- drug effects KW - Biological Assay KW - Antineoplastic Agents -- toxicity KW - Myeloid Progenitor Cells -- metabolism KW - Myeloid Progenitor Cells -- cytology KW - Antigens, CD34 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1752354936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+in+vitro+%3A+an+international+journal+published+in+association+with+BIBRA&rft.atitle=Human+CD34%28%2B%29+progenitor+hematopoiesis+in+liquid+culture+for+in+vitro+assessment+of+drug-induced+myelotoxicity.&rft.au=Guo%2C+Liang%3BHamre%2C+John%3BDavis%2C+Myrtle%3BParchment%2C+Ralph+E&rft.aulast=Guo&rft.aufirst=Liang&rft.date=2016-03-01&rft.volume=31&rft.issue=&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Toxicology+in+vitro+%3A+an+international+journal+published+in+association+with+BIBRA&rft.issn=1879-3177&rft_id=info:doi/10.1016%2Fj.tiv.2015.11.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-11 N1 - Date created - 2015-12-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.tiv.2015.11.017 ER - TY - JOUR T1 - The Macrophage-depleting Agent Clodronate Promotes Durable Hematopoietic Chimerism and Donor-specific Skin Allograft Tolerance in Mice. AN - 1768555520; 26917238 AB - Hematopoietic chimerism is known to promote donor-specific organ allograft tolerance; however, clinical translation has been impeded by the requirement for toxic immunosuppression and large doses of donor bone marrow (BM) cells. Here, we investigated in mice whether durable chimerism might be enhanced by pre-treatment of the recipient with liposomal clodronate, a macrophage depleting agent, with the goal of vacating BM niches for preferential reoccupation by donor hematopoietic stem cells (HSC). We found that liposomal clodronate pretreatment of C57BL/6 mice permitted establishment of durable hematopoietic chimerism when the mice were given a low dose of donor BM cells and transient immunosuppression. Moreover, clodronate pre-treatment increased durable donor-specific BALB/c skin allograft tolerance. These results provide proof-of-principle that clodronate is effective at sparing the number of donor BM cells required to achieve durable hematopoietic chimerism and donor-specific skin allograft tolerance and justify further development of a tolerance protocol based on this principle. JF - Scientific reports AU - Li, Zhanzhuo AU - Xu, Xin AU - Feng, Xingmin AU - Murphy, Philip M AD - Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA. ; Hematology Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/02/26/ PY - 2016 DA - 2016 Feb 26 SP - 22143 VL - 6 KW - Clodronic Acid KW - 0813BZ6866 KW - Index Medicus KW - Bone Marrow Transplantation -- methods KW - Animals KW - Mice, Inbred CBA KW - Allografts KW - Mice, Inbred C57BL KW - Mice KW - Mice, Inbred BALB C KW - Male KW - Clodronic Acid -- pharmacology KW - Transplantation Tolerance -- drug effects KW - Chimerism -- drug effects KW - Skin Transplantation -- methods KW - Macrophages -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768555520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=The+Macrophage-depleting+Agent+Clodronate+Promotes+Durable+Hematopoietic+Chimerism+and+Donor-specific+Skin+Allograft+Tolerance+in+Mice.&rft.au=Li%2C+Zhanzhuo%3BXu%2C+Xin%3BFeng%2C+Xingmin%3BMurphy%2C+Philip+M&rft.aulast=Li&rft.aufirst=Zhanzhuo&rft.date=2016-02-26&rft.volume=6&rft.issue=&rft.spage=22143&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep22143 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2017-01-09 N1 - Date created - 2016-02-26 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10122-6 [15218097] Transpl Immunol. 2015 Oct;33(2):125-9 [26209354] Blood. 1989 Nov 1;74(6):1905-14 [2478216] Blood. 2006 May 1;107(9):3764-71 [16439683] N Engl J Med. 2008 Jan 24;358(4):362-8 [18216356] Am J Transplant. 2008 Dec;8(12):2527-36 [18853957] J Immunol. 2009 Feb 1;182(3):1617-30 [19155511] Transplantation. 2009 May 15;87(9 Suppl):S79-84 [19424016] J Am Coll Surg. 2009 Jun;208(6):1051-8.e3 [19476891] Blood. 2009 Aug 13;114(7):1331-9 [19141863] Blood. 2009 Aug 13;114(7):1340-3 [19571319] Am J Transplant. 2010 Apr;10(4):751-62 [20148810] Plast Reconstr Surg. 2010 Jul;126(1):308-15 [20595877] Nat Rev Nephrol. 2010 Oct;6(10):594-605 [20808286] Blood. 2010 Oct 14;116(15):e41-55 [20647571] Blood. 2010 Dec 2;116(23):4815-28 [20713966] J Exp Med. 2011 Feb 14;208(2):251-60 [21282380] J Exp Med. 2011 Feb 14;208(2):261-71 [21282381] J Exp Med. 2011 Mar 14;208(3):421-8 [21402747] Blood. 2011 Nov 3;118(18):4957-62 [21890643] Curr Opin Organ Transplant. 2012 Feb;17(1):63-70 [22186093] Clin Dev Immunol. 2012;2012:438078 [23251216] Curr Opin Organ Transplant. 2013 Dec;18(6):640-4 [24126807] Curr Opin Organ Transplant. 2014 Dec;19(6):545-51 [25373855] Trends Immunol. 2004 Oct;25(10):518-23 [15364053] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep22143 ER - TY - JOUR T1 - Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines. AN - 1767626394; 26896068 AB - The link between inflammation and cancer has been confirmed by the use of anti-inflammatory therapies in cancer prevention and treatment. 5-aminosalicylic acid (5-ASA) was shown to decrease the growth and survival of colorectal cancer (CRC) cells. Studies also revealed that metformin induced apoptosis in several cancer cell lines. We investigated the combinatory effect of 5-ASA and metformin on HCT-116 and Caco-2 CRC cell lines. Apoptotic markers were determined using western blotting. Expression of pro-inflammatory cytokines was determined by RT-PCR. Inflammatory transcription factors and metastatic markers were measured by ELISA. Metformin enhanced CRC cell death induced by 5-ASA through significant increase in oxidative stress and activation of apoptotic machinery. Moreover, metformin enhanced the anti-inflammatory effect of 5-ASA by decreasing the gene expression of IL-1β, IL-6, COX-2 and TNF-α and its receptors; TNF-R1 and TNF-R2. Significant inhibition of activation of NF-κB and STAT3 transcription factors, and their downstream targets was also observed. Metformin also enhanced the inhibitory effect of 5-ASA on MMP-2 and MMP-9 enzyme activity, indicating a decrease in metastasis. The current data demonstrate that metformin potentiates the antitumor effect of 5-ASA on CRC cells suggesting their potential use as an adjuvant treatment in CRC. JF - BMC cancer AU - Saber, Mona M AU - Galal, May A AU - Ain-Shoka, Afaf A AU - Shouman, Samia A AD - Pharmacology and Toxicolgy Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. mona.magdy@pharma.cu.edu.eg. ; Pharmacology and Toxicolgy Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. mayouya2010@yahoo.com. ; Pharmacology and Toxicolgy Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. drafafainshoka@yahoo.com. ; Parmacology Unit,Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt. samia.shouman@nci.cu.edu.eg. Y1 - 2016/02/19/ PY - 2016 DA - 2016 Feb 19 SP - 126 VL - 16 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Mesalamine KW - 4Q81I59GXC KW - Metformin KW - 9100L32L2N KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Apoptosis KW - Humans KW - Signal Transduction -- drug effects KW - Oxidative Stress -- drug effects KW - Caco-2 Cells KW - HCT116 Cells KW - Drug Synergism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Metformin -- pharmacology KW - Mesalamine -- pharmacology KW - Colorectal Neoplasms -- metabolism KW - Colorectal Neoplasms -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767626394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+cancer&rft.atitle=Combination+of+metformin+and+5-aminosalicylic+acid+cooperates+to+decrease+proliferation+and+induce+apoptosis+in+colorectal+cancer+cell+lines.&rft.au=Saber%2C+Mona+M%3BGalal%2C+May+A%3BAin-Shoka%2C+Afaf+A%3BShouman%2C+Samia+A&rft.aulast=Saber&rft.aufirst=Mona&rft.date=2016-02-19&rft.volume=16&rft.issue=&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=BMC+cancer&rft.issn=1471-2407&rft_id=info:doi/10.1186%2Fs12885-016-2157-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-01 N1 - Date created - 2016-02-20 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nature. 2009 Jan 1;457(7225):102-6 [19122641] Cell Death Differ. 2006 Feb;13(2):202-11 [16082388] Dig Liver Dis. 2009 May;41(5):328-37 [18976971] Nat Rev Cancer. 2009 May;9(5):361-71 [19343034] Carcinogenesis. 2009 Jul;30(7):1073-81 [19468060] Toxicol Pathol. 2010 Jan;38(1):76-87 [20019355] Br J Pharmacol. 2010 Jul;160(5):1195-211 [20590612] Diabetes Care. 2011 Oct;34(10):2323-8 [21949223] Mol Cancer Res. 2011 Dec;9(12):1718-31 [21994466] Mol Med Rep. 2012 Apr;5(4):1068-74 [22246099] Eur J Endocrinol. 2012 Sep;167(3):409-16 [22778198] Biochem Biophys Res Commun. 2012 Sep 7;425(4):866-72 [22898050] PLoS One. 2013;8(11):e81264 [24278407] PLoS One. 2014;9(1):e84369 [24465408] Biochim Biophys Acta. 2014 Apr;1845(2):136-54 [24388873] PLoS One. 2014;9(5):e98207 [24858012] Nature. 2006 May 25;441(7092):431-6 [16724054] Biochem Pharmacol. 2000 Apr 1;59(7):887-90 [10718348] Nature. 2000 Mar 23;404(6776):398-402 [10746728] Immunity. 2000 Apr;12(4):419-29 [10795740] Am J Gastroenterol. 2000 Dec;95(12):3452-7 [11151876] J Clin Oncol. 2002 Jan 1;20(1):42-51 [11773152] Trends Mol Med. 2002 Jan;8(1):10-6 [11796261] Nature. 2002 Dec 19-26;420(6917):860-7 [12490959] Cancer Res. 2003 Feb 1;63(3):586-92 [12566300] Am J Physiol Cell Physiol. 2003 Apr;284(4):C953-61 [12466150] Carcinogenesis. 2003 Mar;24(3):443-51 [12663503] Nat Rev Immunol. 2003 Jul;3(7):521-33 [12876555] Eur J Cancer. 2006 Oct;42(15):2609-16 [16914308] Clin Gastroenterol Hepatol. 2006 Nov;4(11):1346-50 [17059900] Carcinogenesis. 2006 Dec;27(12):2371-82 [16728434] Cancer Res. 2007 Feb 1;67(3):1062-71 [17283139] Virchows Arch. 2007 Feb;450(2):243-4 [17123105] Clin Cancer Res. 2007 Nov 1;13(21):6527-31 [17975166] Biochem Pharmacol. 2008 Feb 1;75(3):668-76 [17981262] Curr Opin Genet Dev. 2008 Feb;18(1):19-26 [18440219] BMC Cancer. 2008;8:218 [18671849] Inflamm Bowel Dis. 2008 Oct;14(10):1341-7 [18452197] Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3108-15 [18990751] Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:15-21 [12950416] Nat Rev Drug Discov. 2004 Jan;3(1):17-26 [14708018] Mol Cancer. 2003 Dec 15;2:42 [14675489] Aliment Pharmacol Ther. 2004 Oct;20 Suppl 4:24-30 [15352890] Br J Surg. 1985 Sep;72 Suppl:S84-6 [3899269] Scand J Gastroenterol Suppl. 1990;172:66 [1972297] Gut. 1994 Jul;35(7):950-4 [8063223] N Engl J Med. 1995 Aug 31;333(9):541-9 [7623902] Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3336-40 [9096394] Ann Oncol. 2005 Jan;16(1):102-8 [15598946] J Exp Clin Cancer Res. 2004 Dec;23(4):651-60 [15743036] J Exp Med. 2005 Apr 18;201(8):1205-15 [15824083] Cell Cycle. 2005 Feb;4(2):217-20 [15655344] Neoplasia. 2005 Jun;7(6):545-55 [16036105] J Natl Cancer Inst. 2005 Nov 16;97(22):1679-87 [16288121] Cancer Cell. 2009 Feb 3;15(2):79-80 [19185839] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s12885-016-2157-9 ER - TY - JOUR T1 - Human J-protein DnaJB6b Cures a Subset of Saccharomyces cerevisiae Prions and Selectively Blocks Assembly of Structurally Related Amyloids. AN - 1767068811; 26702057 AB - Human chaperone DnaJB6, an Hsp70 co-chaperone whose defects cause myopathies, protects cells from polyglutamine toxicity and prevents purified polyglutamine and Aβ peptides from forming amyloid. Yeast prions [URE3] and [PSI(+)] propagate as amyloid forms of Ure2 and Sup35 proteins, respectively. Here we find DnaJB6-protected yeast cells from polyglutamine toxicity and cured yeast of both [URE3] prions and weak variants of [PSI(+)] prions but not strong [PSI(+)] prions. Weak and strong variants of [PSI(+)] differ only in the structural conformation of their amyloid cores. In line with its anti-prion effects, DnaJB6 prevented purified Sup35NM from forming amyloids at 37 °C, which produce predominantly weak [PSI(+)] variants when used to infect yeast, but not at 4 °C, which produces mostly strong [PSI(+)] variants. Thus, structurally distinct amyloids composed of the same protein were differentially sensitive to the anti-amyloid activity of DnaJB6 both in vitro and in vivo. These findings have important implications for strategies using DnaJB6 as a target for therapy in amyloid disorders. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Reidy, Michael AU - Sharma, Ruchika AU - Roberts, Brittany-Lee AU - Masison, Daniel C AD - From the Laboratory of Biochemistry and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892. ; From the Laboratory of Biochemistry and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 danielmas@helix.nih.gov. Y1 - 2016/02/19/ PY - 2016 DA - 2016 Feb 19 SP - 4035 EP - 4047 VL - 291 IS - 8 KW - Amyloid KW - 0 KW - DNAJB6 protein, human KW - HSP40 Heat-Shock Proteins KW - Molecular Chaperones KW - Nerve Tissue Proteins KW - Peptide Termination Factors KW - Prions KW - SUP35 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - URE2 protein, S cerevisiae KW - Index Medicus KW - prion KW - heat shock protein (HSP) KW - chaperone KW - yeast KW - amyloid KW - DnaJB6 KW - Hot Temperature KW - Humans KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Molecular Chaperones -- genetics KW - Molecular Chaperones -- metabolism KW - Saccharomyces cerevisiae Proteins -- genetics KW - Amyloid -- genetics KW - Nerve Tissue Proteins -- genetics KW - Peptide Termination Factors -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Prions -- genetics KW - HSP40 Heat-Shock Proteins -- genetics KW - Saccharomyces cerevisiae -- metabolism KW - Glutathione Peroxidase -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - Prions -- metabolism KW - Glutathione Peroxidase -- genetics KW - Peptide Termination Factors -- genetics KW - HSP40 Heat-Shock Proteins -- metabolism KW - Amyloid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767068811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Human+J-protein+DnaJB6b+Cures+a+Subset+of+Saccharomyces+cerevisiae+Prions+and+Selectively+Blocks+Assembly+of+Structurally+Related+Amyloids.&rft.au=Reidy%2C+Michael%3BSharma%2C+Ruchika%3BRoberts%2C+Brittany-Lee%3BMasison%2C+Daniel+C&rft.aulast=Reidy&rft.aufirst=Michael&rft.date=2016-02-19&rft.volume=291&rft.issue=8&rft.spage=4035&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/10.1074%2Fjbc.M115.700393 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-07 N1 - Date created - 2016-02-20 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cell Stress Chaperones. 2014 Mar;19(2):227-39 [23904097] Mol Cell Biol. 2001 Oct;21(20):7035-46 [11564886] PLoS Genet. 2014 Jul;10(7):e1004510 [25058638] Mol Microbiol. 2014 Sep;93(6):1156-71 [25060529] PLoS Genet. 2014 Oct;10(10):e1004720 [25329162] Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4615-22 [25313080] Mol Cell Biol. 2002 Jun;22(11):3590-8 [11997496] J Cell Biol. 2002 Jun 10;157(6):997-1004 [12058016] Methods Enzymol. 2002;350:248-57 [12073316] Mol Biol Cell. 2003 Mar;14(3):1172-81 [12631732] Genetics. 2003 Sep;165(1):23-33 [14504215] Nature. 2004 Mar 18;428(6980):323-8 [15029196] Genetics. 1989 May;122(1):19-27 [2659436] Gene. 1992 Jan 2;110(1):119-22 [1544568] Science. 1994 Apr 22;264(5158):566-9 [7909170] Science. 1995 May 12;268(5212):880-4 [7754373] EMBO J. 1996 Jun 17;15(12):3127-34 [8670813] Cell. 1998 Jul 10;94(1):73-82 [9674429] Science. 1999 Feb 26;283(5406):1339-43 [10037606] J Biol Chem. 2005 Jun 17;280(24):22809-18 [15824100] EMBO J. 2005 Sep 7;24(17):3082-92 [16096644] Genetics. 2006 Jun;173(2):611-20 [16582428] Nature. 2006 Aug 3;442(7102):585-9 [16810177] Methods Enzymol. 2006;412:185-200 [17046659] J Biol Chem. 2007 Apr 20;282(16):11931-40 [17324933] Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7163-8 [17438278] Mol Microbiol. 2008 Apr;68(1):87-97 [18312264] Proc Natl Acad Sci U S A. 2008 May 20;105(20):7206-11 [18480252] Genetics. 2008 Jul;179(3):1301-11 [18562668] Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16596-601 [18955697] Mol Cell. 2008 Nov 21;32(4):584-91 [19026788] Genetics. 2009 Jan;181(1):129-37 [19015537] J Mol Biol. 2009 Jul 10;390(2):155-67 [19422835] Mol Cell. 2010 Feb 12;37(3):355-69 [20159555] Curr Pharm Biotechnol. 2010 Feb;11(2):188-97 [20166962] Nat Rev Mol Cell Biol. 2010 Aug;11(8):579-92 [20651708] J Mol Biol. 2011 May 6;408(3):432-48 [21392508] Genetics. 2011 Jul;188(3):565-77 [21555396] Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13665-70 [21808014] Ann Neurol. 2012 Mar;71(3):407-16 [22334415] Nat Genet. 2012 Apr;44(4):450-5, S1-2 [22366786] PLoS Genet. 2012;8(4):e1002634 [22536159] J Biol Chem. 2012 Jul 6;287(28):23346-55 [22573320] Genetics. 2012 Sep;192(1):185-93 [22732191] Mol Cell. 2013 Feb 7;49(3):464-73 [23260660] J Biol Chem. 2013 Jun 14;288(24):17225-37 [23612975] J Biol Chem. 2014 Jul 25;289(30):21120-30 [24920671] J Biol Chem. 2014 Nov 7;289(45):31066-76 [25217638] Curr Pharm Biotechnol. 2014;15(11):1008-18 [25373385] Prion. 2015;9(2):80-9 [25738774] Acta Neuropathol Commun. 2015;3:44 [26205529] J Biol Chem. 2015 Oct 9;290(41):25062-71 [26265470] Nat Genet. 1999 Dec;23(4):425-8 [10581028] Mol Cell Biol. 2000 Dec;20(23):8916-22 [11073991] Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1459-64 [11171973] Acta Myol. 2014 May;33(1):1-12 [24843229] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1074/jbc.M115.700393 ER - TY - JOUR T1 - Normal vs cancer thyroid stem cells: the road to transformation. AN - 1767071290; 25961919 AB - Recent investigations in thyroid carcinogenesis have led to the isolation and characterisation of a subpopulation of stem-like cells, responsible for tumour initiation, progression and metastasis. Nevertheless, the cellular origin of thyroid cancer stem cells (SCs) remains unknown and it is still necessary to define the process and the target population that sustain malignant transformation of tissue-resident SCs or the reprogramming of a more differentiated cell. Here, we will critically discuss new insights into thyroid SCs as a potential source of cancer formation in light of the available information on the oncogenic role of genetic modifications that occur during thyroid cancer development. Understanding the fine mechanisms that regulate tumour transformation may provide new ground for clinical intervention in terms of prevention, diagnosis and therapy. JF - Oncogene AU - Zane, M AU - Scavo, E AU - Catalano, V AU - Bonanno, M AU - Todaro, M AU - De Maria, R AU - Stassi, G AD - Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy. ; Regina Elena National Cancer Institute, Rome, Italy. Y1 - 2016/02/18/ PY - 2016 DA - 2016 Feb 18 SP - 805 EP - 815 VL - 35 IS - 7 KW - Index Medicus KW - Humans KW - Cell Transformation, Neoplastic -- pathology KW - Thyroid Gland -- pathology KW - Neoplastic Stem Cells -- pathology KW - Thyroid Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767071290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Normal+vs+cancer+thyroid+stem+cells%3A+the+road+to+transformation.&rft.au=Zane%2C+M%3BScavo%2C+E%3BCatalano%2C+V%3BBonanno%2C+M%3BTodaro%2C+M%3BDe+Maria%2C+R%3BStassi%2C+G&rft.aulast=Zane&rft.aufirst=M&rft.date=2016-02-18&rft.volume=35&rft.issue=7&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2015.138 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-18 N1 - Date created - 2016-02-18 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2015.138 ER - TY - JOUR T1 - ENmix: a novel background correction method for Illumina HumanMethylation450 BeadChip. AN - 1767068341; 26384415 AB - The Illumina HumanMethylation450 BeadChip is increasingly utilized in epigenome-wide association studies, however, this array-based measurement of DNA methylation is subject to measurement variation. Appropriate data preprocessing to remove background noise is important for detecting the small changes that may be associated with disease. We developed a novel background correction method, ENmix, that uses a mixture of exponential and truncated normal distributions to flexibly model signal intensity and uses a truncated normal distribution to model background noise. Depending on data availability, we employ three approaches to estimate background normal distribution parameters using (i) internal chip negative controls, (ii) out-of-band Infinium I probe intensities or (iii) combined methylated and unmethylated intensities. We evaluate ENmix against other available methods for both reproducibility among duplicate samples and accuracy of methylation measurement among laboratory control samples. ENmix out-performed other background correction methods for both these measures and substantially reduced the probe-design type bias between Infinium I and II probes. In reanalysis of existing EWAS data we show that ENmix can identify additional CpGs, and results in smaller P-value estimates for previously-validated CpGs. We incorporated the method into R package ENmix, which is freely available from Bioconductor website. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. JF - Nucleic acids research AU - Xu, Zongli AU - Niu, Liang AU - Li, Leping AU - Taylor, Jack A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA. ; Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, USA. ; Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA li3@niehs.nih.gov. ; Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA taylor@niehs.nih.gov. Y1 - 2016/02/18/ PY - 2016 DA - 2016 Feb 18 SP - 1 VL - 44 IS - 3 KW - DNA Probes KW - 0 KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Epigenesis, Genetic KW - Genome-Wide Association Study KW - DNA Methylation KW - Oligonucleotide Array Sequence Analysis -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1767068341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=ENmix%3A+a+novel+background+correction+method+for+Illumina+HumanMethylation450+BeadChip.&rft.au=Xu%2C+Zongli%3BNiu%2C+Liang%3BLi%2C+Leping%3BTaylor%2C+Jack+A&rft.aulast=Xu&rft.aufirst=Zongli&rft.date=2016-02-18&rft.volume=44&rft.issue=3&rft.spage=e20&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/10.1093%2Fnar%2Fgkv907 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-08 N1 - Date created - 2016-02-18 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Biostatistics. 2003 Apr;4(2):249-64 [12925520] Biostatistics. 2007 Jan;8(1):118-27 [16632515] PLoS One. 2009;4(12):e8274 [20019873] Mol Biotechnol. 2010 Jan;44(1):71-81 [19842073] Genomics. 2011 Oct;98(4):288-95 [21839163] Epigenomics. 2011 Dec;3(6):771-84 [22126295] Epigenomics. 2012 Jun;4(3):325-41 [22690668] Genome Biol. 2012;13(6):R44 [22703947] Environ Health Perspect. 2012 Oct;120(10):1425-31 [22851337] BMC Bioinformatics. 2012;13:86 [22568884] Bioinformatics. 2013 Jan 15;29(2):189-96 [23175756] Nat Biotechnol. 2013 Feb;31(2):142-7 [23334450] Nat Struct Mol Biol. 2013 Mar;20(3):274-81 [23463312] Epigenetics. 2013 Mar;8(3):333-46 [23422812] Nucleic Acids Res. 2013 Apr;41(7):e90 [23476028] J Natl Cancer Inst. 2013 May 15;105(10):694-700 [23578854] BMC Genomics. 2013;14:293 [23631413] Environ Health Perspect. 2014 Oct;122(10):1147-53 [24906187] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/nar/gkv907 ER - TY - JOUR T1 - Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis. AN - 1765921750; 26876222 AB - Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8(th) week post infection) and late (16(th) week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10(th) month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone. JF - Scientific reports AU - Hammam, Olfat A AU - Elkhafif, Nagwa AU - Attia, Yasmeen M AU - Mansour, Mohamed T AU - Elmazar, Mohamed M AU - Abdelsalam, Rania M AU - Kenawy, Sanaa A AU - El-Khatib, Aiman S AD - Department of Pathology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt. ; Department of Electron Microscopy, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt. ; Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, P.O. Box 43, Cairo 11837, Egypt. ; Department of Virology and Immunology, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr El-Aini, Cairo 11712, Egypt. ; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt. Y1 - 2016/02/15/ PY - 2016 DA - 2016 Feb 15 SP - 21005 VL - 6 KW - Praziquantel KW - 6490C9U457 KW - Index Medicus KW - Animals KW - Schistosoma mansoni -- pathogenicity KW - Schistosoma mansoni -- drug effects KW - Humans KW - Mice KW - Cell- and Tissue-Based Therapy KW - Praziquantel -- administration & dosage KW - Mesenchymal Stromal Cells -- cytology KW - Schistosomiasis mansoni -- therapy KW - Liver Cirrhosis -- parasitology KW - Liver Cirrhosis -- pathology KW - Wharton Jelly -- cytology KW - Schistosomiasis mansoni -- parasitology KW - Wharton Jelly -- transplantation KW - Schistosomiasis mansoni -- pathology KW - Mesenchymal Stem Cell Transplantation KW - Liver Cirrhosis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1765921750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scientific+reports&rft.atitle=Wharton%27s+jelly-derived+mesenchymal+stem+cells+combined+with+praziquantel+as+a+potential+therapy+for+Schistosoma+mansoni-induced+liver+fibrosis.&rft.au=Hammam%2C+Olfat+A%3BElkhafif%2C+Nagwa%3BAttia%2C+Yasmeen+M%3BMansour%2C+Mohamed+T%3BElmazar%2C+Mohamed+M%3BAbdelsalam%2C+Rania+M%3BKenawy%2C+Sanaa+A%3BEl-Khatib%2C+Aiman+S&rft.aulast=Hammam&rft.aufirst=Olfat&rft.date=2016-02-15&rft.volume=6&rft.issue=&rft.spage=21005&rft.isbn=&rft.btitle=&rft.title=Scientific+reports&rft.issn=2045-2322&rft_id=info:doi/10.1038%2Fsrep21005 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-16 N1 - Date created - 2016-02-15 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Immunol Today. 2000 Sep;21(9):465-6 [10953099] Biochemistry. 2015 May 19;54(19):3110-21 [25897652] Methods. 2001 Dec;25(4):402-8 [11846609] Annu Rev Immunol. 2003;21:425-56 [12615888] Bone. 2003 Dec;33(6):919-26 [14678851] Histopathology. 1990 Jan;16(1):53-8 [2307416] Semin Liver Dis. 1990 Feb;10(1):1-10 [2186485] Curr Opin Immunol. 1995 Aug;7(4):505-11 [7495514] J Hepatol. 1998 Sep;29(3):455-63 [9764994] Am J Trop Med Hyg. 1962 Mar;11:201-15 [14484966] Am J Pathol. 1962 Dec;41:711-31 [13930476] Trans R Soc Trop Med Hyg. 1962 Nov;56:510-9 [13998984] Hepatology. 2004 Dec;40(6):1275-84 [15562440] Liver Int. 2005 Apr;25(2):420-8 [15780068] Biochem Biophys Res Commun. 2005 May 20;330(4):1153-61 [15823564] Biochem Biophys Res Commun. 2005 Jun 24;332(1):297-303 [15896330] Clin Exp Metastasis. 2005;22(4):285-95 [16170665] Stem Cells. 2006 Mar;24(3):781-92 [16223852] Cytotherapy. 2006;8(3):215-27 [16793731] Cytotherapy. 2006;8(4):315-7 [16923606] J Pathol. 2008 Jan;214(2):199-210 [18161745] Pharm Res. 2008 Feb;25(2):249-58 [17577645] Gastroenterology. 2008 Mar;134(3):833-48 [18243183] Differentiation. 2008 Dec;76(10):1057-67 [18557762] Liver Transpl. 2009 May;15(5):484-95 [19399744] Hepatology. 2009 Jul;50(1):230-43 [19441105] Cytotherapy. 2009;11(5):548-58 [19657806] Am J Pathol. 2010 Jan;176(1):85-97 [20008127] APMIS. 2011 Jan;119(1):66-75 [21143528] Cell Transplant. 2010;19(11):1451-63 [20587139] PLoS One. 2011;6(5):e20247 [21629648] Cell Immunol. 2011;272(1):33-8 [22004796] In Vitro Cell Dev Biol Anim. 2012 Feb;48(2):75-83 [22274909] Immunology. 2004 Mar;111(3):343-52 [15009436] Rev Inst Med Trop Sao Paulo. 1974 May-Jun;16(3):132-4 [4418583] Z Parasitenkd. 1977 Jul 21;52(2):129-50 [410178] Histochem J. 1979 Jul;11(4):447-55 [91593] J Histochem Cytochem. 1981 Apr;29(4):577-80 [6166661] Hepatology. 1982 May-Jun;2(3):366-71 [7076120] Mol Biochem Parasitol. 1983 Dec;9(4):289-95 [6318107] Ann Trop Med Parasitol. 1986 Apr;80(2):189-96 [3092752] Am Rev Respir Dis. 1990 Feb;141(2):307-13 [2301849] Exp Biol Med (Maywood). 2012 May;237(5):585-92 [22678013] Biochem Biophys Res Commun. 2012 Jun 15;422(4):539-45 [22580002] Hepatobiliary Pancreat Dis Int. 2012 Aug 15;11(4):360-71 [22893462] Parasitol Res. 2012 Nov;111(5):1871-7 [23052781] Stem Cells Dev. 2012 Dec 10;21(18):3309-23 [22651824] Am J Respir Crit Care Med. 2013 Oct 1;188(7):820-30 [23924232] Toxicol In Vitro. 2014 Feb;28(1):113-9 [23820183] Matrix Biol. 2014 Feb;34:132-43 [24140982] Exp Parasitol. 2014 Jul;142:17-26 [24746639] Mediators Inflamm. 2014;2014:753483 [25110399] Biol Neonate. 2001;80(3):202-9 [11585983] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/srep21005 ER - TY - JOUR T1 - Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study). AN - 1762959365; 26540314 AB - Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression. This open-label, randomized phase 2 trial recruited chemotherapy-naive patients with advanced BTC displaying a wild-type (WT) KRAS status. Patients were randomized to gemcitabine (1000 mg/m(2) ) and oxaliplatin (100 mg/m(2) ) with (arm A) or without (arm B) panitumumab (6 mg/kg) for up to 12 cycles. The primary endpoint was progression-free survival (PFS) analyzed in an intention-to-treat fashion. Eighty-nine patients (45 in arm A and 44 in arm B) were enrolled between June 2010 and September 2013. After a median follow-up of 10.1 months, the median PFS was 5.3 months (95% confidence interval, 3.3-7.2 months) in arm A and 4.4 months (95% confidence interval, 2.6-6.2 months) in arm B (P = .27). No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). As for safety, skin toxicity was the main adverse event in arm A (80% of the patients). A higher incidence of diarrhea (55.5% vs 31.8%), mucositis (22.2% vs 13.6%), and constipation (24.4% vs 15.9%) was seen in arm A. These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC. © 2015 American Cancer Society. JF - Cancer AU - Leone, Francesco AU - Marino, Donatella AU - Cereda, Stefano AU - Filippi, Roberto AU - Belli, Carmen AU - Spadi, Rosella AU - Nasti, Guglielmo AU - Montano, Massimo AU - Amatu, Alessio AU - Aprile, Giuseppe AU - Cagnazzo, Celeste AU - Fasola, Gianpiero AU - Siena, Salvatore AU - Ciuffreda, Libero AU - Reni, Michele AU - Aglietta, Massimo AD - Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy. ; Department of Medical Oncology, San Raffaele Scientific Institute, IRCCS, Milan, Italy. ; Department of Oncology, Medical Oncology 1 Division, Città Della Salute e Della Scienza Hospital and University, Turin, Italy. ; Department of Colorectal Oncology, National Cancer Institute G. Pascale Foundation, Naples, Italy. ; Niguarda Cancer Center, Niguarda Ca' Granda Hospita, Milan, Italy. ; Department of Oncology, University and General Hospital, Udine, Italy. Y1 - 2016/02/15/ PY - 2016 DA - 2016 Feb 15 SP - 574 EP - 581 VL - 122 IS - 4 KW - Antibodies, Monoclonal KW - 0 KW - KRAS protein, human KW - Organoplatinum Compounds KW - oxaliplatin KW - 04ZR38536J KW - Deoxycytidine KW - 0W860991D6 KW - panitumumab KW - 6A901E312A KW - gemcitabine KW - B76N6SBZ8R KW - EGFR protein, human KW - EC 2.7.10.1 KW - Receptor, Epidermal Growth Factor KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Abridged Index Medicus KW - Index Medicus KW - gemcitabine and oxaliplatin (GEMOX) KW - KRAS KW - cholangiocarcinoma KW - biliary cancer KW - chemotherapy KW - Biliary Tract Neoplasms -- pathology KW - Disease-Free Survival KW - Organoplatinum Compounds -- administration & dosage KW - Humans KW - Deoxycytidine -- analogs & derivatives KW - Prognosis KW - Aged KW - Adenocarcinoma -- genetics KW - Antibodies, Monoclonal -- administration & dosage KW - Biliary Tract Neoplasms -- drug therapy KW - Adenocarcinoma -- pathology KW - Adult KW - Biliary Tract Neoplasms -- genetics KW - Treatment Outcome KW - Deoxycytidine -- administration & dosage KW - Middle Aged KW - Adenocarcinoma -- drug therapy KW - Male KW - Female KW - Proto-Oncogene Proteins p21(ras) -- genetics KW - Bile Duct Neoplasms -- genetics KW - Receptor, Epidermal Growth Factor -- antagonists & inhibitors KW - Bile Duct Neoplasms -- drug therapy KW - Gallbladder Neoplasms -- drug therapy KW - Cholangiocarcinoma -- pathology KW - Cholangiocarcinoma -- genetics KW - Gallbladder Neoplasms -- pathology KW - Bile Duct Neoplasms -- pathology KW - Bile Ducts, Intrahepatic -- pathology KW - Cholangiocarcinoma -- drug therapy KW - Gallbladder Neoplasms -- genetics KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Bile Ducts, Extrahepatic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762959365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer&rft.atitle=Panitumumab+in+combination+with+gemcitabine+and+oxaliplatin+does+not+prolong+survival+in+wild-type+KRAS+advanced+biliary+tract+cancer%3A+A+randomized+phase+2+trial+%28Vecti-BIL+study%29.&rft.au=Leone%2C+Francesco%3BMarino%2C+Donatella%3BCereda%2C+Stefano%3BFilippi%2C+Roberto%3BBelli%2C+Carmen%3BSpadi%2C+Rosella%3BNasti%2C+Guglielmo%3BMontano%2C+Massimo%3BAmatu%2C+Alessio%3BAprile%2C+Giuseppe%3BCagnazzo%2C+Celeste%3BFasola%2C+Gianpiero%3BSiena%2C+Salvatore%3BCiuffreda%2C+Libero%3BReni%2C+Michele%3BAglietta%2C+Massimo&rft.aulast=Leone&rft.aufirst=Francesco&rft.date=2016-02-15&rft.volume=122&rft.issue=4&rft.spage=574&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=1097-0142&rft_id=info:doi/10.1002%2Fcncr.29778 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-20 N1 - Date created - 2016-02-05 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT01389414; ClinicalTrials.gov N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/cncr.29778 ER - TY - JOUR T1 - Monomeric Aβ(1-40) and Aβ(1-42) Peptides in Solution Adopt Very Similar Ramachandran Map Distributions That Closely Resemble Random Coil. AN - 1764339723; 26780756 AB - The pathogenesis of Alzheimer's disease is characterized by the aggregation and fibrillation of amyloid peptides Aβ(1-40) and Aβ(1-42) into amyloid plaques. Despite strong potential therapeutic interest, the structural pathways associated with the conversion of monomeric Aβ peptides into oligomeric species remain largely unknown. In particular, the higher aggregation propensity and associated toxicity of Aβ(1-42) compared to that of Aβ(1-40) are poorly understood. To explore in detail the structural propensity of the monomeric Aβ(1-40) and Aβ(1-42) peptides in solution, we recorded a large set of nuclear magnetic resonance (NMR) parameters, including chemical shifts, nuclear Overhauser effects (NOEs), and J couplings. Systematic comparisons show that at neutral pH the Aβ(1-40) and Aβ(1-42) peptides populate almost indistinguishable coil-like conformations. Nuclear Overhauser effect spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings ((3)JHNHα, (3)JC'C', (3)JC'Hα, (1)JHαCα, (2)JNCα, and (1)JNCα) recorded for Aβ(1-40) were used as input for the recently developed MERA Ramachandran map analysis, yielding residue-specific backbone ϕ/ψ torsion angle distributions that closely resemble random coil distributions, the absence of a significantly elevated propensity for β-conformations in the C-terminal region of the peptide, and a small but distinct propensity for αL at K28. Our results suggest that the self-association of Aβ peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt β-strand-like conformations. Instead, the accelerated disappearance of Aβ NMR signals in D2O over H2O, particularly pronounced for Aβ(1-42), suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process. JF - Biochemistry AU - Roche, Julien AU - Shen, Yang AU - Lee, Jung Ho AU - Ying, Jinfa AU - Bax, Ad AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892-0510, United States. Y1 - 2016/02/09/ PY - 2016 DA - 2016 Feb 09 SP - 762 EP - 775 VL - 55 IS - 5 KW - Amyloid beta-Peptides KW - 0 KW - Peptide Fragments KW - Solutions KW - amyloid beta-protein (1-40) KW - amyloid beta-protein (1-42) KW - Index Medicus KW - Protein Conformation KW - Magnetic Resonance Spectroscopy KW - Peptide Fragments -- chemistry KW - Amyloid beta-Peptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1764339723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Monomeric+A%CE%B2%281-40%29+and+A%CE%B2%281-42%29+Peptides+in+Solution+Adopt+Very+Similar+Ramachandran+Map+Distributions+That+Closely+Resemble+Random+Coil.&rft.au=Roche%2C+Julien%3BShen%2C+Yang%3BLee%2C+Jung+Ho%3BYing%2C+Jinfa%3BBax%2C+Ad&rft.aulast=Roche&rft.aufirst=Julien&rft.date=2016-02-09&rft.volume=55&rft.issue=5&rft.spage=762&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=1520-4995&rft_id=info:doi/10.1021%2Facs.biochem.5b01259 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-22 N1 - Date created - 2016-02-09 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Biochemistry. 2009 Sep 1;48(34):8120-8 [19618915] J Am Chem Soc. 2010 Jul 28;132(29):9948-51 [20604554] Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15595-600 [20713699] J Mol Biol. 2011 Jan 14;405(2):570-83 [21056574] J Biomol NMR. 2011 Feb;49(2):139-49 [21234644] FEBS Lett. 2011 Apr 6;585(7):1097-102 [21402073] Nature. 2011 Dec 8;480(7376):268-72 [22037310] Biochemistry. 2012 Jan 17;51(2):631-42 [22242826] Nat Neurosci. 2012 Mar;15(3):349-57 [22286176] Biochem Biophys Res Commun. 2012 May 11;421(3):554-60 [22525674] J Biomol NMR. 2012 Mar;52(3):211-32 [22314702] Biochem Biophys Res Commun. 2000 Jul 14;273(3):1003-7 [10891362] J Struct Biol. 2000 Jun;130(2-3):130-41 [10940221] Amyloid. 2000 Sep;7(3):166-78 [11019857] Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2352-7 [11226243] Trends Neurosci. 2001 Apr;24(4):219-24 [11250006] J Biomol NMR. 2001 Apr;19(4):305-20 [11370777] Nat Neurosci. 2001 Sep;4(9):859-60 [11528409] J Biomol NMR. 2001 Aug;20(4):297-310 [11563554] Eur J Biochem. 2001 Nov;268(22):5930-6 [11722581] J Neurosci Res. 2002 Sep 1;69(5):567-77 [12210822] Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16742-7 [12481027] J Am Chem Soc. 2004 Feb 25;126(7):1992-2005 [14971932] J Am Chem Soc. 2004 May 26;126(20):6232-3 [15149211] J Phys Chem. 1965 Sep;69(9):3132-44 [5845676] J Mol Biol. 1984 Dec 15;180(3):741-51 [6084720] Sci Am. 1991 Jan;264(1):54-7, 60-3 [1992509] Biochemistry. 1993 May 11;32(18):4693-7 [8490014] J Biomol NMR. 1994 Nov;4(6):871-8 [7812158] J Biomol NMR. 1995 Nov;6(3):277-93 [8520220] Fold Des. 1996;1(5):R95-106 [9080177] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12366-71 [9356455] J Mol Biol. 1998 Dec 18;284(5):1597-609 [9878373] Biochemistry. 2005 Feb 8;44(5):1444-52 [15683229] J Neurosci. 2005 Feb 2;25(5):1071-80 [15689542] Proteins. 2005 Mar 1;58(4):852-4 [15657933] Protein Sci. 2005 Jun;14(6):1581-96 [15930005] FEBS J. 2005 Aug;272(15):3938-49 [16045764] Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17342-7 [16293696] Nature. 2006 Mar 16;440(7082):352-7 [16541076] Magn Reson Chem. 2006 Jul;44 Spec No:S114-21 [16826550] Acc Chem Res. 2006 Sep;39(9):635-45 [16981680] J Mol Biol. 2006 Dec 15;364(5):853-62 [17046788] J Biomol NMR. 2007 Mar;37(3):195-204 [17245527] Biopolymers. 2007 Feb 15;85(3):264-73 [17143859] J Mol Biol. 2007 May 18;368(5):1448-57 [17397862] J Am Chem Soc. 2007 Aug 1;129(30):9377-85 [17608477] Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16522-7 [17940047] Biochemistry. 2012 Jun 26;51(25):5004-13 [22694188] J Mol Biol. 2012 Aug 10;421(2-3):160-71 [22406275] Nat Struct Mol Biol. 2012 Oct;19(10):1053-7 [22940676] Biophys J. 2008 Jan 15;94(2):379-91 [17890392] Nature. 2008 Feb 7;451(7179):720-4 [18256671] Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5099-104 [18375754] J Am Chem Soc. 2008 Apr 23;130(16):5394-5 [18376837] J Am Chem Soc. 2008 May 14;130(19):6145-58 [18412346] Curr Alzheimer Res. 2008 Jun;5(3):319-41 [18537546] J Chem Phys. 2013 Mar 7;138(9):094112 [23485282] Biophys J. 2013 Jun 18;104(12):2714-24 [23790380] J Mol Biol. 2014 Feb 6;426(3):722-34 [24211721] Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1548-51 [24449148] J Am Chem Soc. 2014 Mar 12;136(10):3752-5 [24568736] J Magn Reson. 2014 Apr;241:97-102 [24360766] J Biol Inorg Chem. 2014 Jun;19(4-5):623-34 [24737040] Nat Rev Mol Cell Biol. 2014 Jun;15(6):384-96 [24854788] J Phys Chem B. 2014 Jun 19;118(24):6405-16 [24410358] Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9384-9 [24938782] Protein Sci. 2014 Sep;23(9):1275-90 [24976112] Chem Soc Rev. 2014 Oct 7;43(19):6692-700 [24464312] Angew Chem Int Ed Engl. 2014 Sep 22;53(39):10345-9 [25130489] J Am Chem Soc. 2015 Feb 4;137(4):1432-5 [25590347] Chemphyschem. 2015 Feb 23;16(3):572-8 [25511552] Chembiochem. 2015 Mar 2;16(4):659-69 [25676345] Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5407-12 [25825723] Neuron. 2015 May 6;86(3):632-45 [25950632] Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9614-9 [26195786] J Biomol NMR. 2015 Sep;63(1):85-95 [26219516] J Biomol NMR. 2016 Jan;64(1):1-7 [26660434] Phys Chem Chem Phys. 2016 Feb 17;18(8):5759-70 [26415896] Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8926-31 [18579777] J Biol Chem. 2009 Feb 20;284(8):4749-53 [18845536] J Biomol NMR. 2009 May;44(1):35-42 [19330299] Biochemistry. 2009 Mar 10;48(9):1870-7 [19216516] J Biomol NMR. 2011 Jun;50(2):157-65 [21604143] Biochem Biophys Res Commun. 2011 Jul 29;411(2):312-6 [21726530] Biochemistry. 2011 Sep 6;50(35):7612-28 [21797254] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.biochem.5b01259 ER - TY - JOUR T1 - Selenoprotein Expression in Macrophages Is Critical for Optimal Clearance of Parasitic Helminth Nippostrongylus brasiliensis. AN - 1762965057; 26644468 AB - The plasticity of macrophages is evident in helminthic parasite infections, providing protection from inflammation. Previously we demonstrated that the micronutrient selenium induces a phenotypic switch in macrophage activation from a classically activated (pro-inflammatory; M1/CAM) toward an alternatively activated (anti-inflammatory; M2/AAM) phenotype, where cyclooxygenase (COX)-dependent cyclopentenone prostaglandin J2 (15d-PGJ2) plays a key role. Here, we hypothesize that dietary selenium modulates macrophage polarization toward an AAM phenotype to assist in the increasing clearance of adult Nippostrongylus brasiliensis, a gastrointestinal nematode parasite. Mice on a selenium-adequate (0.08 ppm) diet significantly augmented intestinal AAM presence while decreasing adult worms and fecal egg production when compared with infection of mice on selenium-deficient (<0.01 ppm) diet. Further increase in dietary selenium to supraphysiological levels (0.4 ppm) had very little or no impact on worm expulsion. Normal adult worm clearance and enhanced AAM marker expression were observed in the selenium-supplemented Trsp(fl/fl)Cre(WT) mice that express selenoproteins driven by tRNA(Sec) (Trsp), whereas N. brasiliensis-infected Trsp(fl/fl)Cre(LysM) selenium-supplemented mice showed a decreased clearance, with lowered intestinal expression of several AAM markers. Inhibition of the COX pathway with indomethacin resulted in delayed worm expulsion in selenium-adequate mice. This was rescued with 15d-PGJ2, which partially recapitulated the effect of selenium supplementation on fecal egg output in addition to increasing markers of AAMs in the small intestine. Antagonism of PPARγ blocked the effect of selenium. These results suggest that optimal expression of selenoproteins and selenium-dependent production of COX-derived endogenous prostanoids, such as Δ(12)-PGJ2 and 15d-PGJ2, may regulate AAM activation to enhance anti-helminthic parasite responses. