FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Maximova, OA Whitehead, SS Murphy, BR Pletnev, AG AF Maximova, Olga A. Whitehead, Stephen S. Murphy, Brian R. Pletnev, Alexander G. TI Neuropathogenesis and Neurovirulence of Live Flaviviral Vaccines in Monkeys Reply SO JOURNAL OF VIROLOGY LA English DT Letter ID TICK-BORNE ENCEPHALITIS; NONHUMAN-PRIMATES; VIRUS-VACCINE; SAFETY; RECOMBINANT; MICE C1 [Maximova, Olga A.; Whitehead, Stephen S.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,Room 3W10A, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov NR 19 TC 2 Z9 2 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 15 PY 2009 VL 83 IS 10 BP 5290 EP 5292 PG 3 WC Virology SC Virology GA 436IS UT WOS:000265407700055 ER PT J AU Xie, YL Hassan, SA Qazi, AM Tsai-Morris, CH Dufau, ML AF Xie, Y. -L. Hassan, S. A. Qazi, A. M. Tsai-Morris, C. H. Dufau, M. L. TI Intramolecular Disulfide Bonds of the Prolactin Receptor Short Form Are Required for Its Inhibitory Action on the Function of the Long Form of the Receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SCREENED COULOMB POTENTIALS; ERYTHROPOIETIN RECEPTOR; GROWTH-HORMONE; DYNAMICS SIMULATIONS; PROMOTER UTILIZATION; SIGNAL-TRANSDUCTION; KINASE-ACTIVITY; BINDING DOMAIN; PRL RECEPTOR; BETA-CHAIN AB The short form (S1b) of the prolactin receptor (PRLR) silences prolactin-induced activation of gene transcription by the PRLR long form (LF). The functional and structural contributions of two intramolecular disulfide (S-S) bonds within the extracellular subdomain 1 (D1) of S1b to its inhibitory function on the LF were investigated. Mutagenesis of the paired cysteines eliminated the inhibitory action of S1b. The expression of the mutated S1b (S1bx) on the cell surface was not affected, indicating native-like folding of the receptor. The constitutive JAK2 phosphorylation observed in S1b was not present in cells expressing S1bx, and JAK2 association was disrupted. BRET(50) (BRET(50) represents the relative affinity as acceptor/donor ratio required to reach half-maximal BRET [bioluminescence resonance energy transfer] values) showed decreased LF/S1bx heterodimeric-association and increased affinity in S1bx homodimerization, thus favoring LF homodimerization and prolactin-induced signaling. Computer modeling based on the PRLR crystal structure showed that minor changes in the tertiary structure of D1 upon S-S bond disruption propagated to the quaternary structure of the homodimer, affecting the dimerization interface. These changes explain the higher homodimerization affinity of S1bx and provide a structural basis for its lack of inhibitory function. The PRLR conformation as stabilized by S-S bonds is required for the inhibitory action of S1b on prolactin-induced LF-mediated function and JAK2 association. C1 [Hassan, S. A.] NIH, Ctr Mol Modeling, DCB CIT, Bethesda, MD 20892 USA. [Xie, Y. -L.; Qazi, A. M.; Tsai-Morris, C. H.; Dufau, M. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bldg 49,Rm 6A-36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov FU NIH Intramural Research Program; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Center for Information Technology FX The study utilized the high-performance computer capabilities of the Biowulf PC/Linux cluster at the NIH. NR 36 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2009 VL 29 IS 10 BP 2546 EP 2555 DI 10.1128/MCB.01716-08 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439ZD UT WOS:000265665900006 PM 19273600 ER PT J AU Kang, HS Beak, JY Kim, YS Herbert, R Jetten, AM AF Kang, Hong Soon Beak, Ju Youn Kim, Yong-Sik Herbert, Ronald Jetten, Anton M. TI Glis3 Is Associated with Primary Cilia and Wwtr1/TAZ and Implicated in Polycystic Kidney Disease SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; NEONATAL DIABETES-MELLITUS; STEM-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR; REPRESSOR FUNCTIONS; CONGENITAL HYPOTHYROIDISM; GENE-EXPRESSION; HIPPO PATHWAY; RENAL CYSTS; TAZ AB In this study, we describe the generation and partial characterization of Kruppel-like zinc finger protein Glis3 mutant (Glis3(zf/zf)) mice. These mice display abnormalities very similar to those of patients with neonatal diabetes and hypothyroidism syndrome, including the development of diabetes and polycystic kidney disease. We demonstrate that Glis3 localizes to the primary cilium, suggesting that Glis3 is part of a cilium-associated signaling pathway. Although Glis3(zf/zf) mice form normal primary cilia, renal cysts contain relatively fewer cells with a primary cilium. We further show that Glis3 