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Nelson, Shakira M AU - Shay, Ashley E AU - James, Jamaal L AU - Carlson, Bradley A AU - Urban, Joseph F AU - Prabhu, K Sandeep AD - From the Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, Division of Cancer Epidemiology and Genetics, NCI, National Institutes of Health, Rockville, Maryland 20850. ; From the Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802. ; Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, NCI, National Institutes of Health, Bethesda, Maryland 20892, and. ; United States Department of Agriculture, Agriculture Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland 20705. ; From the Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, ksprabhu@psu.edu. Y1 - 2016/02/05/ PY - 2016 DA - 2016 Feb 05 SP - 2787 EP - 2798 VL - 291 IS - 6 KW - 15-deoxyprostaglandin J2 KW - 0 KW - Selenoproteins KW - delta(12)-prostaglandin J(2) KW - Selenium KW - H6241UJ22B KW - Prostaglandin D2 KW - RXY07S6CZ2 KW - Index Medicus KW - selenoprotein KW - inflammation KW - selenium KW - prostaglandin KW - parasite KW - macrophage KW - resolution of inflammation KW - Animals KW - Prostaglandin D2 -- immunology KW - Prostaglandin D2 -- analogs & derivatives KW - Selenium -- pharmacology KW - Mice KW - Dietary Supplements KW - Male KW - Nippostrongylus -- immunology KW - Strongylida Infections -- immunology KW - Macrophages -- pathology KW - Macrophages -- immunology KW - Gene Expression Regulation -- immunology KW - Macrophage Activation KW - Selenoproteins -- immunology KW - Macrophages -- parasitology KW - Strongylida Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762965057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Selenoprotein+Expression+in+Macrophages+Is+Critical+for+Optimal+Clearance+of+Parasitic+Helminth+Nippostrongylus+brasiliensis.&rft.au=Nelson%2C+Shakira+M%3BShay%2C+Ashley+E%3BJames%2C+Jamaal+L%3BCarlson%2C+Bradley+A%3BUrban%2C+Joseph+F%3BPrabhu%2C+K+Sandeep&rft.aulast=Nelson&rft.aufirst=Shakira&rft.date=2016-02-05&rft.volume=291&rft.issue=6&rft.spage=2787&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/10.1074%2Fjbc.M115.684738 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-27 N1 - Date created - 2016-02-06 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Immunol. 2002 Oct 15;169(8):4417-22 [12370375] PLoS One. 2015;10(10):e0140353 [26452064] Trends Immunol. 2003 May;24(5):269-77 [12738422] J Immunol. 2003 Jul 15;171(2):948-54 [12847266] Immunity. 2003 Sep;19(3):329-39 [14499109] J Helminthol. 1986 Dec;60(4):260-2 [3794288] Immunity. 1998 Feb;8(2):255-64 [9492006] Infect Immun. 2005 Jan;73(1):385-94 [15618176] Exp Parasitol. 2005 Apr;109(4):201-8 [15755417] Nat Med. 2006 Aug;12(8):955-60 [16892038] Antioxid Redox Signal. 2007 Jul;9(7):775-806 [17508906] J Leukoc Biol. 2007 Jun;81(6):1434-44 [17339609] Eur J Immunol. 2007 Jun;37(6):1642-52 [17458857] J Biol Chem. 2007 Jun 22;282(25):17964-73 [17439952] Nature. 2007 Jun 28;447(7148):1116-20 [17515919] Curr Opin Immunol. 2007 Aug;19(4):448-53 [17702561] Nat Rev Immunol. 2007 Dec;7(12):975-87 [18007680] Parasite Immunol. 2007 Dec;29(12):609-19 [18042168] Curr Protoc Immunol. 2001 May;Chapter 3:Unit 3.19 [18432783] Curr Protoc Immunol. 2003 Aug;Chapter 19:Unit 19.12 [18432905] Gastroenterology. 2008 Jul;135(1):217-225.e1 [18471439] Biochem J. 2009 Aug 15;422(1):11-22 [19627257] FASEB J. 2009 Aug;23(8):2394-402 [19351701] J Exp Med. 2009 Sep 28;206(10):2059-66 [19770272] BMC Immunol. 2009;10:57 [19863805] Chem Res Toxicol. 2009 Aug;22(8):1376-85 [19645497] J Exp Med. 2009 Dec 21;206(13):2947-57 [19995957] Parasitol Res. 2010 May;106(6):1293-8 [20195635] Circ Res. 2010 May 28;106(10):1559-69 [20508200] Immunobiology. 2010 Sep-Oct;215(9-10):704-8 [20594611] Immunity. 2010 Nov 24;33(5):699-712 [21093321] Nat Med. 2001 Jan;7(1):48-52 [11135615] Immunity. 2001 Aug;15(2):303-11 [11520464] J Immunol. 2001 Dec 1;167(11):6078-81 [11714764] Mol Cell Biol. 2002 Jun;22(11):3565-76 [11997494] J Immunol. 2002 Jul 15;169(2):1021-7 [12097410] Biochem J. 2002 Aug 15;366(Pt 1):203-9 [12006087] Nat Rev Immunol. 2011 Jun;11(6):375-88 [21610741] J Biol Chem. 2011 Aug 5;286(31):27471-82 [21669866] J Nutr. 2011 Sep;141(9):1754-61 [21775527] Nat Rev Immunol. 2011 Nov;11(11):750-61 [22025054] J Immunol. 2012 Jan 15;188(2):615-23 [22156341] Infect Immun. 2013 Jul;81(7):2546-53 [23649095] Nat Immunol. 2014 Oct;15(10):938-46 [25173346] Mol Cell Proteomics. 2014 Oct;13(10):2736-51 [24994561] Nat Immunol. 2015 Feb;16(2):161-9 [25531830] Antioxid Redox Signal. 2015 Oct 1;23(10):854-62 [26058750] J Nutr. 2003 May;133(5 Suppl 1):1457S-9S [12730442] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1074/jbc.M115.684738 ER - TY - JOUR T1 - Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota. AN - 1762964578; 26696396 AB - Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state. JF - Journal of proteome research AU - Cai, Jingwei AU - Zhang, Limin AU - Jones, Richard A AU - Correll, Jared B AU - Hatzakis, Emmanuel AU - Smith, Philip B AU - Gonzalez, Frank J AU - Patterson, Andrew D AD - Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, Pennsylvania State University , University Park, State College, Pennsylvania 16802, United States. ; Department of Chemistry, Pennsylvania State University , University Park, State College, Pennsylvania 16802, United States. ; Metabolomics Facility, Huck Institutes of Life Sciences, Pennsylvania State University , University Park, State College, Pennsylvania 16802, United States. ; Laboratory of Metabolism, National Cancer Institute, NIH , Bethesda, Maryland 20892, United States. Y1 - 2016/02/05/ PY - 2016 DA - 2016 Feb 05 SP - 563 EP - 571 VL - 15 IS - 2 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Spin Labels KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - bomb calorimetry KW - GC−MS KW - obesity KW - SCFAs KW - NMR KW - metabolomics KW - Gene Expression -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Energy Metabolism -- genetics KW - Gastrointestinal Tract -- metabolism KW - Liver -- metabolism KW - Gastrointestinal Tract -- microbiology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Inbred BALB C KW - Host-Pathogen Interactions KW - Antioxidants -- pharmacology KW - Liver -- drug effects KW - Energy Metabolism -- drug effects KW - Gastrointestinal Tract -- drug effects KW - Gas Chromatography-Mass Spectrometry KW - Male KW - Gastrointestinal Microbiome -- drug effects KW - Metabolomics -- methods KW - Metabolome -- drug effects KW - Cyclic N-Oxides -- pharmacology KW - Metabolome -- genetics KW - Gastrointestinal Microbiome -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762964578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+proteome+research&rft.atitle=Antioxidant+Drug+Tempol+Promotes+Functional+Metabolic+Changes+in+the+Gut+Microbiota.&rft.au=Cai%2C+Jingwei%3BZhang%2C+Limin%3BJones%2C+Richard+A%3BCorrell%2C+Jared+B%3BHatzakis%2C+Emmanuel%3BSmith%2C+Philip+B%3BGonzalez%2C+Frank+J%3BPatterson%2C+Andrew+D&rft.aulast=Cai&rft.aufirst=Jingwei&rft.date=2016-02-05&rft.volume=15&rft.issue=2&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Journal+of+proteome+research&rft.issn=1535-3907&rft_id=info:doi/10.1021%2Facs.jproteome.5b00957 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-14 N1 - Date created - 2016-02-06 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Nutr. 2003 Nov;133(11):3509-15 [14608066] Environ Health Perspect. 2015 Jul;123(7):679-88 [25768209] Gut. 1981 Sep;22(9):763-79 [7028579] Am J Clin Nutr. 1984 Feb;39(2):338-42 [6320630] Proc Soc Exp Biol Med. 1984 Nov;177(2):372-6 [6091151] J Biol Chem. 1989 Jun 25;264(18):10347-50 [2732225] J Lipid Res. 1991 Jun;32(6):993-9 [1682408] Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18933-8 [20937875] Diabetes. 2010 Dec;59(12):3049-57 [20876719] IUBMB Life. 2010 Dec;62(12):869-77 [21171012] Saudi Med J. 2012 Jan;33(1):70-5 [22273652] Br J Nutr. 2013 Mar 14;109(5):914-9 [23200109] PLoS One. 2013;8(4):e62039 [23620802] Nat Commun. 2013;4:2384 [24064762] Atherosclerosis. 2015 May;240(1):234-41 [25818249] Pharmacol Ther. 2010 May;126(2):119-45 [20153367] Free Radic Biol Med. 2003 Jan 1;34(1):93-102 [12498984] Lancet. 2003 Feb 8;361(9356):512-9 [12583961] Cell Host Microbe. 2013 Nov 13;14(5):582-90 [24237703] PLoS One. 2014;9(2):e87140 [24586264] Genome Biol. 2014;15(6):R76 [24995464] J Clin Invest. 2015 Jan;125(1):386-402 [25500885] Nutrition. 2015 May;31(5):733-9 [25837221] FASEB J. 1992 Apr;6(7):2405-12 [1563593] Bull Soc Chim Biol (Paris). 1954;36(11-12):1525-37 [14378852] Diabetes. 2005 Jul;54(7):2219-26 [15983225] Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5 [16033867] Am J Physiol Endocrinol Metab. 2006 May;290(5):E940-51 [16352677] Nutr Clin Pract. 2006 Aug;21(4):351-66 [16870803] Nature. 2006 Dec 21;444(7122):1022-3 [17183309] Nature. 2006 Dec 21;444(7122):1027-31 [17183312] Niger J Med. 2007 Jan-Mar;16(1):77-8 [17563975] ISME J. 2007 May;1(1):56-66 [18043614] Bratisl Lek Listy. 2007;108(8):354-8 [18203540] Nat Rev Drug Discov. 2008 Feb;7(2):123-9 [18239669] Cell Host Microbe. 2008 Apr 17;3(4):213-23 [18407065] Epilepsia. 2008 Nov;49 Suppl 8:94-6 [19049600] Obesity (Silver Spring). 2010 Jan;18(1):190-5 [19498350] PLoS One. 2010;5(3):e9836 [20352091] J Physiol. 2004 Jul 1;558(Pt 1):5-30 [15131240] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.jproteome.5b00957 ER - TY - JOUR T1 - Epitelial-to-mesenchimal transition and invasion are upmodulated by tumor-expressed granzyme B and inhibited by docosahexaenoic acid in human colorectal cancer cells. AN - 1762346582; 26830472 AB - Granzyme B (GrB) is a serine protease, traditionally known as expressed by cytotoxic lymphocytes to induce target cell apoptosis. However, it is emerging that GrB, being also produced by a variety of normal and neoplastic cells and potentially acting on multiple targets, might represent a powerful regulator of a wide range of fundamental biological processes. We have previously shown that GrB is expressed in urothelial carcinoma tissues and its expression is associated to both pathological tumor spreading and EMT. We have also shown that docosahexaenoic acid (DHA), a dietary ω-3 polyunsaturated fatty acid with anti-tumor activity, while inhibiting urothelial and pancreatic carcinoma cell invasion also inhibited their GrB expression in vitro. In this study, we characterized a panel of colorectal carcinoma (CRC) cells, with different invasive capabilities, for GrB expression and for the contribution of GrB to their EMT and invasive phenotype. In addition, we investigated the effect of DHA on CRC cell-associated GrB expression, EMT and invasion. The expression levels of GrB and EMT-related markers were evaluated by Western blotting. GrB knockdown was performed by Stealth RNAi small interfering RNA silencing and ectopic GrB expression by transfection of human GrB vector. Cell invasion was determined by the BioCoat Matrigel invasion chamber test. GrB was produced in 57.1% CRC cell lines and 100% CRC-derived Cancer Stem Cells. Although GrB was constitutive expressed in both invasive and noninvasive CRC cells, GrB depletion in invasive CRC cells downmodulated their invasion in vitro, suggesting a contribution of GrB to CRC invasiveness. GrB loss or gain of function downmodulated or upmodulated EMT, respectively, according to the analysis of cancer cell expression of three EMT biomarkers (Snail1, E-cadherin, N-cadherin). Moreover, TGF-β1-driven EMT was associated to the enhancement of GrB expression in CRC cell lines, and GrB depletion led to downmodulation of TGF-β1-driven EMT. In addition, DHA inhibited GrB expression, EMT and invasion in CRC cells in vitro. These findings present a novel role for GrB as upmodulator of EMT in CRC cells. Moreover, these results support the use of DHA, a dietary compound without toxic effects, as adjuvant in CRC therapy. JF - Journal of experimental & clinical cancer research : CR AU - D'Eliseo, Donatella AU - Di Rocco, Giuliana AU - Loria, Rossella AU - Soddu, Silvia AU - Santoni, Angela AU - Velotti, Francesca AD - Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161, Rome, Italy. donatella.deliseo@uniroma1.it. ; Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, 00144, Rome, Italy. dirocco@ifo.it. ; Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, 00144, Rome, Italy. loria@ifo.it. ; Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, 00144, Rome, Italy. soddu@ifo.it. ; Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161, Rome, Italy. angela.santoni@uniroma1.it. ; Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell'Università, 01100, Viterbo, Italy. velotti@unitus.it. Y1 - 2016/02/02/ PY - 2016 DA - 2016 Feb 02 SP - 24 VL - 35 KW - Antineoplastic Agents KW - 0 KW - Docosahexaenoic Acids KW - 25167-62-8 KW - GZMB protein, human KW - EC 3.4.21.- KW - Granzymes KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Neoplasm Invasiveness KW - Gene Knockdown Techniques KW - Cell Survival -- drug effects KW - Humans KW - Up-Regulation -- drug effects KW - Cell Line, Tumor KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Neoplastic Stem Cells -- metabolism KW - Neoplastic Stem Cells -- drug effects KW - Granzymes -- genetics KW - Docosahexaenoic Acids -- pharmacology KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- metabolism KW - Epithelial-Mesenchymal Transition -- drug effects KW - Colorectal Neoplasms -- genetics KW - Antineoplastic Agents -- pharmacology KW - Granzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762346582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Epitelial-to-mesenchimal+transition+and+invasion+are+upmodulated+by+tumor-expressed+granzyme+B+and+inhibited+by+docosahexaenoic+acid+in+human+colorectal+cancer+cells.&rft.au=D%27Eliseo%2C+Donatella%3BDi+Rocco%2C+Giuliana%3BLoria%2C+Rossella%3BSoddu%2C+Silvia%3BSantoni%2C+Angela%3BVelotti%2C+Francesca&rft.aulast=D%27Eliseo&rft.aufirst=Donatella&rft.date=2016-02-02&rft.volume=35&rft.issue=&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=1756-9966&rft_id=info:doi/10.1186%2Fs13046-016-0302-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-13 N1 - Date created - 2016-02-02 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Cell Death Differ. 2012 Jan;19(1):28-35 [22052191] Cell. 2011 Nov 23;147(5):992-1009 [22118458] PLoS One. 2012;7(3):e33163 [22479366] J Nutr Biochem. 2012 May;23(5):452-7 [21684140] J Androl. 2012 Jul-Aug;33(4):752-60 [22096086] J Biomed Sci. 2012;19:53 [22631075] Trends Mol Med. 2012 Dec;18(12):732-41 [23099058] Br J Cancer. 2013 Feb 19;108(3):486-92 [23299528] Cancer Treat Rev. 2013 Aug;39(5):473-88 [22850619] Biomed Res Int. 2013;2013:310186 [23762838] Cancer Genomics Proteomics. 2013 Jul-Aug;10(4):187-96 [23893926] Br J Surg. 2014 Jan;101(2):33-42 [24281905] Biol Chem. 2014 Feb;395(2):181-202 [24002663] J Natl Cancer Inst. 2014 Feb;106(2):djt369 [24511106] PLoS Genet. 2014 Feb;10(2):e1004177 [24586203] Cancer Gene Ther. 2014 May;21(5):181-7 [24787239] Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1164-75 [24793954] Mol Cell Biol. 2014 Sep 15;34(18):3486-99 [25002532] Gut. 2014 Nov;63(11):1760-8 [24470281] Immunity. 2014 Dec 18;41(6):960-72 [25526309] J Immunol. 2015 Jan 15;194(2):491-7 [25556251] World J Gastroenterol. 2014 Dec 28;20(48):18260-70 [25561793] Biochim Biophys Acta. 2015 Apr;1851(4):469-84 [25149823] CA Cancer J Clin. 2015 Mar;65(2):87-108 [25651787] Nat Rev Immunol. 2015 Jun;15(6):388-400 [25998963] Biochim Biophys Acta. 2015 Aug;1856(1):55-61 [26050961] Clin Nutr. 2016 Apr;35(2):359-69 [25982417] Blood. 2000 Sep 1;96(5):1914-20 [10961894] Leukemia. 2001 Mar;15(3):458-64 [11237071] Cancer Res. 2001 Mar 1;61(5):1927-33 [11280748] Eur J Surg Oncol. 2001 Mar;27(2):180-6 [11289755] J Pathol. 2002 Dec;198(4):468-75 [12434416] Br J Cancer. 2003 Jul 7;89(1):135-9 [12838314] EMBO J. 1987 Apr;6(4):933-8 [3297674] Cancer Cell. 2005 Nov;8(5):369-80 [16286245] J Clin Oncol. 2006 Oct 1;24(28):4626-33 [16954517] Blood. 2006 Oct 15;108(8):2712-9 [16809616] Nature. 2007 Jan 4;445(7123):111-5 [17122771] Regul Pept. 2007 Jun 7;141(1-3):61-72 [17276526] Mol Cell Proteomics. 2009 Feb;8(2):258-72 [18836177] Cancer Invest. 2008 Jun;26(5):499-503 [18568772] BMC Genomics. 2007;8:98 [17425807] Trends Immunol. 2009 Mar;30(3):117-23 [19217825] J Immunol. 2009 Jul 1;183(1):37-40 [19525394] Lab Invest. 2009 Nov;89(11):1195-220 [19770840] Br J Cancer. 2009 Dec 15;101(12):1978-85 [19920822] J Mol Med (Berl). 2009 Nov;87(11):1097-104 [19727638] Gastroenterology. 2010 Apr;138(4):1406-17 [20026115] J Biol Chem. 2010 Jun 11;285(24):18918-27 [20395300] Immunol Rev. 2010 May;235(1):105-16 [20536558] Int J Cancer. 2010 Sep 1;127(6):1283-94 [20027633] Eur J Gynaecol Oncol. 2010;31(4):459-61 [20882896] Nat Rev Cancer. 2012 Apr;12(4):298-306 [22419253] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s13046-016-0302-6 ER - TY - JOUR T1 - Modeling fecundity in the presence of a sterile fraction using a semi-parametric transformation model for grouped survival data AN - 1855340933 AB - The analysis of fecundity data is challenging and requires consideration of both highly timed and interrelated biologic processes in the context of essential behaviors such as sexual intercourse during the fertile window. Understanding human fecundity is further complicated by presence of a sterile population, i.e. couples unable to achieve pregnancy. Modeling techniques conducted to date have largely relied upon discrete time-to-pregnancy survival or day-specific probability models to estimate the determinants of time-to-pregnancy or acute effects, respectively. We developed a class of semi-parametric grouped transformation cure models that capture day-level variates purported to affect the cycle-level hazards of conception and, possibly, sterility . Our model's performance is assessed using simulation and longitudinal data from one of the few prospective cohort studies with preconception enrollment of women followed for 12 menstrual cycles at risk for pregnancy. JF - Statistical Methods in Medical Research AU - McLain, Alexander C AU - Sundaram, Rajeshwari AU - Buck Louis, Germaine M AD - Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA ; Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA Y1 - 2016/02// PY - 2016 DA - Feb 2016 SP - 22 EP - 36 CY - London PB - Sage Publications Ltd. VL - 25 IS - 1 SN - 0962-2802 KW - Medical Sciences KW - Cure fraction KW - fecundity KW - grouped survival KW - transformation models KW - Discrete time KW - Pregnancy KW - At risk KW - Cohort analysis KW - Enrollment KW - Sterility KW - Menstruation KW - Transformation KW - Simulation KW - Hazards KW - Cure KW - Sexual intercourse KW - Women UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1855340933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistical+Methods+in+Medical+Research&rft.atitle=Modeling+fecundity+in+the+presence+of+a+sterile+fraction+using+a+semi-parametric+transformation+model+for+grouped+survival+data&rft.au=McLain%2C+Alexander+C%3BSundaram%2C+Rajeshwari%3BBuck+Louis%2C+Germaine+M&rft.aulast=McLain&rft.aufirst=Alexander&rft.date=2016-02-01&rft.volume=25&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Statistical+Methods+in+Medical+Research&rft.issn=09622802&rft_id=info:doi/10.1177%2F0962280212438646 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2012 N1 - Last updated - 2017-01-05 DO - http://dx.doi.org/10.1177/0962280212438646 ER - TY - JOUR T1 - QSAR Modeling and Prediction of Drug-Drug Interactions. AN - 1803790057; 26669717 AB - Severe adverse drug reactions (ADRs) are the fourth leading cause of fatality in the U.S. with more than 100,000 deaths per year. As up to 30% of all ADRs are believed to be caused by drug-drug interactions (DDIs), typically mediated by cytochrome P450s, possibilities to predict DDIs from existing knowledge are important. We collected data from public sources on 1485, 2628, 4371, and 27,966 possible DDIs mediated by four cytochrome P450 isoforms 1A2, 2C9, 2D6, and 3A4 for 55, 73, 94, and 237 drugs, respectively. For each of these data sets, we developed and validated QSAR models for the prediction of DDIs. As a unique feature of our approach, the interacting drug pairs were represented as binary chemical mixtures in a 1:1 ratio. We used two types of chemical descriptors: quantitative neighborhoods of atoms (QNA) and simplex descriptors. Radial basis functions with self-consistent regression (RBF-SCR) and random forest (RF) were utilized to build QSAR models predicting the likelihood of DDIs for any pair of drug molecules. Our models showed balanced accuracy of 72-79% for the external test sets with a coverage of 81.36-100% when a conservative threshold for the model's applicability domain was applied. We generated virtually all possible binary combinations of marketed drugs and employed our models to identify drug pairs predicted to be instances of DDI. More than 4500 of these predicted DDIs that were not found in our training sets were confirmed by data from the DrugBank database. JF - Molecular pharmaceutics AU - Zakharov, Alexey V AU - Varlamova, Ekaterina V AU - Lagunin, Alexey A AU - Dmitriev, Alexander V AU - Muratov, Eugene N AU - Fourches, Denis AU - Kuz'min, Victor E AU - Poroikov, Vladimir V AU - Tropsha, Alexander AU - Nicklaus, Marc C AD - Computer-Aided Drug Design Group, Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, NCI-Frederick , 376 Boyles Street, Frederick, Maryland 21702, United States. ; Department of Molecular Structure and Cheminformatics, A.V. Bogatsky Physical Chemical Institute, National Academy of Sciences of Ukraine , Lustdorfskaya Doroga 86, Odessa 65080, Ukraine. ; Institute of Biochemical Chemistry , 10/8, Pogodinskaya street, 119121 Moscow, Russia. ; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina , Beard Hall 301, CB#7568, Chapel Hill, North Carolina 27599, United States. ; Department of Chemistry, Bioinformatics Research Center, North Carolina State University , Raleigh, North Carolina 27695, United States. Y1 - 2016/02/01/ PY - 2016 DA - 2016 Feb 01 SP - 545 EP - 556 VL - 13 IS - 2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - adverse drug reactions KW - toxicity KW - GUSAR KW - mixtures KW - QNA KW - DDI KW - drug−drug interactions KW - simplex descriptors KW - QSAR modeling KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Databases, Factual KW - Models, Biological KW - Drug Interactions KW - Quantitative Structure-Activity Relationship KW - Models, Molecular KW - Cytochrome P-450 Enzyme System -- chemistry KW - Algorithms KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1803790057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmaceutics&rft.atitle=QSAR+Modeling+and+Prediction+of+Drug-Drug+Interactions.&rft.au=Zakharov%2C+Alexey+V%3BVarlamova%2C+Ekaterina+V%3BLagunin%2C+Alexey+A%3BDmitriev%2C+Alexander+V%3BMuratov%2C+Eugene+N%3BFourches%2C+Denis%3BKuz%27min%2C+Victor+E%3BPoroikov%2C+Vladimir+V%3BTropsha%2C+Alexander%3BNicklaus%2C+Marc+C&rft.aulast=Zakharov&rft.aufirst=Alexey&rft.date=2016-02-01&rft.volume=13&rft.issue=2&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmaceutics&rft.issn=1543-8392&rft_id=info:doi/10.1021%2Facs.molpharmaceut.5b00762 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-20 N1 - Date created - 2016-07-07 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.molpharmaceut.5b00762 ER - TY - JOUR T1 - Sensitivity of the modified Children's Yale-Brown Obsessive Compulsive Scale to detect change: Results from two multi-site trials AN - 1790895123 AB - Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all three active treatment groups showed significant improvement (effect sizes: 0.74-0.88). There were no differences between active treatment groups. These results indicate that the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder has acceptable test-retest as evidenced by the medium to high correlations in the placebo group and demonstrated sensitivity to change with treatment. JF - Autism AU - Scahill, Lawrence AU - Sukhodolsky, Denis G AU - Anderberg, Emily AU - Dimitropoulos, Anastasia AU - Dziura, James AU - Aman, Michael G AU - McCracken, James AU - Tierney, Elaine AU - Hallett, Victoria AU - Katz, Karol AU - Vitiello, Benedetto AU - McDougle, Christopher AD - Emory University, USA ; Yale University, USA ; Brigham Young University, University of Washington, USA ; Case Western Reserve University, USA ; The Ohio State University, USA ; University of California, Los Angeles, USA ; Johns Hopkins University, USA ; Kings College London, UK ; National Institute of Mental Health, Child and Adolescent Treatment and Preventive Interventions Research Branch, USA ; Massachusetts General Hospital, USA Y1 - 2016/02// PY - 2016 DA - Feb 2016 SP - 145 EP - 152 CY - London PB - SAGE PUBLICATIONS, INC. VL - 20 IS - 2 SN - 1362-3613 KW - Psychology KW - autism spectrum disorder KW - clinical trials KW - outcome measurement KW - repetitive behavior KW - risperidone KW - Autistic children KW - Autistic spectrum disorders KW - Coefficient alpha KW - Drugs KW - Girls KW - Obsessive-Compulsive neuroses KW - Parenthood education KW - Psychopharmacology KW - Repetitive behaviour KW - Research units KW - Risperidone KW - Sensitivity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1790895123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Autism&rft.atitle=Sensitivity+of+the+modified+Children%27s+Yale-Brown+Obsessive+Compulsive+Scale+to+detect+change%3A+Results+from+two+multi-site+trials&rft.au=Scahill%2C+Lawrence%3BSukhodolsky%2C+Denis+G%3BAnderberg%2C+Emily%3BDimitropoulos%2C+Anastasia%3BDziura%2C+James%3BAman%2C+Michael+G%3BMcCracken%2C+James%3BTierney%2C+Elaine%3BHallett%2C+Victoria%3BKatz%2C+Karol%3BVitiello%2C+Benedetto%3BMcDougle%2C+Christopher&rft.aulast=Scahill&rft.aufirst=Lawrence&rft.date=2016-02-01&rft.volume=20&rft.issue=2&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Autism&rft.issn=13623613&rft_id=info:doi/10.1177%2F1362361315574889 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Copyright - © The Author(s) 2015 N1 - Last updated - 2016-05-25 DO - http://dx.doi.org/10.1177/1362361315574889 ER - TY - JOUR T1 - Chimeric antigen receptor-redirected T cells return to the bench. AN - 1788227300; 26797495 AB - While the clinical progress of chimeric antigen receptor T cell (CAR-T) immunotherapy has garnered attention to the field, our understanding of the biology of these chimeric molecules is still emerging. Our aim within this review is to bring to light the mechanistic understanding of these multi-modular receptors and how these individual components confer particular properties to CAR-Ts. In addition, we will discuss extrinsic factors that can be manipulated to influence CAR-T performance such as choice of cellular population, culturing conditions and additional modifications that enhance their activity particularly in solid tumors. Finally, we will also consider the emerging toxicity associated with CAR-Ts. By breaking apart the CAR and examining the role of each piece, we can build a better functioning cellular vehicle for optimized treatment of cancer patients. Copyright © 2015 Elsevier Ltd. All rights reserved. JF - Seminars in immunology AU - Geldres, Claudia AU - Savoldo, Barbara AU - Dotti, Gianpietro AD - Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, United States. Electronic address: Claudia.Geldres@mail.nih.gov. ; Department of Pediatrics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States. Electronic address: barbar@email.unc.edu. ; Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States. Electronic address: gdotti@med.unc.edu. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 3 EP - 9 VL - 28 IS - 1 KW - Index Medicus KW - Chimeric antigen receptor KW - Adoptive immunotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1788227300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+immunology&rft.atitle=Chimeric+antigen+receptor-redirected+T+cells+return+to+the+bench.&rft.au=Geldres%2C+Claudia%3BSavoldo%2C+Barbara%3BDotti%2C+Gianpietro&rft.aulast=Geldres&rft.aufirst=Claudia&rft.date=2016-02-01&rft.volume=28&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Seminars+in+immunology&rft.issn=1096-3618&rft_id=info:doi/10.1016%2Fj.smim.2015.12.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-05-10 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.smim.2015.12.001 ER - TY - JOUR T1 - Molecular Characterization Reveals Diverse and Unknown Malaria Vectors in the Western Kenyan Highlands AN - 1787964152; PQ0002937373 AB - The success of mosquito-based malaria control is dependent upon susceptible bionomic traits in local malaria vectors. It is crucial to have accurate and reliable methods to determine mosquito species composition in areas subject to malaria. An unexpectedly diverse set of Anopheles species was collected in the western Kenyan highlands, including unidentified and potentially new species carrying the malaria parasite Plasmodium falciparum. This study identified 2,340 anopheline specimens using both ribosomal DNA internal transcribed spacer region 2 and mitochondrial DNA cytochrome oxidase subunit 1 loci. Seventeen distinct sequence groups were identified. Of these, only eight could be molecularly identified through comparison to published and voucher sequences. Of the unidentified species, four were found to carry P. falciparum by circumsporozoite enzyme-linked immunosorbent assay and polymerase chain reaction, the most abundant of which had infection rates comparable to a primary vector in the area, Anopheles funestus. High-quality adult specimens of these unidentified species could not be matched to museum voucher specimens or conclusively identified using multiple keys, suggesting that they may have not been previously described. These unidentified vectors were captured outdoors. Diverse and unknown species have been incriminated in malaria transmission in the western Kenya highlands using molecular identification of unusual morphological variants of field specimens. This study demonstrates the value of using molecular methods to compliment vector identifications and highlights the need for accurate characterization of mosquito species and their associated behaviors for effective malaria control. JF - American Journal of Tropical Medicine and Hygiene AU - St Laurent, Brandyce AU - Cooke, Mary AU - Krishnankutty, Sindhu M AU - Asih, Puji AU - Mueller, John D AU - Kahindi, Samuel AU - Ayoma, Elizabeth AU - Oriango, Robin M AU - Thumloup, Julie AU - Drakeley, Chris AU - Cox, Jonathan AU - Collins, Frank H AU - Lobo, Neil F AU - Stevenson, Jennifer C AD - Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, brandyce.stlaurent@nih.gov Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 327 EP - 335 PB - American Society of Tropical Medicine and Hygiene, 60 Revere Drive, Suite 500 Northbrook IL 60062 United States VL - 94 IS - 2 SN - 0002-9637, 0002-9637 KW - Entomology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Health & Safety Science Abstracts KW - Parasites KW - Bionomics KW - Human diseases KW - Nucleotide sequence KW - Museums KW - Cytochrome-c oxidase KW - Malaria KW - Hosts KW - Infection KW - Public health KW - Disease transmission KW - circumsporozoite protein KW - Population genetics KW - Spacer region KW - Kenya KW - Polymerase chain reaction KW - Species composition KW - Aquatic insects KW - Enzyme-linked immunosorbent assay KW - Vectors KW - Pest control KW - Plasmodium falciparum KW - Keys KW - Mitochondrial DNA KW - Cytochrome KW - Behavior KW - DNA KW - Anopheles funestus KW - Immunoassays KW - New species KW - Z 05310:Taxonomy, Morphology, Geography, and Fossils KW - Q1 08484:Species interactions: parasites and diseases KW - H 0500:General KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1787964152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.atitle=Molecular+Characterization+Reveals+Diverse+and+Unknown+Malaria+Vectors+in+the+Western+Kenyan+Highlands&rft.au=St+Laurent%2C+Brandyce%3BCooke%2C+Mary%3BKrishnankutty%2C+Sindhu+M%3BAsih%2C+Puji%3BMueller%2C+John+D%3BKahindi%2C+Samuel%3BAyoma%2C+Elizabeth%3BOriango%2C+Robin+M%3BThumloup%2C+Julie%3BDrakeley%2C+Chris%3BCox%2C+Jonathan%3BCollins%2C+Frank+H%3BLobo%2C+Neil+F%3BStevenson%2C+Jennifer+C&rft.aulast=St+Laurent&rft.aufirst=Brandyce&rft.date=2016-02-01&rft.volume=94&rft.issue=2&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Tropical+Medicine+and+Hygiene&rft.issn=00029637&rft_id=info:doi/10.4269%2Fajtmh.15-0562 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Population genetics; Human diseases; Nucleotide sequence; Pest control; Malaria; Hosts; Aquatic insects; Disease transmission; Public health; Bionomics; Parasites; Enzyme-linked immunosorbent assay; Museums; Vectors; Cytochrome-c oxidase; Infection; Keys; circumsporozoite protein; Spacer region; Mitochondrial DNA; Polymerase chain reaction; Species composition; New species; Cytochrome; Behavior; DNA; Immunoassays; Anopheles funestus; Plasmodium falciparum; Kenya DO - http://dx.doi.org/10.4269/ajtmh.15-0562 ER - TY - JOUR T1 - Parental smoking during pregnancy and the risk of gestational diabetes in the daughter AN - 1785237790; PQ0002895340 AB - Background: Fetal exposure to parental smoking may have long-term impact on the development of disease in adulthood. We examined the association of parental smoking during pregnancy with risk of gestational diabetes mellitus (GDM) in the daughter.Methods: We included 15665 singleton pregnancies from 10152 women in the Nurses' Health Study II cohort whose mothers participated in the Nurses' Mothers' Cohort Study. Data on maternal and paternal smoking during pregnancy and associated covariates were recalled by the mothers. GDM diagnosis was self-reported by the daughters and was validated by medical record review in a previous study. We used log-binomial models with generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: We observed a positive association between maternal heavy smoking during pregnancy and risk of GDM in the daughter. The multivariable-adjusted RRs (95% CIs) of GDM among women whose mothers did not smoke during pregnancy, continued smoking 1-14, 15-24, and greater than or equal to 25 cigarettes/day were 1.00 (reference), 1.05 (0.81-1.35), 1.27 (0.95-1.70) and 1.98 (1.18-3.30), respectively (P for trend=0.01). Further adjustment for the women's perinatal variables, adult-life characteristics and body mass index during various periods of life modestly attenuated the association. No association was observed between paternal smoking during the pregnancy period and risk of GDM in the daughter.Conclusions: Maternal heavy smoking ( greater than or equal to 25 cigarettes/day) during pregnancy was associated with higher risk of gestational diabetes in the daughter. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. JF - International Journal of Epidemiology AU - Bao, Wei AU - Michels, Karin B AU - Tobias, Deirdre K AU - Li, Shanshan AU - Chavarro, Jorge E AU - Gaskins, Audrey J AU - Vaag, Allan A AU - Hu, Frank B AU - Zhang, Cuilin AD - *Corresponding author. Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Blvd, Rockville, MD 20852, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 160 EP - 169 PB - Oxford University Press, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 45 IS - 1 SN - 0300-5771, 0300-5771 KW - Health & Safety Science Abstracts KW - Gestational diabetes mellitus KW - maternal smoking during pregnancy KW - Diabetes mellitus KW - Smoke KW - Cigarettes KW - Nursing KW - Reviews KW - Body mass KW - Cigarette smoking KW - Medical personnel KW - Pregnancy KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785237790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Epidemiology&rft.atitle=Parental+smoking+during+pregnancy+and+the+risk+of+gestational+diabetes+in+the+daughter&rft.au=Bao%2C+Wei%3BMichels%2C+Karin+B%3BTobias%2C+Deirdre+K%3BLi%2C+Shanshan%3BChavarro%2C+Jorge+E%3BGaskins%2C+Audrey+J%3BVaag%2C+Allan+A%3BHu%2C+Frank+B%3BZhang%2C+Cuilin&rft.aulast=Bao&rft.aufirst=Wei&rft.date=2016-02-01&rft.volume=45&rft.issue=1&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Epidemiology&rft.issn=03005771&rft_id=info:doi/10.1093%2Fije%2Fdyv334 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Smoke; Diabetes mellitus; Cigarettes; Body mass; Reviews; Nursing; Cigarette smoking; Medical personnel; Pregnancy DO - http://dx.doi.org/10.1093/ije/dyv334 ER - TY - JOUR T1 - Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data AN - 1785235725; PQ0002895359 AB - Background: Oesophageal cancer is the fourth leading cause of cancer death in China where essentially all cases are histologically oesophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses of genome-wide association study (GWAS) data combined with tissue-specific expression quantitative trait loci (eQTL) analysis and publicly available functional data can identify biological pathways and/or genes enriched with functionally-relevant disease-associated variants.Method: We used the adaptive multilocus joint test to analyse 1827 pathways containing 6060 genes using GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. We examined the function of risk alleles using in silico and eQTL analyses in oesophageal tissues.Results: Associations with ESCC risk were observed for 36 pathways predominantly involved in apoptosis, cell cycle regulation and DNA repair and containing known GWAS-associated genes. After excluding genes with previous GWAS signals, candidate pathways (and genes) for ESCC risk included taste transduction (KEGG_hsa04742; TAS2R13, TAS2R42, TAS2R14, TAS2R46,TAS2R50), long-patch base excision repair (Reactome_pid; POLD2) and the metabolics pathway (KEGG_hsa01100; MTAP, GAPDH, DCTD, POLD2, AMDHD1). We identified and validated CASP8 rs13016963 and IDH2 rs11630814 as eQTLs, and CASP8 rs3769823 and IDH2 rs4561444 as the potential functional variants in high-linkage disequilibrium with these single nucleotide polymorphisms (SNPs), respectively. Further, IDH2 mRNA levels were down-regulated in ESCC (tumour:normal-fold change=0.69, P=6.75E-14).Conclusion: Agnostic pathway-based analyses and integration of multiple types of functional data provide new evidence for the contribution of genes in taste transduction and metabolism to ESCC susceptibility, and for the functionality of both established and new ESCC risk-related SNPs. JF - International Journal of Epidemiology AU - Hyland, Paula L AU - Zhang, Han AU - Yang, Qi AU - Yang, Howard H AU - Hu, Nan AU - Lin, Shih-Wen AU - Su, Hua AU - Wang, Lemin AU - Wang, Chaoyu AU - Ding, Ti AU - Fan, Jin-Hu AU - Qiao, You-Lin AU - Sung, Hyuna AU - Wheeler, William AU - Giffen, Carol AU - Burdett, Laurie AU - Wang, Zhaoming AU - Lee, Maxwell P AU - Chanock, Stephen J AU - Dawsey, Sanford M AU - Freedman, Neal D AU - Abnet, Christian C AU - Goldstein, Alisa M AU - Yu, Kai AU - Taylor, Philip R AD - *Corresponding author. Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, MD 20852, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 206 EP - 220 PB - Oxford University Press, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 45 IS - 1 SN - 0300-5771, 0300-5771 KW - Health & Safety Science Abstracts KW - Post-GWAS KW - pathways KW - genes KW - SNP KW - eQTLs KW - oesophageal cancer KW - Health risks KW - Mortality KW - Quantitative analysis KW - DNA KW - China, People's Rep. KW - Cancer KW - Metabolism KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1785235725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Epidemiology&rft.atitle=Pathway%2C+in+silico+and+tissue-specific+expression+quantitative+analyses+of+oesophageal+squamous+cell+carcinoma+genome-wide+association+studies+data&rft.au=Hyland%2C+Paula+L%3BZhang%2C+Han%3BYang%2C+Qi%3BYang%2C+Howard+H%3BHu%2C+Nan%3BLin%2C+Shih-Wen%3BSu%2C+Hua%3BWang%2C+Lemin%3BWang%2C+Chaoyu%3BDing%2C+Ti%3BFan%2C+Jin-Hu%3BQiao%2C+You-Lin%3BSung%2C+Hyuna%3BWheeler%2C+William%3BGiffen%2C+Carol%3BBurdett%2C+Laurie%3BWang%2C+Zhaoming%3BLee%2C+Maxwell+P%3BChanock%2C+Stephen+J%3BDawsey%2C+Sanford+M%3BFreedman%2C+Neal+D%3BAbnet%2C+Christian+C%3BGoldstein%2C+Alisa+M%3BYu%2C+Kai%3BTaylor%2C+Philip+R&rft.aulast=Hyland&rft.aufirst=Paula&rft.date=2016-02-01&rft.volume=45&rft.issue=1&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Epidemiology&rft.issn=03005771&rft_id=info:doi/10.1093%2Fije%2Fdyv294 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-05-01 N1 - Last updated - 2016-05-12 N1 - SubjectsTermNotLitGenreText - Mortality; Health risks; Quantitative analysis; DNA; Metabolism; Cancer; China, People's Rep. DO - http://dx.doi.org/10.1093/ije/dyv294 ER - TY - JOUR T1 - The novel, orally available and peripherally restricted selective cannabinoid CB sub(2) receptor agonist LEI-101 prevents cisplatin-induced nephrotoxicity AN - 1780512242; PQ0002768909 AB - Background and Purpose Here, we have characterized 3-cyclopropyl-1-(4-(6-((1,1-dioxidothiomorpholino)methyl)-5-fluoro p yridin-2-yl)benzyl)imidazolidine-2,4-dione hydrochloride (LEI-101) as a novel, peripherally restricted cannabinoid CB sub(2) receptor agonist, using both in vitro and in vivo models. Experimental Approach We investigated the effects of LEI-101 on binding and functional activity. We assessed its in vitro and in vivo selectivity. Efficacy of LEI-101 was determined in a mouse model of cisplatin-induced nephrotoxicity. Key Results LEI-101 behaved as a partial agonist at CB sub(2) receptors using beta -arrestin and GTP gamma S assays and was ~100-fold selective in CB sub(2) /CB sub(1) receptor-binding assays. It did not display any activity on endocannabinoid hydrolases and nor did it react with serine hydrolases in an activity-based protein profiling assay. In mice, LEI-101 had excellent oral bioavailability reaching high concentrations in the kidney and liver with minimal penetration into the brain. LEI-101 up to a dose of 60mg.kg super(-1) (p.o.) did not exert any CNS-mediated effects in the tetrad assay, in mice. LEI-101 (p.o. or i.p.) at 3 or 10mg.kg super(-1) dose-dependently prevented kidney dysfunction and/or morphological damage induced by cisplatin in mice. These protective effects were associated with improved renal histopathology, attenuated oxidative stress and inflammation in the kidney. These effects were absent in CB sub(2) receptor knockout mice. Conclusion and Implications These results indicate that LEI-101 is a selective, largely peripherally restricted, orally available CB sub(2) receptor agonist with therapeutic potential in diseases that are associated with inflammation and/or oxidative stress, including kidney disease. JF - British Journal of Pharmacology AU - Mukhopadhyay, Partha AU - Baggelaar, Marc AU - Erdelyi, Katalin AU - Cao, Zongxian AU - Cinar, Resat AU - Fezza, Filomena AU - Ignatowska-Janlowska, Bogna AU - Wilkerson, Jenny AU - Gils, Noortje AU - Hansen, Thomas AU - Ruben, Marc AU - Soethoudt, Marjolein AU - Heitman, Laura AU - Kunos, George AU - Maccarrone, Mauro AU - Lichtman, Aron AU - Pacher, Pal AU - Van der Stelt, Mario AD - National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 446 EP - 458 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 173 IS - 3 SN - 0007-1188, 0007-1188 KW - Toxicology Abstracts KW - beta -Arrestin KW - Kidney diseases KW - Brain KW - Animal models KW - GTP KW - Inflammation KW - hydrolase KW - Bioavailability KW - Renal function KW - Cisplatin KW - serine hydrolase KW - Oxidative stress KW - Cannabinoid CB2 receptors KW - Liver KW - Cannabinoid CB1 receptors KW - Tetrads KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1780512242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Pharmacology&rft.atitle=The+novel%2C+orally+available+and+peripherally+restricted+selective+cannabinoid+CB+sub%282%29+receptor+agonist+LEI-101+prevents+cisplatin-induced+nephrotoxicity&rft.au=Mukhopadhyay%2C+Partha%3BBaggelaar%2C+Marc%3BErdelyi%2C+Katalin%3BCao%2C+Zongxian%3BCinar%2C+Resat%3BFezza%2C+Filomena%3BIgnatowska-Janlowska%2C+Bogna%3BWilkerson%2C+Jenny%3BGils%2C+Noortje%3BHansen%2C+Thomas%3BRuben%2C+Marc%3BSoethoudt%2C+Marjolein%3BHeitman%2C+Laura%3BKunos%2C+George%3BMaccarrone%2C+Mauro%3BLichtman%2C+Aron%3BPacher%2C+Pal%3BVan+der+Stelt%2C+Mario&rft.aulast=Mukhopadhyay&rft.aufirst=Partha&rft.date=2016-02-01&rft.volume=173&rft.issue=3&rft.spage=446&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Pharmacology&rft.issn=00071188&rft_id=info:doi/10.1111%2Fbph.13338 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-04-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - beta -Arrestin; Animal models; Brain; Kidney diseases; GTP; Inflammation; hydrolase; Bioavailability; Cisplatin; Renal function; Oxidative stress; serine hydrolase; Cannabinoid CB2 receptors; Liver; Tetrads; Cannabinoid CB1 receptors DO - http://dx.doi.org/10.1111/bph.13338 ER - TY - JOUR T1 - Mycobacterium tuberculosis copper-regulated protein SocB is an intrinsically disordered protein that folds upon interaction with a synthetic phospholipid bilayer AN - 1776670406; PQ0002809633 AB - Multiple genes in Mycobacterium tuberculosis (Mtb) are regulated by copper including socAB ( s mall o rf induced by c opper A and B), which is induced by copper and repressed by RicR ( r egulated i n c opper r epressor). socA and socB encode hypothetical proteins of 61 and 54 amino acids, respectively. Here, we use biophysical and computational methods to evaluate the SocB structure. We find that SocB lacks evidence for secondary structure, with no thermal cooperative unfolding event, according to circular dichroism measurements. 2D NMR spectra similarly exhibit hallmarks of a disordered structural state, which is also supported by analyzing SocB diffusion. Altogether, these findings suggest that by itself SocB is intrinsically disordered. Interestingly, SocB interacts with a synthetic phospholipid bilayer and becomes helical, which suggests that it may be membrane-associated. Proteins 2016; 84:193-200. JF - Proteins: Structure, Function and Bioinformatics AU - Nowicka, Urszula AU - Hoffman, Morgan AU - Randles, Leah AU - Shi, Xiaoshan AU - Khavrutskii, Lyuba AU - Stefanisko, Karen AU - Tarasova, Nadya I AU - Darwin, KHeran AU - Walters, Kylie J AD - Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, 21702. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 193 EP - 200 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030 United States VL - 84 IS - 2 SN - 0887-3585, 0887-3585 KW - Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts KW - Protein structure KW - Amino acids KW - C.D. KW - Secondary structure KW - N.M.R. KW - Diffusion KW - Copper KW - Bioinformatics KW - Computer applications KW - Mycobacterium tuberculosis KW - Phospholipids KW - J 02310:Genetics & Taxonomy KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776670406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins%3A+Structure%2C+Function+and+Bioinformatics&rft.atitle=Mycobacterium+tuberculosis+copper-regulated+protein+SocB+is+an+intrinsically+disordered+protein+that+folds+upon+interaction+with+a+synthetic+phospholipid+bilayer&rft.au=Nowicka%2C+Urszula%3BHoffman%2C+Morgan%3BRandles%2C+Leah%3BShi%2C+Xiaoshan%3BKhavrutskii%2C+Lyuba%3BStefanisko%2C+Karen%3BTarasova%2C+Nadya+I%3BDarwin%2C+KHeran%3BWalters%2C+Kylie+J&rft.aulast=Nowicka&rft.aufirst=Urszula&rft.date=2016-02-01&rft.volume=84&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Proteins%3A+Structure%2C+Function+and+Bioinformatics&rft.issn=08873585&rft_id=info:doi/10.1002%2Fprot.24970 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Protein structure; Amino acids; C.D.; Secondary structure; Diffusion; N.M.R.; Bioinformatics; Copper; Computer applications; Phospholipids; Mycobacterium tuberculosis DO - http://dx.doi.org/10.1002/prot.24970 ER - TY - JOUR T1 - Mass spectrometric phosphoproteome analysis of HIV-infected brain reveals novel phosphorylation sites and differential phosphorylation patterns AN - 1776667367; PQ0002809451 AB - Purpose To map the phosphoproteome and identify changes in the phosphorylation patterns in the HIV-infected and uninfected brain. Experimental design Parietal cortex from individuals with and without HIV infection were lysed and trypsinized. The peptides were labeled with iTRAQ reagents, combined, phospho-enriched by titanium dioxide chromatography, and analyzed by LC-MS/MS with high resolution. Results Our phosphoproteomic workflow resulted in the identification of 112 phosphorylated proteins and 17 novel phosphorylation sites in all the samples that were analyzed. The phosphopeptide sequences were searched for kinase substrate motifs, which revealed potential kinases involved in important signaling pathways. The site-specific phosphopeptide quantification showed that peptides from neurofilament medium polypeptide, myelin basic protein, and 2'-3'-cyclic nucleotide-3' phosphodiesterase have relatively higher phosphorylation levels during HIV infection. Conclusions and clinical relevance This study has enriched the global phosphoproteome knowledge of the human brain by detecting novel phosphorylation sites on neuronal proteins and identifying differentially phosphorylated brain proteins during HIV infection. Kinases that lead to unusual phosphorylations could be therapeutic targets for the treatment of HIV-associated neurocognitive disorders. JF - Proteomics Clinical Applications AU - Uzasci, Lerna AU - Auh, Sungyoung AU - Cotter, Robert J AU - Nath, Avindra AD - Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 126 EP - 135 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 10 IS - 2 SN - 1862-8346, 1862-8346 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Neurofilaments KW - Chromatography KW - Multiple sclerosis KW - Brain KW - Therapeutic applications KW - Infection KW - Cognition KW - Cortex (parietal) KW - Titanium dioxide KW - Phosphorylation KW - Human immunodeficiency virus KW - phosphoproteomes KW - proteomics KW - phosphodiesterase KW - Myelin basic protein KW - Signal transduction KW - N3 11007:Neurobiology KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776667367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics+Clinical+Applications&rft.atitle=Mass+spectrometric+phosphoproteome+analysis+of+HIV-infected+brain+reveals+novel+phosphorylation+sites+and+differential+phosphorylation+patterns&rft.au=Uzasci%2C+Lerna%3BAuh%2C+Sungyoung%3BCotter%2C+Robert+J%3BNath%2C+Avindra&rft.aulast=Uzasci&rft.aufirst=Lerna&rft.date=2016-02-01&rft.volume=10&rft.issue=2&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=Proteomics+Clinical+Applications&rft.issn=18628346&rft_id=info:doi/10.1002%2Fprca.201400134 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Neurofilaments; Multiple sclerosis; Chromatography; Brain; Therapeutic applications; Infection; Cognition; Cortex (parietal); Titanium dioxide; Phosphorylation; phosphoproteomes; proteomics; Myelin basic protein; phosphodiesterase; Signal transduction; Human immunodeficiency virus DO - http://dx.doi.org/10.1002/prca.201400134 ER - TY - JOUR T1 - Impact of Environmental Enrichment Devices on NTP In Vivo Studies AN - 1776666231; PQ0002736533 AB - The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices. JF - Toxicologic Pathology AU - Churchill, Sheba R AU - Morgan, Daniel L AU - Kissling, Grace E AU - Travlos, Gregory S AU - King-Herbert, Angela P AD - 1 .National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA, sheba.churchill@nih.gov Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 233 EP - 245 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 2 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - environmental enrichment KW - animal welfare KW - laboratory animals KW - rats KW - mice KW - Food consumption KW - Statistics KW - Body weight KW - Stress KW - Shelter KW - Progeny KW - Toxicity KW - Enrichment KW - polycarbonate KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776666231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Impact+of+Environmental+Enrichment+Devices+on+NTP+In+Vivo+Studies&rft.au=Churchill%2C+Sheba+R%3BMorgan%2C+Daniel+L%3BKissling%2C+Grace+E%3BTravlos%2C+Gregory+S%3BKing-Herbert%2C+Angela+P&rft.aulast=Churchill&rft.aufirst=Sheba&rft.date=2016-02-01&rft.volume=44&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623315625330 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 49 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Food consumption; Statistics; Body weight; Stress; Progeny; Shelter; Toxicity; Enrichment; polycarbonate DO - http://dx.doi.org/10.1177/0192623315625330 ER - TY - JOUR T1 - Recommendations from the INHAND Apoptosis/Necrosis Working Group AN - 1776666050; PQ0002736538 AB - Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are: Use necrosis and apoptosis as separate diagnostic terms. Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.). Use the combined term apoptosis/single cell necrosis when There is no requirement or need to split the processes, or When the nature of cell death cannot be determined with certainty, or When both processes are present together. The diagnosis should be based primarily on the morphological features in H&E-stained sections. When needed, additional, special techniques to identify and characterize apoptosis can also be used. JF - Toxicologic Pathology AU - Elmore, Susan A AU - Dixon, Darlene AU - Hailey, James R AU - Harada, Takanori AU - Herbert, Ronald A AU - Maronpot, Robert R AU - Nolte, Thomas AU - Rehg, Jerold E AU - Rittinghausen, Susanne AU - Rosol, Thomas J AU - Satoh, Hiroshi AU - Vidal, Justin D AU - Willard-Mack, Cynthia L AU - Creasy, Dianne M AD - 1 .Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA, elmore@niehs.nih.gov Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 173 EP - 188 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU United Kingdom VL - 44 IS - 2 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - apoptosis KW - necrosis KW - single cell necrosis KW - cell death KW - INHAND KW - guidance KW - Differentiation KW - Necrosis KW - Apoptosis KW - Toxicity KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776666050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Recommendations+from+the+INHAND+Apoptosis%2FNecrosis+Working+Group&rft.au=Elmore%2C+Susan+A%3BDixon%2C+Darlene%3BHailey%2C+James+R%3BHarada%2C+Takanori%3BHerbert%2C+Ronald+A%3BMaronpot%2C+Robert+R%3BNolte%2C+Thomas%3BRehg%2C+Jerold+E%3BRittinghausen%2C+Susanne%3BRosol%2C+Thomas+J%3BSatoh%2C+Hiroshi%3BVidal%2C+Justin+D%3BWillard-Mack%2C+Cynthia+L%3BCreasy%2C+Dianne+M&rft.aulast=Elmore&rft.aufirst=Susan&rft.date=2016-02-01&rft.volume=44&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F0192623315625859 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Number of references - 64 N1 - Last updated - 2016-08-03 N1 - SubjectsTermNotLitGenreText - Differentiation; Necrosis; Apoptosis; Toxicity DO - http://dx.doi.org/10.1177/0192623315625859 ER - TY - JOUR T1 - Coincident diabetes mellitus modulates Th1-, Th2-, and Th17-cell responses in latent tuberculosis in an IL-10- and TGF- beta -dependent manner AN - 1776653253; PQ0002774179 AB - Type 2 diabetes mellitus (DM) is a risk factor for the development of active tuberculosis (TB), although its role in the TB-induced responses in latent TB (LTB) is not well understood. Since Th1, Th2, and Th17 responses are important in immunity to LTB, we postulated that coincident DM could alter the function of these CD4 super(+) T-cell subsets. To this end, we examined mycobacteria-induced immune responses in the whole blood of individuals with LTB-DM and compared them with responses of individuals without DM (LTB-NDM). T-cell responses from LTB-DM are characterized by diminished frequencies of mono- and dual-functional CD4 super(+) Th1, Th2, and Th17 cells at baseline and following stimulation with mycobacterial antigens-purified protein derivative, early secreted antigen-6, and culture filtrate protein-10. This modulation was at least partially dependent on IL-10 and TGF- beta , since neutralization of either cytokine resulted in significantly increased frequencies of Th1 and Th2 cells but not Th17 cells in LTB-DM but not LTB individuals. LTB-DM is therefore characterized by diminished frequencies of Th1, Th2, and Th17 cells, indicating that DM alters the immune response in latent TB leading to a suboptimal induction of protective CD4 super(+) T-cell responses, thereby providing a potential mechanism for increased susceptibility to active disease. JF - European Journal of Immunology AU - Kumar, Nathella Pavan AU - Moideen, Kadar AU - George, Parakkal Jovvian AU - Dolla, Chandrakumar AU - Kumaran, Paul AU - Babu, Subash AD - National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 390 EP - 399 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 46 IS - 2 SN - 0014-2980, 0014-2980 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Mycobacterium KW - Helper cells KW - Cell culture KW - Interleukin 10 KW - Diabetes mellitus KW - Blood KW - CD4 antigen KW - Risk factors KW - Transforming growth factor- beta KW - Lymphocytes T KW - Tuberculosis KW - Immune response KW - J 02350:Immunology KW - F 06910:Microorganisms & Parasites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1776653253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Immunology&rft.atitle=Coincident+diabetes+mellitus+modulates+Th1-%2C+Th2-%2C+and+Th17-cell+responses+in+latent+tuberculosis+in+an+IL-10-+and+TGF-+beta+-dependent+manner&rft.au=Kumar%2C+Nathella+Pavan%3BMoideen%2C+Kadar%3BGeorge%2C+Parakkal+Jovvian%3BDolla%2C+Chandrakumar%3BKumaran%2C+Paul%3BBabu%2C+Subash&rft.aulast=Kumar&rft.aufirst=Nathella&rft.date=2016-02-01&rft.volume=46&rft.issue=2&rft.spage=390&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Immunology&rft.issn=00142980&rft_id=info:doi/10.1002%2Feji.201545973 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-05-13 N1 - SubjectsTermNotLitGenreText - Diabetes mellitus; Blood; CD4 antigen; Risk factors; Helper cells; Transforming growth factor- beta; Lymphocytes T; Cell culture; Tuberculosis; Immune response; Interleukin 10; Mycobacterium DO - http://dx.doi.org/10.1002/eji.201545973 ER - TY - JOUR T1 - Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study AN - 1773830255; PQ0002694579 AB - Background. Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS. Methods. In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals. Results. In both the discovery and validation cohorts, KS was associated with HLA-A*11:01 (adjusted OR for the combined cohorts, 0.4; P = .002) and HLA-C*07:01 (adjusted OR, 1.6; P = .002). Consistent associations across cohorts were also observed with activating KIR3DS1 plus HLA-B Bw4-80I and homozygosity for HLA-C group 1. With KIR3DS1 plus HLA-B Bw4-80I, the KSHV seroprevalence was 40% lower (adjusted OR for the combined cohorts, 0.6; P = .01), but the KS risk was 2-fold higher (adjusted OR, 2.1; P = .002). Similarly, the KSHV seroprevalence was 40% lower (adjusted OR, 0.6; P = .01) but the KS risk 80% higher with HLA-C group 1 homozygosity (adjusted OR, 1.8; P = .005). Conclusions. KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs. JF - Journal of Infectious Diseases AU - Goedert, James J AU - Martin, Maureen P AU - Vitale, Francesco AU - Lauria, Carmela AU - Whitby, Denise AU - Qi, Ying AU - Gao, Xiaojiang AU - Carrington, Mary AD - Division of Cancer Epidemiology and Genetics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, goedertj@mail.nih.gov Y1 - 2016/02/01/ PY - 2016 DA - 2016 Feb 01 SP - 432 EP - 438 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 3 SN - 0022-1899, 0022-1899 KW - Immunology Abstracts; Health & Safety Science Abstracts KW - Kaposi sarcoma KW - Italy KW - case-control study KW - human genetics KW - major histocompatibility complex KW - human leukocyte antigens KW - natural killer-cell immunoglobulin-like receptors KW - Health risks KW - Infectious diseases KW - Herpesvirus KW - Complications KW - Kaposi's sarcoma-associated herpesvirus KW - Sarcoma KW - Homozygosity KW - Infection KW - H 6000:Natural Disasters/Civil Defense/Emergency Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773830255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Risk+of+Classic+Kaposi+Sarcoma+With+Combinations+of+Killer+Immunoglobulin-Like+Receptor+and+Human+Leukocyte+Antigen+Loci%3A+A+Population-Based+Case-control+Study&rft.au=Goedert%2C+James+J%3BMartin%2C+Maureen+P%3BVitale%2C+Francesco%3BLauria%2C+Carmela%3BWhitby%2C+Denise%3BQi%2C+Ying%3BGao%2C+Xiaojiang%3BCarrington%2C+Mary&rft.aulast=Goedert&rft.aufirst=James&rft.date=2016-02-01&rft.volume=213&rft.issue=3&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiv413 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Health risks; Infectious diseases; Complications; Sarcoma; Homozygosity; Infection; Herpesvirus; Kaposi's sarcoma-associated herpesvirus DO - http://dx.doi.org/10.1093/infdis/jiv413 ER - TY - JOUR T1 - Feeding Behavior Modulates Biofilm-Mediated Transmission of Yersinia pestis by the Cat Flea, Ctenocephalides felis AN - 1768574670; PQ0002669423 AB - Although plague primarily affects wild rodents, human plague outbreaks still occur periodically in some areas of the world. Yersinia pestis, the bacterial agent of plague, is transmitted by fleas. Cat fleas are abundant worldwide, regularly infest human habitations in plague endemic areas, and readily bite humans. The cat flea has long been considered to be a poor vector, but this reputation is based on very limited studies; and in general the reasons why some flea species are better vectors than others are not well understood. We found that cat fleas can transmit Y. pestis, but at rates strongly influenced by feeding frequency after the infectious blood meal. When infected cat fleas had unrestricted access to blood (their preferred feeding pattern), most rapidly cleared the infection and they transmitted only during the first week after infection. However, when post-infection blood meals were limited to mimic patterns typical of efficient flea vectors, cat fleas regularly transmitted for one month after infection. Our results indicate that cat fleas in their natural environments have limited potential to develop transmissible infections. However, if their regular daily feeding habit is interrupted, they can be capable vectors. JF - PLoS Neglected Tropical Diseases AU - Bland, David M AU - Hinnebusch, BJoseph AD - Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America Y1 - 2016/02/01/ PY - 2016 DA - 2016 Feb 01 PB - Public Library of Science, 185 Berry Street San Francisco CA 94107 United States VL - 10 IS - 2 SN - 1935-2727, 1935-2727 KW - Microbiology Abstracts B: Bacteriology; Entomology Abstracts; Health & Safety Science Abstracts KW - Feeding KW - Bites KW - Yersinia pestis KW - Vectors KW - Blood meals KW - Infection KW - Disease transmission KW - Ctenocephalides felis KW - Blood KW - Outbreaks KW - Plague KW - Feeding behavior KW - Rodents KW - J 02410:Animal Diseases KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - Z 05340:Ecology and Behavior UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768574670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+Neglected+Tropical+Diseases&rft.atitle=Feeding+Behavior+Modulates+Biofilm-Mediated+Transmission+of+Yersinia+pestis+by+the+Cat+Flea%2C+Ctenocephalides+felis&rft.au=Bland%2C+David+M%3BHinnebusch%2C+BJoseph&rft.aulast=Bland&rft.aufirst=David&rft.date=2016-02-01&rft.volume=10&rft.issue=2&rft.spage=&rft.isbn=&rft.btitle=&rft.title=PLoS+Neglected+Tropical+Diseases&rft.issn=19352727&rft_id=info:doi/10.1371%2Fjournal.pntd.0004413 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-02-01 N1 - Last updated - 2016-08-17 N1 - SubjectsTermNotLitGenreText - Blood; Bites; Vectors; Blood meals; Plague; Feeding behavior; Infection; Disease transmission; Feeding; Outbreaks; Rodents; Ctenocephalides felis; Yersinia pestis DO - http://dx.doi.org/10.1371/journal.pntd.0004413 ER - TY - JOUR T1 - Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis AN - 1768572536; PQ0002688508 AB - The saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies. Therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of L. biflexa during exponential growth and in stationary phase. Using these data, we identified abundantly produced proteins in each cellular fraction and quantified the transcript levels from a subset of these genes using quantitative reverse transcription-PCR (RT-PCR). These proteins should prove useful as cellular markers and as controls for gene expression studies. We also observed a significant number of L. biflexa membrane-associated proteins with multiple isoforms, each having unique isoelectric focusing points. L. biflexa cell lysates were examined for several posttranslational modifications suggested by the protein patterns. Methylation and acetylation of lysine residues were predominately observed in the proteins of the membrane-associated fraction, while phosphorylation was detected mainly among soluble proteins. These three posttranslational modification systems appear to be conserved between the free-living species L. biflexa and the pathogenic species Leptospira interrogans, suggesting an important physiological advantage despite the varied life cycles of the different species. JF - Antimicrobial Agents & Chemotherapy AU - Stewart, Philip E AU - Carroll, James A AU - Olano, L Rennee AU - Sturdevant, Daniel E AU - Rosa, Patricia A AD - << + $0, pestewart@niaid.nih.gov. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 1183 EP - 1195 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 United States VL - 82 IS - 4 SN - 0099-2240, 0099-2240 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Data processing KW - Lysine KW - Transcription KW - Leptospira biflexa KW - Isoelectric focusing KW - stationary phase KW - Acetylation KW - Phosphorylation KW - Leptospira interrogans KW - Polymerase chain reaction KW - proteomics KW - Saprophytes KW - A 01340:Antibiotics & Antimicrobials KW - J 02320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768572536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Multiple+Posttranslational+Modifications+of+Leptospira+biflexa+Proteins+as+Revealed+by+Proteomic+Analysis&rft.au=Stewart%2C+Philip+E%3BCarroll%2C+James+A%3BOlano%2C+L+Rennee%3BSturdevant%2C+Daniel+E%3BRosa%2C+Patricia+A&rft.aulast=Stewart&rft.aufirst=Philip&rft.date=2016-02-01&rft.volume=82&rft.issue=4&rft.spage=1183&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00992240&rft_id=info:doi/10.1128%2FAEM.03056-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-02-01 N1 - Number of references - 63 N1 - Last updated - 2016-03-17 N1 - SubjectsTermNotLitGenreText - stationary phase; Acetylation; Data processing; Phosphorylation; Polymerase chain reaction; Transcription; Lysine; Isoelectric focusing; proteomics; Saprophytes; Leptospira interrogans; Leptospira biflexa DO - http://dx.doi.org/10.1128/AEM.03056-15 ER - TY - JOUR T1 - Mechanistic insights into the specificity of human cytosolic sulfotransferase 2A1 (hSULT2A1) for hydroxylated polychlorinated biphenyls through the use of fluoro-tagged probes AN - 1768572242; PQ0002649127 AB - Determining the relationships between the structures of substrates and inhibitors and their interactions with drug-metabolizing enzymes is of prime importance in predicting the toxic potential of new and legacy xenobiotics. Traditionally, quantitative structure activity relationship (QSAR) studies are performed with many distinct compounds. Based on the chemical properties of the tested compounds, complex relationships can be established so that models can be developed to predict toxicity of novel compounds. In this study, the use of fluorinated analogues as supplemental QSAR compounds was investigated. Substituting fluorine induces changes in electronic and steric properties of the substrate without substantially changing the chemical backbone of the substrate. In vitro assays were performed using purified human cytosolic sulfotransferase hSULT2A1 as a model enzyme. A mono-hydroxylated polychlorinated biphenyl (4-OH PCB 14) and its four possible mono-fluoro analogues were used as test compounds. Remarkable similarities were found between this approach and previously published QSAR studies for hSULT2A1. Both studies implicate the importance of dipole moment and dihedral angle as being important to PCB structure in respect to being substrates for hSULT2A1. We conclude that mono-fluorinated analogues of a target substrate can be a useful tool to study the structure activity relationships for enzyme specificity. JF - Environmental Science and Pollution Research International AU - Ekuase, E J AU - van 't Erve, TJ AU - Rahaman, A AU - Robertson, L W AU - Duffel, M W AU - Luthe, G AD - Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA, USA, thomas.vanterve@nih.gov Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 2119 EP - 2127 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 23 IS - 3 SN - 0944-1344, 0944-1344 KW - Pollution Abstracts; Meteorological & Geoastrophysical Abstracts; Environment Abstracts KW - Fluorine KW - Environmental sciences KW - Enzymes KW - Toxicity KW - Xenobiotics KW - Chemical properties KW - PCB compounds KW - M2 551.5:General (551.5) KW - P 6000:TOXICOLOGY AND HEALTH KW - ENA 08:International UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1768572242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Science+and+Pollution+Research+International&rft.atitle=Mechanistic+insights+into+the+specificity+of+human+cytosolic+sulfotransferase+2A1+%28hSULT2A1%29+for+hydroxylated+polychlorinated+biphenyls+through+the+use+of+fluoro-tagged+probes&rft.au=Ekuase%2C+E+J%3Bvan+%27t+Erve%2C+TJ%3BRahaman%2C+A%3BRobertson%2C+L+W%3BDuffel%2C+M+W%3BLuthe%2C+G&rft.aulast=Ekuase&rft.aufirst=E&rft.date=2016-02-01&rft.volume=23&rft.issue=3&rft.spage=2119&rft.isbn=&rft.btitle=&rft.title=Environmental+Science+and+Pollution+Research+International&rft.issn=09441344&rft_id=info:doi/10.1007%2Fs11356-015-4886-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-02-01 N1 - Number of references - 56 N1 - Last updated - 2016-09-01 N1 - SubjectsTermNotLitGenreText - Environmental sciences; Fluorine; Enzymes; Xenobiotics; Toxicity; Chemical properties; PCB compounds DO - http://dx.doi.org/10.1007/s11356-015-4886-8 ER - TY - JOUR T1 - Al[ super(18)F]NOTA-T140 Peptide for Noninvasive Visualization of CXCR4 Expression AN - 1765975876; PQ0002538288 AB - Chemokine receptor CXCR4 plays an important role in tumor aggressiveness, invasiveness, and metastasis formation. Quantification of CXCR4 expression by tumors may have an impact on prediction and evaluation of tumor response to therapies. In this study, we developed a robust and straightforward F-18 labeling route of T140, a CXCR4 peptide-based antagonist. T140 derivative was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and labeled with Al[ super(18)F]. Al[ super(18)F]NOTA-T140 was evaluated in vitro in cell-based assay and stability in mouse serum and in vivo using CXCR4 positive and negative tumor xenograft models. Labeling of Al[ super(18)F]NOTA-T140 was completed within 30 min with a radiochemical yield of 58 plus or minus 5.3 % at the end of synthesis, based on fluoride-18 activity. Al[ super(18)F]NOTA-T140 accumulated in CHO-CXCR4 positive but not negative tumors. Al[ super(18)F]NOTA-T140 uptake in the tumors correlated with CXCR4 protein expression. Moreover, Al[ super(18)F]NOTA-T140 had high accumulation in CXCR4-positive metastatic tumors. The simplicity of Al[ super(18)F]NOTA-T140 labeling along with its properties to specifically image CXCR4 expression by tumors warrant further clinical application for the diagnosis of CXCR4 clinically. JF - Molecular Imaging and Biology AU - Yan, Xuefeng AU - Niu, Gang AU - Wang, Zhe AU - Yang, Xiangyu AU - Kiesewetter, Dale O AU - Jacobson, Orit AU - Shen, Baozhong AU - Chen, Xiaoyuan AD - Department of Radiology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China, orit.jacobsonweiss@nih.gov Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 135 EP - 142 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 18 IS - 1 SN - 1536-1632, 1536-1632 KW - Biotechnology and Bioengineering Abstracts KW - Metastases KW - Invasiveness KW - CXCR4 protein KW - Animal models KW - Chemokine receptors KW - Therapeutic applications KW - Peptides KW - Tumors KW - Xenografts KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1765975876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Imaging+and+Biology&rft.atitle=Al%5B+super%2818%29F%5DNOTA-T140+Peptide+for+Noninvasive+Visualization+of+CXCR4+Expression&rft.au=Yan%2C+Xuefeng%3BNiu%2C+Gang%3BWang%2C+Zhe%3BYang%2C+Xiangyu%3BKiesewetter%2C+Dale+O%3BJacobson%2C+Orit%3BShen%2C+Baozhong%3BChen%2C+Xiaoyuan&rft.aulast=Yan&rft.aufirst=Xuefeng&rft.date=2016-02-01&rft.volume=18&rft.issue=1&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Molecular+Imaging+and+Biology&rft.issn=15361632&rft_id=info:doi/10.1007%2Fs11307-015-0872-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-02-01 N1 - Number of references - 42 N1 - Last updated - 2016-02-18 N1 - SubjectsTermNotLitGenreText - Metastases; Invasiveness; CXCR4 protein; Animal models; Therapeutic applications; Chemokine receptors; Peptides; Xenografts; Tumors DO - http://dx.doi.org/10.1007/s11307-015-0872-2 ER - TY - JOUR T1 - Clinical outcomes in octogenarians treated with docetaxel as first-line chemotherapy for castration-resistant prostate cancer. AN - 1762967494; 26776493 AB - To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents. JF - Future oncology (London, England) AU - Veccia, Antonello AU - Caffo, Orazio AU - De Giorgi, Ugo AU - Di Lorenzo, Giuseppe AU - Ortega, Cinzia AU - Scognamiglio, Florinda AU - Aieta, Michele AU - Facchini, Gaetano AU - Mansueto, Giovanni AU - Mattioli, Rodolfo AU - Procopio, Giuseppe AU - Zagonel, Vittorina AU - D'Angelo, Alessandro AU - Spizzo, Gilbert AU - Bortolus, Roberto AU - Donini, Maddalena AU - Lo Re, Giovanni AU - Massari, Francesco AU - Vicario, Giovanni AU - Zucali, Paolo A AU - Alesini, Daniele AU - Bonetti, Andrea AU - Mucciarini, Claudia AU - Nicodemo, Maurizio AU - Berruti, Alfredo AU - Fratino, Lucia AU - Lodde, Michele AU - Messina, Caterina AU - Perin, Alessandra AU - Santini, Daniele AU - Sava, Teodoro AU - Tucci, Marcello AU - Basso, Umberto AU - Maines, Francesca AU - Burgio, Luca S AU - Galligioni, Enzo AD - Medical Oncology Department, Santa Chiara Hospital, Largo Medaglie d'Oro, 38100 Trento, Italy. ; Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014 Meldola, Italy. ; Oncologia Urologica, Azienda Ospedaliera Universitaria "Federico II", Via S. Pansini 5, 80131 Napoli, Italy. ; Medical Oncology Department, Institute for Cancer Research & Treatment, Strada Provinciale 142, Km 3.95, 10060 Candiolo, Italy. ; Medical Oncology Department, Cardarelli Hospital, Via A. Cardarelli 9, 80131 Napoli, Italy. ; Medical Oncology Department, Referral Cancer Center of Basilicata - IRCCS, Via Padre Pio, 1, 85028 Rionero in Vulture, Italy. ; Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS, Via Mariano Semmola, 80131 Naples, Italy. ; Medical Oncology Department, General Hospital, Via Fabi, 03100 Frosinone, Italy. ; Medical Oncology Department, Santa Croce Hospital, Viale Vittorio Veneto 2, 61032 Fano, Italy. ; Oncologia medica genitourinaria - Fondazione Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. ; Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Via Gattamelata 64, 35128 Padua, Italy. ; Medical Oncology Department, San Vincenzo Hospital, Via Sirina, 98039 Taormina, Italy. ; Medical Oncology Department, General Hospital, Via Rossini, 5, 39012 Merano, Italy. ; Radiation Oncology Department, National Cancer Institute, Via Franco Gallini, 2, 33081 Aviano, Italy. ; Medical Oncology Department, Istituti Ospitalieri, Viale Concordia 1, 26100 Cremona, Italy. ; Medical Oncology Department, Santa Maria degli Angeli Hospital, Via Montereale 24, 33170 Pordenone, Italy. ; Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale A. Scuro 10, 37134 Verona, Italy. ; Medical Oncology Department, San Giacomo Apostolo Hospital, Via dei Carpani 16/Z, 31033 Castelfranco Veneto, Italy. ; Department of Medical Oncology & Haematology, Humanitas Clinical & Research Center, Via Manzoni, 56, 20089 Rozzano, Italy. ; Department of Radiological, Oncological & Anatomopathological Sciences, La Sapienza, University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy. ; Medical Oncology Department, Mater Salutis Hospital, Via Gianella, 1, 37045 Legnago, Italy. ; Medical Oncology Department, Ramazzini Hospital, Via Guido Molinari, 2, 41012 Carpi, Italy. ; Medical Oncology Department, Sacro Cuore Don Calabria Hospital, Via don A. Sempreboni, 5, 37024 Negrar, Italy. ; Medical Oncology Department, Spedali Civili Hospital, P.le Spedali Civili, 1, 25123 Brescia, Italy. ; Medical Oncology Department, National Cancer Institute, Via Franco Gallini, 2, 33081 Aviano, Italy. ; Urology Department, General Hospital, Via Böhler 5, 39100 Bolzano, Italy. ; Medical Oncology Department, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy. ; Medical Oncology Department, General Hospital, via Garziere n. 42, 36014 Santorso, Italy. ; Medical Oncology Department, University Campus Bio-Medico, Via Álvaro del Portillo, 00128 Rome, Italy. ; Medical Oncology Department, General Hospital, P.le A. Stefani 1, 37126 Verona, Italy. ; Medical Oncology Department, University of Torino, San Luigi Hospital, Regione Gonzole, 10, 10043 Orbassano, Italy. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 493 EP - 502 VL - 12 IS - 4 KW - Antineoplastic Agents KW - 0 KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Index Medicus KW - geriatric assessment KW - castration-resistant prostate cancer KW - elderly KW - Aged, 80 and over KW - Humans KW - Treatment Outcome KW - Retrospective Studies KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Retreatment KW - Male KW - Proportional Hazards Models KW - Prostatic Neoplasms, Castration-Resistant -- mortality KW - Prostatic Neoplasms, Castration-Resistant -- pathology KW - Antineoplastic Agents -- administration & dosage KW - Taxoids -- adverse effects KW - Taxoids -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Taxoids -- administration & dosage KW - Prostatic Neoplasms, Castration-Resistant -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762967494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Future+oncology+%28London%2C+England%29&rft.atitle=Clinical+outcomes+in+octogenarians+treated+with+docetaxel+as+first-line+chemotherapy+for+castration-resistant+prostate+cancer.&rft.au=Veccia%2C+Antonello%3BCaffo%2C+Orazio%3BDe+Giorgi%2C+Ugo%3BDi+Lorenzo%2C+Giuseppe%3BOrtega%2C+Cinzia%3BScognamiglio%2C+Florinda%3BAieta%2C+Michele%3BFacchini%2C+Gaetano%3BMansueto%2C+Giovanni%3BMattioli%2C+Rodolfo%3BProcopio%2C+Giuseppe%3BZagonel%2C+Vittorina%3BD%27Angelo%2C+Alessandro%3BSpizzo%2C+Gilbert%3BBortolus%2C+Roberto%3BDonini%2C+Maddalena%3BLo+Re%2C+Giovanni%3BMassari%2C+Francesco%3BVicario%2C+Giovanni%3BZucali%2C+Paolo+A%3BAlesini%2C+Daniele%3BBonetti%2C+Andrea%3BMucciarini%2C+Claudia%3BNicodemo%2C+Maurizio%3BBerruti%2C+Alfredo%3BFratino%2C+Lucia%3BLodde%2C+Michele%3BMessina%2C+Caterina%3BPerin%2C+Alessandra%3BSantini%2C+Daniele%3BSava%2C+Teodoro%3BTucci%2C+Marcello%3BBasso%2C+Umberto%3BMaines%2C+Francesca%3BBurgio%2C+Luca+S%3BGalligioni%2C+Enzo&rft.aulast=Veccia&rft.aufirst=Antonello&rft.date=2016-02-01&rft.volume=12&rft.issue=4&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=Future+oncology+%28London%2C+England%29&rft.issn=1744-8301&rft_id=info:doi/10.2217%2Ffon.15.302 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-04 N1 - Date created - 2016-02-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.2217/fon.15.302 ER - TY - JOUR T1 - Environmental Chemicals in Urine and Blood: Improving Methods for Creatinine and Lipid Adjustment. AN - 1762342753; 26219104 AB - Investigators measuring exposure biomarkers in urine typically adjust for creatinine to account for dilution-dependent sample variation in urine concentrations. Similarly, it is standard to adjust for serum lipids when measuring lipophilic chemicals in serum. However, there is controversy regarding the best approach, and existing methods may not effectively correct for measurement error. We compared adjustment methods, including novel approaches, using simulated case-control data. Using a directed acyclic graph framework, we defined six causal scenarios for epidemiologic studies of environmental chemicals measured in urine or serum. The scenarios include variables known to influence creatinine (e.g., age and hydration) or serum lipid levels (e.g., body mass index and recent fat intake). Over a range of true effect sizes, we analyzed each scenario using seven adjustment approaches and estimated the corresponding bias and confidence interval coverage across 1,000 simulated studies. For urinary biomarker measurements, our novel method, which incorporates both covariate-adjusted standardization and the inclusion of creatinine as a covariate in the regression model, had low bias and possessed 95% confidence interval coverage of nearly 95% for most simulated scenarios. For serum biomarker measurements, a similar approach involving standardization plus serum lipid level adjustment generally performed well. To control measurement error bias caused by variations in serum lipids or by urinary diluteness, we recommend improved methods for standardizing exposure concentrations across individuals. JF - Environmental health perspectives AU - O'Brien, Katie M AU - Upson, Kristen AU - Cook, Nancy R AU - Weinberg, Clarice R AD - Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 220 EP - 227 VL - 124 IS - 2 KW - Biomarkers KW - 0 KW - Environmental Pollutants KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Regression Analysis KW - Humans KW - Environmental Exposure KW - Case-Control Studies KW - Biomarkers -- urine KW - Creatinine -- urine KW - Environmental Pollutants -- urine KW - Lipid Metabolism KW - Environmental Monitoring -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762342753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Environmental+Chemicals+in+Urine+and+Blood%3A+Improving+Methods+for+Creatinine+and+Lipid+Adjustment.&rft.au=O%27Brien%2C+Katie+M%3BUpson%2C+Kristen%3BCook%2C+Nancy+R%3BWeinberg%2C+Clarice+R&rft.aulast=O%27Brien&rft.aufirst=Katie&rft.date=2016-02-01&rft.volume=124&rft.issue=2&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&rft_id=info:doi/10.1289%2Fehp.1509693 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-24 N1 - Date created - 2016-02-02 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Environ Health Perspect. 2016 Mar;124(3):321-8 [26161573] N Engl J Med. 1988 Jul 28;319(4):189-94 [3393170] Arch Environ Contam Toxicol. 1989 Jul-Aug;18(4):495-500 [2505694] Cancer Epidemiol Biomarkers Prev. 1996 Sep;5(9):753-5 [8877068] N Engl J Med. 1997 Oct 30;337(18):1253-8 [9345073] Hum Reprod. 1997 Dec;12(12):2607-13 [9455822] Epidemiology. 1999 Jan;10(1):37-48 [9888278] Environ Health Perspect. 2005 Feb;113(2):192-200 [15687057] Am J Epidemiol. 2005 Apr 15;161(8):714-24 [15800263] Environ Health Perspect. 2005 Jul;113(7):853-7 [16002372] Int J Epidemiol. 2010 Apr;39(2):417-20 [19926667] Epidemiology. 2013 Nov;24(6):921-8 [24051893] Comment In: Environ Health Perspect. 2016 Feb;124(2):A37 [26829818] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1289/ehp.1509693 ER - TY - JOUR T1 - Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment. AN - 1762342185; 26828330 AB - This overview is an update of the unit originally published in 2004. While the basic tenets of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available, and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. Copyright © 2016 John Wiley & Sons, Inc. JF - Current protocols in toxicology AU - DeWitt, Jamie C AU - Germolec, Dori R AU - Luebke, Robert W AU - Johnson, Victor J AD - Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina. ; Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina. ; Cardiopulmonary and Immunotoxicology Branch, United States Environmental Protection Agency, Research Triangle Park, North Carolina. ; Burleson Research Technologies, Morrisville, North Carolina. Y1 - 2016/02/01/ PY - 2016 DA - 2016 Feb 01 SP - 18.1.1 EP - 18.1.22 VL - 67 KW - Biomarkers KW - 0 KW - Immunotoxins KW - Xenobiotics KW - Index Medicus KW - immunosuppression KW - immunotoxicity KW - xenobiotic exposure KW - Animals KW - Humans KW - Biomarkers -- analysis KW - Disease Models, Animal KW - Risk Assessment KW - Immunosuppression KW - Immune Tolerance -- drug effects KW - Immune System -- drug effects KW - Immune System -- physiopathology KW - Communicable Diseases -- immunology KW - Xenobiotics -- toxicity KW - Neoplasms -- immunology KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762342185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+protocols+in+toxicology&rft.atitle=Associating+Changes+in+the+Immune+System+with+Clinical+Diseases+for+Interpretation+in+Risk+Assessment.&rft.au=DeWitt%2C+Jamie+C%3BGermolec%2C+Dori+R%3BLuebke%2C+Robert+W%3BJohnson%2C+Victor+J&rft.aulast=DeWitt&rft.aufirst=Jamie&rft.date=2016-02-01&rft.volume=67&rft.issue=&rft.spage=18.1.1&rft.isbn=&rft.btitle=&rft.title=Current+protocols+in+toxicology&rft.issn=1934-9262&rft_id=info:doi/10.1002%2F0471140856.tx1801s67 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-24 N1 - Date created - 2016-02-02 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Clin Nephrol. 1996 Jan;45(1):22-8 [8616953] J Toxicol Environ Health. 1996 Jun 28;48(3):215-29 [8656446] Psychother Psychosom. 1997;66(1):3-26 [8996711] Am J Hematol. 1997 Feb;54(2):131-8 [9034287] Am J Clin Nutr. 1997 Aug;66(2):478S-484S [9250135] Toxicol Pathol. 1997 Jul-Aug;25(4):351-62 [9280118] J Appl Toxicol. 1997 Nov-Dec;17(6):377-83 [9418945] Surg Clin North Am. 1998 Feb;78(1):95-112 [9531938] Chemosphere. 1998 Oct-Nov;37(9-12):1855-65 [9828314] Toxicol Ind Health. 1999 Jan-Mar;15(1-2):119-32 [10188195] Psychosom Med. 1999 Mar-Apr;61(2):175-80 [10204970] Proc Nutr Soc. 1999 Feb;58(1):85-98 [10343345] Environ Health Perspect. 1999 Oct;107(10):835-41 [10504152] Pediatrics. 1962 Apr;29:539-49 [14473162] Toxicol Appl Pharmacol. 2005 Aug 7;206(2):229-36 [15967213] J Occup Environ Med. 2006 Aug;48(8):771-9 [16902369] Toxicol Sci. 2006 Nov;94(1):22-7 [16882865] J Immunotoxicol. 2008 Jan;5(1):23-31 [18382855] Neuroimmunomodulation. 2008;15(4-6):251-9 [19047802] Environ Health. 2008;7:62 [19055819] Immunol Res. 2009;44(1-3):54-60 [19034396] Methods Mol Biol. 2010;598:97-108 [19967508] Methods Mol Biol. 2010;598:119-41 [19967510] Int J Infect Dis. 2010 Sep;14(9):e796-9 [20637673] Toxicol Sci. 2010 Nov;118(1):19-30 [20702593] Immunity. 2011 May 27;34(5):629-36 [21616433] Pediatr Transplant. 2011 Aug;15(5):505-9 [21504523] Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):5995-9 [22474371] J Immunotoxicol. 2012 Oct-Dec;9(4):411-25 [22734811] Occup Environ Med. 2012 Dec;69(12):932 [22918899] Brain Behav Immun. 2013 Jan;27(1):8-12 [22771426] Toxicology. 2013 May 10;307:123-35 [23116691] Stem Cells. 2013 Jul;31(7):1245-51 [23554173] Crit Care Clin. 2013 Oct;29(4):953-73 [24094386] J Immunotoxicol. 2013 Oct-Dec;10(4):373-9 [23350954] Environ Health Prev Med. 2013 Nov;18(6):429-50 [23959649] Natl Vital Stat Rep. 2013 Dec 20;62(6):1-96 [24364902] Laryngoscope. 2014 Jan;124(1):301-5 [23649905] Vaccine. 2007 Apr 20;25(16):3066-9 [17275144] J Immunol. 2007 Sep 15;179(6):4249-54 [17785865] Toxicol Appl Pharmacol. 2008 Jan 1;226(1):46-59 [17942131] Eur J Pediatr. 2001 Jul;160(7):407-13 [11475577] Environ Health Perspect. 2001 Aug;109(8):757-64 [11564609] Stem Cells. 2014 Sep;32(9):2386-96 [24801626] Brain Behav Immun. 2014 Oct;41:232-8 [24945717] Transplant Proc. 2014 Oct;46(8):2777-81 [25380916] Pediatrics. 1999 Dec;104(6):1327-33 [10585984] Transplantation. 1999 Nov 27;68(10):1597-603 [10589961] Environ Health Perspect. 2000 Mar;108(3):205-11 [10706525] J Immunol. 2001 Oct 15;167(8):4543-52 [11591782] Transplantation. 2001 Oct 27;72(8):1460-3 [11685123] Health Care Food Nutr Focus. 2001 Nov;18(3):1, 3-7 [11688342] Toxicol Appl Pharmacol. 2001 Dec 15;177(3):208-18 [11749120] Arch Environ Health. 2001 Nov-Dec;56(6):485-92 [11958547] J Consult Clin Psychol. 2002 Jun;70(3):537-47 [12090368] Infect Immun. 2002 Sep;70(9):5208-15 [12183572] Lancet Infect Dis. 2002 Nov;2(11):659-66 [12409046] Infect Immun. 2002 Dec;70(12):6583-8 [12438328] Microbes Infect. 2002 Dec;4(15):1545-58 [12505527] Physiol Behav. 2002 Dec;77(4-5):711-6 [12527024] Crit Rev Toxicol. 2003;33(1):61-103 [12585507] J Immunol. 2003 Mar 15;170(6):3423-8 [12626603] Scand J Work Environ Health. 2003 Aug;29(4):304-13 [12934724] Pharmacoeconomics. 2004;22(5):275-84 [15061677] Toxicol Lett. 2004 Apr 1;149(1-3):109-14 [15093255] Pediatrics. 1966 May;37(5):715-27 [4956666] Am J Dis Child. 1978 Mar;132(3):287-90 [629246] Psychosom Med. 1979 Oct;41(6):445-66 [231279] Infect Immun. 1980 Jan;27(1):61-7 [6766905] J Am Geriatr Soc. 1983 Jan;31(1):34-9 [6848575] Pediatr Res. 1984 Nov;18(11):1148-53 [6096799] Environ Health Perspect. 1985 Feb;59:17-29 [3921359] Environ Health Perspect. 1985 Feb;59:31-6 [3921360] J Pediatr. 1986 Jan;108(1):1-12 [3511202] J Behav Med. 1986 Feb;9(1):5-21 [2939253] Psychosom Med. 1987 Sep-Oct;49(5):523-35 [3671639] Fundam Appl Toxicol. 1988 Jan;10(1):2-19 [3280374] Brain Behav Immun. 1987 Mar;1(1):7-20 [2837297] J Fam Pract. 1989 May;28(5):535-9 [2715769] Transplantation. 1990 Mar;49(3):506-9 [2316011] Blood. 1990 Apr 1;75(7):1583-6 [2317564] N Engl J Med. 1991 Aug 29;325(9):606-12 [1713648] Psychosom Med. 1992 Jan-Feb;54(1):22-9 [1553399] J Toxicol Environ Health. 1992 Sep;37(1):123-37 [1326057] Transpl Int. 1993 Jan;6(1):18-21 [8383974] Health Psychol. 1993 Mar;12(2):132-9 [8500440] Fundam Appl Toxicol. 1993 Jul;21(1):71-82 [8365588] Health Psychol. 1993 Nov;12(6):435-42 [8293726] Isr J Med Sci. 1994 May-Jun;30(5-6):331-5 [8034475] J Perinat Med. 1994;22 Suppl 1:84-7 [7932010] Am J Respir Crit Care Med. 1995 Jul;152(1):76-80 [7599866] Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 2):S53-8 [7551414] Regul Toxicol Pharmacol. 2014 Feb;68(1):96-107 [24280359] Toxicol Sci. 2014 Mar;138(1):76-88 [24284791] Natl Vital Stat Rep. 2013 Dec 18;62(8):1-26 [24735562] J Clin Immunol. 2014 May;34(4):398-424 [24619621] Biomed Pharmacother. 2000 Jun;54(5):245-50 [10917461] Drug Saf. 2000 Aug;23(2):101-13 [10945373] Biol Neonate. 2000;78(2):77-82 [10970998] Blood. 2000 Nov 1;96(9):3290-3 [11050018] Environ Health Perspect. 2000 Dec;108(12):1113-24 [11133390] Environ Health Perspect. 2000 Dec;108(12):1203-7 [11133402] Psychosom Med. 2000 Nov-Dec;62(6):804-7 [11139000] Am J Epidemiol. 2001 Jan 1;153(1):53-63 [11159147] Toxicol Appl Pharmacol. 2001 Apr 1;172(1):75-82 [11264025] Blood. 1995 Nov 15;86(10):3979-86 [7579369] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3043-7 [8610165] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1002/0471140856.tx1801s67 ER - TY - JOUR T1 - Adherence to World Cancer Research Fund/American Institute for Cancer Research recommendations and pancreatic cancer risk. AN - 1762029170; 26605429 AB - Pancreatic cancer is a leading cause of cancer death. A role of dietary factors in pancreatic carcinogenesis has been suggested. The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published 8 recommendations for cancer prevention. We evaluated the effect of adherence to the WCRF/AICR recommendations on pancreatic cancer risk. We operationalized 7 of the 8 WCRF/AICR recommendations to generate a WCRF/AICR score. We examined the association of WCRF/AICR score with pancreatic cancer in data from an Italian case-control study of 326 incident cases and 652 controls. Adherence to WCRF/AICR recommendations was associated with a significantly decreased risk of pancreatic cancer. Using a WCRF/AICR score <3.5 as a reference, the adjusted odds ratio (OR) for a score 3.5-<4 was 0.80 (95% CI 0.49, 1.28), for a score 4-<5 0.54 (95% CI 0.35, 0.82), and for score 5 or more 0.41 (95% CI 0.24, 0.68; p-value for trend 0.0002). The OR for a continuous increment of one unit of the WCRF/AICR score was 0.72 (95% CI 0.60, 0.87). Adherence to the WCRF/AICR recommendations may reduce pancreatic cancer risk. Copyright © 2015 Elsevier Ltd. All rights reserved. JF - Cancer epidemiology AU - Lucas, Aimee L AU - Bravi, Francesca AU - Boffetta, Paolo AU - Polesel, Jerry AU - Serraino, Diego AU - La Vecchia, Carlo AU - Bosetti, Cristina AD - Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, NY, USA. Electronic address: aimee.lucas@mssm.edu. ; Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri"-IRCCS, Milan, Italy. ; Tisch Cancer Institute and Institute of Translational Epidemiology, Icahn School of Medicine at Mount Sinai, NY, USA. ; Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, Aviano (PN), Italy. ; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 15 EP - 21 VL - 40 KW - Index Medicus KW - American Institute for Cancer Research KW - World Cancer Research Fund KW - Risk factors KW - Pancreatic cancer KW - Diet KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Italy KW - Female KW - Risk Reduction Behavior KW - Pancreatic Neoplasms -- prevention & control KW - Guideline Adherence -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1762029170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology&rft.atitle=Adherence+to+World+Cancer+Research+Fund%2FAmerican+Institute+for+Cancer+Research+recommendations+and+pancreatic+cancer+risk.&rft.au=Lucas%2C+Aimee+L%3BBravi%2C+Francesca%3BBoffetta%2C+Paolo%3BPolesel%2C+Jerry%3BSerraino%2C+Diego%3BLa+Vecchia%2C+Carlo%3BBosetti%2C+Cristina&rft.aulast=Lucas&rft.aufirst=Aimee&rft.date=2016-02-01&rft.volume=40&rft.issue=&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology&rft.issn=1877-783X&rft_id=info:doi/10.1016%2Fj.canep.2015.10.026 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-19 N1 - Date created - 2016-02-01 N1 - Date revised - 2017-02-02 N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.canep.2015.10.026 ER - TY - JOUR T1 - Effect of Blood Collection Time on Measured Δ9-Tetrahydrocannabinol Concentrations: Implications for Driving Interpretation and Drug Policy. AN - 1761472672; 26823611 AB - In driving-under-the-influence cases, blood typically is collected approximately 1.5-4 h after an incident, with unknown last intake time. This complicates blood Δ(9)-tetrahydrocannabinol (THC) interpretation, owing to rapidly decreasing concentrations immediately after inhalation. We evaluated how decreases in blood THC concentration before collection may affect interpretation of toxicological results. Adult cannabis smokers (≥1×/3 months, ≤3 days/week) drank placebo or low-dose alcohol (approximately 0.065% peak breath alcohol concentration) 10 min before inhaling 500 mg placebo, 2.9%, or 6.7% vaporized THC (within-individuals), then took simulated drives 0.5-1.3 h postdose. Blood THC concentrations were determined before and up to 8.3 h postdose (limit of quantification 1 μg/L). In 18 participants, observed Cmax (at 0.17 h) for active (2.9 or 6.7% THC) cannabis were [median (range)] 38.2 μg/L (11.4-137) without alcohol and 47.9 μg/L (13.0-210) with alcohol. THC Cmax concentration decreased 73.5% (3.3%-89.5%) without alcohol and 75.1% (11.5%-85.4%) with alcohol in the first half-hour after active cannabis and 90.3% (76.1%-100%) and 91.3% (53.8%-97.0%), respectively, by 1.4 h postdose. When residual THC (from previous self-administration) was present, concentrations rapidly decreased to preinhalation baselines and fluctuated around them. During-drive THC concentrations previously associated with impairment (≥8.2 μg/L) decreased to median <5 μg/L by 3.3 h postdose and <2 μg/L by 4.8 h postdose; only 1 participant had THC ≥5 μg/L after 3.3 h. Forensic blood THC concentrations may be lower than common per se cutoffs despite greatly exceeding them while driving. Concentrations during driving cannot be back-extrapolated because of unknown time after intake and interindividual variability in rates of decrease. © 2015 American Association for Clinical Chemistry. JF - Clinical chemistry AU - Hartman, Rebecca L AU - Brown, Timothy L AU - Milavetz, Gary AU - Spurgin, Andrew AU - Gorelick, David A AU - Gaffney, Gary R AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; ; National Advanced Driving Simulator, University of Iowa, Iowa City, IA; ; College of Pharmacy, University of Iowa, Iowa City, IA; ; Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD; ; Carver College of Medicine, University of Iowa, Iowa City, IA. ; Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD; mhuestis@intra.nida.nih.gov. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 367 EP - 377 VL - 62 IS - 2 KW - Ethanol KW - 3K9958V90M KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Marijuana Smoking -- blood KW - Young Adult KW - Humans KW - Forensic Medicine -- methods KW - Blood Chemical Analysis -- methods KW - Adult KW - Ethanol -- administration & dosage KW - Ethanol -- analysis KW - Accidents, Traffic KW - Time Factors KW - Male KW - Female KW - Automobile Driving KW - Blood Specimen Collection -- methods KW - Dronabinol -- blood KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761472672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+chemistry&rft.atitle=Effect+of+Blood+Collection+Time+on+Measured+%CE%949-Tetrahydrocannabinol+Concentrations%3A+Implications+for+Driving+Interpretation+and+Drug+Policy.&rft.au=Hartman%2C+Rebecca+L%3BBrown%2C+Timothy+L%3BMilavetz%2C+Gary%3BSpurgin%2C+Andrew%3BGorelick%2C+David+A%3BGaffney%2C+Gary+R%3BHuestis%2C+Marilyn+A&rft.aulast=Hartman&rft.aufirst=Rebecca&rft.date=2016-02-01&rft.volume=62&rft.issue=2&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=1530-8561&rft_id=info:doi/10.1373%2Fclinchem.2015.248492 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-07 N1 - Date created - 2016-01-29 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1373/clinchem.2015.248492 ER - TY - JOUR T1 - Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. AN - 1760922192; 26598537 AB - Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs. Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome. None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including ≥3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression. In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Cierna, Z AU - Mego, M AU - Miskovska, V AU - Machalekova, K AU - Chovanec, M AU - Svetlovska, D AU - Hainova, K AU - Rejlekova, K AU - Macak, D AU - Spanik, S AU - Ondrus, D AU - Kajo, K AU - Mardiak, J AU - Babal, P AD - Department of Pathology, Faculty of Medicine. ; 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava misomego@gmail.com. ; Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava. ; Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava. ; 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava. ; Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute. ; Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Cancer Research Institute, Slovak, Academy of Sciences, Bratislava. ; Department of Pathology, National Cancer Institute, Bratislava. ; 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava. ; Department of Pathology, Faculty of Medicine Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 300 EP - 305 VL - 27 IS - 2 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD274 KW - Antineoplastic Agents KW - Biomarkers, Tumor KW - CD274 protein, human KW - PDCD1 protein, human KW - Programmed Cell Death 1 Receptor KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - programmed death receptor 1 KW - immunotherapy KW - programmed death-ligand 1 KW - testicular germ cell tumors KW - prognosis KW - Young Adult KW - Disease-Free Survival KW - Humans KW - Aged KW - Antibodies, Monoclonal -- immunology KW - Immunotherapy -- methods KW - Translational Medical Research KW - Cisplatin -- therapeutic use KW - Adult KW - Middle Aged KW - Adolescent KW - Antineoplastic Agents -- therapeutic use KW - Male KW - Testicular Neoplasms -- mortality KW - Neoplasms, Germ Cell and Embryonal -- mortality KW - Choriocarcinoma -- pathology KW - Testicular Neoplasms -- drug therapy KW - Testicular Neoplasms -- pathology KW - Antigens, CD274 -- antagonists & inhibitors KW - Neoplasms, Germ Cell and Embryonal -- pathology KW - Neoplasms, Germ Cell and Embryonal -- drug therapy KW - Programmed Cell Death 1 Receptor -- antagonists & inhibitors KW - Biomarkers, Tumor -- blood KW - Antigens, CD274 -- metabolism KW - Programmed Cell Death 1 Receptor -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760922192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=Prognostic+value+of+programmed-death-1+receptor+%28PD-1%29+and+its+ligand+1+%28PD-L1%29+in+testicular+germ+cell+tumors.&rft.au=Cierna%2C+Z%3BMego%2C+M%3BMiskovska%2C+V%3BMachalekova%2C+K%3BChovanec%2C+M%3BSvetlovska%2C+D%3BHainova%2C+K%3BRejlekova%2C+K%3BMacak%2C+D%3BSpanik%2C+S%3BOndrus%2C+D%3BKajo%2C+K%3BMardiak%2C+J%3BBabal%2C+P&rft.aulast=Cierna&rft.aufirst=Z&rft.date=2016-02-01&rft.volume=27&rft.issue=2&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=1569-8041&rft_id=info:doi/10.1093%2Fannonc%2Fmdv574 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-11 N1 - Date created - 2016-01-23 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Neoplasma. 2005;52(6):497-501 [16284696] J Clin Oncol. 1990 Nov;8(11):1777-81 [1700077] J Clin Oncol. 2000 Jun;18(12):2413-8 [10856101] Br J Cancer. 2015 Jul 28;113(3):411-3 [26171934] Cell Commun Signal. 2015;13:14 [25889536] Oncology (Williston Park). 2014 Nov;28 Suppl 3:15-28 [25387682] Ann Oncol. 2014 Oct;25(10):1935-40 [25009014] Breast Cancer Res Treat. 2014 Jul;146(1):15-24 [24842267] FEBS Lett. 2014 Jan 21;588(2):368-76 [24161671] PLoS One. 2013;8(10):e76012 [24124529] J Clin Pathol. 2013 Jul;66(7):607-12 [23486608] J Biol Chem. 2013 Apr 26;288(17):11771-85 [23417675] Cancer. 2012 Feb 15;118(4):981-6 [21792865] Immunol Rev. 2010 Jul;236:219-42 [20636820] BMC Cancer. 2010;10:151 [20403162] Cancer Res. 2006 Apr 1;66(7):3381-5 [16585157] Int Immunol. 2007 Jul;19(7):813-24 [17606980] J Pathol. 2009 Feb;217(3):431-41 [19023884] Cancer. 2010 Apr 1;116(7):1757-66 [20143437] Transplantation. 2009 Jun 27;87(12):1778-86 [19543053] Cancer. 1993 May 15;71(10):3182-4 [8490849] Cancer. 1991 Mar 1;67(5):1305-10 [1703917] J Clin Oncol. 1997 Feb;15(2):594-603 [9053482] Comment In: Nat Rev Urol. 2016 Feb;13(2):62 [26666362] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1093/annonc/mdv574 ER - TY - JOUR T1 - Delayed emergence of methamphetamine's enhanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence. AN - 1760913118; 26775284 AB - Methamphetamine abuse is linked with brain abnormalities, but its peripheral effects constitute an integral aspect of long-term methamphetamine use. Eight male rhesus monkeys with long histories of intravenous methamphetamine self-administration were evaluated 1 day, and 1, 4, 12, 26, and 52 weeks after their last methamphetamine self-administration session. On test days, isoflurane-anesthetized animals received a 0.35 mg/kg IV methamphetamine challenge. A control group consisted of 10 age and gender matched drug naïve monkeys. Cardiovascular responses to methamphetamine were followed for 2.5h. Echocardiograms were acquired at 3 and 12 months of abstinence and in the control animals. No pre-methamphetamine baseline differences existed among 7 physiological measures across all conditions and controls. As expected, methamphetamine increased heart rate and blood pressure in controls. However, immediately following the self-administration period, the blood pressure response to methamphetamine challenge was reduced when compared to control monkeys. The peak and 150-min average heart rate increases, as well as peak blood pressure increases following methamphetamine were significantly elevated between weeks 12 to 26 of abstinence. These data indicate the development of tolerance followed by sensitization to methamphetamine cardiovascular effects. Echocardiography demonstrated decreased left ventricular ejection fraction and cardiac output at 3 months of abstinence. Importantly, both cardiovascular sensitization and cardiotoxicity appeared to be reversible as they returned toward control group levels after 1 year of abstinence. Enhanced cardiovascular effects may occur after prolonged abstinence in addicts relapsing to methamphetamine and may underlie clinically reported acute cardiotoxic events. Published by Elsevier Ireland Ltd. JF - Drug and alcohol dependence AU - Vaupel, D B AU - Schindler, C W AU - Chefer, S AU - Belcher, A M AU - Ahmet, I AU - Scheidweiler, K B AU - Huestis, M A AU - Stein, E A AD - Neuroimaging Research Branch, National Institute on Drug Abuse, Baltimore, MD, United States. ; Preclinical Pharmacology Section, National Institute on Drug Abuse, Baltimore, MD, United States. Electronic address: cschind@helix.nih.gov. ; National Institute on Aging, National Institutes of Health, Baltimore, MD, United States. ; Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, Baltimore, MD, United States. Y1 - 2016/02/01/ PY - 2016 DA - 2016 Feb 01 SP - 181 EP - 189 VL - 159 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Abstinence KW - Rhesus monkey KW - Heart rate KW - Blood pressure KW - Drug Tolerance KW - Animals KW - Self Administration KW - Echocardiography KW - Case-Control Studies KW - Macaca mulatta KW - Time Factors KW - Male KW - Ventricular Function, Left -- drug effects KW - Methamphetamine -- administration & dosage KW - Heart Rate -- drug effects KW - Methamphetamine -- blood KW - Methamphetamine -- pharmacology KW - Blood Pressure -- drug effects KW - Cardiac Output -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760913118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Delayed+emergence+of+methamphetamine%27s+enhanced+cardiovascular+effects+in+nonhuman+primates+during+protracted+methamphetamine+abstinence.&rft.au=Vaupel%2C+D+B%3BSchindler%2C+C+W%3BChefer%2C+S%3BBelcher%2C+A+M%3BAhmet%2C+I%3BScheidweiler%2C+K+B%3BHuestis%2C+M+A%3BStein%2C+E+A&rft.aulast=Vaupel&rft.aufirst=D&rft.date=2016-02-01&rft.volume=159&rft.issue=&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=1879-0046&rft_id=info:doi/10.1016%2Fj.drugalcdep.2015.12.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-04 N1 - Date created - 2016-01-24 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: J Pharmacol Exp Ther. 1988 Aug;246(2):466-71 [2900325] N Engl J Med. 1988 May 5;318(18):1173-82 [3283549] Brain Res. 1989 May 1;486(1):73-8 [2720435] J Pharmacol Exp Ther. 1990 Feb;252(2):491-9 [1968971] Eur J Pharmacol. 1991 Feb 26;194(1):119-22 [2060588] Clin Neuropharmacol. 1991 Aug;14(4):352-8 [1913701] Pharmacol Biochem Behav. 1992 Aug;42(4):791-6 [1325059] J Pharmacol Exp Ther. 1993 Dec;267(3):1538-43 [8263815] Eur J Pharmacol. 1996 Nov 7;315(1):43-51 [8960863] Brain Res. 1998 Jun 22;797(1):29-34 [9630493] Psychopharmacology (Berl). 1999 Mar;142(4):343-51 [10229058] Ann N Y Acad Sci. 2004 Oct;1025:279-87 [15542728] Mayo Clin Proc. 2006 Jan;81(1):77-84 [16438482] J Chromatogr B Analyt Technol Biomed Life Sci. 2006 May 1;835(1-2):90-9 [16580268] Addiction. 2007 Aug;102(8):1204-11 [17565561] Drug Alcohol Rev. 2008 May;27(3):253-62 [18368606] Brain Res Rev. 2009 May;60(2):379-407 [19328213] Addiction. 2009 Jul;104(7):1085-99 [19426289] Eur J Pharmacol. 2010 May 10;633(1-3):44-9 [20153314] Exp Clin Psychopharmacol. 2011 Feb;19(1):1-10 [21341918] Addiction. 2012 Apr;107(4):783-91 [22050030] Addict Biol. 2015 Jan;20(1):69-79 [23910722] Eur J Pharmacol. 1999 Oct 21;383(1):57-68 [10556682] J Pharmacol Exp Ther. 2002 Apr;301(1):152-9 [11907169] Arch Gen Psychiatry. 2004 Jan;61(1):73-84 [14706946] Clin Pharmacol Ther. 1971 Mar-Apr;12(2):245-58 [5554941] Pharmacol Biochem Behav. 1984 Nov;21(5):737-41 [6514766] Brain Res. 1986 Jun;396(2):157-98 [3527341] Nihon Hoigaku Zasshi. 1987 Aug;41(4):335-41 [3694875] Psychopharmacology (Berl). 1989;97(1):59-64 [2496428] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.drugalcdep.2015.12.008 ER - TY - JOUR T1 - 5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer. AN - 1760909286; 26684645 AB - Genetic tools for the analysis of human tumors have developed rapidly over the past 20 years. Adrenocortical neoplasms have been subject to multiple analyses using these new genetic tools. Analysis of adrenocortical carcinomas (ACCs) has been complicated by the fact that these tumors tend to exhibit multiple somatic abnormalities, so that identifying driver mutations is complex task. In contrast, benign adrenocortical neoplasms have proven to be a fertile ground for the identification of the genetic causes of adrenocortical adenomas, as well as a variety of adrenocortical hyperplasia. Analysis of cortisol-producing adrenocortical adenomas has revealed alterations leading to enhanced signaling through the cAMP-dependent protein kinase (PKA) pathway. In contrast, macronodular cortisol-producing neoplasias have been shown to result from mutations in the ARMC5 gene, whose function is not yet quite so clear. In contrast, adrenal tumors resulting in excess production of the blood pressure hormone aldosterone almost always result from abnormalities of calcium handling, both in single adenomas and in bilateral hyperplasias. In both cases, there is elevation of a signaling pathway responsible both for hormone secretion and for gland growth and maintenance, thus confirming the linkage of these two output of cellular physiology. The connection between the benign hyperplasia observed in these states and adrenocortical carcinogenesis is not nearly as clear, although genetic studies are beginning to elucidate the relationship between benign and malignant tumors of this gland. JF - Hormones & cancer AU - Kirschner, Lawrence S AU - Stratakis, Constantine A AD - Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University Wexner Medical Center, 460 W 12th Ave, Rm 510, Columbus, OH, 43210, USA. Lawrence.Kirschner@osumc.edu. ; National Institute of Child Health and Human Development, National Institutes of Health, 31 Center Dr. Room 2A46 MSC 2425, Bethesda, MD, 20892-2425, USA. stratakc@mail.nih.gov. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 9 EP - 16 VL - 7 IS - 1 KW - ARMC5 protein, human KW - 0 KW - Tumor Suppressor Proteins KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Hyperplasia KW - Humans KW - Tumor Suppressor Proteins -- genetics KW - Cyclic AMP-Dependent Protein Kinases -- genetics KW - Congresses as Topic KW - Mutation KW - Signal Transduction KW - Adrenal Cortex Neoplasms -- pathology KW - Adrenal Cortex -- pathology KW - Adrenocortical Adenoma -- pathology KW - Adrenal Cortex Neoplasms -- genetics KW - Adrenocortical Adenoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760909286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hormones+%26+cancer&rft.atitle=5th+International+ACC+Symposium%3A+The+New+Genetics+of+Benign+Adrenocortical+Neoplasia%3A+Hyperplasias%2C+Adenomas%2C+and+Their+Implications+for+Progression+into+Cancer.&rft.au=Kirschner%2C+Lawrence+S%3BStratakis%2C+Constantine+A&rft.aulast=Kirschner&rft.aufirst=Lawrence&rft.date=2016-02-01&rft.volume=7&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Hormones+%26+cancer&rft.issn=1868-8500&rft_id=info:doi/10.1007%2Fs12672-015-0246-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-19 N1 - Date created - 2016-01-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s12672-015-0246-x ER - TY - JOUR T1 - Estrogen Metabolism and Risk of Postmenopausal Endometrial and Ovarian Cancer: the B ∼ FIT Cohort. AN - 1760909047; 26728471 AB - Estrogen metabolites may have different genotoxic and mitogenic properties yet their relationship with endometrial and ovarian cancer risk remains unclear. Within the Breast and Bone Follow-up to the Fracture Intervention Trial (B ∼ FIT, n = 15,595), we conducted a case-cohort study to evaluate 15 pre-diagnostic serum estrogens and estrogen metabolites with risk of incident endometrial and ovarian cancer among postmenopausal women not on hormone therapy. Participants included 66 endometrial and 67 ovarian cancer cases diagnosed during follow-up (∼ 10 years) and subcohorts of 346 and 416 women, respectively, after relevant exclusions. Serum concentrations were measured by liquid chromatography-tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. Exposures were categorized in tertiles (T) and analyzed individually, as metabolic pathways (C-2, -4, or -16) and as ratios to parent estrogens (estradiol, estrone). Estradiol was significantly associated with increased endometrial cancer risk (BMI-adjusted HRT3vsT1 = 4.09, 95% CI 1.70, 9.85; p trend = 0.003). 2-Hydroxyestrone and 16α-hydroxyestrone were not associated with endometrial risk after estradiol adjustment (2-OHE1:HRT3vsT1 = 1.97, 95% CI 0.78, 4.94; 16-OHE1:HRT3vsT1 = 1.50, 95% CI 0.65, 3.46; p trend = 0.16 and 0.36, respectively). Ratios of 2- and 4-pathway catechol-to-methylated estrogens remained positively associated with endometrial cancer after BMI or estradiol adjustment (2-pathway catechols-to-methylated: HRT3vsT1 = 4.02, 95% CI 1.60, 10.1; 4-pathway catechols-to-methylated: HRT3vsT1 = 4.59, 95% CI 1.64, 12.9; p trend = 0.002 for both). Estrogens and estrogen metabolites were not associated with ovarian cancer risk; however, larger studies are needed to better evaluate these relationships. Estrogen metabolism may be important in endometrial carcinogenesis, particularly with less extensive methylation of 2- or 4-pathway catechols associated with elevated endometrial cancer risk. JF - Hormones & cancer AU - Dallal, Cher M AU - Lacey, James V AU - Pfeiffer, Ruth M AU - Bauer, Douglas C AU - Falk, Roni T AU - Buist, Diana S M AU - Cauley, Jane A AU - Hue, Trisha F AU - LaCroix, Andrea Z AU - Tice, Jeffrey A AU - Veenstra, Timothy D AU - Xu, Xia AU - Brinton, Louise A AU - B∼FIT Research Group AD - Department of Epidemiology and Biostatistics, University of Maryland School of Public Health, College Park, MD, 20742, USA. cdallal@umd.edu. ; Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. ; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Department of Medicine, University of California, San Francisco, CA, USA. ; Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Group Health Research Institute, Seattle, WA, USA. ; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. ; Department of Epidemiology and Biostatistics, University of San Francisco, San Francisco, CA, USA. ; Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, CA, USA. ; C2N Diagnostics, Saint Louis, MO, USA. ; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MA, USA. ; B∼FIT Research Group Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 49 EP - 64 VL - 7 IS - 1 KW - Estrogens KW - 0 KW - Index Medicus KW - Chromatography, Liquid -- methods KW - Prospective Studies KW - Postmenopause KW - Humans KW - Aged KW - Middle Aged KW - Tandem Mass Spectrometry KW - Longitudinal Studies KW - Female KW - Proportional Hazards Models KW - Ovarian Neoplasms -- etiology KW - Estrogens -- metabolism KW - Ovarian Neoplasms -- blood KW - Endometrial Neoplasms -- blood KW - Endometrial Neoplasms -- etiology KW - Estrogens -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760909047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hormones+%26+cancer&rft.atitle=Estrogen+Metabolism+and+Risk+of+Postmenopausal+Endometrial+and+Ovarian+Cancer%3A+the+B+%E2%88%BC+FIT+Cohort.&rft.au=Dallal%2C+Cher+M%3BLacey%2C+James+V%3BPfeiffer%2C+Ruth+M%3BBauer%2C+Douglas+C%3BFalk%2C+Roni+T%3BBuist%2C+Diana+S+M%3BCauley%2C+Jane+A%3BHue%2C+Trisha+F%3BLaCroix%2C+Andrea+Z%3BTice%2C+Jeffrey+A%3BVeenstra%2C+Timothy+D%3BXu%2C+Xia%3BBrinton%2C+Louise+A%3BB%E2%88%BCFIT+Research+Group&rft.aulast=Dallal&rft.aufirst=Cher&rft.date=2016-02-01&rft.volume=7&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Hormones+%26+cancer&rft.issn=1868-8500&rft_id=info:doi/10.1007%2Fs12672-015-0237-y LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-19 N1 - Date created - 2016-01-26 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s12672-015-0237-y ER - TY - JOUR T1 - An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis. AN - 1760908965; 25792707 AB - Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. ClinicalTrials.gov number N01-CN95040. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ JF - Gut AU - Lynch, Patrick M AU - Burke, Carol A AU - Phillips, Robin AU - Morris, Jeffrey S AU - Slack, Rebecca AU - Wang, Xuemei AU - Liu, Jun AU - Patterson, Sherri AU - Sinicrope, Frank A AU - Rodriguez-Bigas, Miguel A AU - Half, Elizabeth AU - Bulow, Steffen AU - Latchford, Andrew AU - Clark, Sue AU - Ross, William A AU - Malone, Bonnie AU - Hasson, Hennie AU - Richmond, Ellen AU - Hawk, Ernest AD - Department of Gastroenterology, Hepatology and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. ; Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA. ; The Polyposis Registry, St. Mark's Hospital, London, UK. ; Division of Quantitative Sciences, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. ; Department of Plastic Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. ; Department of Cancer Prevention and Pop Science, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. ; Division of Gastroenterology, Hepatology and Oncology, Mayo Clinic, Rochester, Minnesota, USA. ; Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. ; Gatroenterology Department, Rambam Medical Center, Haifa, Israel. ; Hvidore Hospital, Denmark, UK. ; Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, The National Cancer Institute, Bethesda, Maryland, USA. ; Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 286 EP - 295 VL - 65 IS - 2 KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Celecoxib KW - JCX84Q7J1L KW - Eflornithine KW - ZQN1G5V6SR KW - Abridged Index Medicus KW - Index Medicus KW - CHEMOPREVENTION KW - POLYP KW - CANCER KW - ADENOMA KW - FAMILIAL ADENOMATOUS POLYPOSIS KW - Young Adult KW - Sigmoidoscopy KW - Humans KW - Adult KW - Tumor Burden KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Adenomatous Polyps -- genetics KW - Cyclooxygenase 2 Inhibitors -- adverse effects KW - Cyclooxygenase 2 Inhibitors -- administration & dosage KW - Adenomatous Polyps -- pathology KW - Celecoxib -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Eflornithine -- administration & dosage KW - Celecoxib -- therapeutic use KW - Celecoxib -- administration & dosage KW - Adenomatous Polyps -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760908965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=An+international+randomised+trial+of+celecoxib+versus+celecoxib+plus+difluoromethylornithine+in+patients+with+familial+adenomatous+polyposis.&rft.au=Lynch%2C+Patrick+M%3BBurke%2C+Carol+A%3BPhillips%2C+Robin%3BMorris%2C+Jeffrey+S%3BSlack%2C+Rebecca%3BWang%2C+Xuemei%3BLiu%2C+Jun%3BPatterson%2C+Sherri%3BSinicrope%2C+Frank+A%3BRodriguez-Bigas%2C+Miguel+A%3BHalf%2C+Elizabeth%3BBulow%2C+Steffen%3BLatchford%2C+Andrew%3BClark%2C+Sue%3BRoss%2C+William+A%3BMalone%2C+Bonnie%3BHasson%2C+Hennie%3BRichmond%2C+Ellen%3BHawk%2C+Ernest&rft.aulast=Lynch&rft.aufirst=Patrick&rft.date=2016-02-01&rft.volume=65&rft.issue=2&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2014-307235 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-09 N1 - Date created - 2016-01-08 N1 - Date revised - 2017-01-14 N1 - Genetic sequence - NCT00033371; ClinicalTrials.gov N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/gutjnl-2014-307235 ER - TY - JOUR T1 - The effect of ageing on isoniazid pharmacokinetics and hepatotoxicity in Fischer 344 rats. AN - 1760907389; 26454000 AB - Isoniazid is the first-line treatment for tuberculosis; however, its use is limited by hepatotoxicity. Age-related differences in isoniazid pharmacokinetics and hepatotoxicity are uncertain. We aimed to investigate these in young (3 ± 0 months, n = 26) and old (23.0 ± 0.2 months, n = 27) male Fischer 344 rats following a low- or high-dose toxic regimen of isoniazid or vehicle (4 doses/day over 2 days; low: 100, 75, 75, 75 mg/kg; high: 150, 105, 105, 105 mg/kg i.p. every 3 h). Fifteen hours after the last dose, animals were euthanized and sera and livers were prepared for analysis. Isoniazid treatment increased serum hepatotoxicity markers (alanine and aspartate transaminase) in young animals but not in old animals, and only reached significance with the high dose in young animals. Isoniazid treatment caused a trend towards an increase in necrosis in young animals with both doses. In contrast, microvesicular steatosis was increased in old isoniazid-treated animals, reaching significance only with the low dose (steatosis prevalence in old: vehicle 1/9, isoniazid 4/5; P < 0.05). Among isoniazid-treated animals, concentrations of toxic intermediates acetylhydrazine and hydrazine were higher in old than young animals (P < 0.05). With both doses, hepatic cytochrome P450 2E1 activity was higher in young animals compared with old (P < 0.05). There were no other age effects seen on any of the other measured enzymes involved in isoniazid metabolism (N-acetyl transferase, amidase, glutathione-S-transferase). These results show age-related changes in isoniazid pharmacokinetics may contribute towards differential patterns of toxicity and confirm that standard hepatotoxicity markers do not detect isoniazid-induced microvesicular steatosis. © 2015 Société Française de Pharmacologie et de Thérapeutique. JF - Fundamental & clinical pharmacology AU - Mach, John AU - Huizer-Pajkos, Aniko AU - Mitchell, Sarah J AU - McKenzie, Catriona AU - Phillips, Leo AU - Kane, Alice AU - Jones, Brett AU - de Cabo, Rafael AU - Cogger, Victoria AU - Le Couteur, David G AU - Hilmer, Sarah N AD - Laboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Sydney, NSW, Australia. ; Translational Gerontology Branch, National Institute on Aging, National Institute of Health, Baltimore, Maryland, USA. ; Pathology Department, Royal Prince Alfred Hosp, Sydney, NSW, Australia. ; Mass Spec Imaging and Proteomics Laboratory, Kolling institute of Medical Research, Sydney, NSW, Australia. ; Sydney Medical School, Univ of Sydney, Sydney, NSW, Australia. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 23 EP - 34 VL - 30 IS - 1 KW - Antitubercular Agents KW - 0 KW - Biomarkers KW - Isoniazid KW - V83O1VOZ8L KW - Index Medicus KW - isoniazid KW - toxicity KW - liver KW - ageing KW - pharmacokinetics KW - Injections, Intraperitoneal KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Biomarkers -- blood KW - Chemical and Drug Induced Liver Injury -- blood KW - Aging -- metabolism KW - Liver -- pathology KW - Liver -- enzymology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Isoniazid -- toxicity KW - Aging -- blood KW - Isoniazid -- pharmacokinetics KW - Chemical and Drug Induced Liver Injury -- etiology KW - Antitubercular Agents -- toxicity KW - Antitubercular Agents -- pharmacokinetics KW - Liver -- drug effects KW - Antitubercular Agents -- administration & dosage KW - Chemical and Drug Induced Liver Injury -- metabolism KW - Isoniazid -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760907389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+%26+clinical+pharmacology&rft.atitle=The+effect+of+ageing+on+isoniazid+pharmacokinetics+and+hepatotoxicity+in+Fischer+344+rats.&rft.au=Mach%2C+John%3BHuizer-Pajkos%2C+Aniko%3BMitchell%2C+Sarah+J%3BMcKenzie%2C+Catriona%3BPhillips%2C+Leo%3BKane%2C+Alice%3BJones%2C+Brett%3Bde+Cabo%2C+Rafael%3BCogger%2C+Victoria%3BLe+Couteur%2C+David+G%3BHilmer%2C+Sarah+N&rft.aulast=Mach&rft.aufirst=John&rft.date=2016-02-01&rft.volume=30&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Fundamental+%26+clinical+pharmacology&rft.issn=1472-8206&rft_id=info:doi/10.1111%2Ffcp.12157 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-17 N1 - Date created - 2016-01-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1111/fcp.12157 ER - TY - JOUR T1 - The proteome of methylmalonic acidemia (MMA): the elucidation of altered pathways in patient livers. AN - 1760904812; 26672496 AB - Methylmalonic acidemia (MMA) is a heterogeneous and severe autosomal recessive inborn error of metabolism most commonly caused by the deficient activity of the vitamin B12 dependent enzyme, methylmalonyl-CoA mutase (MUT). The main treatment for MMA patients is the dietary restriction of propiogenic amino acids and carnitine supplementation. Despite treatment, the prognosis for vitamin B12 non-responsive patients remains poor and is associated with neonatal lethality, persistent morbidity and decreased life expectancy. While multi-organ pathology is a feature of MMA, the liver is severely impacted by mitochondrial dysfunction which likely underlies the metabolic instability experienced by the patients. Liver and/or combined liver/kidney transplantation is therefore sometimes performed in severely affected patients. Using liver specimens from donors and MMA patients undergoing elective liver transplantation collected under a dedicated natural history protocol (clinicaltrials.gov: NCT00078078), we employed proteomics to characterize the liver pathology and impaired hepatic metabolism observed in the patients. Pathway analysis revealed perturbations of enzymes involved in energy metabolism, gluconeogenesis and Krebs cycle anaplerosis. Our findings identify new pathophysiologic and therapeutic targets that could be valuable for designing alternative therapies to alleviate clinical manifestations seen in this disorder. JF - Molecular bioSystems AU - Caterino, Marianna AU - Chandler, Randy J AU - Sloan, Jennifer L AU - Dorko, Kenneth AU - Cusmano-Ozog, Kristina AU - Ingenito, Laura AU - Strom, Stephen C AU - Imperlini, Esther AU - Scolamiero, Emanuela AU - Venditti, Charles P AU - Ruoppolo, Margherita AD - Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli, "Federico II", Naples, Italy and CEINGE Biotecnologie Avanzate, Naples, Italy. ; Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institute of Health, Bethesda MD 2092, USA. venditti@mail.nih.gov. ; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA. ; Division Genetics and Metabolism, Children's National Medical Center, Washington DC, USA. ; CEINGE Biotecnologie Avanzate, Naples, Italy. ; Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 566 EP - 574 VL - 12 IS - 2 KW - Proteome KW - 0 KW - Index Medicus KW - Infant KW - Metabolic Networks and Pathways KW - Humans KW - Case-Control Studies KW - Male KW - Liver Transplantation KW - Female KW - Two-Dimensional Difference Gel Electrophoresis KW - Child, Preschool KW - Amino Acid Metabolism, Inborn Errors -- metabolism KW - Proteome -- metabolism KW - Liver -- metabolism KW - Amino Acid Metabolism, Inborn Errors -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760904812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+bioSystems&rft.atitle=The+proteome+of+methylmalonic+acidemia+%28MMA%29%3A+the+elucidation+of+altered+pathways+in+patient+livers.&rft.au=Caterino%2C+Marianna%3BChandler%2C+Randy+J%3BSloan%2C+Jennifer+L%3BDorko%2C+Kenneth%3BCusmano-Ozog%2C+Kristina%3BIngenito%2C+Laura%3BStrom%2C+Stephen+C%3BImperlini%2C+Esther%3BScolamiero%2C+Emanuela%3BVenditti%2C+Charles+P%3BRuoppolo%2C+Margherita&rft.aulast=Caterino&rft.aufirst=Marianna&rft.date=2016-02-01&rft.volume=12&rft.issue=2&rft.spage=566&rft.isbn=&rft.btitle=&rft.title=Molecular+bioSystems&rft.issn=1742-2051&rft_id=info:doi/10.1039%2Fc5mb00736d LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-21 N1 - Date created - 2016-01-26 N1 - Date revised - 2017-02-02 N1 - Genetic sequence - NCT00078078; ClinicalTrials.gov N1 - SuppNotes - Cited By: J Neurochem. 2014 Jun;129(6):1002-12 [24548049] J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S91-4 [20157782] J Pediatr. 1988 Dec;113(6):1022-7 [3193307] Ann Neurol. 1986 Sep;20(3):364-6 [3767321] J Inherit Metab Dis. 2015 Sep;38(5):969-79 [25585586] Eur J Pediatr. 1989 Jan;148(4):344-8 [2707280] J Pediatr. 1994 Feb;124(2):239-43 [8301430] J Pediatr. 1994 Dec;125(6 Pt 1):903-8 [7996362] J Inherit Metab Dis. 1995;18(2):138-42 [7564229] J Pediatr. 1998 Jun;132(6):1043-4 [9627602] Arch Dis Child. 1998 Jun;78(6):508-12 [9713004] J Inherit Metab Dis. 2005;28(3):415-23 [15868474] J Inherit Metab Dis. 2005;28(4):517-24 [15902554] Mol Genet Metab. 2006 Jun;88(2):123-30 [16406646] J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):383-9 [16763906] Biochem J. 2006 Aug 15;398(1):107-12 [16686602] Mol Genet Metab. 2006 Aug;88(4):322-6 [16750411] Pediatr Transplant. 2006 Dec;10(8):943-7 [17096763] Am J Transplant. 2007 Dec;7(12):2782-7 [17908273] BMC Med Genet. 2007;8:64 [17937813] FASEB J. 2009 Apr;23(4):1252-61 [19088183] Am J Clin Nutr. 2011 Jan;93(1):47-56 [21048060] Toxicol Appl Pharmacol. 2013 Feb 1;266(3):470-80 [23200777] Proteomics. 2013 Apr;13(7):1220-7 [23412928] Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13552-7 [23898205] Mol Genet Metab. 2013 Sep-Oct;110(1-2):106-10 [23751327] Ultrastruct Pathol. 2014 Oct;38(5):309-14 [24933007] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1039/c5mb00736d ER - TY - JOUR T1 - Pharmacological Modulation of Lung Carcinogenesis in Smokers: Preclinical and Clinical Evidence. AN - 1760899661; 26726119 AB - Many drugs in common use possess pleiotropic properties that make them capable of interfering with carcinogenesis mechanisms. We discuss here the ability of pharmacological agents to mitigate the pulmonary carcinogenicity of mainstream cigarette smoke. The evaluated agents include anti-inflammatory drugs (budesonide, celecoxib, aspirin, naproxen, licofelone), antidiabetic drugs (metformin, pioglitazone), antineoplastic agents (lapatinib, bexarotene, vorinostat), and other drugs and supplements (phenethyl isothiocyanate, myo-inositol, N-acetylcysteine, ascorbic acid, berry extracts). These drugs have been evaluated in mouse models mimicking interventions either in current smokers or in ex-smokers, or in prenatal chemoprevention. They display a broad spectrum of activities by attenuating either smoke-induced preneoplastic lesions or benign tumors and/or malignant tumors. Together with epidemiological data, these findings provide useful information to predict the potential effects of pharmacological agents in smokers. Copyright © 2015 Elsevier Ltd. All rights reserved. JF - Trends in pharmacological sciences AU - De Flora, Silvio AU - Ganchev, Gancho AU - Iltcheva, Marietta AU - La Maestra, Sebastiano AU - Micale, Rosanna T AU - Steele, Vernon E AU - Balansky, Roumen AD - Department of Health Sciences, University of Genoa, 16132 Genoa, Italy. Electronic address: sdf@unige.it. ; National Center of Oncology, Sofia 1756, Bulgaria. ; Department of Health Sciences, University of Genoa, 16132 Genoa, Italy. ; Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20892, USA. ; Department of Health Sciences, University of Genoa, 16132 Genoa, Italy; National Center of Oncology, Sofia 1756, Bulgaria. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 120 EP - 142 VL - 37 IS - 2 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - cigarette smoke KW - lung cancer KW - pharmacological prevention KW - anti-inflammatory drugs KW - antineoplastic drugs KW - antidiabetic drugs KW - Animals KW - Humans KW - Smoking Cessation KW - Disease Models, Animal KW - Lung Neoplasms -- prevention & control KW - Lung Neoplasms -- epidemiology KW - Anticarcinogenic Agents -- pharmacology KW - Carcinogenesis -- drug effects KW - Smoking -- prevention & control KW - Smoking -- epidemiology KW - Anticarcinogenic Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760899661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+pharmacological+sciences&rft.atitle=Pharmacological+Modulation+of+Lung+Carcinogenesis+in+Smokers%3A+Preclinical+and+Clinical+Evidence.&rft.au=De+Flora%2C+Silvio%3BGanchev%2C+Gancho%3BIltcheva%2C+Marietta%3BLa+Maestra%2C+Sebastiano%3BMicale%2C+Rosanna+T%3BSteele%2C+Vernon+E%3BBalansky%2C+Roumen&rft.aulast=De+Flora&rft.aufirst=Silvio&rft.date=2016-02-01&rft.volume=37&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Trends+in+pharmacological+sciences&rft.issn=1873-3735&rft_id=info:doi/10.1016%2Fj.tips.2015.11.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-24 N1 - Date created - 2016-01-25 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Mol Cancer Ther. 2006 Apr;5(4):1060-72 [16648578] Proc Natl Acad Sci U S A. 2006 May 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Int J Cancer. 2012 Dec 15;131(12):2724-32 [22945513] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.tips.2015.11.003 ER - TY - JOUR T1 - Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial. AN - 1760898810; 26589415 AB - Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial. In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3α-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples. We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA. Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis. JF - Cancer causes & control : CCC AU - Schenk, Jeannette M AU - Till, Cathee AU - Hsing, Ann W AU - Stanczyk, Frank Z AU - Gong, Zhihong AU - Neuhouser, Marian L AU - Reichardt, Juergen K AU - Hoque, Ashraful M AU - Figg, William D AU - Goodman, Phyllis J AU - Tangen, Catherine M AU - Thompson, Ian M AD - Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jschenk@fredhutch.org. ; Cancer Prevention Program, SWOG, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ctill@fredhutch.org. ; Cancer Prevention Institute of California, Fremont, CA, USA. Ann.Hsing@CPIC.org. ; Department of Obstetrics/Gynecology, University of Southern California, Los Angeles, CA, USA. stanczyk@usc.edu. ; Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA. Zhihong.Gong@RoswellPark.org. ; Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. mneuhous@fredhutch.org. ; Division of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia. jreichardt@yachaytech.edu.ec. ; Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ahoque@mdanderson.org. ; Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA. figgw@helix.nih.gov. ; Cancer Prevention Program, SWOG, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. pgoodman@fredhutch.org. ; Cancer Prevention Program, SWOG, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ctangen@fredhutch.org. ; Cancer Therapy and Research Center, University of Texas Health Sciences Center San Antonio, San Antonio, TX, USA. ThompsonI@uthscsa.edu. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 175 EP - 182 VL - 27 IS - 2 KW - Androgens KW - 0 KW - Sex Hormone-Binding Globulin KW - Androstane-3,17-diol KW - 25126-76-5 KW - androstane-3,17-diol glucuronide KW - 27195-25-1 KW - Estrone KW - 2DI9HA706A KW - Testosterone KW - 3XMK78S47O KW - Estradiol KW - 4TI98Z838E KW - Kallikreins KW - EC 3.4.21.- KW - kallikrein-related peptidase 3, human KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Prostate cancer KW - Prostate Cancer Prevention Trial KW - Androgens -- blood KW - Kallikreins -- blood KW - Risk Factors KW - Humans KW - Prostate-Specific Antigen -- blood KW - Linear Models KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Biopsy KW - Arm KW - Male KW - Androstane-3,17-diol -- analogs & derivatives KW - Prostatic Neoplasms -- epidemiology KW - Estradiol -- blood KW - Testosterone -- blood KW - Prostatic Neoplasms -- blood KW - Sex Hormone-Binding Globulin -- metabolism KW - Androstane-3,17-diol -- blood KW - Estrone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760898810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Serum+androgens+and+prostate+cancer+risk%3A+results+from+the+placebo+arm+of+the+Prostate+Cancer+Prevention+Trial.&rft.au=Schenk%2C+Jeannette+M%3BTill%2C+Cathee%3BHsing%2C+Ann+W%3BStanczyk%2C+Frank+Z%3BGong%2C+Zhihong%3BNeuhouser%2C+Marian+L%3BReichardt%2C+Juergen+K%3BHoque%2C+Ashraful+M%3BFigg%2C+William+D%3BGoodman%2C+Phyllis+J%3BTangen%2C+Catherine+M%3BThompson%2C+Ian+M&rft.aulast=Schenk&rft.aufirst=Jeannette&rft.date=2016-02-01&rft.volume=27&rft.issue=2&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=1573-7225&rft_id=info:doi/10.1007%2Fs10552-015-0695-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-15 N1 - Date created - 2016-01-21 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: J Urol. 2002 Jul;168(1):9-12 [12050481] N Engl J Med. 2003 Jul 17;349(3):215-24 [12824459] Prostate. 1982;3(6):563-8 [7155989] Lancet. 1992 Apr 11;339(8798):887-9 [1348296] Cancer Epidemiol Biomarkers Prev. 1993 Jan-Feb;2(1):27-32 [8420607] J Natl Cancer Inst. 1996 Aug 21;88(16):1118-26 [8757191] Cancer Epidemiol Biomarkers Prev. 1996 Aug;5(8):621-5 [8824364] Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1262-9 [15894683] JAMA. 2005 Jul 13;294(2):238-44 [16014598] Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):86-91 [16434592] Cancer Causes Control. 2006 Dec;17(10):1237-44 [17111254] Steroids. 2007 Apr;72(4):375-80 [17368496] Front Biosci. 2007;12:3436-60 [17485312] J Natl Cancer Inst. 2008 Feb 6;100(3):170-83 [18230794] Int J Cancer. 2008 May 15;122(10):2345-50 [18172860] Curr Opin Endocrinol Diabetes Obes. 2008 Jun;15(3):261-70 [18438175] Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2525-30 [18842992] Prostate. 2010 Jun 1;70(8):906-15 [20166103] Urology. 2010 Nov;76(5):1034-40 [20451981] Cancer Prev Res (Phila). 2010 Dec;3(12):1523-33 [21149329] Cancer Causes Control. 2011 Aug;22(8):1121-31 [21667068] Eur Urol. 2012 Nov;62(5):757-64 [22658758] Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2374-82 [25178985] Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1823-32 [22879203] Prostate. 2013 May;73(6):668-76 [23129512] J Steroid Biochem Mol Biol. 2013 Sep;137:199-222 [23688836] Eur Urol. 2014 Apr;65(4):683-9 [23340241] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1007/s10552-015-0695-0 ER - TY - JOUR T1 - Categorization of drugs implicated in causing liver injury: Critical assessment based on published case reports. AN - 1760897729; 26517184 AB - An important element in assessing causality in drug-induced liver injury is whether the implicated agent is known to cause hepatotoxicity. We classified drugs into categories based on the number of published reports of convincingly documented, clinically apparent, idiosyncratic liver injury. Drugs described in the website LiverTox (http://livertox.nih.gov) were classified into five categories based on the number of published cases (category A, ≥50; category B, 12-49; category C, 4-11; category D, 1-3; category E, none). Case reports in categories C and D were individually reanalyzed using the Roussel Uclaf Causality Assessment Method. Drugs with fatal cases or with rechallenge were noted. Among 671 individual drugs or closely related agents, 353 (53%) were considered convincingly linked to liver injury in published case reports; 48 (13%) were assigned to category A, 76 (22%) were assigned to category B, 96 (27%) were assigned to category C, and 126 (36%) were assigned to category D. Another 7 (2%) were direct hepatotoxins but only in high doses and placed in a separate category (T). The remaining 318 (47%) drugs had no convincing case report of hepatoxicity in the literature (category E). All except one in category A have been available since 1999, 98% had at least one fatal case and 89% a positive rechallenge. In category B, 54% had a fatal case and 41% a rechallenge. Drugs in categories C and D less frequently had instances of fatal (23% and 7%) or rechallenge cases (26% and 11%). Documentation of hepatoxicity in the medical literature is variable, and many published instances do not stand up to critical review. A standardized system for categorizing drugs for hepatotoxicity potential will help develop objective and reliable, computer-based instruments for assessing causality in drug-induced liver injury. © 2015 by the American Association for the Study of Liver Diseases. JF - Hepatology (Baltimore, Md.) AU - Björnsson, Einar S AU - Hoofnagle, Jay H AD - The National University Hospital of Iceland, Reykjavik, Iceland. ; Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 590 EP - 603 VL - 63 IS - 2 KW - Pharmaceutical Preparations KW - 0 KW - Index Medicus KW - Humans KW - Medical Records KW - Chemical and Drug Induced Liver Injury -- etiology KW - Pharmaceutical Preparations -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760897729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Categorization+of+drugs+implicated+in+causing+liver+injury%3A+Critical+assessment+based+on+published+case+reports.&rft.au=Bj%C3%B6rnsson%2C+Einar+S%3BHoofnagle%2C+Jay+H&rft.aulast=Bj%C3%B6rnsson&rft.aufirst=Einar&rft.date=2016-02-01&rft.volume=63&rft.issue=2&rft.spage=590&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=1527-3350&rft_id=info:doi/10.1002%2Fhep.28323 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-06 N1 - Date created - 2016-01-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1002/hep.28323 ER - TY - JOUR T1 - Critical role of the Mac1/NOX2 pathway in mediating reactive microgliosis-generated chronic neuroinflammation and progressive neurodegeneration. AN - 1760875362; 26498406 AB - As average life expectancy rises throughout the world, neurodegenerative diseases have emerged as one of the greatest global public heath challenges in modern times. Substantial efforts have been made in researching neurodegenerative diseases over the last few decades, yet their predominantly sporadic nature has made uncovering their etiologies challenging. Mounting evidence has suggested that factors like damage-associated molecular patterns (DAMPs) released by stressed and dying neurons are likely involved in disease pathology and in stimulating chronic activation of microglia that contributes to neuronal oxidative stress and degeneration. This review focuses on how the microglial integrin receptor Mac1 and its downstream effector NADPH oxidase (NOX2) contribute to maintaining chronic neuroinflammation and are crucial in inflammation-driven neurotoxicity in neurodegenerative diseases. Our hope is to provide new insights on novel targets and therapies that could slow or even halt neurodegeneration. Published by Elsevier Ltd. JF - Current opinion in pharmacology AU - Chen, Shih-Heng AU - Oyarzabal, Esteban A AU - Hong, Jau-Shyong AD - Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Electronic address: chens3@niehs.nih.gov. ; Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; Neurobiology Curriculum, University of North Carolina Chapel Hill, Chapel Hill, NC, USA. ; Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 54 EP - 60 VL - 26 KW - CYBB protein, human KW - 0 KW - Macrophage-1 Antigen KW - Membrane Glycoproteins KW - Toll-Like Receptors KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Index Medicus KW - Animals KW - Humans KW - Inflammation -- metabolism KW - Toll-Like Receptors -- metabolism KW - Signal Transduction KW - NADPH Oxidase -- metabolism KW - Macrophage-1 Antigen -- metabolism KW - Neurodegenerative Diseases -- metabolism KW - Microglia -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760875362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+pharmacology&rft.atitle=Critical+role+of+the+Mac1%2FNOX2+pathway+in+mediating+reactive+microgliosis-generated+chronic+neuroinflammation+and+progressive+neurodegeneration.&rft.au=Chen%2C+Shih-Heng%3BOyarzabal%2C+Esteban+A%3BHong%2C+Jau-Shyong&rft.aulast=Chen&rft.aufirst=Shih-Heng&rft.date=2016-02-01&rft.volume=26&rft.issue=&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+pharmacology&rft.issn=1471-4973&rft_id=info:doi/10.1016%2Fj.coph.2015.10.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-13 N1 - Date created - 2016-01-18 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Nat Med. 1999 Dec;5(12):1403-9 [10581083] J Neurochem. 2013 Jun;125(5):756-65 [23470120] J Cell Sci. 2000 Aug;113 ( Pt 15):2737-45 [10893189] JAMA. 2002 Jun 26;287(24):3230-7 [12076219] J Pharmacol Exp Ther. 2003 Apr;305(1):212-8 [12649371] Eur J Pharmacol. 2003 Mar 28;465(1-2):171-81 [12650847] J Mol Neurosci. 2003;21(1):65-72 [14500997] Arch Neurol. 2004 Jan;61(1):82-8 [14732624] Immunopharmacology. 1992 Mar-Apr;23(2):139-49 [1351048] Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10540-4 [7479836] Nat Rev Immunol. 2005 Jun;5(6):446-58 [15928677] Ann N Y Acad Sci. 2005 Aug;1053:107-20 [16179514] Shock. 2006 Aug;26(2):174-9 [16878026] Nat Rev Neurosci. 2007 Jan;8(1):57-69 [17180163] Physiol Rev. 2007 Jan;87(1):245-313 [17237347] Nat Immunol. 2007 May;8(5):487-96 [17417641] Glia. 2007 Oct;55(13):1362-73 [17654704] Cell Physiol Biochem. 2007;20(6):947-56 [17982277] J Neuroinflammation. 2007;4:23 [17880684] Parkinsonism Relat Disord. 2007;13 Suppl 3:S316-20 [18267257] J Immunol. 2008 Nov 15;181(10):7194-204 [18981141] Brain Res Rev. 2009 Mar;59(2):278-92 [18822314] J Thromb Haemost. 2009 Jul;7 Suppl 1:151-4 [19630789] Neuron. 2009 Oct 15;64(1):110-22 [19840553] Am J Pathol. 2009 Nov;175(5):2121-32 [19834064] Glia. 2010 Feb;58(3):253-63 [19705460] Mediators Inflamm. 2010;2010. pii: 672395. doi: 10.1155/2010/672395 [20706656] J Neurosci. 2011 Jan 19;31(3):1081-92 [21248133] J Neuroinflammation. 2011;8(1):3 [21232086] Biochem Pharmacol. 2011 Apr 1;81(7):825-37 [21241665] J Immunol. 2011 Apr 1;186(7):4443-54 [21335487] Nat Rev Neurosci. 2014 Feb;15(2):84-97 [24399084] Neuron. 2014 Jan 22;81(2):229-48 [24462092] J Neuroinflammation. 2014;11:48 [24625061] Nat Rev Neurosci. 2014 May;15(5):300-12 [24713688] JAMA Neurol. 2014 May;71(5):543-52 [24664227] Antioxid Redox Signal. 2014 Jun 10;20(17):2815-37 [24206089] Nat Rev Immunol. 2014 Jul;14(7):463-77 [24962261] Glia. 2015 Jan;63(1):118-31 [25130274] Biochemistry. 2015 Feb 17;54(6):1408-20 [25613106] Lancet Neurol. 2015 Apr;14(4):388-405 [25792098] Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1926-35 [25825709] Brain. 2015 May;138(Pt 5):1247-62 [25716193] J Neuroimmunol. 1990 Nov;30(1):81-93 [1977769] Trends Immunol. 2008 Aug;29(8):357-65 [18599350] Physiol Rev. 2011 Apr;91(2):461-553 [21527731] Immunity. 2011 May 27;34(5):637-50 [21616434] Front Biosci (Elite Ed). 2012;4:2183-93 [22202030] J Immunol. 2012 Feb 1;188(3):1098-107 [22198949] Trends Pharmacol Sci. 2012 Jun;33(6):295-303 [22503440] Trends Immunol. 2012 Jul;33(7):333-42 [22521509] J Neuroinflammation. 2012;9:124 [22695044] J Neurol Sci. 2012 Nov 15;322(1-2):254-62 [22669122] Nat Commun. 2013;4:1562 [23463005] Glia. 2013 Jun;61(6):855-68 [23536230] J Pharmacol Exp Ther. 2000 May;293(2):607-17 [10773035] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.coph.2015.10.001 ER - TY - JOUR T1 - Anniston community health survey: Follow-up and dioxin analyses (ACHS-II)--methods. AN - 1760875272; 25982988 AB - High serum concentrations of polychlorinated biphenyls (PCBs) have been reported previously among residents of Anniston, Alabama, where a PCB production facility was located in the past. As the second of two cross-sectional studies of these Anniston residents, the Anniston Community Health Survey: Follow-Up and Dioxin Analyses (ACHS-II) will yield repeated measurements to be used to evaluate changes over time in ortho-PCB concentrations and selected health indicators in study participants. Dioxins, non-ortho PCBs, other chemicals, heavy metals, and a variety of additional clinical tests not previously measured in the original ACHS cohort will be examined in ACHS-II. The follow-up study also incorporates a questionnaire with extended sections on diet and occupational history for a more comprehensive assessment of possible exposure sources. Data collection for ACHS-II from 359 eligible participants took place in 2014, 7 to 9 years after ACHS. JF - Environmental science and pollution research international AU - Birnbaum, Linda S AU - Dutton, N D AU - Cusack, C AU - Mennemeyer, S T AU - Pavuk, M AD - National Cancer Institute, National Institutes of Health, Research Triangle, NC, USA. birnbaumls@niehs.nih.gov. ; Oak Ridge Institute for Science and Education (ORISE) Research Participation Program, Agency for Toxic Substances and Disease Registry, Atlanta, GA, USA. ; Agency for Toxic Substances and Disease Registry, Atlanta, GA, USA. ; University of Alabama at Birmingham, Birmingham, AL, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 2014 EP - 2021 VL - 23 IS - 3 KW - Dietary Fats KW - 0 KW - Environmental Pollutants KW - Fatty Acids KW - Plant Oils KW - Polychlorinated Dibenzodioxins KW - Sucrose KW - 57-50-1 KW - sucrose polyester KW - 6742Y30KGK KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Polychlorinated biphenyls KW - PBDEs KW - Heavy metals KW - PCDFs KW - Anniston KW - PCBs KW - Dioxins KW - PCDDs KW - Young Adult KW - Cross-Sectional Studies KW - Sucrose -- analogs & derivatives KW - Plant Oils -- pharmacology KW - Humans KW - Follow-Up Studies KW - Diet KW - Alabama KW - Male KW - Female KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Polychlorinated Dibenzodioxins -- chemistry KW - Polychlorinated Biphenyls -- chemistry KW - Health Surveys KW - Environmental Pollutants -- chemistry KW - Polychlorinated Biphenyls -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760875272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+science+and+pollution+research+international&rft.atitle=Anniston+community+health+survey%3A+Follow-up+and+dioxin+analyses+%28ACHS-II%29--methods.&rft.au=Birnbaum%2C+Linda+S%3BDutton%2C+N+D%3BCusack%2C+C%3BMennemeyer%2C+S+T%3BPavuk%2C+M&rft.aulast=Birnbaum&rft.aufirst=Linda&rft.date=2016-02-01&rft.volume=23&rft.issue=3&rft.spage=2014&rft.isbn=&rft.btitle=&rft.title=Environmental+science+and+pollution+research+international&rft.issn=1614-7499&rft_id=info:doi/10.1007%2Fs11356-015-4684-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-26 N1 - Date created - 2016-01-19 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Int J Obes Relat Metab Disord. 2000 Oct;24(10):1272-8 [11093288] Environ Res. 2009 Jan;109(1):66-72 [18950754] J Hypertens. 2010 Oct;28(10):2053-60 [20644494] Environ Health Perspect. 2011 Feb;119(2):225-31 [20934951] Sci Total Environ. 2014 Oct 15;496:624-34 [25115605] J Expo Sci Environ Epidemiol. 2011 May-Jun;21(3):234-46 [20216575] Environ Health Perspect. 2012 May;120(5):727-32 [22334129] Environ Health. 2013;12:108 [24325314] Sci Total Environ. 2014 Mar 1;473-474:286-97 [24374590] Environ Health Perspect. 2011 Mar;119(3):319-25 [21362590] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11356-015-4684-3 ER - TY - JOUR T1 - Ensuring the Quality, Fairness, and Integrity of Journal Peer Review: A Possible Role of Editors. AN - 1760872927; 25633924 AB - A growing body of literature has identified potential problems that can compromise the quality, fairness, and integrity of journal peer review, including inadequate review, inconsistent reviewer reports, reviewer biases, and ethical transgressions by reviewers. We examine the evidence concerning these problems and discuss proposed reforms, including double-blind and open review. Regardless of the outcome of additional research or attempts at reforming the system, it is clear that editors are the linchpin of peer review, since they make decisions that have a significant impact on the process and its outcome. We consider some of the steps editors should take to promote quality, fairness and integrity in different stages of the peer review process and make some recommendations for editorial conduct and decision-making. JF - Science and engineering ethics AU - Resnik, David B AU - Elmore, Susan A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Box 12233, Mail Drop CU 03, Research Triangle Park, NC, 27709, USA. resnikd@niehs.nih.gov. ; National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 169 EP - 188 VL - 22 IS - 1 KW - Bioethics KW - Index Medicus KW - Integrity KW - Quality KW - Reliability KW - Ethics KW - Peer review KW - Publication KW - Fairness KW - Editors KW - Bias UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760872927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+and+engineering+ethics&rft.atitle=Ensuring+the+Quality%2C+Fairness%2C+and+Integrity+of+Journal+Peer+Review%3A+A+Possible+Role+of+Editors.&rft.au=Resnik%2C+David+B%3BElmore%2C+Susan+A&rft.aulast=Resnik&rft.aufirst=David&rft.date=2016-02-01&rft.volume=22&rft.issue=1&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Science+and+engineering+ethics&rft.issn=1471-5546&rft_id=info:doi/10.1007%2Fs11948-015-9625-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2016-01-20 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s11948-015-9625-5 ER - TY - JOUR T1 - Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. AN - 1760864720; 25591978 AB - Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25-dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25(OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006). High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ JF - Gut AU - Song, Mingyang AU - Nishihara, Reiko AU - Wang, Molin AU - Chan, Andrew T AU - Qian, Zhi Rong AU - Inamura, Kentaro AU - Zhang, Xuehong AU - Ng, Kimmie AU - Kim, Sun A AU - Mima, Kosuke AU - Sukawa, Yasutaka AU - Nosho, Katsuhiko AU - Fuchs, Charles S AU - Giovannucci, Edward L AU - Wu, Kana AU - Ogino, Shuji AD - Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. ; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. ; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. ; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. ; Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan. ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. ; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 296 EP - 304 VL - 65 IS - 2 KW - Antigens, CD3 KW - 0 KW - Interleukin-6 KW - Tumor Necrosis Factors KW - Vitamin D KW - 1406-16-2 KW - 25-hydroxyvitamin D KW - 64719-49-9 KW - C-Reactive Protein KW - 9007-41-4 KW - Abridged Index Medicus KW - Index Medicus KW - IMMUNOLOGY KW - IMMUNOTHERAPY KW - NUTRITION KW - EPIDEMIOLOGY KW - COLORECTAL CANCER KW - Regression Analysis KW - T-Lymphocytes -- cytology KW - Cell Count KW - Tumor Necrosis Factors -- blood KW - Databases as Topic KW - Humans KW - Aged KW - C-Reactive Protein -- analysis KW - Interleukin-6 -- blood KW - Antigens, CD3 -- analysis KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Female KW - Male KW - Vitamin D -- blood KW - Vitamin D -- analogs & derivatives KW - Colorectal Neoplasms -- immunology KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760864720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gut&rft.atitle=Plasma+25-hydroxyvitamin+D+and+colorectal+cancer+risk+according+to+tumour+immunity+status.&rft.au=Song%2C+Mingyang%3BNishihara%2C+Reiko%3BWang%2C+Molin%3BChan%2C+Andrew+T%3BQian%2C+Zhi+Rong%3BInamura%2C+Kentaro%3BZhang%2C+Xuehong%3BNg%2C+Kimmie%3BKim%2C+Sun+A%3BMima%2C+Kosuke%3BSukawa%2C+Yasutaka%3BNosho%2C+Katsuhiko%3BFuchs%2C+Charles+S%3BGiovannucci%2C+Edward+L%3BWu%2C+Kana%3BOgino%2C+Shuji&rft.aulast=Song&rft.aufirst=Mingyang&rft.date=2016-02-01&rft.volume=65&rft.issue=2&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Gut&rft.issn=1468-3288&rft_id=info:doi/10.1136%2Fgutjnl-2014-308852 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-09 N1 - Date created - 2016-01-08 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: PLoS One. 2014;9(3):e92614 [24667823] Nat Rev Cancer. 2014 May;14(5):342-57 [24705652] World J Gastroenterol. 2014 May 28;20(20):6055-72 [24876728] Cancer Res. 2014 Aug 15;74(16):4398-408 [24938764] Cancer Causes Control. 2014 Oct;25(10):1397-405 [25053407] Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2613-7 [25277796] Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2694-702 [25472679] Gut. 2015 Sep;64(9):1419-25 [25239119] Methods Enzymol. 1997;282:174-86 [9330287] N Engl J Med. 2006 Feb 16;354(7):684-96 [16481636] Science. 2006 Mar 24;311(5768):1770-3 [16497887] J Mol Diagn. 2006 May;8(2):209-17 [16645207] Nat Immunol. 2007 Mar;8(3):285-93 [17259988] N Engl J Med. 2007 May 24;356(21):2131-42 [17522398] J Natl Cancer Inst. 2007 Jul 18;99(14):1120-9 [17623801] Nat Clin Pract Endocrinol Metab. 2008 Feb;4(2):80-90 [18212810] PLoS One. 2008;3(11):e3698 [19002263] Gut. 2009 Jan;58(1):90-6 [18832519] Clin Cancer Res. 2009 Oct 15;15(20):6412-20 [19825961] J Natl Cancer Inst. 2010 Mar 17;102(6):365-7 [20208016] Nat Immunol. 2010 Apr;11(4):344-9 [20208539] J Pathol. 2010 Dec;222(4):350-66 [20927778] Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22593-8 [21149724] Gut. 2011 Mar;60(3):397-411 [21036793] Gastroenterology. 2011 Mar;140(3):799-808, quiz e11 [21115010] Mod Pathol. 2011 May;24(5):671-82 [21240258] J Clin Oncol. 2011 Oct 1;29(28):3775-82 [21876081] Nat Rev Clin Oncol. 2011 Dec;8(12):711-9 [21826083] Biochim Biophys Acta. 2012 Jan;1825(1):77-85 [22056543] Genome Res. 2012 Feb;22(2):292-8 [22009990] Nat Med. 2012 Feb;18(2):224-6 [22270723] Nat Rev Cancer. 2012 Apr;12(4):298-306 [22419253] J Immunol. 2001 Nov 1;167(9):4974-80 [11673504] Am J Pathol. 2001 Feb;158(2):527-35 [11159189] Ann Epidemiol. 2012 Jul;22(7):520-30 [22481034] J Nutr. 1995 Jun;125(6 Suppl):1704S-1708S [7782931] Biometrics. 1995 Jun;51(2):524-32 [7662841] Nat Rev Immunol. 2012 Oct;12(10):696-708 [23007570] N Engl J Med. 2012 Oct 25;367(17):1596-606 [23094721] Innate Immun. 2013 Feb;19(1):76-85 [22781631] World J Gastroenterol. 2013 Jan 14;19(2):174-84 [23345940] J Transl Med. 2012;10:205 [23034130] Br J Cancer. 2013 May 14;108(9):1891-8 [23591192] Cancer Prev Res (Phila). 2013 Aug;6(8):764-73 [23918793] Int J Mol Sci. 2013;14(8):16365-85 [23965959] Nat Immunol. 2013 Oct;14(10):1014-22 [24048123] J Cell Mol Med. 2013 Sep;17(9):1088-95 [24151976] Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2303-11 [24127414] J Pathol. 2014 Jan;232(2):199-209 [24122236] J Natl Cancer Inst. 2013 Dec 18;105(24):1907-11 [24316595] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1136/gutjnl-2014-308852 ER - TY - JOUR T1 - Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells. AN - 1760864702; 26574516 AB - According to the catecholaldehyde hypothesis, the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) contributes to the loss of nigrostriatal dopaminergic neurons in Parkinson's disease. Monoamine oxidase-A (MAO-A) catalyzes the conversion of intraneuronal dopamine to DOPAL and may serve as a therapeutic target. The "cheese effect"-paroxysmal hypertension evoked by tyramine-containing foodstuffs-limits clinical use of irreversible MAO-A inhibitors. Combined MAO-A/B inhibition decreases DOPAL production in rat pheochromocytoma PC12 cells, but whether reversible MAO-A inhibitors or MAO-B inhibitors decrease endogenous DOPAL production is unknown. We compared the potencies of MAO inhibitors in attenuating DOPAL production and examined possible secondary effects on dopamine storage, constitutive release, synthesis, and auto-oxidation. Catechol concentrations were measured in cells and medium after incubation with the irreversible MAO-A inhibitor clorgyline, three reversible MAO-A inhibitors, or the MAO-B inhibitors selegiline or rasagiline for 180 minutes. Reversible MAO-A inhibitors were generally ineffective, whereas clorgyline (1 nM), rasagiline (500 nM), and selegiline (500 nM) decreased DOPAL levels in the cells and medium. All three drugs also increased dopamine and norepinephrine, decreased 3,4-dihydroxyphenylalanine, and increased cysteinyl-dopamine concentrations in the medium, suggesting increased vesicular uptake and constitutive release, decreased dopamine synthesis, and increased dopamine spontaneous oxidation. In conclusion, clorgyline, rasagiline, and selegiline decrease production of endogenous DOPAL. At relatively high concentrations, the latter drugs probably lose their selectivity for MAO-B. Possibly offsetting increased formation of potentially toxic oxidation products and decreased formation of DOPAL might account for the failure of large clinical trials of MAO-B inhibitors to demonstrate slowing of neurodegeneration in Parkinson's disease. U.S. Government work not protected by U.S. copyright. JF - The Journal of pharmacology and experimental therapeutics AU - Goldstein, David S AU - Jinsmaa, Yunden AU - Sullivan, Patti AU - Holmes, Courtney AU - Kopin, Irwin J AU - Sharabi, Yehonatan AD - Clinical Neurocardiology Section, Clinical Neuroscience Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (D.S.G., Y.J., P.S., C.H., I.J.K.); and Hypertension Unit, Chaim Sheba Medical Center and Tel-Aviv University, Tel-HaShomer, Israel (Y.S.) goldsteind@ninds.nih.gov. ; Clinical Neurocardiology Section, Clinical Neuroscience Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (D.S.G., Y.J., P.S., C.H., I.J.K.); and Hypertension Unit, Chaim Sheba Medical Center and Tel-Aviv University, Tel-HaShomer, Israel (Y.S.). Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 483 EP - 492 VL - 356 IS - 2 KW - Monoamine Oxidase Inhibitors KW - 0 KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - 3,4-dihydroxyphenylacetaldehyde KW - 5707-55-1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Parkinson Disease -- metabolism KW - PC12 Cells KW - Dopaminergic Neurons -- drug effects KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Dopaminergic Neurons -- metabolism KW - Dopamine -- metabolism KW - 3,4-Dihydroxyphenylacetic Acid -- antagonists & inhibitors KW - Monoamine Oxidase Inhibitors -- pharmacology KW - 3,4-Dihydroxyphenylacetic Acid -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760864702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Comparison+of+Monoamine+Oxidase+Inhibitors+in+Decreasing+Production+of+the+Autotoxic+Dopamine+Metabolite+3%2C4-Dihydroxyphenylacetaldehyde+in+PC12+Cells.&rft.au=Goldstein%2C+David+S%3BJinsmaa%2C+Yunden%3BSullivan%2C+Patti%3BHolmes%2C+Courtney%3BKopin%2C+Irwin+J%3BSharabi%2C+Yehonatan&rft.aulast=Goldstein&rft.aufirst=David&rft.date=2016-02-01&rft.volume=356&rft.issue=2&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=1521-0103&rft_id=info:doi/10.1124%2Fjpet.115.230201 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-06 N1 - Date created - 2016-01-19 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Neuropsychopharmacology. 2015 Feb;40(3):650-7 [25249059] Pharmacol Ther. 2014 Dec;144(3):268-82 [24945828] J Neurosci Res. 2000 May 15;60(4):552-8 [10797558] J Neurochem. 2002 Apr;81(1):122-9 [12067224] Brain Res. 2003 Nov 7;989(2):205-13 [14556942] Neurotoxicology. 2004 Jan;25(1-2):243-50 [14697899] Proc Natl Acad Sci U S A. 1971 Oct;68(10):2370-3 [4400211] J Neural Transm. 1976;39(1-2):1-19 [1086343] J Biol Chem. 1978 Jan 10;253(1):27-31 [22545] Psychopharmacology (Berl). 1978 Apr 14;57(1):33-8 [96466] Neuropharmacology. 1986 Apr;25(4):451-4 [3086766] Naunyn Schmiedebergs Arch Pharmacol. 1986 Apr;332(4):346-50 [2874501] Clin Chem. 1986 Nov;32(11):2030-3 [3096593] J Clin Endocrinol Metab. 1987 Apr;64(4):856-61 [3102548] J Neurochem. 1987 Oct;49(4):1183-90 [3305788] N Engl J Med. 1988 Apr 7;318(14):876-80 [3352672] Neuropharmacology. 1989 Aug;28(8):791-7 [2506486] Neurology. 1991 May;41(5 Suppl 2):50-1; discussion 52 [2041593] Neuropharmacology. 1991 May;30(5):463-8 [1907723] J Pharmacol Exp Ther. 1992 Jun;261(3):899-909 [1602395] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7603-7 [8102799] J Chromatogr B Biomed Appl. 1994 Mar 4;653(2):131-8 [8205240] J Clin Invest. 1996 Feb 15;97(4):1010-9 [8613523] Neuropsychopharmacology. 1996 Sep;15(3):296-301 [8873113] Eur J Pharmacol. 1996 Oct 24;314(1-2):51-9 [8957218] Exp Neurol. 1997 Nov;148(1):26-33 [9398447] J Nucl Med. 1999 Feb;40(2):323-30 [10025842] J Neurochem. 1999 Sep;73(3):1127-37 [10461904] JAMA. 1964 Jun 29;188:1108-10 [14163106] Pharmacotherapy. 2004 Oct;24(10):1295-305 [15628826] Hum Gene Ther. 2004 Dec;15(12):1177-96 [15684695] J Neurosci. 2006 Sep 6;26(36):9304-11 [16957086] Clin Auton Res. 2007 Apr;17(2):118-21 [17334896] Synapse. 2007 Sep;61(9):715-23 [17559092] Acta Neuropathol. 2008 Feb;115(2):193-203 [17965867] J Neurochem. 2008 Aug;106(4):1614-23 [18513370] Expert Opin Pharmacother. 2008 Nov;9(16):2881-91 [18937619] PLoS One. 2010;5(12):e15251 [21179455] Parkinsonism Relat Disord. 2010 Jul;16(6):365-9 [20471298] Neurotoxicology. 2009 Nov;30(6):1030-5 [19619580] Mov Disord. 2011 Mar;26(4):569-77 [21370266] Neurotoxicology. 2011 Aug;32(4):471-7 [21514317] J Biol Chem. 2011 Jul 29;286(30):26978-86 [21642436] Brain. 2012 Jun;135(Pt 6):1900-13 [22451506] Biometals. 2012 Aug;25(4):795-803 [22302610] J Neurochem. 2012 Dec;123(6):932-43 [22906103] J Neurochem. 2013 Sep;126(5):591-603 [23786406] J Neurosci. 2014 Jun 11;34(24):8210-8 [24920625] Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9977-82 [24979780] Mov Disord. 2016 Feb;31(2):152-60 [26340605] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/jpet.115.230201 ER - TY - JOUR T1 - Salting-out-assisted liquid-liquid extraction as a suitable approach for determination of methoxetamine in large sets of tissue samples. AN - 1760861928; 26661068 AB - A new designer drug, a dissociative anesthetic, and a putative N-methyl-D-aspartate receptor antagonist, methoxetamine (MXE) noted by the EU Early Warning System has been already identified as a cause of several fatalities worldwide. The primary objective of this work was to develop a suitable sample preparation method allowing for isolation of MXE and its main metabolites in high yields from rat brain, liver, and lungs. For the purpose of the project, MXE and five metabolites were synthesized in-house, specifically O-desmethyl-normethoxetamine, O-desmethylmethoxetamine, dihydro-O-desmethylmethoxetamine, normethoxetamine, and dihydromethoxetamine. A sample preparation procedure consisted in the homogenization of the tissue applying salting-out-assisted liquid-liquid extraction (SALLE). A subsequent liquid chromatography-mass spectrometry (LC-MS) analysis was based on reversed-phased chromatography hyphenated with a triple quad MS system in a positive electrospray mode. Multiple reaction monitoring (MRM) was used for qualification and quantification of the analytes. The quantification was based on the application of an isotopically labeled internal standard, normethoxetamine-d3. The matrix-matched calibrations were prepared for each type of matrix with regression coefficients 0.9943-1.0000. The calibration curves were linear in the concentration range of 2.5-250 ng g(-1). Limits of quantification (LOQs) were estimated as 2.5 and 5 ng g(-1), respectively. Recovery (80-117%) and matrix effect (94-110%) at 100 ng g(-1) and intra- and inter-day accuracy and precision at low (2.5 ng g(-1)), middle (25 ng g(-1)), and upper (250 ng g(-1)) concentration levels for all the analytes in all three types of tissues were also determined. The developed analytical method was applied to a set of real samples gathered in toxicological trials on rats and MXE, and its metabolites were determined successfully. JF - Analytical and bioanalytical chemistry AU - Hajkova, Katerina AU - Jurasek, Bronislav AU - Sykora, David AU - Palenicek, Tomas AU - Miksatkova, Petra AU - Kuchar, Martin AD - Forensic Laboratory of Biologically Active Substances, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Dejvice, Czech Republic. ; Department of Analytical Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Dejvice, Czech Republic. david.sykora@vscht.cz. ; National Institute of Mental Health, Topolová 748, 250 67, Klecany, Czech Republic. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 1171 EP - 1181 VL - 408 IS - 4 KW - 2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone KW - 0 KW - Cyclohexanones KW - Cyclohexylamines KW - Designer Drugs KW - Index Medicus KW - Tissues KW - SALLE KW - New psychoactive substances KW - LC-MS/MS KW - Methoxetamine KW - Rats KW - Animals KW - Chromatography, Liquid -- methods KW - Brain Chemistry KW - Lung -- chemistry KW - Calibration KW - Limit of Detection KW - Liver -- chemistry KW - Designer Drugs -- analysis KW - Cyclohexylamines -- pharmacokinetics KW - Cyclohexanones -- metabolism KW - Tandem Mass Spectrometry -- methods KW - Cyclohexylamines -- metabolism KW - Liquid-Liquid Extraction -- methods KW - Cyclohexylamines -- analysis KW - Cyclohexanones -- analysis KW - Cyclohexanones -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760861928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+and+bioanalytical+chemistry&rft.atitle=Salting-out-assisted+liquid-liquid+extraction+as+a+suitable+approach+for+determination+of+methoxetamine+in+large+sets+of+tissue+samples.&rft.au=Hajkova%2C+Katerina%3BJurasek%2C+Bronislav%3BSykora%2C+David%3BPalenicek%2C+Tomas%3BMiksatkova%2C+Petra%3BKuchar%2C+Martin&rft.aulast=Hajkova&rft.aufirst=Katerina&rft.date=2016-02-01&rft.volume=408&rft.issue=4&rft.spage=1171&rft.isbn=&rft.btitle=&rft.title=Analytical+and+bioanalytical+chemistry&rft.issn=1618-2650&rft_id=info:doi/10.1007%2Fs00216-015-9221-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-11-07 N1 - Date created - 2016-01-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1007/s00216-015-9221-1 ER - TY - JOUR T1 - Evidence that bacteriophage λ lysogens may induce in response to the proton motive force uncoupler CCCP. AN - 1760860094; 26705574 AB - We describe a genetic β-galactoside reporter system using a disk diffusion assay on MacConkey Lactose agar petri plates to monitor maintenance of the bacteriophage λ prophage state and viral induction in Escherichia coli K-12. Evidence is presented that the phage λ major lytic promoters, pL and pR, are activated when cells containing the reporters are exposed to the energy poison carbonyl cyanide m-chlorophenyl hydrazine, CCCP. This uncoupler of oxidative phosphorylation inhibits ATP synthesis by collapsing the proton motive force. Expression of the λ lytic promoters in response to CCCP requires host RecA function and an autocleavable CI repressor, as does SOS induction of the λ prophage that occurs by a DNA damage-dependent pathway. λ Cro function is required for CCCP-mediated activation of the λ lytic promoters. CCCP does not induce an sfi-lacZ SOS reporter. Published by Oxford University Press on behalf of FEMS 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US. JF - FEMS microbiology letters AU - Thomason, Lynn C AU - Court, Donald L AD - Basic Science Program, GRCBL-Molecular Control & Genetics Section, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA Gene Regulation and Chromosome Biology Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA thomasol@mail.nih.gov. ; Gene Regulation and Chromosome Biology Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 VL - 363 IS - 3 KW - Carbonyl Cyanide m-Chlorophenyl Hydrazone KW - 555-60-2 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - bacteriophage λ KW - DNA damage KW - carbonyl cyanide m-chlorophenyl hydrazone (CCCP) KW - uncoupler KW - Mitomycin C KW - prophage induction KW - Promoter Regions, Genetic KW - Proton-Motive Force -- drug effects KW - Genes, Reporter KW - beta-Galactosidase -- genetics KW - Artificial Gene Fusion KW - beta-Galactosidase -- analysis KW - Escherichia coli K12 -- virology KW - Virus Activation -- drug effects KW - Escherichia coli K12 -- drug effects KW - Carbonyl Cyanide m-Chlorophenyl Hydrazone -- metabolism KW - Bacteriophage lambda -- physiology KW - Bacteriophage lambda -- drug effects KW - Lysogeny -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760860094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+microbiology+letters&rft.atitle=Evidence+that+bacteriophage+%CE%BB+lysogens+may+induce+in+response+to+the+proton+motive+force+uncoupler+CCCP.&rft.au=Thomason%2C+Lynn+C%3BCourt%2C+Donald+L&rft.aulast=Thomason&rft.aufirst=Lynn&rft.date=2016-02-01&rft.volume=363&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=FEMS+microbiology+letters&rft.issn=1574-6968&rft_id=info:doi/10.1093%2Ffemsle%2Ffnv244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-13 N1 - Date created - 2016-01-15 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Basic Life Sci. 1975;5A:355-67 [1103845] Proc Natl Acad Sci U S A. 1975 Dec;72(12):4785-89 [1061069] Proc Natl Acad Sci U S A. 1978 Oct;75(10):4714-8 [368796] Proc Natl Acad Sci U S A. 1980 Jun;77(6):3225-9 [6447873] Cell. 1982 May;29(1):11-22 [7049397] Genes Dev. 1992 Mar;6(3):497-510 [1372278] Nature. 1961 Jul 8;191:144-8 [13771349] J Bacteriol. 2005 Feb;187(4):1515-8 [15687217] Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4465-9 [15728734] Curr Opin Genet Dev. 2005 Apr;15(2):145-52 [15797197] Annu Rev Genet. 2005;39:409-29 [16285866] Methods Enzymol. 2007;421:171-99 [17352923] Genes Dev. 2007 Oct 1;21(19):2461-72 [17908932] Appl Environ Microbiol. 2003 Mar;69(3):1759-74 [12620868] Appl Microbiol Biotechnol. 2003 Dec;63(3):293-9 [12898065] Proc Natl Acad Sci U S A. 1968 Aug;60(4):1282-7 [5244737] Genetics. 2009 May;182(1):55-68 [19270270] J Biol Chem. 2009 Dec 25;284(52):36191-201 [19840931] DNA Repair (Amst). 2010 Mar 2;9(3):210-23 [20093100] Biochim Biophys Acta. 2011 Dec;1807(12):1507-38 [22082452] Nucleic Acids Res. 2013 Dec;41(22):e204 [24203710] Mol Cell. 2015 Nov 5;60(3):374-84 [26481664] J Mol Biol. 1975 Apr 5;93(2):289-309 [1152054] Proc Natl Acad Sci U S A. 1970 Jul;66(3):855-62 [5269249] Proc Natl Acad Sci U S A. 1975 Jan;72(1):147-51 [1090931] Mol Microbiol. 2011 Oct;82(1):145-63 [21854465] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1093/femsle/fnv244 ER - TY - JOUR T1 - A Gene Expression Signature Associated with Overall Survival in Patients with Hepatocellular Carcinoma Suggests a New Treatment Strategy. AN - 1760858211; 26668215 AB - Despite improvements in the management of liver cancer, the survival rate for patients with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two independent cohorts of patients with advanced HCC, with the aim of finding ways to improve survival in this poor-prognosis cancer. Taqman-based quantitative polymerase chain reaction revealed a 45-gene signature that predicts overall survival (OS) in patients with HCC. Using the Connectivity Map Tool, we were able to identify drugs that converted the gene expression profiles of HCC cell lines from ones matching patients with poor OS to profiles associated with good OS. We found three compounds that convert the gene expression profiles of three HCC cell lines to gene expression profiles associated with good OS. These compounds increase histone acetylation, which correlates with the synergistic sensitization of those MDR tumor cells to conventional chemotherapeutic agents, including cisplatin, sorafenib, and 5-fluorouracil. Our results indicate that it is possible to modulate gene expression profiles in HCC cell lines to those associated with better outcome. This approach also increases sensitization of HCC cells toward conventional chemotherapeutic agents. This work suggests new treatment strategies for a disease for which few therapeutic options exist. U.S. Government work not protected by U.S. copyright. JF - Molecular pharmacology AU - Gillet, Jean-Pierre AU - Andersen, Jesper B AU - Madigan, James P AU - Varma, Sudhir AU - Bagni, Rachel K AU - Powell, Katie AU - Burgan, William E AU - Wu, Chung-Pu AU - Calcagno, Anna Maria AU - Ambudkar, Suresh V AU - Thorgeirsson, Snorri S AU - Gottesman, Michael M AD - Laboratory of Cell Biology (J-P.G., J.P.M., C-P.W., A.M.C., S.V.A., M.M.G.) and Laboratory of Experimental Carcinogenesis (J.B.A., S.S.T.), Center for Cancer Research, National Cancer Institute, and Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, Office of Science Management and Operations, National Institute of Allergy and Infectious Diseases (S.V.), National Institutes of Health, Bethesda, Maryland; and the Viral Technologies Group and Molecular Detection Group, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, Marylanld (R.K.B., K.P., W.E.B.). ; Laboratory of Cell Biology (J-P.G., J.P.M., C-P.W., A.M.C., S.V.A., M.M.G.) and Laboratory of Experimental Carcinogenesis (J.B.A., S.S.T.), Center for Cancer Research, National Cancer Institute, and Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, Office of Science Management and Operations, National Institute of Allergy and Infectious Diseases (S.V.), National Institutes of Health, Bethesda, Maryland; and the Viral Technologies Group and Molecular Detection Group, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, Marylanld (R.K.B., K.P., W.E.B.) mgottesman@nih.gov. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 263 EP - 272 VL - 89 IS - 2 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Survival Rate -- trends KW - Humans KW - Cohort Studies KW - Treatment Outcome KW - Cell Line, Tumor KW - Gene Expression Regulation, Neoplastic KW - Carcinoma, Hepatocellular -- drug therapy KW - Liver Neoplasms -- drug therapy KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- mortality KW - Antineoplastic Agents -- therapeutic use KW - Carcinoma, Hepatocellular -- mortality KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760858211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=A+Gene+Expression+Signature+Associated+with+Overall+Survival+in+Patients+with+Hepatocellular+Carcinoma+Suggests+a+New+Treatment+Strategy.&rft.au=Gillet%2C+Jean-Pierre%3BAndersen%2C+Jesper+B%3BMadigan%2C+James+P%3BVarma%2C+Sudhir%3BBagni%2C+Rachel+K%3BPowell%2C+Katie%3BBurgan%2C+William+E%3BWu%2C+Chung-Pu%3BCalcagno%2C+Anna+Maria%3BAmbudkar%2C+Suresh+V%3BThorgeirsson%2C+Snorri+S%3BGottesman%2C+Michael+M&rft.aulast=Gillet&rft.aufirst=Jean-Pierre&rft.date=2016-02-01&rft.volume=89&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=1521-0111&rft_id=info:doi/10.1124%2Fmol.115.101360 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-13 N1 - Date created - 2016-01-12 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Nat Rev Drug Discov. 2006 Mar;5(3):219-34 [16518375] N Engl J Med. 1996 Mar 14;334(11):693-9 [8594428] Science. 2006 Sep 29;313(5795):1929-35 [17008526] Nat Rev Cancer. 2007 Jan;7(1):54-60 [17186018] Int J Cancer. 2009 Feb 1;124(3):644-52 [19003983] Cancer Metastasis Rev. 2007 Mar;26(1):71-83 [17318448] Cancer Metastasis Rev. 2007 Mar;26(1):183-201 [17323126] Biochim Biophys Acta. 2007 Jun;1775(2):237-62 [17572300] BMC Bioinformatics. 2008;9:258 [18518950] N Engl J Med. 2008 Jul 24;359(4):378-90 [18650514] Eur J Pharm Sci. 2008 Oct 2;35(3):161-74 [18656534] Cancer Lett. 2006 Aug 8;239(2):168-82 [16169662] Mol Cancer Ther. 2008 Sep;7(9):3081-91 [18790787] Mol Aspects Med. 2009 Oct;30(5):297-343 [19427329] Mol Cancer Ther. 2010 Feb;9(2):319-26 [20103600] Hepatology. 2010 Apr;51(4):1401-9 [20054870] J Natl Cancer Inst. 2010 Nov 3;102(21):1637-52 [20935265] Gastroenterology. 2011 Mar;140(3):1063-70 [21094160] Curr Pharm Biotechnol. 2011 Apr;12(4):686-92 [21118086] Mol Pharm. 2011 Dec 5;8(6):2080-8 [21761824] J Hepatol. 2012 Apr;56(4):908-43 [22424438] Curr Opin Gastroenterol. 2012 May;28(3):266-72 [22395571] Nat Rev Gastroenterol Hepatol. 2013 Jan;10(1):34-42 [23147664] J Pharmacol Exp Ther. 2013 Sep;346(3):486-94 [23843632] Clin Cancer Res. 2014 Apr 15;20(8):2072-9 [24589894] Expert Rev Mol Diagn. 2014 Sep;14(7):803-17 [25098554] Semin Liver Dis. 2014 Nov;34(4):363-75 [25369299] Int J Cancer. 2015 Mar 1;136(5):E359-86 [25220842] Eur J Pediatr Surg. 2014 Dec;24(6):461-6 [25486412] Gastroenterology. 2015 Apr;148(4):806-18.e10 [25557953] J Hepatol. 2015 Apr;62(1 Suppl):S144-56 [25920083] Nat Rev Clin Oncol. 2015 Jul;12(7):408-24 [26054909] Clin Gastroenterol Hepatol. 2015 Nov;13(12):2140-51 [26284591] Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):E5916-25 [26489647] Pflugers Arch. 2004 Feb;447(5):735-43 [12838422] Cancer Res. 2004 Jun 15;64(12):4294-301 [15205344] Hepatology. 2004 Sep;40(3):667-76 [15349906] Nat Med. 2006 Apr;12(4):410-6 [16532004] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1124/mol.115.101360 ER - TY - JOUR T1 - Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer. AN - 1760855905; 26671626 AB - Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer. In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1055 cases/1101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.26, 95%CI=1.06-4.79), HIN1 (OR=2.14, 95%CI=1.34-3.42) and RARβ (OR=1.80, 95%CI=1.16-2.78) and decreased ORs for BRCA1 (OR=0.44, 95%CI=0.30-0.66). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 (OR=0.59, 95%CI=0.41-0.86). PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the associations between PAHs and breast cancer incidence. Published by Elsevier Inc. JF - Environmental research AU - White, Alexandra J AU - Chen, Jia AU - Teitelbaum, Susan L AU - McCullough, Lauren E AU - Xu, Xinran AU - Hee Cho, Yoon AU - Conway, Kathleen AU - Beyea, Jan AU - Stellman, Steven D AU - Steck, Susan E AU - Mordukhovich, Irina AU - Eng, Sybil M AU - Beth Terry, Mary AU - Engel, Lawrence S AU - Hatch, Maureen AU - Neugut, Alfred I AU - Hibshoosh, Hanina AU - Santella, Regina M AU - Gammon, Marilie D AD - Department of Epidemiology University of North Carolina, Chapel Hill, NC, USA. Electronic address: whitea@unc.edu. ; Departments of Preventive Medicine, New York, NY, USA; Departments of Oncological Science, New York, NY, USA; Departments of Pediatrics, Ichan School of Medicine at Mt. Sinai, New York, NY, USA. ; Departments of Preventive Medicine, New York, NY, USA. ; Department of Epidemiology University of North Carolina, Chapel Hill, NC, USA. ; Departments of Preventive Medicine, New York, NY, USA; Departments of Biometrics, Roche Product Development in Asia-Pacific, Shanghai, China. ; Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA. ; Department of Consulting in the Public Interest (CIPI), Lambertville, NJ, USA. ; Departments of Epidemiology, Columbia University, New York, NY, USA. ; Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA. ; Departments of Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. ; Departments of Epidemiology, Columbia University, New York, NY, USA; Departments of Medicine, Columbia University, New York, NY, USA. ; Departments of Pathology and Cell Biology, Columbia University, New York, NY, USA. ; Departments of Environmental Health Sciences; Columbia University, New York, NY, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 93 EP - 100 VL - 145 KW - Environmental Pollutants KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Air pollution KW - Smoking KW - Grilled meat. KW - Methylation KW - Environmental tobacco smoke KW - Young Adult KW - Odds Ratio KW - Aged, 80 and over KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Female KW - Long Interspersed Nucleotide Elements -- genetics KW - Polycyclic Aromatic Hydrocarbons -- toxicity KW - Breast Neoplasms -- genetics KW - Environmental Pollutants -- toxicity KW - Promoter Regions, Genetic -- drug effects KW - Epigenesis, Genetic -- drug effects KW - Environmental Exposure -- analysis KW - DNA Methylation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760855905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Sources+of+polycyclic+aromatic+hydrocarbons+are+associated+with+gene-specific+promoter+methylation+in+women+with+breast+cancer.&rft.au=White%2C+Alexandra+J%3BChen%2C+Jia%3BTeitelbaum%2C+Susan+L%3BMcCullough%2C+Lauren+E%3BXu%2C+Xinran%3BHee+Cho%2C+Yoon%3BConway%2C+Kathleen%3BBeyea%2C+Jan%3BStellman%2C+Steven+D%3BSteck%2C+Susan+E%3BMordukhovich%2C+Irina%3BEng%2C+Sybil+M%3BBeth+Terry%2C+Mary%3BEngel%2C+Lawrence+S%3BHatch%2C+Maureen%3BNeugut%2C+Alfred+I%3BHibshoosh%2C+Hanina%3BSantella%2C+Regina+M%3BGammon%2C+Marilie+D&rft.aulast=White&rft.aufirst=Alexandra&rft.date=2016-02-01&rft.volume=145&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=1096-0953&rft_id=info:doi/10.1016%2Fj.envres.2015.11.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-09 N1 - Date created - 2016-01-07 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Genome Res. 1996 Oct;6(10):995-1001 [8908519] Cancer Res. 1999 May 15;59(10):2302-6 [10344733] Ann Epidemiol. 2006 Mar;16(3):230-40 [16230024] J Mol Diagn. 2006 May;8(2):209-17 [16645207] Arch Environ Health. 2004 Dec;59(12):640-9 [16789472] Environ Health Perspect. 2006 Jul;114(7):1053-8 [16835058] Toxicol Appl Pharmacol. 2006 Nov 1;216(3):458-68 [16926039] Epidemiology. 2007 May;18(3):373-82 [17435448] Cancer Causes Control. 2007 Nov;18(9):947-55 [17632764] JAMA. 2008 Jun 25;299(24):2877-83 [18577732] Breast Cancer Res Treat. 2009 May;115(2):397-404 [18521744] Cancer Causes Control. 2009 Nov;20(9):1539-50 [19768562] Heredity (Edinb). 2010 Jul;105(1):105-12 [20179736] IARC Monogr Eval Carcinog Risks Hum. 2010;92:1-853 [21141735] Cancer Causes Control. 2010 Dec;21(12):2101-11 [20711807] Epigenetics. 2011 Jul;6(7):828-37 [21636973] Breast Cancer Res Treat. 2011 Oct;129(3):919-28 [21537933] Breast Cancer Res Treat. 2012 Jan;131(1):197-205 [21837480] FASEB J. 2012 Jun;26(6):2657-66 [22371529] Epigenetics. 2011 Nov;6(11):1276-83 [22048254] Nat Rev Genet. 2012 Jul;13(7):484-92 [22641018] Cancer Prev Res (Phila). 2012 Dec;5(12):1345-57 [23135621] Sci Signal. 2013 Apr 2;6(269):pl1 [23550210] J Natl Cancer Inst. 2013 Apr 17;105(8):515-25 [23449445] PLoS One. 2013;8(5):e63812 [23691101] Epidemiology. 2013 Sep;24(5):712-6 [23867811] Arch Toxicol. 2013 Nov;87(11):2013-22 [23543013] Carcinogenesis. 2014 Feb;35(2):333-8 [24130171] Environ Health Perspect. 2014 Feb;122(2):131-7 [24273234] PLoS One. 2014;9(3):e91805 [24651077] Epigenetics. 2014 Oct;9(10):1382-96 [25424692] Environ Int. 2015 Jan;74:240-8 [25454241] Environ Res. 2014 Oct;134:325-30 [25199973] Environ Health. 2014;13:108 [25495350] Nucleic Acids Res. 2000 Apr 15;28(8):E32 [10734209] Cancer Res. 2000 Sep 15;60(18):5021-6 [11016622] Cancer Res. 2001 Oct 1;61(19):7110-7 [11585742] Environ Mol Mutagen. 2002;39(2-3):89-95 [11921174] Environ Mol Mutagen. 2002;39(2-3):119-26 [11921179] Environ Health Perspect. 2002 Jun;110 Suppl 3:451-88 [12060843] Breast Cancer Res Treat. 2002 Jun;74(3):235-54 [12206514] Life Sci. 2003 Aug 29;73(15):1963-72 [12899921] J Nutr. 2003 Nov;133(11 Suppl 1):3740S-3747S [14608108] Environ Res. 2004 Oct;96(2):176-85 [15325878] Br J Cancer. 1979 Oct;40(4):513-22 [497103] Cell. 1983 Jan;32(1):239-46 [6825170] Carcinogenesis. 1984 Aug;5(8):1027-31 [6086166] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Am J Epidemiol. 1995 Nov 1;142(9):904-8 [7572970] Am J Epidemiol. 1996 May 1;143(9):918-28 [8610705] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.envres.2015.11.033 ER - TY - JOUR T1 - Malignant Transformation of Teratoma to Adenocarcinoma With Complete Remission With All-Trans Retinoic Acid-Based Treatment and Surgery. AN - 1753230943; 26549823 JF - Clinical genitourinary cancer AU - Chovanec, Michal AU - Oravcova, Iveta AU - Demitrovicova, Ludmila AU - Mego, Michal AU - Mardiak, Jozef AD - Second Department of Oncology, Comenius University Faculty of Medicine, Bratislava, Slovakia; National Cancer Institute, Bratislava, Slovakia. Electronic address: michal.chovanec1@gmail.com. ; Second Department of Oncology, Comenius University Faculty of Medicine, Bratislava, Slovakia; National Cancer Institute, Bratislava, Slovakia. ; Second Department of Oncology, Comenius University Faculty of Medicine, Bratislava, Slovakia. ; Second Department of Oncology, Comenius University Faculty of Medicine, Bratislava, Slovakia; National Cancer Institute, Bratislava, Slovakia; Translational Research Unit, Comenius University Faculty of Medicine, Bratislava, Slovakia. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - e131 EP - e133 VL - 14 IS - 1 KW - Antineoplastic Agents KW - 0 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - All-trans retinoic acid KW - Complete remission KW - Malignant transformation KW - Unresectable KW - Teratoma KW - Humans KW - Adult KW - Treatment Outcome KW - Maintenance Chemotherapy KW - Radiography KW - Male KW - Cell Transformation, Neoplastic KW - Adenocarcinoma -- diagnostic imaging KW - Retroperitoneal Neoplasms -- diagnostic imaging KW - Teratoma -- drug therapy KW - Retroperitoneal Neoplasms -- drug therapy KW - Adenocarcinoma -- secondary KW - Retroperitoneal Neoplasms -- pathology KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Teratoma -- secondary KW - Teratoma -- diagnostic imaging KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1753230943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+genitourinary+cancer&rft.atitle=Malignant+Transformation+of+Teratoma+to+Adenocarcinoma+With+Complete+Remission+With+All-Trans+Retinoic+Acid-Based+Treatment+and+Surgery.&rft.au=Chovanec%2C+Michal%3BOravcova%2C+Iveta%3BDemitrovicova%2C+Ludmila%3BMego%2C+Michal%3BMardiak%2C+Jozef&rft.aulast=Chovanec&rft.aufirst=Michal&rft.date=2016-02-01&rft.volume=14&rft.issue=1&rft.spage=e131&rft.isbn=&rft.btitle=&rft.title=Clinical+genitourinary+cancer&rft.issn=1938-0682&rft_id=info:doi/10.1016%2Fj.clgc.2015.10.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-05 N1 - Date created - 2016-01-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.clgc.2015.10.001 ER - TY - JOUR T1 - Safety and Clinical Outcomes of Abiraterone Acetate After Docetaxel in Octogenarians With Metastatic Castration-Resistant Prostate Cancer: Results of the Italian Compassionate Use Named Patient Programme. AN - 1753230537; 26382222 AB - Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population. Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population. We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression-free survival (PFS). Safety and clinical outcomes were also analyzed by age group ( 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables. In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature. Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population. Copyright © 2016 Elsevier Inc. All rights reserved. JF - Clinical genitourinary cancer AU - Maines, Francesca AU - Caffo, Orazio AU - De Giorgi, Ugo AU - Fratino, Lucia AU - Lo Re, Giovanni AU - Zagonel, Vittorina AU - D'Angelo, Alessandro AU - Donini, Maddalena AU - Verderame, Francesco AU - Ratta, Raffaele AU - Procopio, Giuseppe AU - Campadelli, Enrico AU - Massari, Francesco AU - Gasparro, Donatello AU - Ermacora, Paola AU - Messina, Caterina AU - Giordano, Monica AU - Alesini, Daniele AU - Basso, Umberto AU - Fraccon, Anna Paola AU - Vicario, Giovanni AU - Conteduca, Vincenza AU - Galligioni, Enzo AD - Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. ; Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. Electronic address: orazio.caffo@apss.tn.it. ; Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. ; Medical Oncology Department, National Cancer Institute, Aviano, Italy. ; Medical Oncology Department, Santa Maria degli Angeli Hospital, Pordenone, Italy. ; Medical Oncology Unit 1, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy. ; Medical Oncology Department, San Vincenzo Hospital, Taormina, Italy. ; Medical Oncology Department, Civil Hospital, Cremona, Italy. ; Medical Oncology Department, Villa Sofia Cervello Hospital, Palermo, Italy. ; Medical Oncology Department, Unicampus University, Rome, Italy. ; Medical Oncology Department, National Cancer Institute, Milan, Italy. ; Medical Oncology Department, Civil Hospital, Lugo di Romagna, Italy. ; Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy. ; Medical Oncology Department, Civil Hospital, Parma, Italy. ; Medical Oncology Department, Santa Maria della Misericordia Hospital, Udine, Italy. ; Medical Oncology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy. ; Medical Oncology Department, Sant'Anna Hospital, Como, Italy. ; Department of Radiological, Oncological and Anatomopathological Sciences, La Sapienza, University of Rome, Rome, Italy. ; Medical Oncology Department, Casa di Cura Pederzoli, Peschiera del Garda, Italy. ; Medical Oncology Department, San Giacomo Apostolo Hospital, Castelfranco Veneto, Italy. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 48 EP - 55 VL - 14 IS - 1 KW - Antineoplastic Agents KW - 0 KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Abiraterone Acetate KW - EM5OCB9YJ6 KW - Index Medicus KW - Safety KW - Outcomes KW - Elderly KW - Castration-resistant prostate cancer KW - Abiraterone KW - Kaplan-Meier Estimate KW - Disease-Free Survival KW - Aged, 80 and over KW - Humans KW - Treatment Outcome KW - Retrospective Studies KW - Aged KW - Compassionate Use Trials KW - Male KW - Proportional Hazards Models KW - Prostatic Neoplasms, Castration-Resistant -- mortality KW - Antineoplastic Agents -- administration & dosage KW - Abiraterone Acetate -- administration & dosage KW - Taxoids -- administration & dosage KW - Prostatic Neoplasms, Castration-Resistant -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1753230537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+genitourinary+cancer&rft.atitle=Safety+and+Clinical+Outcomes+of+Abiraterone+Acetate+After+Docetaxel+in+Octogenarians+With+Metastatic+Castration-Resistant+Prostate+Cancer%3A+Results+of+the+Italian+Compassionate+Use+Named+Patient+Programme.&rft.au=Maines%2C+Francesca%3BCaffo%2C+Orazio%3BDe+Giorgi%2C+Ugo%3BFratino%2C+Lucia%3BLo+Re%2C+Giovanni%3BZagonel%2C+Vittorina%3BD%27Angelo%2C+Alessandro%3BDonini%2C+Maddalena%3BVerderame%2C+Francesco%3BRatta%2C+Raffaele%3BProcopio%2C+Giuseppe%3BCampadelli%2C+Enrico%3BMassari%2C+Francesco%3BGasparro%2C+Donatello%3BErmacora%2C+Paola%3BMessina%2C+Caterina%3BGiordano%2C+Monica%3BAlesini%2C+Daniele%3BBasso%2C+Umberto%3BFraccon%2C+Anna+Paola%3BVicario%2C+Giovanni%3BConteduca%2C+Vincenza%3BGalligioni%2C+Enzo&rft.aulast=Maines&rft.aufirst=Francesca&rft.date=2016-02-01&rft.volume=14&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Clinical+genitourinary+cancer&rft.issn=1938-0682&rft_id=info:doi/10.1016%2Fj.clgc.2015.07.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-05 N1 - Date created - 2016-01-03 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.clgc.2015.07.019 ER - TY - JOUR T1 - New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases. AN - 1752350448; 26547877 AB - Wide utilization of phthalates-containing products results in the significant exposure of humans to these compounds. Many adverse effects of phthalates have been documented in rodent models, but their effects in humans exposed to these chemicals remain unclear until more mechanistic studies on phthalate toxicities can be carried out. To provide new insights to predict the potential adverse effects of phthalates in humans, the recent study investigated the inhibition of representative phthalates di-n-octyl ortho-phthalate (DNOP) and diphenyl phthalate (DPhP) towards the important xenobiotic and endobiotic-metabolizing UDP-glucuronosyltransferases (UGTs). An in vitro UGTs incubation system was employed to study the inhibition of DNOP and DPhP towards UGT isoforms. DPhP and DNOP weakly inhibited the activities of UGT1A1, UGT1A7, and UGT1A8. 100 µM of DNOP inhibited the activities of UGT1A3, UGT1A9, and UGT2B7 by 41.8% (p [I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), these studies predicted in vivo drug-drug interaction might occur when the plasma concentration of DPhP was above 0.089 µM. Taken together, this study reveales the potential for adverse effects of phthalates DNOP and DPhP as a result of UGT inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved. JF - Chemosphere AU - Liu, Xin AU - Cao, Yun-Feng AU - Ran, Rui-Xue AU - Dong, Pei-Pei AU - Gonzalez, Frank J AU - Wu, Xue AU - Huang, Ting AU - Chen, Jian-Xin AU - Fu, Zhi-Wei AU - Li, Rong-Shan AU - Liu, Yong-Zhe AU - Sun, Hong-Zhi AU - Fang, Zhong-Ze AD - First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, China. ; Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, China. ; School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, China. ; Institute of Integrative Medicine, Dalian Medical University, Dalian, China. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the First Affiliated Hospital of Liaoning Medical University, Dalian, China; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the Affiliated Zhongshan Hospital of Dalian University, Zhongshan, Dalian, China. ; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, 300070, China. ; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, 300070, China. Electronic address: fangzhongze@tmu.edu.cn. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 1966 EP - 1972 VL - 144 KW - Isoenzymes KW - 0 KW - Phthalic Acids KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Index Medicus KW - Di-n-octyl ortho-phthalate (DNOP) KW - Phthalates KW - Diphenyl phthalate (DPhP) KW - UDP-glucuronosyltransferases (UGTs) KW - Isoenzymes -- antagonists & inhibitors KW - Risk KW - Kinetics KW - Humans KW - Isoenzymes -- metabolism KW - Phthalic Acids -- pharmacology KW - Glucuronosyltransferase -- antagonists & inhibitors KW - Glucuronosyltransferase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1752350448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=New+insights+into+the+risk+of+phthalates%3A+Inhibition+of+UDP-glucuronosyltransferases.&rft.au=Liu%2C+Xin%3BCao%2C+Yun-Feng%3BRan%2C+Rui-Xue%3BDong%2C+Pei-Pei%3BGonzalez%2C+Frank+J%3BWu%2C+Xue%3BHuang%2C+Ting%3BChen%2C+Jian-Xin%3BFu%2C+Zhi-Wei%3BLi%2C+Rong-Shan%3BLiu%2C+Yong-Zhe%3BSun%2C+Hong-Zhi%3BFang%2C+Zhong-Ze&rft.aulast=Liu&rft.aufirst=Xin&rft.date=2016-02-01&rft.volume=144&rft.issue=&rft.spage=1966&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=1879-1298&rft_id=info:doi/10.1016%2Fj.chemosphere.2015.10.076 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-12 N1 - Date created - 2015-12-28 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.chemosphere.2015.10.076 ER - TY - JOUR T1 - CD34+ selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation. AN - 1751990689; 26190358 AB - The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis. We analyzed the incidence and severity of OM in a cohort of 105 consecutive patients who underwent CD34+ selected (peripheral blood stem cells (PBSCs) from human leukocyte antigen (HLA)-identical siblings) allo-SCT with total body irradiation (TBI) conditioning. OM was graded by the World Health organization (WHO) and the Bearman regimen-related toxicity (RRT) scales. The incidence of WHO grade 3-4 OM was 34.3 %. There were no cases of grade 3-4 OM by the RRT scale. Significant correlation was found between the severity of OM and the use of intravenous (IV) narcotic medications (r (2) = 0.15, p = 0.004), total parenteral nutrition (TPN; r (2) = 0.68, p < 0.001), and hospital length of stay (LOS) (r (2) = 0.12, p = 0.01). TBI-induced OM can inflict significant morbidity in the early transplant period, and the incidence of WHO grade 3-4 OM can exceed 50 % when methotrexate is used for GVHD prophylaxis. In the CD34+ selected setting, methotrexate is avoided and the incidence of WHO grade 3-4 OM, use of TPN, and need for narcotic analgesia appear to be lower than historic evidence from standard T-replete allogeneic transplantation. We conclude that toxicity from OM is tolerable in CD34+ selected allo-SCT and should be prospectively measured in randomized trials comparing CD34+ selection versus T-replete transplantation. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Anand, Ankit AU - Anandi, Prathima AU - Jain, Natasha A AU - Lu, Kit AU - Dunavin, Neil AU - Hourigan, Christopher S AU - Le, Robert Q AU - Chokshi, Puja D AU - Ito, Sawa AU - Stroncek, David F AU - Sabatino, Marianna AU - Barrett, A John AU - Battiwalla, Minoo AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. ; Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA. ; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. minoo.battiwalla@nih.gov. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 815 EP - 822 VL - 24 IS - 2 KW - Antigens, CD34 KW - 0 KW - Index Medicus KW - Stem cell transplant KW - T cell depleted transplantation KW - Oral mucositis KW - CD34 selection KW - Methotrexate KW - Oropharyngeal mucositis KW - Total body irradiation KW - Quality of life KW - Allogeneic KW - Severity of Illness Index KW - Humans KW - Adult KW - Graft vs Host Disease -- drug therapy KW - Middle Aged KW - Transplantation, Homologous KW - T-Lymphocytes -- immunology KW - Male KW - Female KW - Whole-Body Irradiation -- methods KW - Transplantation Conditioning -- adverse effects KW - Mucositis -- etiology KW - Pharyngeal Diseases -- etiology KW - Antigens, CD34 -- blood KW - Mouth Diseases -- etiology KW - Hematopoietic Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1751990689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=CD34%2B+selection+and+the+severity+of+oropharyngeal+mucositis+in+total+body+irradiation-based+allogeneic+stem+cell+transplantation.&rft.au=Anand%2C+Ankit%3BAnandi%2C+Prathima%3BJain%2C+Natasha+A%3BLu%2C+Kit%3BDunavin%2C+Neil%3BHourigan%2C+Christopher+S%3BLe%2C+Robert+Q%3BChokshi%2C+Puja+D%3BIto%2C+Sawa%3BStroncek%2C+David+F%3BSabatino%2C+Marianna%3BBarrett%2C+A+John%3BBattiwalla%2C+Minoo&rft.aulast=Anand&rft.aufirst=Ankit&rft.date=2016-02-01&rft.volume=24&rft.issue=2&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=1433-7339&rft_id=info:doi/10.1007%2Fs00520-015-2848-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-08-09 N1 - Date created - 2015-12-24 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Bone Marrow Transplant. 2006 Apr;37(8):799-800 [16501586] Pharmacogenomics J. 2015 Jun;15(3):248-54 [25348617] N Engl J Med. 2004 Dec 16;351(25):2590-8 [15602019] Cancer. 1999 May 15;85(10):2103-13 [10326686] J Clin Oncol. 1988 Oct;6(10):1562-8 [3049951] Ann Oncol. 2008 Sep;19(9):1644-9 [18453519] Bone Marrow Transplant. 2008 Aug;42(4):275-9 [18500368] Leukemia. 2009 Mar;23(3):545-56 [19005482] Biol Blood Marrow Transplant. 2011 Aug;17(8):1112-3 [21382501] Biol Blood Marrow Transplant. 2011 Sep;17(9):1335-42 [21232623] Biol Blood Marrow Transplant. 2011 Sep;17(9):1343-51 [21320619] Onkologie. 2011;34(10):518-24 [21985850] Eur J Haematol. 2012 Jan;88(1):46-51 [22023368] Biol Blood Marrow Transplant. 2012 May;18(5):722-30 [21920473] J Clin Oncol. 2012 Sep 10;30(26):3194-201 [22869882] Bone Marrow Transplant. 2012 Oct;47(10):1350-5 [22327131] Bone Marrow Transplant. 2013 Jan;48(1):99-104 [22750997] Biol Blood Marrow Transplant. 2014 Jun;20(6):852-7 [24607557] Blood. 2014 Aug 21;124(8):1372-7 [24982504] Pharmacogenomics. 2014 Aug;15(11):1479-94 [25303299] Biol Blood Marrow Transplant. 2007 Jul;13(7):806-13 [17580258] Ann Oncol. 2007 May;18(5):817-26 [17030544] Blood. 2006 Nov 1;108(9):3216-22 [16835378] J Clin Oncol. 2004 Apr 1;22(7):1268-75 [15051775] Bone Marrow Transplant. 2004 Oct;34(7):621-5 [15300236] Blood. 2001 Jul 1;98(1):231-4 [11418485] Cancer Invest. 2002;20(5-6):793-800 [12197238] Br J Haematol. 2000 Aug;110(2):292-9 [10971384] Biol Blood Marrow Transplant. 2005 May;11(5):383-8 [15846292] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1007/s00520-015-2848-9 ER - TY - JOUR T1 - Couples' urinary concentrations of benzophenone-type ultraviolet filters and the secondary sex ratio. AN - 1751486001; 26575635 AB - The secondary sex ratio (SSR), defined as the ratio of males to females at birth, has been investigated in relation to endocrine disruptors to search for environmental toxicants perturbing human sex selection. Benzophenone (BP)-type ultraviolet (UV) filters, which are used in sunscreens and personal care products, have been reported to exert estrogenic and anti-androgenic activities. This study aimed to evaluate the association between maternal, paternal, and couple urinary concentrations of BP-type UV filters and the SSR, given the absence of previous investigation. The study cohort comprised 220 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and who had a singleton birth during the follow-up period. Couples' urinary concentrations of five BP-type UV filters (ng/mL) were measured using triple-quadrupole tandem mass spectrometry: 2,4-dihydroxybenzophenone (BP-1), 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), and 4-hydroxybenzophenone (4-OH-BP). Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each BP-type UV filter, after adjusting for potential confounders. When maternal and paternal urinary BP-type UV filter concentrations were modeled jointly, both maternal BP-2 (2nd vs 1st tertile, RR, 0.62, 95% confidence interval [CI], 0.43-0.91) and paternal BP-2 (3rd vs 1st tertile, RR, 0.67, 95% CI, 0.45-0.99; p-trend, 0.04) were significantly associated with an excess of female births. Contrarily, maternal 4-OH-BP was significantly associated with an excess of male births (2nd vs 1st tertile, RR, 1.87, 95% CI, 1.27-2.74; 3rd vs 1st tertile, RR, 1.80, 95% CI, 1.13-2.87; p-trend, 0.02). Our findings provide the first evidence suggesting that BP-type UV filters may affect the SSR. However, future corroboration is needed, given the exploratory design of this study. Copyright © 2015 Elsevier B.V. All rights reserved. JF - The Science of the total environment AU - Bae, Jisuk AU - Kim, Sungduk AU - Kannan, Kurunthachalam AU - Buck Louis, Germaine M AD - Department of Preventive Medicine, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of Korea; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Boulevard, Rockville, MD 20852, USA. Electronic address: jialove@cu.ac.kr. ; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Boulevard, Rockville, MD 20852, USA. Electronic address: kims2@mail.nih.gov. ; Wadsworth Center, New York State Department of Health, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, USA; Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, USA. Electronic address: kurunthachalam.kannan@health.ny.gov. ; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Boulevard, Rockville, MD 20852, USA. Electronic address: louisg@mail.nih.gov. Y1 - 2016/02/01/ PY - 2016 DA - 2016 Feb 01 SP - 28 EP - 36 VL - 543 KW - Benzophenones KW - 0 KW - Environmental Pollutants KW - Sunscreening Agents KW - Index Medicus KW - Sunscreen agents KW - Fertility KW - Sex ratio KW - Endocrine disruptors KW - Humans KW - Male KW - Female KW - Benzophenones -- urine KW - Environmental Exposure -- statistics & numerical data KW - Sex Ratio KW - Sunscreening Agents -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1751486001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Science+of+the+total+environment&rft.atitle=Couples%27+urinary+concentrations+of+benzophenone-type+ultraviolet+filters+and+the+secondary+sex+ratio.&rft.au=Bae%2C+Jisuk%3BKim%2C+Sungduk%3BKannan%2C+Kurunthachalam%3BBuck+Louis%2C+Germaine+M&rft.aulast=Bae&rft.aufirst=Jisuk&rft.date=2016-02-01&rft.volume=543&rft.issue=&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=1879-1026&rft_id=info:doi/10.1016%2Fj.scitotenv.2015.11.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-09 N1 - Date created - 2015-12-22 N1 - Date revised - 2017-02-02 N1 - SuppNotes - Cited By: Environ Res. 2013 Oct;126:164-70 [23932849] Environ Sci Technol. 2013;47(21):12532-8 [24073792] Sci Total Environ. 2014 Feb 1;470-471:1243-9 [24246946] Environ Sci Technol. 2014 Apr 1;48(7):4103-9 [24588714] BMC Genomics. 2014;15:293 [24886317] Environ Int. 2014 Sep;70:143-57 [24934855] Am J Epidemiol. 2014 Dec 15;180(12):1168-75 [25395025] Toxicol Lett. 2014 Dec 1;231(2):261-9 [24956590] Environ Res. 2015 Feb;137:101-7 [25531814] Environ Res. 2015 Feb;137:450-7 [25677702] Environ Sci Pollut Res Int. 2015 Apr;22(8):5711-41 [25548011] Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):E2102-11 [25825766] Chemosphere. 2015 Aug;133:31-40 [25863705] Environ Res. 2015 Jul;140:369-76 [25929801] Fertil Steril. 2015 Oct;104(4):989-96 [26253817] Environ Res. 2015 Oct;142:414-23 [26233661] Paediatr Perinat Epidemiol. 2011 Sep;25(5):413-24 [21819423] Br J Clin Pharmacol. 1999 Oct;48(4):635-7 [10583038] Hum Reprod. 1999 Dec;14(12):3120-5 [10601107] J Epidemiol Community Health. 2000 Apr;54(4):244-6 [10827905] Lancet. 2000 May 27;355(9218):1858-63 [10866441] Toxicology. 2000 Dec 7;156(1):27-36 [11162873] Environ Health Perspect. 2001 Mar;109(3):239-44 [11333184] Arch Toxicol. 2001 Apr;75(2):74-9 [11354909] Chem Biol Interact. 2002 Feb 20;139(2):115-28 [11823001] Arch Toxicol. 2002 Jun;76(5-6):257-61 [12107642] Toxicology. 2003 Feb 1;183(1-3):93-115 [12504345] Am J Epidemiol. 2003 Feb 15;157(4):355-63 [12578806] Toxicol Sci. 2003 Jul;74(1):43-50 [12730620] Am J Epidemiol. 2004 Apr 1;159(7):702-6 [15033648] J Invest Dermatol. 2004 Jul;123(1):57-61 [15191542] Toxicology. 2004 Dec 1;205(1-2):113-22 [15458796] Toxicology. 2004 Dec 1;205(1-2):123-30 [15458797] Soc Biol. 1988 Fall-Winter;35(3-4):214-35 [3071849] Australas J Dermatol. 1999 Feb;40(1):51-3 [10098293] Am J Hum Biol. 2016 Jan-Feb;28(1):67-73 [26087675] Chemosphere. 2010 Nov;81(10):1171-83 [21030064] Am J Prev Med. 2004 Dec;27(5):422-66 [15556744] Toxicol Sci. 2005 Feb;83(2):264-72 [15537743] Toxicol Appl Pharmacol. 2005 Feb 15;203(1):9-17 [15694459] Toxicol In Vitro. 2005 Jun;19(4):457-69 [15826804] Natl Vital Stat Rep. 2005 Jun 14;53(20):1-17 [15974501] Skin Pharmacol Physiol. 2005 Nov-Dec;18(6):253-62 [16113595] Am J Epidemiol. 2006 Feb 15;163(4):374-83 [16394206] Food Addit Contam. 2006 Apr;23(4):422-30 [16546889] Int J Pharm. 2006 Sep 28;322(1-2):161-70 [16824709] Arch Toxicol. 2006 Oct;80(10):656-61 [16586070] Aquat Toxicol. 2006 Oct 12;79(4):305-24 [16911836] Environ Health Perspect. 2007 Jun;115(6):941-6 [17589604] J Urol. 2007 Oct;178(4 Pt 2):1637-42 [17707034] Toxicol Appl Pharmacol. 2007 Dec 15;225(3):255-66 [17889917] J Eur Acad Dermatol Venereol. 2008 Apr;22(4):456-61 [18221342] Environ Health Perspect. 2008 Jul;116(7):893-7 [18629311] Environ Health Perspect. 2008 Aug;116(8):1092-7 [18709157] J Theor Biol. 2008 Nov 21;255(2):199-204 [18687340] Environ Health Perspect. 2012 Mar;120(3):464-70 [21900077] Environ Sci Technol. 2012 Apr 17;46(8):4624-32 [22417702] Toxicol Appl Pharmacol. 2012 Sep 1;263(2):184-94 [22721600] J Theor Biol. 2012 Oct 7;310:183-6 [22776504] Chemosphere. 2013 Apr;91(2):131-8 [23260246] Toxicology. 2013 Mar 8;305:41-8 [23328252] Environ Sci Technol. 2013 Apr 2;47(7):3439-47 [23469879] Int J Cosmet Sci. 2013 Jun;35(3):208-19 [23237547] Sci Total Environ. 2013 Sep 1;461-462:49-55 [23712115] J Theor Biol. 2013 Oct 7;334:141-8 [23810932] N1 - Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.scitotenv.2015.11.019 ER - TY - JOUR T1 - The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue. AN - 1749999118; 26362361 AB - In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users. Copyright © 2015 Elsevier Ltd. All rights reserved. JF - Neuropharmacology AU - Marusich, Julie A AU - Antonazzo, Kateland R AU - Blough, Bruce E AU - Brandt, Simon D AU - Kavanagh, Pierce V AU - Partilla, John S AU - Baumann, Michael H AD - Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research Triangle Park, NC 27709, USA. Electronic address: jmarusich@rti.org. ; Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research Triangle Park, NC 27709, USA. ; School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, L3 3AF, Liverpool, UK. ; Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland. ; Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2016/02// PY - 2016 DA - February 2016 SP - 68 EP - 75 VL - 101 KW - 5-(2-aminopropyl)indole KW - 0 KW - Adrenergic Uptake Inhibitors KW - Central Nervous System Stimulants KW - Indoles KW - Neurotransmitter Transport Proteins KW - Tritium KW - 10028-17-8 KW - Serotonin KW - 333DO1RDJY KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Index Medicus KW - 5-(2-Aminopropyl)indole (5-IT) KW - Locomotor activity KW - 6-(2-Aminopropyl)indole (6-IT) KW - Synthetic stimulants KW - Monoamine releaser KW - 3,4-Methylenedioxymethamphetamine (MDMA) KW - Tritium -- pharmacokinetics KW - Animals KW - Central Nervous System Stimulants -- pharmacology KW - Dose-Response Relationship, Drug KW - N-Methyl-3,4-methylenedioxyamphetamine -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Adrenergic Uptake Inhibitors -- pharmacology KW - In Vitro Techniques KW - Motor Activity -- drug effects KW - Serotonin -- pharmacokinetics KW - Time Factors KW - Male KW - Neurotransmitter Transport Proteins -- metabolism KW - Brain -- drug effects KW - Indoles -- pharmacology KW - Neurotransmitter Transport Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1749999118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=The+new+psychoactive+substances+5-%282-aminopropyl%29indole+%285-IT%29+and+6-%282-aminopropyl%29indole+%286-IT%29+interact+with+monoamine+transporters+in+brain+tissue.&rft.au=Marusich%2C+Julie+A%3BAntonazzo%2C+Kateland+R%3BBlough%2C+Bruce+E%3BBrandt%2C+Simon+D%3BKavanagh%2C+Pierce+V%3BPartilla%2C+John+S%3BBaumann%2C+Michael+H&rft.aulast=Marusich&rft.aufirst=Julie&rft.date=2016-02-01&rft.volume=101&rft.issue=&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=1873-7064&rft_id=info:doi/10.1016%2Fj.neuropharm.2015.09.004 LA - English DB - 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Last updated - 2017-02-02 DO - http://dx.doi.org/10.1016/j.neuropharm.2015.09.004 ER - TY - JOUR T1 - Antigenic Determinants of the Bilobal Cockroach Allergen Bla g 2. AN - 1761472169; 26644466 AB - Bla g 2 is a major indoor cockroach allergen associated with the development of asthma. Antigenic determinants on Bla g 2 were analyzed by mutagenesis based on the structure of the allergen alone and in complex with monoclonal antibodies that interfere with IgE antibody binding. The structural analysis revealed mechanisms of allergen-antibody recognition through cation-π interactions. Single and multiple Bla g 2 mutants were expressed in Pichia pastoris and purified. The triple mutant K132A/K251A/F162Y showed an ∼100-fold reduced capacity to bind IgE, while preserving the native molecular fold, as proven by x-ray crystallography. This mutant was still able to induce mast cell release. T-cell responses were assessed by analyzing Th1/Th2 cytokine production and the CD4(+) T-cell phenotype in peripheral blood mononuclear cell cultures. Although T-cell activating capacity was similar for the KKF mutant and Bla g 2 based on CD25 expression, the KKF mutant was a weaker inducer of the Th2 cytokine IL-13. Furthermore, this mutant induced IL-10 from a non-T-cell source at higher levels that those induced by Bla g 2. Our findings demonstrate that a rational design of site-directed mutagenesis was effective in producing a mutant with only 3 amino acid substitutions that maintained the same fold as wild type Bla g 2. These residues, which were involved in IgE antibody binding, endowed Bla g 2 with a T-cell modulatory capacity. The antigenic analysis of Bla g 2 will be useful for the subsequent development of recombinant allergen vaccines. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Woodfolk, Judith A AU - Glesner, Jill AU - Wright, Paul W AU - Kepley, Christopher L AU - Li, Mi AU - Himly, Martin AU - Muehling, Lyndsey M AU - Gustchina, Alla AU - Wlodawer, Alexander AU - Chapman, Martin D AU - Pomés, Anna AD - From the Allergy Division, Department of Medicine, University of Virginia, Charlottesville, Virginia 22903. ; INDOOR Biotechnologies, Inc., Charlottesville, Virginia 22908. ; the Joint School of Nanoscience and Nanoengineering, University of North Carolina, Greensboro, North Carolina 27401. ; the Macromolecular Crystallography Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland 21702, and. ; the Department of Molecular Biology, University of Salzburg, 5020 Salzburg, Austria. ; the Macromolecular Crystallography Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702. ; INDOOR Biotechnologies, Inc., Charlottesville, Virginia 22908, apomes@inbio.com. Y1 - 2016/01/29/ PY - 2016 DA - 2016 Jan 29 SP - 2288 EP - 2301 VL - 291 IS - 5 KW - Allergens KW - 0 KW - Antibodies, Monoclonal KW - Epitopes, T-Lymphocyte KW - Insect Proteins KW - Immunoglobulin E KW - 37341-29-0 KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - allergen Bla g 2 KW - Index Medicus KW - allergen KW - antigenic determinant KW - aspartic protease KW - Bla g 2 KW - cockroach allergy KW - site-directed mutagenesis KW - immunotherapy KW - asthma KW - epitope mapping KW - x-ray crystallography KW - Th1 Cells -- cytology KW - Animals KW - CD4-Positive T-Lymphocytes -- cytology KW - Asthma -- etiology KW - Humans KW - Pichia KW - Protein Binding KW - Antibodies, Monoclonal -- immunology KW - Mutagenesis KW - Immunoglobulin E -- immunology KW - Th2 Cells -- cytology KW - Crystallography, X-Ray KW - Mutation KW - Protein Conformation KW - Epitopes, T-Lymphocyte -- chemistry KW - Cockroaches -- chemistry KW - Allergens -- immunology KW - Allergens -- chemistry KW - Insect Proteins -- chemistry KW - Aspartic Acid Endopeptidases -- chemistry KW - Insect Proteins -- immunology KW - Aspartic Acid Endopeptidases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761472169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Antigenic+Determinants+of+the+Bilobal+Cockroach+Allergen+Bla+g+2.&rft.au=Woodfolk%2C+Judith+A%3BGlesner%2C+Jill%3BWright%2C+Paul+W%3BKepley%2C+Christopher+L%3BLi%2C+Mi%3BHimly%2C+Martin%3BMuehling%2C+Lyndsey+M%3BGustchina%2C+Alla%3BWlodawer%2C+Alexander%3BChapman%2C+Martin+D%3BPom%C3%A9s%2C+Anna&rft.aulast=Woodfolk&rft.aufirst=Judith&rft.date=2016-01-29&rft.volume=291&rft.issue=5&rft.spage=2288&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=1083-351X&rft_id=info:doi/10.1074%2Fjbc.M115.702324 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-15 N1 - Date created - 2016-01-30 N1 - Date revised - 2017-01-31 N1 - Genetic sequence - 2NR6; PDB; 1yg9; 3liz; 3LIZ; 1YG9; 5HVP; 2nr6 N1 - SuppNotes - Cited By: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32 [15572765] J Allergy. 1964 Nov-Dec;35:506-13 [14226309] J Allergy Clin Immunol. 2005 Mar;115(3):478-85 [15753892] J Allergy Clin Immunol. 2005 Apr;115(4):803-9 [15806002] J Mol Biol. 2005 Apr 29;348(2):433-44 [15811379] J Allergy Clin Immunol. 2005 Jul;116(1):140-5 [15990787] Int Arch Allergy Immunol. 2005 Sep;138(1):29-39 [16088210] J Allergy Clin Immunol. 2006 Jun;117(6):1336-43 [16750995] J Allergy Clin Immunol. 2007 Feb;119(2):428-33 [17196246] J Mol Recognit. 2007 Mar-Apr;20(2):75-82 [17205610] J Allergy Clin Immunol. 2007 Nov;120(5):1126-31 [17825887] J Immunol. 2008 May 1;180(9):6317-24 [18424755] Mol Immunol. 2008 Jul;45(12):3477-89 [18023478] J Allergy Clin Immunol. 2008 Aug;122(2):298-304 [18572230] J Biol Chem. 2008 Aug 15;283(33):22806-14 [18519566] Biochem Biophys Res Commun. 2008 Oct 31;375(4):671-4 [18760997] J Allergy Clin Immunol. 2010 Jan;125(1):247-56.e1-8 [20109752] J Immunol. 2011 Jan 1;186(1):333-40 [21123808] Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67 [21460454] J Allergy Clin Immunol. 2011 Jun;127(6):1571-8.e9 [21420160] PLoS One. 2011;6(7):e22223 [21789239] J Allergy Clin Immunol. 2011 Nov;128(5):1022-30.e1-7 [21571358] J Immunol Methods. 2011 Nov 30;374(1-2):53-61 [21130094] Ann Allergy Asthma Immunol. 2012 Apr;108(4):243-8 [22469443] J Allergy Clin Immunol. 2012 May;129(5):1321-1328.e5 [22444503] J Immunol. 2012 Jul 15;189(2):679-88 [22706084] Acc Chem Res. 2013 Apr 16;46(4):885-93 [23214924] Immunogenetics. 2013 Oct;65(10):711-24 [23900783] J Dairy Sci. 2013;96(11):6870-6 [24035023] PLoS One. 2013;8(11):e78605 [24244326] Allergy. 2014 Feb;69(2):208-15 [24224690] Curr Allergy Asthma Rep. 2014 Apr;14(4):428 [24563284] J Allergy Clin Immunol. 2014 Mar;133(3):846-52.e6 [24184147] J Allergy Clin Immunol. 2001 Jan;107(1):48-54 [11149990] J Allergy Clin Immunol. 2001 Mar;107(3):419-28 [11240940] J Immunol. 2003 Sep 15;171(6):3084-90 [12960334] Clin Exp Allergy. 2004 Mar;34(3):429-36 [15005737] Zhejiang Da Xue Xue Bao Yi Xue Ban. 2004 Mar;33(2):155-9 [15067739] Int Arch Allergy Immunol. 2004 Aug;134(4):324-31 [15240999] J Biol Chem. 2004 Aug 20;279(34):35139-49 [15151996] J Immunol. 2004 Oct 15;173(8):5258-67 [15470071] Nature. 1978 Feb 16;271(5646):618-21 [24179] J Allergy Clin Immunol. 1989 May;83(5):875-82 [2715548] J Immunol. 1990 Feb 15;144(4):1353-60 [1689351] FEBS Lett. 1990 Dec 10;276(1-2):59-62 [2265712] J Immunol. 1991 Dec 1;147(11):3768-73 [1940366] Am Rev Respir Dis. 1993 Mar;147(3):573-8 [8442589] J Biol Chem. 1995 Aug 18;270(33):19563-8 [7642642] N Engl J Med. 1997 May 8;336(19):1356-63 [9134876] Arch Biochem Biophys. 1997 Jun 15;342(2):244-53 [9186485] Nat Biotechnol. 1997 Aug;15(8):754-8 [9255789] J Allergy Clin Immunol. 1998 Mar;101(3):423-5 [9525463] J Allergy Clin Immunol. 2005 Jan;115(1):74-9 [15637550] N1 - Last updated - 2017-01-31 DO - http://dx.doi.org/10.1074/jbc.M115.702324 ER - TY - JOUR T1 - Dual-enhanced photothermal conversion properties of reduced graphene oxide-coated gold superparticles for light-triggered acoustic and thermal theranostics. AN - 1760914151; 26726809 AB - A rational design of highly efficient photothermal agents that possess excellent light-to-heat conversion properties is a fascinating topic in nanotheranostics. Herein, we present a facile route to fabricate size-tunable reduced graphene oxide (rGO)-coated gold superparticles (rGO-GSPs) and demonstrate their dual-enhanced photothermal conversion properties for photoacoustic imaging and photothermal therapy. For the first time, graphene oxide (GO) was directly used as an emulsifying agent for the preparation of gold superparticles (GSPs) with near-infrared absorption by the emulsion method. Moreover, GO spontaneously deposited on the surface of GSPs could also act as the precursor of the rGO shell. Importantly, both the plasmonic coupling of the self-assembled gold nanoparticles and the interaction between GSPs and rGO endow rGO-GSPs with enhanced photothermal conversion properties, allowing rGO-GSPs to be used for sensitive photoacoustic detection and efficient photothermal ablation of tumours in vivo. This study provides a facile approach to prepare colloidal superparticles-graphene hybrid nanostructures and will pave the way toward the design and optimization of photothermal nanomaterials with improved properties for theranostic applications. JF - Nanoscale AU - Lin, Li-Sen AU - Yang, Xiangyu AU - Niu, Gang AU - Song, Jibin AU - Yang, Huang-Hao AU - Chen, Xiaoyuan AD - The Key Lab of Analysis and Detection Technology for Food Safety of the MOE, College of Chemistry, Fuzhou University, Fuzhou 350108, China. hhyang@fio.org.cn and Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. jibin.song@nih.gov shawn.chen@nih.gov. ; Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. jibin.song@nih.gov shawn.chen@nih.gov. ; The Key Lab of Analysis and Detection Technology for Food Safety of the MOE, College of Chemistry, Fuzhou University, Fuzhou 350108, China. hhyang@fio.org.cn. Y1 - 2016/01/28/ PY - 2016 DA - 2016 Jan 28 SP - 2116 EP - 2122 VL - 8 IS - 4 KW - Coated Materials, Biocompatible KW - 0 KW - Gold KW - 7440-57-5 KW - Graphite KW - 7782-42-5 KW - Index Medicus KW - Theranostic Nanomedicine -- methods KW - Graphite -- pharmacology KW - Neoplasms -- diagnostic imaging KW - Coated Materials, Biocompatible -- chemistry KW - Graphite -- chemistry KW - Gold -- pharmacology KW - Coated Materials, Biocompatible -- pharmacology KW - Neoplasms -- therapy KW - Hyperthermia, Induced -- methods KW - Gold -- chemistry KW - Phototherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760914151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nanoscale&rft.atitle=Dual-enhanced+photothermal+conversion+properties+of+reduced+graphene+oxide-coated+gold+superparticles+for+light-triggered+acoustic+and+thermal+theranostics.&rft.au=Lin%2C+Li-Sen%3BYang%2C+Xiangyu%3BNiu%2C+Gang%3BSong%2C+Jibin%3BYang%2C+Huang-Hao%3BChen%2C+Xiaoyuan&rft.aulast=Lin&rft.aufirst=Li-Sen&rft.date=2016-01-28&rft.volume=8&rft.issue=4&rft.spage=2116&rft.isbn=&rft.btitle=&rft.title=Nanoscale&rft.issn=2040-3372&rft_id=info:doi/10.1039%2Fc5nr07552a LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-12-13 N1 - Date created - 2016-01-22 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1039/c5nr07552a ER - TY - JOUR T1 - Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease. AN - 1760897340; 26735910 AB - Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 μM, and a similar inhibition profile of the human isoform (IC50 = 5.7 μM). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 μM, which indicates drug-conform behavior. Also, compound 26 is capable of crossing the blood-brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti-Alzheimer drugs from CNSL is worth of further pursuit and development. Copyright © 2015 Elsevier Masson SAS. All rights reserved. JF - European journal of medicinal chemistry AU - Lemes, Laís Flávia Nunes AU - de Andrade Ramos, Giselle AU - de Oliveira, Andressa Souza AU - da Silva, Fernanda Motta R AU - de Castro Couto, Gina AU - da Silva Boni, Marina AU - Guimarães, Marcos Jorge R AU - Souza, Isis Nem O AU - Bartolini, Manuela AU - Andrisano, Vincenza AU - do Nascimento Nogueira, Patrícia Coelho AU - Silveira, Edilberto Rocha AU - Brand, Guilherme D AU - Soukup, Ondřej AU - Korábečný, Jan AU - Romeiro, Nelilma C AU - Castro, Newton G AU - Bolognesi, Maria Laura AU - Romeiro, Luiz Antonio Soares AD - Department of Pharmacy, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, 70910-900, Brasília, DF, Brazil; LADETER, Catholic University of Brasília, QS 07, Lote 01, EPCT, Águas Claras, 71966-700, Brasília, DF, Brazil. ; Biomedical Sciences Institute (ICB), Federal University of Rio de Janeiro, 21941-902, Rio de Janeiro, RJ, Brazil. ; Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy. ; Department for Life Quality Studies, University of Bologna, Corso D'Augusto 237, 47921, Rimini, Italy. ; CENAUREMN, Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60021-970, Fortaleza, CE, Brazil. ; Chemistry Institute, University of Brasília, Campus Universitário Darcy Ribeiro, 70910-900, Brasília, DF, Brazil. ; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic; National Institute of Mental Health, Topolová 748, 250 67, Klecany, Czech Republic. ; LICC - Laboratório Integrado de Computação Científica, NUPEM, Federal University of Rio de Janeiro, 27901-000, Macaé, RJ, Brazil. ; Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy. Electronic address: marialaura.bolognesi@unibo.it. ; Department of Pharmacy, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, 70910-900, Brasília, DF, Brazil; LADETER, Catholic University of Brasília, QS 07, Lote 01, EPCT, Águas Claras, 71966-700, Brasília, DF, Brazil. Electronic address: luizromeiro@unb.br. Y1 - 2016/01/27/ PY - 2016 DA - 2016 Jan 27 SP - 687 EP - 700 VL - 108 KW - Cholinesterase Inhibitors KW - 0 KW - Phenols KW - cardanol KW - 37330-39-5 KW - Cholinesterases KW - EC 3.1.1.8 KW - Index Medicus KW - Cashew nut shell liquid KW - Multitarget compounds KW - Acetylcholinesterase KW - Alzheimer's disease KW - Dual binding site AChE inhibitors KW - Molecular Structure KW - Dose-Response Relationship, Drug KW - Humans KW - Binding Sites -- drug effects KW - HT29 Cells KW - Structure-Activity Relationship KW - Cholinesterase Inhibitors -- pharmacology KW - Cholinesterase Inhibitors -- chemical synthesis KW - Cholinesterases -- metabolism KW - Phenols -- pharmacology KW - Cholinesterase Inhibitors -- chemistry KW - Alzheimer Disease -- drug therapy KW - Phenols -- chemistry KW - Phenols -- chemical synthesis KW - Alzheimer Disease -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760897340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+medicinal+chemistry&rft.atitle=Cardanol-derived+AChE+inhibitors%3A+Towards+the+development+of+dual+binding+derivatives+for+Alzheimer%27s+disease.&rft.au=Lemes%2C+La%C3%ADs+Fl%C3%A1via+Nunes%3Bde+Andrade+Ramos%2C+Giselle%3Bde+Oliveira%2C+Andressa+Souza%3Bda+Silva%2C+Fernanda+Motta+R%3Bde+Castro+Couto%2C+Gina%3Bda+Silva+Boni%2C+Marina%3BGuimar%C3%A3es%2C+Marcos+Jorge+R%3BSouza%2C+Isis+Nem+O%3BBartolini%2C+Manuela%3BAndrisano%2C+Vincenza%3Bdo+Nascimento+Nogueira%2C+Patr%C3%ADcia+Coelho%3BSilveira%2C+Edilberto+Rocha%3BBrand%2C+Guilherme+D%3BSoukup%2C+Ond%C5%99ej%3BKor%C3%A1be%C4%8Dn%C3%BD%2C+Jan%3BRomeiro%2C+Nelilma+C%3BCastro%2C+Newton+G%3BBolognesi%2C+Maria+Laura%3BRomeiro%2C+Luiz+Antonio+Soares&rft.aulast=Lemes&rft.aufirst=La%C3%ADs+Fl%C3%A1via&rft.date=2016-01-27&rft.volume=108&rft.issue=&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=European+journal+of+medicinal+chemistry&rft.issn=1768-3254&rft_id=info:doi/10.1016%2Fj.ejmech.2015.12.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-17 N1 - Date created - 2016-01-21 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1016/j.ejmech.2015.12.024 ER - TY - JOUR T1 - Versatile strategy for controlling the specificity and activity of engineered T cells. AN - 1761077550; 26759368 AB - The adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a promising cancer therapy. Despite impressive clinical efficacy, the general application of current CAR-T--cell therapy is limited by serious treatment-related toxicities. One approach to improve the safety of CAR-T cells involves making their activation and proliferation dependent upon adaptor molecules that mediate formation of the immunological synapse between the target cancer cell and T-cell. Here, we describe the design and synthesis of structurally defined semisynthetic adaptors we refer to as "switch" molecules, in which anti-CD19 and anti-CD22 antibody fragments are site-specifically modified with FITC using genetically encoded noncanonical amino acids. This approach allows the precise control over the geometry and stoichiometry of complex formation between CD19- or CD22-expressing cancer cells and a "universal" anti-FITC-directed CAR-T cell. Optimization of this CAR-switch combination results in potent, dose-dependent in vivo antitumor activity in xenograft models. The advantage of being able to titrate CAR-T-cell in vivo activity was further evidenced by reduced in vivo toxicity and the elimination of persistent B-cell aplasia in immune-competent mice. The ability to control CAR-T cell and cancer cell interactions using intermediate switch molecules may expand the scope of engineered T-cell therapy to solid tumors, as well as indications beyond cancer therapy. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Ma, Jennifer S Y AU - Kim, Ji Young AU - Kazane, Stephanie A AU - Choi, Sei-Hyun AU - Yun, Hwa Young AU - Kim, Min Soo AU - Rodgers, David T AU - Pugh, Holly M AU - Singer, Oded AU - Sun, Sophie B AU - Fonslow, Bryan R AU - Kochenderfer, James N AU - Wright, Timothy M AU - Schultz, Peter G AU - Young, Travis S AU - Kim, Chan Hyuk AU - Cao, Yu AD - Department of Biology, California Institute for Biomedical Research, La Jolla, CA 92037; ; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037; ; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037; SCIEX Separations, Brea, CA 92821; ; Experimental Transplantation and Immunology Branch, National Institutes of Health, National Cancer Institute, Bethesda, MD 20892. ; Department of Biology, California Institute for Biomedical Research, La Jolla, CA 92037; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037; schultz@scripps.edu tyoung@calibr.org chkim@calibr.org. ; Department of Biology, California Institute for Biomedical Research, La Jolla, CA 92037; schultz@scripps.edu tyoung@calibr.org chkim@calibr.org. Y1 - 2016/01/26/ PY - 2016 DA - 2016 Jan 26 SP - E450 EP - E458 VL - 113 IS - 4 KW - Antigens, CD19 KW - 0 KW - Antigens, Neoplasm KW - Azides KW - CD22 protein, human KW - CTL019 chimeric antigen receptor KW - Receptors, Antigen, T-Cell KW - Recombinant Fusion Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Single-Chain Antibodies KW - 4-azidophenylalanine KW - 33173-53-4 KW - Phenylalanine KW - 47E5O17Y3R KW - Fluorescein-5-isothiocyanate KW - I223NX31W9 KW - Index Medicus KW - cytokine release syndrome KW - cancer immunotherapy KW - chimeric antigen receptor T cell KW - B-cell aplasia KW - noncanonical amino acids KW - Animals KW - B-Lymphocytes -- pathology KW - Humans KW - Lymphopenia -- prevention & control KW - Transduction, Genetic KW - Single-Chain Antibodies -- genetics KW - Lymphocyte Activation KW - Phenylalanine -- analogs & derivatives KW - Genetic Vectors KW - Xenograft Model Antitumor Assays KW - Lentivirus -- genetics KW - Protein Conformation KW - Single-Chain Antibodies -- immunology KW - Models, Molecular KW - Recombinant Fusion Proteins -- immunology KW - Mice, Inbred NOD KW - Cell Line, Tumor KW - B-Lymphocytes -- immunology KW - Mice KW - Lymphopenia -- etiology KW - Cytotoxicity, Immunologic KW - Mice, Inbred C57BL KW - Mice, SCID KW - Female KW - Antigens, CD19 -- immunology KW - Sialic Acid Binding Ig-like Lectin 2 -- immunology KW - T-Lymphocytes -- transplantation KW - Protein Engineering -- methods KW - T-Cell Antigen Receptor Specificity KW - Leukemia, B-Cell -- therapy KW - Receptors, Antigen, T-Cell -- immunology KW - Immunotherapy, Adoptive -- adverse effects KW - Immunotherapy, Adoptive -- methods KW - Antigens, Neoplasm -- immunology KW - Receptors, Antigen, T-Cell -- genetics KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761077550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Versatile+strategy+for+controlling+the+specificity+and+activity+of+engineered+T+cells.&rft.au=Ma%2C+Jennifer+S+Y%3BKim%2C+Ji+Young%3BKazane%2C+Stephanie+A%3BChoi%2C+Sei-Hyun%3BYun%2C+Hwa+Young%3BKim%2C+Min+Soo%3BRodgers%2C+David+T%3BPugh%2C+Holly+M%3BSinger%2C+Oded%3BSun%2C+Sophie+B%3BFonslow%2C+Bryan+R%3BKochenderfer%2C+James+N%3BWright%2C+Timothy+M%3BSchultz%2C+Peter+G%3BYoung%2C+Travis+S%3BKim%2C+Chan+Hyuk%3BCao%2C+Yu&rft.aulast=Ma&rft.aufirst=Jennifer+S&rft.date=2016-01-26&rft.volume=113&rft.issue=4&rft.spage=E450&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=1091-6490&rft_id=info:doi/10.1073%2Fpnas.1524193113 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-13 N1 - Date created - 2016-01-27 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16101-6 [22988081] Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68 [26759369] J Immunother. 2013 Feb;36(2):133-51 [23377668] Blood. 2013 Feb 14;121(7):1165-74 [23243285] Mol Ther. 2013 Apr;21(4):904-12 [23423337] PLoS One. 2013;8(4):e61338 [23585892] N Engl J Med. 2013 Apr 18;368(16):1509-18 [23527958] Curr Opin Chem Biol. 2013 Jun;17(3):412-9 [23664497] Clin Cancer Res. 2013 Jun 15;19(12):3153-64 [23620405] Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17796-801 [24127589] Sci Transl Med. 2013 Dec 11;5(215):215ra172 [24337479] Cancer Res. 2014 Jan 1;74(1):93-103 [24197131] Annu Rev Med. 2014;65:333-47 [24274181] Sci Transl Med. 2014 Feb 19;6(224):224ra25 [24553386] Cancer J. 2014 Mar-Apr;20(2):119-22 [24667956] Cancer Immunol Res. 2013 Jul;1(1):26-31 [24777247] N Engl J Med. 2014 Oct 16;371(16):1507-17 [25317870] Mol Ther. 2015 Jan;23(1):184-91 [25174587] Cancer Immunol Res. 2015 Feb;3(2):125-35 [25212991] J Am Chem Soc. 2015 Mar 4;137(8):2832-5 [25692571] Angew Chem Int Ed Engl. 2015 Jun 8;54(24):7022-7 [25919418] Nat Med. 2015 Jun;21(6):581-90 [25939063] Immunotherapy. 2015;7(5):487-97 [26065475] Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10701-5 [10984501] Biophys J. 1994 Dec;67(6):2167-83 [7696460] Protein Eng. 1997 Aug;10(8):959-66 [9415446] Nat Biotechnol. 1996 Mar;14(3):309-14 [9630891] J Exp Med. 1965 Mar 1;121:323-38 [14271318] Eur J Immunol. 2005 Apr;35(4):1257-66 [15761847] J Immunother. 2005 May-Jun;28(3):203-11 [15838376] J Immunol. 2009 Aug 15;183(4):2554-64 [19625641] Mol Ther. 2010 Apr;18(4):843-51 [20179677] Cancer Immunol Immunother. 2010 Aug;59(8):1197-209 [20309546] Blood. 2010 Nov 11;116(19):3875-86 [20631379] Blood. 2010 Nov 18;116(20):4099-102 [20668228] Mol Ther. 2011 Mar;19(3):620-6 [21157437] Sci Transl Med. 2011 Aug 10;3(95):95ra73 [21832238] N Engl J Med. 2011 Aug 25;365(8):725-33 [21830940] Nat Med. 2011 Oct;17(10):1315-9 [21926976] N Engl J Med. 2011 Nov 3;365(18):1673-83 [22047558] Blood. 2012 Mar 22;119(12):2709-20 [22160384] Cancer Res. 2012 Apr 1;72(7):1844-52 [22315351] J Am Chem Soc. 2012 Jun 20;134(24):9918-21 [22642368] J Clin Immunol. 2012 Oct;32(5):1059-70 [22526592] Blood. 2015 Jul 30;126(5):629-39 [26041741] Leukemia. 2015 Aug;29(8):1637-47 [25721896] Science. 2015 Oct 16;350(6258):aab4077 [26405231] Clin Cancer Res. 2012 Dec 1;18(23):6436-45 [23032741] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1073/pnas.1524193113 ER - TY - JOUR T1 - Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization. AN - 1761077405; 26811972 AB - Target-specific, mechanism-oriented in vitro assays post a promising alternative to traditional animal toxicology studies. Here we report the first comprehensive analysis of the Tox21 effort, a large-scale in vitro toxicity screening of chemicals. We test ∼ 10,000 chemicals in triplicates at 15 concentrations against a panel of nuclear receptor and stress response pathway assays, producing more than 50 million data points. Compound clustering by structure similarity and activity profile similarity across the assays reveals structure-activity relationships that are useful for the generation of mechanistic hypotheses. We apply structural information and activity data to build predictive models for 72 in vivo toxicity end points using a cluster-based approach. Models based on in vitro assay data perform better in predicting human toxicity end points than animal toxicity, while a combination of structural and activity data results in better models than using structure or activity data alone. Our results suggest that in vitro activity profiles can be applied as signatures of compound mechanism of toxicity and used in prioritization for more in-depth toxicological testing. JF - Nature communications AU - Huang, Ruili AU - Xia, Menghang AU - Sakamuru, Srilatha AU - Zhao, Jinghua AU - Shahane, Sampada A AU - Attene-Ramos, Matias AU - Zhao, Tongan AU - Austin, Christopher P AU - Simeonov, Anton AD - Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, USA. Y1 - 2016/01/26/ PY - 2016 DA - 2016 Jan 26 SP - 10425 VL - 7 KW - Organic Chemicals KW - 0 KW - Index Medicus KW - Humans KW - Cell Line KW - Structure-Activity Relationship KW - Models, Theoretical KW - Organic Chemicals -- chemistry KW - Organic Chemicals -- toxicity KW - Toxicity Tests -- methods KW - Toxicity Tests -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761077405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+communications&rft.atitle=Modelling+the+Tox21+10+K+chemical+profiles+for+in+vivo+toxicity+prediction+and+mechanism+characterization.&rft.au=Huang%2C+Ruili%3BXia%2C+Menghang%3BSakamuru%2C+Srilatha%3BZhao%2C+Jinghua%3BShahane%2C+Sampada+A%3BAttene-Ramos%2C+Matias%3BZhao%2C+Tongan%3BAustin%2C+Christopher+P%3BSimeonov%2C+Anton&rft.aulast=Huang&rft.aufirst=Ruili&rft.date=2016-01-26&rft.volume=7&rft.issue=&rft.spage=10425&rft.isbn=&rft.btitle=&rft.title=Nature+communications&rft.issn=2041-1723&rft_id=info:doi/10.1038%2Fncomms10425 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-09 N1 - Date created - 2016-01-27 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/ncomms10425 ER - TY - JOUR T1 - Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters. AN - 1774536064; 26811318 AB - Bacteria use multidrug efflux pumps to export drugs and toxic compounds out of the cell. One of the most important efflux pumps in Escherichia coli is the AcrAB-TolC system. Small regulatory RNAs (sRNAs) are known to be major posttranscriptional regulators that can enhance or repress translation by binding to the 5' untranslated region (UTR) of mRNA targets with the help of a chaperone protein, Hfq. In this study, we investigated the expression of acrA, acrB, and tolC translational fusions using 27 Hfq-dependent sRNAs overexpressed from plasmids. No significant sRNA regulation of acrA or acrB was detected. SdsR (also known as RyeB), an abundant and well-conserved stationary-phase sRNA, was found to repress the expression of tolC, the gene encoding the outer membrane protein of many multidrug resistance efflux pumps. This repression was shown to be by direct base pairing occurring upstream from the ribosomal binding site. SdsR overexpression and its regulation of tolC were found to reduce resistance to novobiocin and crystal violet. Our results suggest that additional targets for SdsR exist that contribute to increased antibiotic sensitivity and reduced biofilm formation. In an effort to identify phenotypes associated with single-copy SdsR and its regulation of tolC, the effect of a deletion of sdsR or mutations in tolC that should block SdsR pairing were investigated using a Biolog phenotypic microarray. However, no significant phenotypes were identified. Therefore, SdsR appears to modulate rather than act as a major regulator of its targets. AcrAB-TolC is a major efflux pump present in E. coli and Gram-negative bacteria used to export toxic compounds; the pump confers resistance to many antibiotics of unrelated classes. In this study, we found that SdsR, a small RNA expressed in stationary phase, repressed the expression of tolC, resulting in increased sensitivity to some antibiotics. This extends the findings of previous studies showing that sRNAs contribute to the regulation of many outer membrane proteins; manipulating or enhancing their action might help in sensitizing bacteria to antibiotics. Copyright © 2016, American Society for Microbiology. All Rights Reserved. JF - Journal of bacteriology AU - Parker, Ashley AU - Gottesman, Susan AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA Department of Microbiology, College of Medicine, Howard University, Washington, DC, USA. ; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA gottesms@helix.nih.gov. Y1 - 2016/01/25/ PY - 2016 DA - 2016 Jan 25 SP - 1101 EP - 1113 VL - 198 IS - 7 KW - AcrAB-TolC protein, E coli KW - 0 KW - Bacterial Outer Membrane Proteins KW - Carrier Proteins KW - Escherichia coli Proteins KW - Membrane Transport Proteins KW - RNA, Bacterial KW - RNA, Messenger KW - tolC protein, E coli KW - Index Medicus KW - RNA, Messenger -- metabolism KW - Biofilms KW - RNA, Messenger -- genetics KW - Mutation KW - Escherichia coli -- metabolism KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Gene Expression Regulation, Bacterial -- physiology KW - RNA, Bacterial -- metabolism KW - Bacterial Outer Membrane Proteins -- metabolism KW - Escherichia coli -- genetics KW - RNA, Bacterial -- genetics KW - RNA, Bacterial -- classification KW - Escherichia coli Proteins -- metabolism KW - Bacterial Outer Membrane Proteins -- genetics KW - Membrane Transport Proteins -- genetics KW - Membrane Transport Proteins -- metabolism KW - Escherichia coli Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1774536064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Small+RNA+Regulation+of+TolC%2C+the+Outer+Membrane+Component+of+Bacterial+Multidrug+Transporters.&rft.au=Parker%2C+Ashley%3BGottesman%2C+Susan&rft.aulast=Parker&rft.aufirst=Ashley&rft.date=2016-01-25&rft.volume=198&rft.issue=7&rft.spage=1101&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=1098-5530&rft_id=info:doi/10.1128%2FJB.00971-15 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-07-28 N1 - Date created - 2016-03-18 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Antimicrob Chemother. 2010 May;65(5):853-8 [20211861] Antimicrob Agents Chemother. 2010 May;54(5):2125-34 [20211899] Proc Natl Acad Sci U S A. 2010 May 25;107(21):9602-7 [20457943] Mol Microbiol. 2010 Aug;77(3):743-54 [20545840] Mol Microbiol. 2010 Aug;77(3):771-86 [20545866] Nat Commun. 2013;4:1610 [23511474] J Biol Chem. 2013 Mar 22;288(12):7996-8003 [23362267] Virulence. 2013 Apr 1;4(3):223-9 [23380871] PLoS Genet. 2014 Jan;10(1):e1004026 [24391513] J Antimicrob Chemother. 2015;70(6):1659-68 [25724987] EMBO J. 2010 Sep 15;29(18):3094-107 [20683441] J Bacteriol. 2010 Nov;192(21):5559-71 [20802038] Cell. 2011 Jan 7;144(1):143-56 [21185072] Adv Enzymol Relat Areas Mol Biol. 2011;77:1-60 [21692366] J Bacteriol. 2011 Nov;193(21):5887-97 [21908668] Mol Microbiol. 2011 Dec;82(6):1545-62 [22040174] Nature. 2011 Dec 22;480(7378):565-9 [22121023] Mol Microbiol. 2012 Apr;84(1):17-35 [22289118] Nucleic Acids Res. 2012 Apr;40(8):3623-40 [22180532] J Bacteriol. 2012 May;194(10):2470-8 [22408168] Expert Opin Drug Discov. 2012 Jul;7(7):633-42 [22607346] Clin Microbiol Rev. 2012 Oct;25(4):661-81 [23034325] RNA Biol. 2012 Apr;9(4):489-502 [22336758] Mol Microbiol. 2012 Nov;86(3):524-38 [22925049] Nucleic Acids Res. 2013 Jan;41(Database issue):D605-12 [23143106] Antimicrob Agents Chemother. 2001 Apr;45(4):1126-36 [11257026] Genome Res. 2001 Jul;11(7):1246-55 [11435407] FEMS Microbiol Lett. 2001 Jul 10;201(1):9-14 [11445160] Mol Cell. 2002 Jan;9(1):11-22 [11804582] Mol Microbiol. 2002 Nov;46(3):813-26 [12410838] J Antimicrob Chemother. 2003 Jan;51(1):9-11 [12493781] Mol Microbiol. 2003 Apr;48(1):253-67 [12657059] Mol Microbiol. 2003 Jun;48(6):1609-19 [12791142] Nucleic Acids Res. 2003 Jul 1;31(13):3406-15 [12824337] Biotechnol Bioeng. 2003 Sep 30;83(7):864-70 [12889026] Microbiology. 2003 Oct;149(Pt 10):2819-28 [14523115] J Bacteriol. 2004 Mar;186(6):1851-60 [14996816] J Biol Chem. 2004 Jul 30;279(31):32116-24 [15155734] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1966-70 [6201848] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2172-5 [2648393] J Biol Chem. 1989 Oct 25;264(30):17961-70 [2478539] Genes Dev. 1993 Dec;7(12B):2618-28 [8276244] Mol Microbiol. 1995 Apr;16(1):45-55 [7651136] Biotechniques. 1995 Jul;19(1):18-20 [7669288] J Bacteriol. 1996 Oct;178(20):5853-9 [8830678] Science. 1999 May 21;284(5418):1318-22 [10334980] Trends Microbiol. 1999 Oct;7(10):410-3 [10498949] J Mol Evol. 2005 Apr;60(4):462-74 [15883881] Trends Genet. 2005 Jul;21(7):399-404 [15913835] J Bacteriol. 2005 Oct;187(20):6962-71 [16199566] Genes Dev. 2005 Oct 1;19(19):2355-66 [16204185] Mol Microbiol. 2006 Jan;59(1):231-47 [16359331] J Biol Chem. 2006 May 5;281(18):12253-9 [16513633] Genes Dev. 2006 Sep 1;20(17):2338-48 [16951250] J Mol Biol. 2006 Nov 17;364(1):1-8 [17007876] Curr Opin Microbiol. 2006 Dec;9(6):605-11 [17055775] Cold Spring Harb Symp Quant Biol. 2006;71:1-11 [17381274] J Bacteriol. 2007 Jun;189(11):4243-56 [17416652] Genes Dev. 2007 Nov 1;21(21):2804-17 [17974919] Infect Immun. 2008 Mar;76(3):1247-56 [18160483] FEMS Microbiol Ecol. 2008 Apr;64(1):28-36 [18318713] J Bacteriol. 2008 Sep;190(18):6276-9 [18567659] Mol Microbiol. 2008 Sep;69(6):1450-5 [18673442] J Bacteriol. 2009 Jan;191(2):461-76 [18978044] Cell. 2009 Feb 20;136(4):615-28 [19239884] Biochim Biophys Acta. 2009 May;1794(5):769-81 [19026770] Mol Microbiol. 2009 May;72(3):551-65 [19426207] J Bacteriol. 2009 Aug;191(16):5283-92 [19502391] Curr Opin Microbiol. 2010 Feb;13(1):24-33 [20080057] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1128/JB.00971-15 ER - TY - JOUR T1 - NAG-1/GDF15 accumulates in the nucleus and modulates transcriptional regulation of the Smad pathway. AN - 1760881599; 25893289 AB - Protein dynamics, modifications and trafficking are all processes that can modulate protein activity. Accumulating evidence strongly suggests that many proteins have distinctive roles dependent on cellular location. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor-β (TGF-β) superfamily protein that has a role in cancer, obesity and inflammation. NAG-1 is synthesized and cleaved into a mature peptide, which is ultimately secreted into the extracellular matrix (ECM). In this study, we have found that full-length NAG-1 is expressed in not only the cytoplasm and ECM, but also in the nucleus. NAG-1 is dynamically moved to the nucleus, exported into cytoplasm and further transported into the ECM. We have also found that nuclear NAG-1 contributes to inhibition of the Smad pathway by interrupting the Smad complex. Overall, our study indicates that NAG-1 is localized in the nucleus and provides new evidence that NAG-1 controls transcriptional regulation in the Smad pathway. JF - Oncogene AU - Min, K-W AU - Liggett, J L AU - Silva, G AU - Wu, W W AU - Wang, R AU - Shen, R-F AU - Eling, T E AU - Baek, S J AD - Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA. ; Facility for Biotechnology Resources, CBER, Food and Drug Administration, Bethesda, MD, USA. ; Laboratory of Molecular Carcinogenesis, NIH/NIEHS, Research Triangle Park, NC, USA. Y1 - 2016/01/21/ PY - 2016 DA - 2016 Jan 21 SP - 377 EP - 388 VL - 35 IS - 3 KW - GDF15 protein, human KW - 0 KW - Growth Differentiation Factor 15 KW - Smad Proteins KW - Index Medicus KW - Extracellular Matrix -- genetics KW - Promoter Regions, Genetic KW - Apoptosis -- genetics KW - Cytoplasm -- genetics KW - Humans KW - Cell Line, Tumor KW - Signal Transduction KW - Smad Proteins -- genetics KW - Smad Proteins -- metabolism KW - Growth Differentiation Factor 15 -- biosynthesis KW - Growth Differentiation Factor 15 -- genetics KW - Transcription, Genetic KW - Cell Nucleus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760881599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=NAG-1%2FGDF15+accumulates+in+the+nucleus+and+modulates+transcriptional+regulation+of+the+Smad+pathway.&rft.au=Min%2C+K-W%3BLiggett%2C+J+L%3BSilva%2C+G%3BWu%2C+W+W%3BWang%2C+R%3BShen%2C+R-F%3BEling%2C+T+E%3BBaek%2C+S+J&rft.aulast=Min&rft.aufirst=K-W&rft.date=2016-01-21&rft.volume=35&rft.issue=3&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=1476-5594&rft_id=info:doi/10.1038%2Fonc.2015.95 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-03 N1 - Date created - 2016-01-21 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: J Biol Chem. 2000 Jun 30;275(26):20127-35 [10777512] Mol Cell Biol. 2000 Dec;20(23):9041-54 [11074002] Mol Pharmacol. 2001 Apr;59(4):901-8 [11259636] J Cell Sci. 2010 May 1;123(Pt 9):1438-48 [20356926] Nat Rev Cancer. 2010 Jun;10(6):415-24 [20495575] J Cell Biochem. 2010 Oct 15;111(3):755-67 [20665536] Mol Cell. 2010 Nov 24;40(4):521-32 [21095583] J Biol Chem. 2010 Dec 3;285(49):38720-9 [20937808] Biochem Pharmacol. 2011 Nov 1;82(9):1090-9 [21803025] Nat Cell Biol. 2011 Nov;13(11):1368-75 [21947082] FEBS J. 2011 Dec;278(24):4756-67 [22051117] J Biol Chem. 2012 Jan 6;287(2):819-31 [22110128] Nat Protoc. 2012 Mar;7(3):562-78 [22383036] Biochem Pharmacol. 2012 Apr 15;83(8):1021-32 [22209898] PLoS One. 2012;7(4):e34868 [22514681] J Cell Biochem. 2012 Jul;113(7):2193-200 [22388977] Toxicol Appl Pharmacol. 2012 Sep 1;263(2):225-32 [22750490] Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30 [22992590] Nat Rev Drug Discov. 2012 Oct;11(10):790-811 [23000686] Cardiovasc Pathol. 2012 Nov-Dec;21(6):499-505 [22386250] Biochem Pharmacol. 2013 Mar 1;85(5):597-606 [23220538] Mediators Inflamm. 2013;2013:641851 [23737651] Life Sci. 2014 Apr 1;100(2):75-84 [24530873] Nat Med. 2014 May;20(5):493-502 [24784232] Cancer Res. 2001 Sep 1;61(17):6307-12 [11522616] J Biol Chem. 2001 Sep 7;276(36):33384-92 [11445565] Carcinogenesis. 2002 Mar;23(3):425-34 [11895857] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11514-9 [9326641] Biochim Biophys Acta. 1997 Oct 9;1354(1):40-4 [9375789] J Biol Chem. 1998 May 29;273(22):13760-7 [9593718] Genes Dev. 1998 Jul 15;12(14):2114-9 [9679056] Proc Natl Acad Sci U S A. 1997 May 13;94(10):5095-100 [9144196] Gene. 1999 Sep 3;237(1):105-11 [10524241] J Pharmacol Exp Ther. 2002 Jun;301(3):1126-31 [12023546] Oncogene. 2002 Jun 20;21(27):4212-9 [12082608] J Biol Chem. 2003 Feb 21;278(8):5845-53 [12475986] Cancer Res. 2003 May 1;63(9):2256-67 [12727848] Nat Rev Mol Cell Biol. 2003 Sep;4(9):690-9 [14506472] J Biol Chem. 2004 Feb 20;279(8):6883-92 [14662774] J Biol Chem. 2004 Nov 26;279(48):49617-23 [15377673] Carcinogenesis. 2004 Dec;25(12):2425-32 [15308587] Biochem Biophys Res Commun. 2005 Mar 4;328(1):63-9 [15670751] Cancer Res. 2005 Mar 15;65(6):2330-6 [15781647] J Biol Chem. 2005 May 13;280(19):18636-42 [15757899] Shock. 2005 Jun;23(6):543-8 [15897808] Mol Pharmacol. 2005 Dec;68(6):1782-92 [16155208] Genes Dev. 2005 Dec 1;19(23):2783-810 [16322555] Prog Lipid Res. 2006 Jan;45(1):1-16 [16337272] Circ Res. 2006 Feb 17;98(3):342-50 [16397142] Cancer Gene Ther. 2006 Feb;13(2):115-24 [16138117] Carcinogenesis. 2006 May;27(5):972-81 [16286461] Gastroenterology. 2006 Nov;131(5):1553-60 [17101328] Trends Cell Biol. 2007 Apr;17(4):193-201 [17317185] J Biol Chem. 2007 Sep 21;282(38):27685-92 [17652081] Mol Carcinog. 2008 Mar;47(3):197-208 [18058799] J Biol Chem. 2008 Apr 4;283(14):8984-94 [18238777] Mol Cancer Ther. 2008 Sep;7(9):2779-87 [18790758] Mol Cancer Ther. 2008 Dec;7(12):3739-50 [19074849] Cancer Prev Res (Phila). 2009 May;2(5):450-8 [19401523] Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10171-6 [19520826] BMC Bioinformatics. 2009;10:202 [19563654] Future Oncol. 2009 Sep;5(7):993-1003 [19792968] Cell. 2009 Nov 13;139(4):757-69 [19914168] J Cancer Res Clin Oncol. 2010 Apr;136(4):571-6 [19784846] BMC Cell Biol. 2010;11:20 [20230640] Int J Obes (Lond). 2014 Dec;38(12):1555-64 [24531647] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):109-14 [10618379] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1038/onc.2015.95 ER - TY - JOUR T1 - Hypermethylation of genes in testicular embryonal carcinomas. AN - 1760911345; 26625006 AB - Testicular embryonal carcinoma (EC) is a major subtype of non-seminomatous germ cell tumours in males. Embryonal carcinomas are pluripotent, undifferentiated germ cell tumours believed to originate from primordial germ cells. Epigenetic changes during testicular EC tumorigenesis require better elucidation. To identify epigenetic changes during testicular neoplastic transformation, we profiled DNA methylation of six ECs. These samples represent different stages (stage I and stage III) of divergent invasiveness. Non-cancerous testicular tissues were included. Expression of a number of hypermethylated genes were examined by quantitative RT-PCR and immunohistochemistry (IHC). A total of 1167 tumour-hypermethylated differentially methylated regions (DMRs) were identified across the genome. Among them, 40 genes/ncRNAs were found to have hypermethylated promoters. Quantitative RT-PCR confirmed downregulation of 8 out of 9 of the genes. Among the confirmed genes, five were sex-linked genes, including X-linked genes STAG2, SPANXD/E and MIR1184, and Y-linked genes RBMY1A1/1B/1D and FAM197Y2P. RBMY1A is a testis-specific gene for spermatogenesis. RNF168 and USP13 are potential tumour suppressors. Expression of RBMY1A was lost in EC and seminoma as documented in the Protein Atlas. We confirmed downregulation of USP13 in EC by IHC. Our genome-wide analysis of testicular EC identified methylation changes in several previously unknown genes. This may provide insight of crosstalk between normal germ cell development and carcinogenesis. JF - British journal of cancer AU - Cheung, Hoi-Hung AU - Yang, Yanzhou AU - Lee, Tin-Lap AU - Rennert, Owen AU - Chan, Wai-Yee AD - The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. ; Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Ningxia Medical University, Ningxia 750004, China. ; Reproduction, Development and Endocrinology Theme, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. ; The Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2016/01/19/ PY - 2016 DA - 2016 Jan 19 SP - 230 EP - 236 VL - 114 IS - 2 KW - Nuclear Proteins KW - 0 KW - RBMY1A1 protein, human KW - RNA-Binding Proteins KW - SPANXD protein, human KW - Acyltransferases KW - EC 2.3.- KW - 2-acylglycerophosphate acyltransferase KW - EC 2.3.1.52 KW - RNF168 protein, human KW - EC 2.3.2.27 KW - Ubiquitin-Protein Ligases KW - Endopeptidases KW - EC 3.4.- KW - USP13 protein, human KW - Index Medicus KW - Real-Time Polymerase Chain Reaction KW - Young Adult KW - Nuclear Proteins -- genetics KW - RNA-Binding Proteins -- genetics KW - Neoplasm Staging KW - Humans KW - Epigenesis, Genetic KW - Endopeptidases -- genetics KW - Gene Expression Profiling KW - Promoter Regions, Genetic KW - Tissue Array Analysis KW - Acyltransferases -- genetics KW - Ubiquitin-Protein Ligases -- genetics KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Middle Aged KW - Adolescent KW - Immunohistochemistry KW - Male KW - Gene Expression Regulation, Neoplastic KW - DNA Methylation KW - Carcinoma, Embryonal -- genetics KW - Testicular Neoplasms -- pathology KW - Carcinoma, Embryonal -- pathology KW - Testicular Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760911345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Hypermethylation+of+genes+in+testicular+embryonal+carcinomas.&rft.au=Cheung%2C+Hoi-Hung%3BYang%2C+Yanzhou%3BLee%2C+Tin-Lap%3BRennert%2C+Owen%3BChan%2C+Wai-Yee&rft.aulast=Cheung&rft.aufirst=Hoi-Hung&rft.date=2016-01-19&rft.volume=114&rft.issue=2&rft.spage=230&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=1532-1827&rft_id=info:doi/10.1038%2Fbjc.2015.408 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-06 N1 - Date created - 2016-01-20 N1 - Date revised - 2017-01-24 N1 - SuppNotes - Cited By: Acta Med Indones. 2009 Jan;41(1):25-9 [19258677] Br J Cancer. 2010 Jan 19;102(2):419-27 [20051947] Br J Cancer. 2010 Oct 12;103(8):1269-76 [20823885] Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19891-6 [21041627] J Reprod Dev. 2011 Feb;57(1):107-12 [21422736] PLoS Genet. 2011 Apr;7(4):e1001381 [21552324] Int J Cancer. 2011 Nov 15;129(10):2485-91 [21207375] Anticancer Res. 2011 Nov;31(11):3783-8 [22110200] Arch Dis Child. 2013 Jan;98(1):20-6 [23193201] Mod Pathol. 2013 Apr;26(4):579-86 [23238629] Iran Biomed J. 2013 Apr;17(2):54-61 [23567846] Int J Dev Biol. 2013;57(2-4):309-17 [23784842] Methods Mol Biol. 2013;1067:225-33 [23975795] Nat Cell Biol. 2013 Dec;15(12):1486-94 [24270891] Histopathology. 2014 Jan;64(2):293-305 [24330150] Pediatr Endocrinol Rev. 2014 Feb;11 Suppl 2:251-62 [24683949] Epigenetics. 2014 Jan;9(1):119-28 [23959088] Nat Genet. 2000 Feb;24(2):197-200 [10655070] J Urol. 2002 Jan;167(1):335-8 [11743352] Oncogene. 2002 May 30;21(24):3909-16 [12032829] Development. 2003 Apr;130(8):1691-700 [12620992] Gene. 2003 May 8;309(2):125-33 [12758128] Am J Surg Pathol. 2004 Jul;28(7):935-40 [15223965] J Urol. 1997 May;157(5):1701-4 [9112509] Oncogene. 2005 Mar 10;24(11):1882-94 [15674339] J Natl Cancer Inst. 2005 Aug 17;97(16):1204-10 [16106025] Mol Cell Proteomics. 2005 Dec;4(12):1920-32 [16127175] BJU Int. 2006 Apr;97(4):724-6 [16536762] Mol Hum Reprod. 2006 Nov;12(11):703-16 [17012309] Urol Oncol. 2007 Mar-Apr;25(2):141-6 [17349529] Prostate. 2007 Jun 1;67(8):820-8 [17373721] Arch Pathol Lab Med. 2007 Aug;131(8):1267-80 [17683189] Hum Pathol. 2007 Oct;38(10):1470-81 [17521702] J Hum Genet. 2008;53(2):185-91 [18200438] Urol J. 2007 Fall;4(4):192-206 [18270942] Mol Cell Endocrinol. 2008 Jun 25;288(1-2):111-8 [18420341] Cell. 2009 Feb 6;136(3):420-34 [19203578] N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1038/bjc.2015.408 ER - TY - JOUR T1 - A Simple Pharmacokinetic Model of Prenatal and Postnatal Exposure to Perfluoroalkyl Substances (PFASs). AN - 1760897645; 26691063 AB - Most children are exposed to perfluoroalkyl substances (PFASs) through placental transfer, breastfeeding, and other environmental sources. To date, there are no validated tools to estimate exposure and body burden during infancy and childhood. In this study, we aimed to (i) develop a two-generation pharmacokinetic model of prenatal and postnatal exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS); and to (ii) evaluate it against measured children's levels in two studies. We developed a pharmacokinetic model consisting of a maternal and a child compartment to simulate lifetime exposure in women and transfer to the child across the placenta and through breastfeeding. To evaluate the model, we performed simulations for each mother-child dyad from two studies in which maternal PFAS levels at delivery and children's PFAS levels were available. Model predictions based on maternal PFAS levels, sex of child, body weight, and duration of breastfeeding explained between 52% and 60% of the variability in measured children's levels at 6 months of age and between 52% and 62% at 36 months. Monte Carlo simulations showed that the daily intake through breastfeeding and resulting internal PFAS levels can be much higher in nursing infants than in mothers. This pharmacokinetic model shows potential for postnatal exposure assessment in the context of epidemiological studies and risk assessment. JF - Environmental science & technology AU - Verner, Marc-André AU - Ngueta, Gérard AU - Jensen, Elizabeth T AU - Fromme, Hermann AU - Völkel, Wolfgang AU - Nygaard, Unni Cecilie AU - Granum, Berit AU - Longnecker, Matthew P AD - National Institute of Environmental Health Sciences, National Institutes of Health , Department of Health and Human Services, Research Triangle Park, North Carolina 27709, United States. ; Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority , D-80538 Munich, Germany. ; Division of Environmental Medicine, Norwegian Institute of Public Health , PO Box 4404 Nydalen, 0403 Oslo, Norway. Y1 - 2016/01/19/ PY - 2016 DA - 2016 Jan 19 SP - 978 EP - 986 VL - 50 IS - 2 KW - Alkanesulfonic Acids KW - 0 KW - Caprylates KW - Environmental Pollutants KW - Fluorocarbons KW - Sulfonic Acids KW - perfluorohexanesulfonic acid KW - 355-46-4 KW - perfluorooctanoic acid KW - 947VD76D3L KW - perfluorooctane sulfonic acid KW - 9H2MAI21CL KW - Index Medicus KW - Fluorocarbons -- pharmacokinetics KW - Caprylates -- adverse effects KW - Breast Feeding KW - Mothers KW - Alkanesulfonic Acids -- pharmacokinetics KW - Humans KW - Infant, Newborn KW - Placenta -- drug effects KW - Child KW - Monte Carlo Method KW - Pregnancy KW - Child, Preschool KW - Infant KW - Sulfonic Acids -- pharmacokinetics KW - Adult KW - Alkanesulfonic Acids -- adverse effects KW - Fluorocarbons -- adverse effects KW - Caprylates -- pharmacokinetics KW - Sulfonic Acids -- adverse effects KW - Male KW - Female KW - Prenatal Exposure Delayed Effects KW - Models, Theoretical KW - Environmental Exposure -- adverse effects KW - Environmental Pollutants -- blood KW - Environmental Pollutants -- pharmacokinetics KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760897645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+science+%26+technology&rft.atitle=A+Simple+Pharmacokinetic+Model+of+Prenatal+and+Postnatal+Exposure+to+Perfluoroalkyl+Substances+%28PFASs%29.&rft.au=Verner%2C+Marc-Andr%C3%A9%3BNgueta%2C+G%C3%A9rard%3BJensen%2C+Elizabeth+T%3BFromme%2C+Hermann%3BV%C3%B6lkel%2C+Wolfgang%3BNygaard%2C+Unni+Cecilie%3BGranum%2C+Berit%3BLongnecker%2C+Matthew+P&rft.aulast=Verner&rft.aufirst=Marc-Andr%C3%A9&rft.date=2016-01-19&rft.volume=50&rft.issue=2&rft.spage=978&rft.isbn=&rft.btitle=&rft.title=Environmental+science+%26+technology&rft.issn=1520-5851&rft_id=info:doi/10.1021%2Facs.est.5b04399 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-12 N1 - Date created - 2016-01-19 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acs.est.5b04399 ER - TY - JOUR T1 - Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK. AN - 1760864969; 26780950 AB - Activation of NADPH oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in methamphetamine (MA)-induced neurotoxic and inflammatory changes in mice. We examined changes in mitogen-activated protein kinases (MAPKs), mitochondrial function [i.e., mitochondrial membrane potential, intramitochondrial Ca(2+) accumulation, mitochondrial oxidative burdens, mitochondrial superoxide dismutase expression, and mitochondrial translocation of the cleaved form of protein kinase C delta type (cleaved PKCδ)], microglial activity, and pro-apoptotic changes [i.e., cytosolic cytochrome c release, cleaved caspase 3, and terminal deoxynucleotidyl transferase dUDP nick-end labeling (TUNEL) positive populations] after a neurotoxic dose of MA in the striatum of mice to achieve a better understanding of the effects of apocynin, a non-specific PHOX inhibitor, or genetic inhibition of p47phox (by using p47phox knockout mice or p47phox antisense oligonucleotide) against MA-induced dopaminergic neurotoxicity. Phosphorylation of extracellular signal-regulated kinases (ERK1/2) was most pronounced out of MAPKs after MA. We observed MA-induced phosphorylation and membrane translocation of p47phox in the striatum of mice. The activation of p47phox promoted mitochondrial stresses followed by microglial activation into the M1 phenotype, and pro-apoptotic changes, and led to dopaminergic impairments. ERK activated these signaling pathways. Apocynin or genetic inhibition of p47phox significantly protected these signaling processes induced by MA. ERK inhibitor U0126 did not exhibit any additional positive effects against protective activity mediated by apocynin or p47phox genetic inhibition, suggesting that ERK regulates p47phox activation, and ERK constitutes the crucial target for apocynin-mediated inhibition of PHOX activation. Our results indicate that the neuroprotective mechanism of apocynin against MA insult is via preventing mitochondrial burdens, microglial activation, and pro-apoptotic signaling process by the ERK-dependent activation of p47phox. JF - Journal of neuroinflammation AU - Dang, Duy-Khanh AU - Shin, Eun-Joo AU - Nam, Yunsung AU - Ryoo, Sungwoo AU - Jeong, Ji Hoon AU - Jang, Choon-Gon AU - Nabeshima, Toshitaka AU - Hong, Jau-Shyong AU - Kim, Hyoung-Chun AD - Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea. dkluckystar@yahoo.com. ; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea. shinej@kangwon.ac.kr. ; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea. namsaak@naver.com. ; Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon, South Korea. ryoosw08@kangwon.ac.kr. ; Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. jhjeong3@cau.ac.kr. ; Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. jang@skku.edu. ; Department of Regional Pharmaceutical Care and Sciences, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, Japan. tnabeshi@ccalumni.meijo-u.ac.jp. ; Neuropharmacology Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA. hong3@niehs.nih.gov. ; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, South Korea. kimhc@kangwon.ac.kr. Y1 - 2016/01/18/ PY - 2016 DA - 2016 Jan 18 SP - 12 VL - 13 KW - Acetophenones KW - 0 KW - Antigens, CD KW - Antioxidants KW - Central Nervous System Stimulants KW - Oligodeoxyribonucleotides, Antisense KW - Methamphetamine KW - 44RAL3456C KW - acetovanillone KW - B6J7B9UDTR KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Tyrosine 3-Monooxygenase -- metabolism KW - Cytosol -- drug effects KW - Antigens, CD -- genetics KW - Mice KW - Oligodeoxyribonucleotides, Antisense -- pharmacology KW - Mice, Knockout KW - Calcium -- metabolism KW - Membrane Potential, Mitochondrial -- drug effects KW - Antioxidants -- pharmacology KW - Antigens, CD -- metabolism KW - Mice, Inbred C57BL KW - Time Factors KW - Microglia -- drug effects KW - NADPH Oxidase -- metabolism KW - Acetophenones -- pharmacology KW - Central Nervous System Stimulants -- toxicity KW - Corpus Striatum -- ultrastructure KW - Mitochondria -- drug effects KW - Apoptosis -- drug effects KW - Corpus Striatum -- drug effects KW - Corpus Striatum -- pathology KW - NADPH Oxidase -- genetics KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760864969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroinflammation&rft.atitle=Apocynin+prevents+mitochondrial+burdens%2C+microglial+activation%2C+and+pro-apoptosis+induced+by+a+toxic+dose+of+methamphetamine+in+the+striatum+of+mice+via+inhibition+of+p47phox+activation+by+ERK.&rft.au=Dang%2C+Duy-Khanh%3BShin%2C+Eun-Joo%3BNam%2C+Yunsung%3BRyoo%2C+Sungwoo%3BJeong%2C+Ji+Hoon%3BJang%2C+Choon-Gon%3BNabeshima%2C+Toshitaka%3BHong%2C+Jau-Shyong%3BKim%2C+Hyoung-Chun&rft.aulast=Dang&rft.aufirst=Duy-Khanh&rft.date=2016-01-18&rft.volume=13&rft.issue=&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroinflammation&rft.issn=1742-2094&rft_id=info:doi/10.1186%2Fs12974-016-0478-x LA - 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Last updated - 2017-01-19 DO - http://dx.doi.org/10.1186/s12974-016-0478-x ER - TY - JOUR T1 - Evolutionary Dynamics of Influenza A Viruses in US Exhibition Swine AN - 1773830207; PQ0002694555 AB - The role of exhibition swine in influenza A virus transmission was recently demonstrated by >300 infections with influenza A(H3N2) variant viruses among individuals who attended agricultural fairs. Through active influenza A virus surveillance in US exhibition swine and whole-genome sequencing of 380 isolates, we demonstrate that exhibition swine are actively involved in the evolution of influenza A viruses, including zoonotic strains. First, frequent introduction of influenza A viruses from commercial swine populations provides new genetic diversity in exhibition pigs each year locally. Second, genomic reassortment between viruses cocirculating in exhibition swine increases viral diversity. Third, viral migration between exhibition swine in neighboring states demonstrates that movements of exhibition pigs contributes to the spread of genetic diversity. The unexpected frequency of viral exchange between commercial and exhibition swine raises questions about the understudied interface between these populations. Overall, the complexity of viral evolution in exhibition swine indicates that novel viruses are likely to continually reemerge, presenting threats to humans. JF - Journal of Infectious Diseases AU - Nelson, Martha I AU - Wentworth, David E AU - Das, Suman R AU - Sreevatsan, Srinand AU - Killian, Mary L AU - Nolting, Jacqueline M AU - Slemons, Richard D AU - Bowman, Andrew S AD - Fogarty International Center, National Institutes of Health, Bethesda, bowman.214@osu.edu Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - 173 EP - 182 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP United Kingdom VL - 213 IS - 2 SN - 0022-1899, 0022-1899 KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - influenza A virus KW - swine KW - human-animal interface KW - evolution KW - genomics KW - gene flow KW - United States KW - exhibition animals KW - Influenza A KW - Viruses KW - Genetic diversity KW - Infection KW - Migration KW - Influenza KW - Population genetics KW - Infectious diseases KW - Influenza A virus KW - Evolution KW - H 6000:Natural Disasters/Civil Defense/Emergency Management KW - V 22400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1773830207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Evolutionary+Dynamics+of+Influenza+A+Viruses+in+US+Exhibition+Swine&rft.au=Nelson%2C+Martha+I%3BWentworth%2C+David+E%3BDas%2C+Suman+R%3BSreevatsan%2C+Srinand%3BKillian%2C+Mary+L%3BNolting%2C+Jacqueline+M%3BSlemons%2C+Richard+D%3BBowman%2C+Andrew+S&rft.aulast=Nelson&rft.aufirst=Martha&rft.date=2016-01-15&rft.volume=213&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/10.1093%2Finfdis%2Fjiv399 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-03-01 N1 - Last updated - 2016-04-13 N1 - SubjectsTermNotLitGenreText - Population genetics; Influenza A; Genetic diversity; genomics; Infection; Migration; Evolution; Influenza; Infectious diseases; Viruses; Influenza A virus DO - http://dx.doi.org/10.1093/infdis/jiv399 ER - TY - JOUR T1 - Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma. AN - 1760903355; 26405193 AB - Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous hepatobiliary neoplasm with poor prognosis and limited therapeutic options. The incidence of this neoplasm is growing globally. One third of iCCA tumors are amenable to surgical resection, but most cases are diagnosed at advanced stages with chemotherapy as the only established standard of practice. No molecular therapies are currently available for the treatment of this neoplasm. The poor understanding of the biology of iCCA and the lack of known oncogenic addiction loops has hindered the development of effective targeted therapies. Studies with sophisticated animal models defined IDH mutation as the first gatekeeper in the carcinogenic process and led to the discovery of striking alternative cellular origins. RNA- and exome-sequencing technologies revealed the presence of recurrent novel fusion events (FGFR2 and ROS1 fusions) and somatic mutations in metabolic (IDH1/2) and chromatin-remodeling genes (ARID1A, BAP1). These latest advancements along with known mutations in KRAS/BRAF/EGFR and 11q13 high-level amplification have contributed to a better understanding of the landscape of molecular alterations in iCCA. More than 100 clinical trials testing molecular therapies alone or in combination with chemotherapy including iCCA patients have not reported conclusive clinical benefits. Recent discoveries have shown that up to 70% of iCCA patients harbor potential actionable alterations that are amenable to therapeutic targeting in early clinical trials. Thus, the first biomarker-driven trials are currently underway. ©2015 American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Moeini, Agrin AU - Sia, Daniela AU - Bardeesy, Nabeel AU - Mazzaferro, Vincenzo AU - Llovet, Josep M AD - Liver Cancer Translational Research Laboratory, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, CIBERehd, Universitat de Barcelona, Barcelona, Catalonia, Spain. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. ; Liver Cancer Translational Research Laboratory, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, CIBERehd, Universitat de Barcelona, Barcelona, Catalonia, Spain. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Gastrointestinal Surgery and Liver Transplantation Unit, Department of Surgery, National Cancer Institute IRCCS Foundation, Milan, Italy. ; Cancer Center, Center for Regenerative Medicine, and Department of Molecular Biology, Massachusetts General Hospital, Harvard University, Boston, Massachusetts. ; Gastrointestinal Surgery and Liver Transplantation Unit, Department of Surgery, National Cancer Institute IRCCS Foundation, Milan, Italy. ; Liver Cancer Translational Research Laboratory, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, CIBERehd, Universitat de Barcelona, Barcelona, Catalonia, Spain. Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain. jmllovet@clinic.cat. Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - 291 EP - 300 VL - 22 IS - 2 SN - 1078-0432, 1078-0432 KW - Index Medicus KW - Animals KW - Pathology, Molecular -- methods KW - Humans KW - Prognosis KW - Mutation -- genetics KW - Molecular Targeted Therapy -- methods KW - Cholangiocarcinoma -- genetics KW - Cholangiocarcinoma -- drug therapy KW - Cholangiocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760903355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Molecular+Pathogenesis+and+Targeted+Therapies+for+Intrahepatic+Cholangiocarcinoma.&rft.au=Moeini%2C+Agrin%3BSia%2C+Daniela%3BBardeesy%2C+Nabeel%3BMazzaferro%2C+Vincenzo%3BLlovet%2C+Josep+M&rft.aulast=Moeini&rft.aufirst=Agrin&rft.date=2016-01-15&rft.volume=22&rft.issue=2&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-14-3296 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-14 N1 - Date created - 2016-01-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1078-0432.CCR-14-3296 ER - TY - JOUR T1 - Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity. AN - 1760903332; 26350263 AB - Adult T-cell leukemia (ATL) is usually CD25(+) and rapidly fatal. Anti-CD25 recombinant immunotoxin LMB-2 had phase I activity limited by immunogenicity and rapid growth. To prevent antidrug antibodies and leukemic progression between cycles, a phase II trial was performed with LMB-2 after cyclophosphamide and fludarabine. ATL patients received cyclophosphamide and fludarabine days 1 to 3 and 2 weeks later began up to 6 cycles at 3-week intervals of cyclophosphamide and fludarabine days 1 to 3 followed by LMB-2 30-40 μg/kg i.v. days 3, 5, and 7. Three different dose levels of cyclophosphamide and fludarabine were used, 20+200 (n = 3), 25+250 (n = 12), and 30+300 mg/m(2) (n = 2). Of 17 patients enrolled and treated with fludarabine and cyclophosphamide for cycle-1, 15 received subsequent cycle(s) containing LMB-2 and were therefore evaluable for response. Lack of antibody formation permitted retreatment in most patients. Of 10 evaluable leukemic patients receiving 25+250 or 30+300 mg/m(2) of fludarabine and cyclophosphamide, 6 (60%) achieved complete remission (CR) and 2 (20%) partial remission (PR), and all 5 with >25% leukemic cells achieved CR. No responses were achieved in 5 with lymphomatous ATL or lower fludarabine and cyclophosphamide doses. Median CR duration for the 6 CRs was 40 weeks. One is without detectable ATL at 47 months. Toxicity was mostly attributable to fludarabine and cyclophosphamide. Capillary leak from LMB-2 was non-dose limiting. One patient in CR died of a preexisting infection. LMB-2, administered with fludarabine and cyclophosphamide to prevent antidrug antibodies and rapid intercycle progression, is highly effective in achieving CR in leukemia ATL. Fludarabine and cyclophosphamide dose/schedule is important for safety and efficacy in this high-risk population. ©2015 American Association for Cancer Research. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kreitman, Robert J AU - Stetler-Stevenson, Maryalice AU - Jaffe, Elaine S AU - Conlon, Kevin C AU - Steinberg, Seth M AU - Wilson, Wyndham AU - Waldmann, Thomas A AU - Pastan, Ira AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland. kreitmar@mail.nih.gov. ; Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland. ; Lymphoid Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland. ; Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. ; Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland. Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - 310 EP - 318 VL - 22 IS - 2 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - B3(Fv)-PE38KDEL recombinant immunotoxin KW - Exotoxins KW - IL2RA protein, human KW - Immunotoxins KW - Interleukin-2 Receptor alpha Subunit KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Vidarabine -- analogs & derivatives KW - Drug Administration Schedule KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Remission Induction -- methods KW - Middle Aged KW - Vidarabine -- administration & dosage KW - Exotoxins -- therapeutic use KW - Male KW - Female KW - Interleukin-2 Receptor alpha Subunit -- antagonists & inhibitors KW - Immunotoxins -- therapeutic use KW - Leukemia-Lymphoma, Adult T-Cell -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antibody Formation -- drug effects KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760903332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Complete+Remissions+of+Adult+T-cell+Leukemia+with+Anti-CD25+Recombinant+Immunotoxin+LMB-2+and+Chemotherapy+to+Block+Immunogenicity.&rft.au=Kreitman%2C+Robert+J%3BStetler-Stevenson%2C+Maryalice%3BJaffe%2C+Elaine+S%3BConlon%2C+Kevin+C%3BSteinberg%2C+Seth+M%3BWilson%2C+Wyndham%3BWaldmann%2C+Thomas+A%3BPastan%2C+Ira&rft.aulast=Kreitman&rft.aufirst=Robert&rft.date=2016-01-15&rft.volume=22&rft.issue=2&rft.spage=310&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/10.1158%2F1078-0432.CCR-15-1412 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-14 N1 - Date created - 2016-01-16 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1158/1078-0432.CCR-15-1412 ER - TY - JOUR T1 - NEDD4-mediated HSF1 degradation underlies α-synucleinopathy. AN - 1760887358; 26503960 AB - Cellular protein homeostasis is achieved by a delicate network of molecular chaperones and various proteolytic processes such as ubiquitin-proteasome system (UPS) to avoid a build-up of misfolded protein aggregates. The latter is a common denominator of neurodegeneration. Neurons are found to be particularly vulnerable to toxic stress from aggregation-prone proteins such as α-synuclein. Induction of heat-shock proteins (HSPs), such as through activated heat shock transcription factor 1 (HSF1) via Hsp90 inhibition, is being investigated as a therapeutic option for proteinopathic diseases. HSF1 is a master stress-protective transcription factor which activates genes encoding protein chaperones (e.g. iHsp70) and anti-apoptotic proteins. However, whether and how HSF1 is dysregulated during neurodegeneration has not been studied. Here, we discover aberrant HSF1 degradation by aggregated α-synuclein (or α-synuclein-induced proteotoxic stress) in transfected neuroblastoma cells. HSF1 dysregulation via α-synuclein was confirmed by in vivo assessment of mouse and in situ studies of human specimens with α-synucleinopathy. We demonstrate that elevated NEDD4 is implicated as the responsible ubiquitin E3 ligase for HSF1 degradation through UPS. Furthermore, pharmacologically induced SIRT1-mediated deacetylation can attenuate aberrant NEDD4-mediated HSF1 degradation. Indeed, we define the acetylation status of the Lys 80 residue located in the DNA-binding domain of HSF1 as a critical factor in modulating HSF1 protein stability in addition to its previously identified role in the transcriptional activity. Together with the finding that preserving HSF1 can alleviate α-synuclein toxicity, this study strongly suggests that aberrant HSF1 degradation is a key neurodegenerative mechanism underlying α-synucleinopathy. © The Author 2015. Published by Oxford University Press. JF - Human molecular genetics AU - Kim, Eunhee AU - Wang, Bin AU - Sastry, Namratha AU - Masliah, Eliezer AU - Nelson, Peter T AU - Cai, Huaibin AU - Liao, Francesca-Fang AD - Department of Pharmacology and Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, 874 Union Avenue/Crowe 401, Memphis, TN 38163, USA. ; Transgenics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, Sanders-Brown Center on Aging, 800 South Limestone Street, Lexington, KY 40536, USA and. ; Department of Pharmacology and Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, 874 Union Avenue/Crowe 401, Memphis, TN 38163, USA, fliao@uthsc.edu. Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - 211 EP - 222 VL - 25 IS - 2 KW - DNA-Binding Proteins KW - 0 KW - Endosomal Sorting Complexes Required for Transport KW - Transcription Factors KW - alpha-Synuclein KW - heat shock transcription factor KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Sirtuin 1 KW - EC 3.5.1.- KW - Nedd4 ubiquitin protein ligases KW - EC 6.3.2.- KW - Index Medicus KW - Proteolysis KW - Animals KW - Acetylation KW - Humans KW - Brain -- pathology KW - Ubiquitination KW - Sirtuin 1 -- metabolism KW - Mice KW - Gene Expression Regulation KW - Cell Line, Tumor KW - Brain -- metabolism KW - Proteostasis Deficiencies -- pathology KW - Transcription Factors -- metabolism KW - Ubiquitin-Protein Ligases -- genetics KW - Ubiquitin-Protein Ligases -- metabolism KW - Endosomal Sorting Complexes Required for Transport -- metabolism KW - Endosomal Sorting Complexes Required for Transport -- genetics KW - Proteostasis Deficiencies -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760887358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=NEDD4-mediated+HSF1+degradation+underlies+%CE%B1-synucleinopathy.&rft.au=Kim%2C+Eunhee%3BWang%2C+Bin%3BSastry%2C+Namratha%3BMasliah%2C+Eliezer%3BNelson%2C+Peter+T%3BCai%2C+Huaibin%3BLiao%2C+Francesca-Fang&rft.aulast=Kim&rft.aufirst=Eunhee&rft.date=2016-01-15&rft.volume=25&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=1460-2083&rft_id=info:doi/10.1093%2Fhmg%2Fddv445 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-10-17 N1 - Date created - 2016-01-09 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Curr Alzheimer Res. 2012 Jul;9(6):724-33 [22471862] Nat Rev Drug Discov. 2011 Dec;10(12):930-44 [22129991] Nat Commun. 2013;4:1405 [23360996] Int J Biochem Cell Biol. 2013 Mar;45(3):706-10 [23262292] Brain Res. 2013 Jun 26;1519:105-11 [23665061] Science. 2013 Nov 22;342(6161):983-7 [24158904] Science. 2013 Nov 22;342(6161):979-83 [24158909] J Neurosci. 2014 Jan 29;34(5):1599-612 [24478344] J Neurosci. 2014 Feb 12;34(7):2464-70 [24523537] Cell. 2014 Feb 27;156(5):975-85 [24581496] Nat Cell Biol. 2014 Dec;16(12):1227-37 [25344756] Biomolecules. 2015;5(2):735-57 [25946078] Mol Cell Biol. 2000 Apr;20(8):2670-5 [10733569] Annu Rev Biochem. 1986;55:1151-91 [2427013] EMBO J. 2001 Jul 16;20(14):3800-10 [11447121] J Neurosci. 2012 Jan 4;32(1):124-32 [22219275] J Cell Sci. 1997 Dec;110 ( Pt 23):2925-34 [9359875] Genes Dev. 1998 Mar 1;12(5):654-66 [9499401] Cell. 1998 Aug 21;94(4):471-80 [9727490] Genes Dev. 1998 Dec 15;12(24):3788-96 [9869631] J Biol Chem. 2004 Dec 17;279(51):53892-8 [15466864] Bioessays. 2005 Apr;27(4):408-15 [15770681] FEBS Lett. 2006 Jun 12;580(14):3433-8 [16713599] Genes Cells. 2008 Feb;13(2):105-16 [18233954] Genes Dev. 2008 Jun 1;22(11):1427-38 [18519635] Science. 2009 Feb 20;323(5917):1063-6 [19229036] Neurology. 2009 Oct 6;73(14):1127-33 [19805729] Cell Death Differ. 2010 Jan;17(1):68-77 [19557014] Neuron. 2009 Dec 24;64(6):807-27 [20064389] Neuron. 2010 Sep 23;67(6):953-66 [20869593] J Biol Chem. 2011 Jan 28;286(4):2785-94 [21098017] Annu Rev Biochem. 2011;80:1089-115 [21417720] Cold Spring Harb Perspect Biol. 2011 Aug;3(8):a004374 [21746797] Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17004-9 [21953697] J Neurosci. 2012 Aug 8;32(32):10971-81 [22875931] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1093/hmg/ddv445 ER - TY - JOUR T1 - Pulmonary instillation of MWCNT increases lung permeability, decreases gp130 expression in the lungs, and initiates cardiovascular IL-6 transsignaling. AN - 1760882556; 26589480 AB - Pulmonary instillation of multiwalled carbon nanotubes (MWCNT) has the potential to promote cardiovascular derangements, but the mechanisms responsible are currently unclear. We hypothesized that exposure to MWCNT would result in increased epithelial barrier permeability by 24 h postexposure and initiate a signaling process involving IL-6/gp130 transsignaling in peripheral vascular tissue. To test this hypothesis we assessed the impact of 1 and 10 μg/cm(2) MWCNT on transepithelial electrical resistance (TEER) and expression of barrier proteins and cell activation in vitro using normal human bronchial epithelial primary cells. Parallel studies using male Sprague-Dawley rats instilled with 100 μg MWCNT measured bronchoalveolar lavage (BAL) differential cell counts, BAL fluid total protein, and lung water-to-tissue weight ratios 24 h postexposure and quantified serum concentrations of IL-6, soluble IL-6r, and soluble gp130. Aortic sections were examined immunohistochemically for gp130 expression, and gp130 mRNA/protein expression was evaluated in rat lung, heart, and aortic tissue homogenates. Our in vitro findings indicate that 10 μg/cm(2) MWCNT decreased the development of TEER and zonula occludens-1 expression relative to the vehicle. In rats MWCNT instillation increased BAL protein, lung water, and induced pulmonary eosinophilia. Serum concentrations of soluble gp130 decreased, aortic endothelial expression of gp130 increased, and expression of gp130 in the lung was downregulated in the MWCNT-exposed group. We propose that pulmonary exposure to MWCNT can manifest as a reduced epithelial barrier and activator of vascular gp130-associated transsignaling that may promote susceptibility to cardiovascular derangements. Copyright © 2016 the American Physiological Society. JF - American journal of physiology. Lung cellular and molecular physiology AU - Thompson, Leslie C AU - Holland, Nathan A AU - Snyder, Ryan J AU - Luo, Bin AU - Becak, Daniel P AU - Odom, Jillian T AU - Harrison, Benjamin S AU - Brown, Jared M AU - Gowdy, Kymberly M AU - Wingard, Christopher J AD - Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina; ; NanoHealth Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina; and. ; Department of Pharmacology & Toxicology, Brody School of Medicine at East Carolina University, Greenville, North Carolina; ; Wake Forest University Institute of Regenerative Medicine, Winston-Salem, North Carolina. ; Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina; wingardc@ecu.edu. Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - L142 EP - L154 VL - 310 IS - 2 KW - Interleukin-6 KW - 0 KW - Nanotubes, Carbon KW - Cytokine Receptor gp130 KW - 133483-10-0 KW - Index Medicus KW - carbon nanotubes KW - blood vessels KW - endothelium KW - soluble IL-6 receptor KW - Permeability KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Pulmonary Artery -- metabolism KW - Humans KW - Bronchoalveolar Lavage Fluid -- cytology KW - Signal Transduction KW - Male KW - Coronary Vessels -- metabolism KW - Interleukin-6 -- metabolism KW - Cytokine Receptor gp130 -- metabolism KW - Lung -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760882556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Lung+cellular+and+molecular+physiology&rft.atitle=Pulmonary+instillation+of+MWCNT+increases+lung+permeability%2C+decreases+gp130+expression+in+the+lungs%2C+and+initiates+cardiovascular+IL-6+transsignaling.&rft.au=Thompson%2C+Leslie+C%3BHolland%2C+Nathan+A%3BSnyder%2C+Ryan+J%3BLuo%2C+Bin%3BBecak%2C+Daniel+P%3BOdom%2C+Jillian+T%3BHarrison%2C+Benjamin+S%3BBrown%2C+Jared+M%3BGowdy%2C+Kymberly+M%3BWingard%2C+Christopher+J&rft.aulast=Thompson&rft.aufirst=Leslie&rft.date=2016-01-15&rft.volume=310&rft.issue=2&rft.spage=L142&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Lung+cellular+and+molecular+physiology&rft.issn=1522-1504&rft_id=info:doi/10.1152%2Fajplung.00384.2014 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-06-03 N1 - Date created - 2016-01-16 N1 - Date revised - 2017-01-24 N1 - SuppNotes - Cited By: Part Fibre Toxicol. 2011;8(1):6 [21272353] Circ Res. 2011 Apr 29;108(9):1122-32 [21527742] Am J Physiol Lung Cell Mol Physiol. 2011 May;300(5):L667-78 [21335524] Am J Respir Cell Mol Biol. 2011 Sep;45(3):510-6 [21169556] Part Fibre Toxicol. 2011;8:27 [21896169] J Biol Chem. 1997 Jan 3;272(1):601-8 [8995303] Blood. 1998 Apr 1;91(7):2508-16 [9516152] J Exp Med. 1998 Jun 15;187(12):1927-40 [9625753] J Immunol. 1999 Oct 15;163(8):4583-9 [10510402] J Biol Chem. 1999 Oct 15;274(42):30041-51 [10514490] J Am Soc Nephrol. 2005 Apr;16(4):1099-107 [15716332] Circulation. 2005 May 10;111(18):2319-25 [15870116] J Cereb Blood Flow Metab. 2005 Aug;25(8):1047-59 [15758944] Environ Health Perspect. 2005 Aug;113(8):934-46 [16079061] Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3333-8 [16492782] Mol Biol Cell. 2006 Apr;17(4):1922-32 [16436508] Cell. 2006 Aug 25;126(4):741-54 [16923393] Toxicology. 2008 May 21;247(2-3):102-11 [18394769] FASEB J. 2009 Feb;23(2):473-82 [18838482] J Hypertens. 2009 Mar;27(3):527-34 [19330911] Toxicol Appl Pharmacol. 2009 Apr 15;236(2):183-93 [19371610] Toxicol Sci. 2009 May;109(1):113-23 [19293371] Biochem Pharmacol. 2009 Jun 15;77(12):1763-72 [19428331] Nat Nanotechnol. 2009 Nov;4(11):747-51 [19893520] J Biol Chem. 2010 Jan 15;285(3):1781-9 [19915009] Cardiovasc Toxicol. 2010 Mar;10(1):27-36 [20033351] Chem Res Toxicol. 2011 Dec 19;24(12):2237-48 [22081859] Am J Respir Crit Care Med. 2012 Jul 1;186(1):11-6 [22538803] J Intern Med. 2012 Sep;272(3):224-39 [22724512] Small. 2012 Sep 24;8(18):2904-12 [22777948] Nanotoxicology. 2012 Nov;6(7):724-35 [21830860] Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2012 Nov-Dec;4(6):691-702 [22915448] Part Fibre Toxicol. 2012;9:35 [22931549] Int J Biol Sci. 2012;8(9):1237-47 [23136552] Part Fibre Toxicol. 2012;9:17 [22624622] Int J Mol Sci. 2012;13(11):13781-803 [23203034] Part Fibre Toxicol. 2012;9:38 [23072542] Eur J Biochem. 2001 Jan;268(1):160-7 [11121117] J Biol Chem. 2001 Dec 14;276(50):47038-45 [11602599] Cell Commun Adhes. 2002 Jan-Feb;9(1):29-44 [12200963] Science. 1990 Jan 26;247(4941):456-9 [1967851] Am J Respir Cell Mol Biol. 1992 Aug;7(2):214-21 [1353976] J Toxicol Environ Health A. 2010;73(5):378-95 [20155580] Exp Toxicol Pathol. 2010 Mar;62(2):133-43 [19376691] Inhal Toxicol. 2010 Apr;22(5):355-68 [20121584] J Thromb Haemost. 2010 Mar;8(3):596-604 [20088942] Toxicol Lett. 2010 Sep 1;197(3):163-8 [20576493] Part Fibre Toxicol. 2013;10:35 [23903001] Am J Respir Cell Mol Biol. 2013 Oct;49(4):525-35 [23642096] Cardiovasc Toxicol. 2013 Dec;13(4):323-37 [23645470] Nanotoxicology. 2014 Feb;8(1):38-49 [23102262] Arch Toxicol. 2014 Feb;88(2):489-99 [23948970] Toxicol Sci. 2014 Mar;138(1):104-16 [24431218] Toxicol Sci. 2014 Apr;138(2):365-78 [24431213] Am J Respir Cell Mol Biol. 2014 Jun;50(6):1040-52 [24358952] Part Fibre Toxicol. 2014;11:28 [24915862] Int J Nanomedicine. 2014;9:4093-105 [25187712] Nat Rev Rheumatol. 2014 Dec;10(12):720-7 [25136784] Nanotoxicology. 2015 Mar;9(2):230-41 [24873759] Respir Res. 2015;16:30 [25851441] Microvasc Res. 2015 Jul;100:48-53 [25953589] PLoS One. 2015;10(6):e0128888 [26091108] Reprod Toxicol. 2014 Nov;49:86-100 [25088243] J Allergy Clin Immunol. 2015 Oct;136(4):1065-73 [25930193] Am J Respir Cell Mol Biol. 2015 Nov;53(5):625-36 [25807359] Toxicol Appl Pharmacol. 2010 Nov 15;249(1):8-15 [20800606] Environ Health Perspect. 2011 Jan;119(1):98-103 [20870565] Respirology. 2011 Feb;16(2):340-9 [21122029] Am J Respir Cell Mol Biol. 2011 Feb;44(2):185-96 [20378750] N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1152/ajplung.00384.2014 ER - TY - JOUR T1 - Small Molecule Microarrays Enable the Identification of a Selective, Quadruplex-Binding Inhibitor of MYC Expression. AN - 1760874777; 26462961 AB - The transcription factor MYC plays a pivotal role in cancer initiation, progression, and maintenance. However, it has proven difficult to develop small molecule inhibitors of MYC. One attractive route to pharmacological inhibition of MYC has been the prevention of its expression through small molecule-mediated stabilization of the G-quadruplex (G4) present in its promoter. Although molecules that bind globally to quadruplex DNA and influence gene expression are well-known, the identification of new chemical scaffolds that selectively modulate G4-driven genes remains a challenge. Here, we report an approach for the identification of G4-binding small molecules using small molecule microarrays (SMMs). We use the SMM screening platform to identify a novel G4-binding small molecule that inhibits MYC expression in cell models, with minimal impact on the expression of other G4-associated genes. Surface plasmon resonance (SPR) and thermal melt assays demonstrated that this molecule binds reversibly to the MYC G4 with single digit micromolar affinity, and with weaker or no measurable binding to other G4s. Biochemical and cell-based assays demonstrated that the compound effectively silenced MYC transcription and translation via a G4-dependent mechanism of action. The compound induced G1 arrest and was selectively toxic to MYC-driven cancer cell lines containing the G4 in the promoter but had minimal effects in peripheral blood mononucleocytes or a cell line lacking the G4 in its MYC promoter. As a measure of selectivity, gene expression analysis and qPCR experiments demonstrated that MYC and several MYC target genes were downregulated upon treatment with this compound, while the expression of several other G4-driven genes was not affected. In addition to providing a novel chemical scaffold that modulates MYC expression through G4 binding, this work suggests that the SMM screening approach may be broadly useful as an approach for the identification of new G4-binding small molecules. JF - ACS chemical biology AU - Felsenstein, Kenneth M AU - Saunders, Lindsey B AU - Simmons, John K AU - Leon, Elena AU - Calabrese, David R AU - Zhang, Shuling AU - Michalowski, Aleksandra AU - Gareiss, Peter AU - Mock, Beverly A AU - Schneekloth, John S AD - Laboratory of Cancer Biology and Genetics, National Cancer Institute , Building 37, Room 3146, Bethesda, Maryland 20892-4258, United States. ; Chemical Biology Laboratory, National Cancer Institute , Building 376, Room 225C, P.O. Box B, Frederick, Maryland 21702-1201, United States. ; Yale Center for Molecular Discovery , West Haven, Connecticut, United States. Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - 139 EP - 148 VL - 11 IS - 1 KW - Proto-Oncogene Proteins c-myc KW - 0 KW - Small Molecule Libraries KW - Index Medicus KW - Molecular Structure KW - Blotting, Western KW - Humans KW - Cell Line, Tumor KW - Inhibitory Concentration 50 KW - Proto-Oncogene Proteins c-myc -- antagonists & inhibitors KW - Oligonucleotide Array Sequence Analysis KW - G-Quadruplexes KW - Small Molecule Libraries -- pharmacology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Gene Expression Regulation -- drug effects KW - Small Molecule Libraries -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760874777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ACS+chemical+biology&rft.atitle=Small+Molecule+Microarrays+Enable+the+Identification+of+a+Selective%2C+Quadruplex-Binding+Inhibitor+of+MYC+Expression.&rft.au=Felsenstein%2C+Kenneth+M%3BSaunders%2C+Lindsey+B%3BSimmons%2C+John+K%3BLeon%2C+Elena%3BCalabrese%2C+David+R%3BZhang%2C+Shuling%3BMichalowski%2C+Aleksandra%3BGareiss%2C+Peter%3BMock%2C+Beverly+A%3BSchneekloth%2C+John+S&rft.aulast=Felsenstein&rft.aufirst=Kenneth&rft.date=2016-01-15&rft.volume=11&rft.issue=1&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=ACS+chemical+biology&rft.issn=1554-8937&rft_id=info:doi/10.1021%2Facschembio.5b00577 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-09-13 N1 - Date created - 2016-01-15 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Chem Commun (Camb). 2014 Feb 18;50(14):1704-7 [24394582] Nat Rev Drug Discov. 2011 Apr;10(4):261-75 [21455236] Nat Chem Biol. 2014 Apr;10(4):313-8 [24609361] Bioorg Med Chem Lett. 2014 Jun 15;24(12):2602-12 [24814531] J Am Chem Soc. 2014 Jun 11;136(23):8402-10 [24820959] J Mol Biol. 2014 Jul 15;426(14):2594-604 [24813121] Int J Biol Sci. 2014;10(10):1084-96 [25332683] Biochim Biophys Acta. 2015 May;1849(5):506-16 [24704206] J Org Chem. 2006 May 26;71(11):4130-40 [16709052] Adv Cancer Res. 2011;110:77-106 [21704229] Cell. 2011 Sep 16;146(6):904-17 [21889194] Nat Chem. 2011 Oct;3(10):782-7 [21941250] Chem Soc Rev. 2011 Nov;40(11):5293-307 [21720638] Nucleic Acids Res. 2011 Nov 1;39(20):9023-33 [21795379] J Am Chem Soc. 2011 Nov 9;133(44):17673-80 [21967482] J Biol Chem. 2011 Nov 25;286(47):41018-27 [21956115] Curr Pharm Des. 2012;18(14):1948-72 [22376113] J Med Chem. 2012 Jul 12;55(13):6076-86 [22691117] Org Biomol Chem. 2012 Aug 28;10(32):6537-46 [22790277] Blood. 2012 Sep 20;120(12):2351-2 [22996653] Curr Pharm Des. 2013;19(12):2164-73 [23016840] Int J Biol Macromol. 2013 Jun;57:1-8 [23434432] Anal Biochem. 2013 Nov 1;442(1):97-103 [23896461] Cancer Res. 2005 Feb 15;65(4):1489-96 [15735037] Nat Biotechnol. 2015 Aug;33(8):877-81 [26192317] J Am Chem Soc. 2006 Sep 13;128(36):11940-7 [16953635] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):228-33 [10618400] Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4844-9 [11309493] Expert Opin Pharmacother. 2001 Jun;2(6):917-27 [11585008] Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3830-5 [11891322] Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11593-8 [12195017] Mol Cancer Ther. 2002 Jun;1(8):565-73 [12479216] J Am Chem Soc. 2003 Jul 16;125(28):8420-1 [12848532] Oncogene. 2003 Sep 18;22(40):6151-9 [13679853] J Mol Biol. 2004 Jul 16;340(4):665-79 [15223312] Biochem Biophys Res Commun. 2004 Oct 22;323(3):802-8 [15381071] Proc Natl Acad Sci U S A. 1986 May;83(9):2984-8 [3458257] J Biol Chem. 1996 Aug 23;271(34):20958-64 [8702855] Semin Cancer Biol. 2006 Aug;16(4):253-64 [16904903] Exp Hematol. 2006 Nov;34(11):1480-9 [17046567] Nucleic Acids Res. 2007;35(2):406-13 [17169996] Curr Opin Chem Biol. 2007 Feb;11(1):74-82 [17169601] Curr Biol. 2007 Feb 20;17(4):R113-4 [17307039] Biophys J. 2007 Mar 15;92(6):2007-15 [17172304] J Comb Chem. 2007 Mar-Apr;9(2):245-53 [17348730] J Med Chem. 2007 Apr 5;50(7):1465-74 [17346034] Bioorg Med Chem Lett. 2007 Apr 15;17(8):2293-8 [17276687] Nat Protoc. 2006;1(5):2344-52 [17406478] Mol Cancer Ther. 2007 Sep;6(9):2399-408 [17876039] Angew Chem Int Ed Engl. 2007;46(42):7960-4 [17868168] Cancer Lett. 2008 Mar 18;261(2):226-34 [18096315] Nat Biotechnol. 2008 Mar;26(3):317-25 [18278033] Nat Chem Biol. 2009 Mar;5(3):154-6 [19151731] Cancer Res. 2009 Oct 1;69(19):7653-61 [19738048] Bioorg Med Chem Lett. 2009 Dec 1;19(23):6717-20 [19836948] Annu Rev Pharmacol Toxicol. 2010;50:111-29 [19922264] Nature. 2010 Feb 18;463(7283):899-905 [20164920] Chemistry. 2011 Apr 11;17(16):4571-81 [21387430] Mol Oncol. 2014 Mar;8(2):261-72 [24429254] N1 - Last updated - 2017-01-19 DO - http://dx.doi.org/10.1021/acschembio.5b00577 ER - TY - JOUR T1 - Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression. AN - 1760873490; 26706406 AB - Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4(+) naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. Published by Elsevier Inc. JF - Toxicology and applied pharmacology AU - Fang, Zhong-Ze AU - Zhang, Dunfang AU - Cao, Yun-Feng AU - Xie, Cen AU - Lu, Dan AU - Sun, Dong-Xue AU - Tanaka, Naoki AU - Jiang, Changtao AU - Chen, Qianming AU - Chen, Yu AU - Wang, Haina AU - Gonzalez, Frank J AD - Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, China; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, China. ; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, China. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China. ; School of Pharmaceutical Sciences, Shandong University, Jinan, China. ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: gonzalef@mail.nih.gov. Y1 - 2016/01/15/ PY - 2016 DA - 2016 Jan 15 SP - 21 EP - 27 VL - 291 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Bile Acids and Salts KW - IL10 protein, mouse KW - irinotecan KW - 0H43101T0J KW - Interleukin-10 KW - 130068-27-8 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Bile acids KW - Irinotecan (CPT-11) KW - Metabolomics KW - Animals KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Mice KW - Gene Expression Regulation KW - Male KW - Antineoplastic Agents, Phytogenic -- toxicity KW - Interleukin-10 -- antagonists & inhibitors KW - Camptothecin -- toxicity KW - Camptothecin -- analogs & derivatives KW - Interleukin-10 -- biosynthesis KW - Bile Acids and Salts -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1760873490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Irinotecan+%28CPT-11%29-induced+elevation+of+bile+acids+potentiates+suppression+of+IL-10+expression.&rft.au=Fang%2C+Zhong-Ze%3BZhang%2C+Dunfang%3BCao%2C+Yun-Feng%3BXie%2C+Cen%3BLu%2C+Dan%3BSun%2C+Dong-Xue%3BTanaka%2C+Naoki%3BJiang%2C+Changtao%3BChen%2C+Qianming%3BChen%2C+Yu%3BWang%2C+Haina%3BGonzalez%2C+Frank+J&rft.aulast=Fang&rft.aufirst=Zhong-Ze&rft.date=2016-01-15&rft.volume=291&rft.issue=&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=1096-0333&rft_id=info:doi/10.1016%2Fj.taap.2015.12.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2016-05-20 N1 - Date created - 2016-01-18 N1 - Date revised - 2017-01-24 N1 - SuppNotes - Cited By: Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 2):S174-8 [7554464] Clin Exp Immunol. 2003 Jul;133(1):38-43 [12823276] J Autoimmun. 2003 Jun;20(4):277-9 [12791312] J Exp Med. 2002 Jun 3;195(11):1491-7 [12045247] Mucosal Immunol. 2014 Jul;7(4):869-78 [24301657] Br J Pharmacol. 2014 May;171(9):2335-50 [24428790] Arch Toxicol. 2014 Apr;88(4):983-96 [24385052] J Lipid Res. 2014 Mar;55(3):455-65 [24343899] Scand J Gastroenterol. 2014 Jan;49(1):84-91 [24256029] Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19143-8 [24191041] Arch Toxicol. 2013 Nov;87(11):1975-87 [23575800] Nat Commun. 2013;4:2384 [24064762] Cold Spring Harb Perspect Biol. 2013 Jul;5(7). pii: a018341. doi: 10.1101/cshperspect.a018341 [23818502] Biochim Biophys Acta. 2013 Jan;1830(1):2118-28 [23041070] Anticancer Res. 2000 Nov-Dec;20(6B):4235-42 [11205253] PLoS One. 2012;7(4):e34522 [22496825] J Lipid Res. 2012 Dec;53(12):2698-707 [23034213] Mucosal Immunol. 2014 Sep;7(5):1079-93 [24424522] Trends Mol Med. 2011 Nov;17(11):668-76 [21890412] Gastroenterology. 2011 Jan;140(1):254-64 [20951137] Semin Immunol. 2009 Jun;21(3):130-8 [19386513] Immunity. 2008 Oct 17;29(4):637-49 [18835196] Clin Cancer Res. 2007 Dec 1;13(23):7146-54 [18056195] J Clin Invest. 1998 Feb 15;101(4):847-54 [9466980] N1 - Last updated - 2017-01-25 DO - http://dx.doi.org/10.1016/j.taap.2015.12.003 ER -