interacts with the transcriptional modulator Wwtr1/TAZ, which itself has been implicated in glomerulocystic kidney disease. Wwtr1 recognizes a P/LPXY motif in the C terminus of Glis3 and enhances Glis3-mediated transcriptional activation, indicating that Wwtr1 functions as a coactivator of Glis3. Mutations in the P/LPXY motif abrogate the interaction with Wwtr1 and the transcriptional activity of Glis3, indicating that this motif is part of the transcription activation domain of Glis3. Our study demonstrates that dysfunction of Glis3 leads to the development of cystic renal disease, suggesting that Glis3 plays a critical role in maintaining normal renal functions. We propose that localization to the primary cilium and interaction with Wwtr1 are key elements of the Glis3 signaling pathway. C1 [Kang, Hong Soon; Beak, Ju Youn; Kim, Yong-Sik; Jetten, Anton M.] NIH, LRB, Cell Biol Sect, Div Intramural Res, Res Triangle Pk, NC 27709 USA. [Herbert, Ronald] NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIH, LRB, Cell Biol Sect, Div Intramural Res, Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Intramural Research Program of the NIEHS [Z01-ES-101485] FX This research was supported by the Intramural Research Program of the NIEHS (Z01-ES-101485). NR 57 TC 46 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2009 VL 29 IS 10 BP 2556 EP 2569 DI 10.1128/MCB.01620-08 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439ZD UT WOS:000265665900007 PM 19273592 ER PT J AU Padmakumar, VC Aleem, E Berthet, C Hilton, MB Kaldis, P AF Padmakumar, V. C. Aleem, Eiman Berthet, Cyril Hilton, Mary Beth Kaldis, Philipp TI Cdk2 and Cdk4 Activities Are Dispensable for Tumorigenesis Caused by the Loss of p53 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE CONTROL; GENE AMPLIFICATION; TUMOR-SUPPRESSOR; PROTEIN-KINASE; IN-VIVO; C-MYC; CANCER; OVEREXPRESSION; MICE; P21 AB The loss of p53 induces spontaneous tumors in mice, and p53 mutations are found in approximately 50% of human tumors. These tumors are generally caused by a number of events, including genomic instability, checkpoint defects, mitotic defects, deregulation of transcriptional targets, impaired apoptosis, and G(1) deregulation or a combination of these effects. In order to determine the role of proteins involved in G(1) control in tumorigenesis, we focused on Cdk2 and Cdk4, two cyclin-dependent kinases that in association with cyclin E and cyclin D promote the G(1)/S phase transition. We analyzed the consequence of loss of Cdk2 in p53-null animals by generating Cdk2(-/-) p53(-/-) mice. These mice are viable and developed spontaneous tumors, predominantly lymphoblastic lymphomas, similar to p53(-/-) mice. In contrast, the genotypes Cdk4(-/-) p53(-/-) were mostly lethal, with few exceptions, and Cdk2(-/-) Cdk4(-/-) p53(-/-) mice die during embryogenesis at embryonic day 13.5. To study the oncogenic potential, we generated mouse embryonic fibroblasts (MEFs) and found that p53(-/-), Cdk2(-/-) p53(-/-), Cdk4(-/-) p53(-/-), and Cdk2(-/-) Cdk4(-/-) p53(-/-) MEFs grew at similar rates without entering senescence. Ras-transformed MEFs of these genotypes were able to form colonies in vitro and induce tumors in nude mice. Our results suggest that tumorigenicity mediated by p53 loss does not require either Cdk2 or Cdk4, which necessitates considering the use of broad-spectrum cell cycle inhibitors as a means of effective anti-Cdk cancer therapy. C1 [Kaldis, Philipp] Natl Univ Singapore, Inst Mol & Cell Biol, Canc Lab PRK, Singapore 138673, Singapore. [Kaldis, Philipp] Natl Univ Singapore, Inst Mol & Cell Biol, Cell Div, Singapore 138673, Singapore. [Padmakumar, V. C.; Aleem, Eiman; Berthet, Cyril; Hilton, Mary Beth; Kaldis, Philipp] Natl Canc Inst Frederick, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), Natl Univ Singapore, Inst Mol & Cell Biol, Cell Div, 61 Biopolis Dr, Singapore 138673, Singapore. EM kaldis@imcb.a-star.edu.sg RI Kaldis, Philipp/G-2714-2010; ASTAR, IMCB/E-2320-2012; Aleem, Eiman/I-3777-2012; OI Kaldis, Philipp/0000-0002-7247-7591; Aleem, Eiman/0000-0002-9215-8213 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 19 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2009 VL 29 IS 10 BP 2582 EP 2593 DI 10.1128/MCB.00952-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439ZD UT WOS:000265665900009 PM 19307310 ER PT J AU Kuwano, Y Rabinovic, A Srikantan, S Gorospe, M Demple, B AF Kuwano, Yuki Rabinovic, Ariel Srikantan, Subramanya Gorospe, Myriam Demple, Bruce TI Analysis of Nitric Oxide-Stabilized mRNAs in Human Fibroblasts Reveals HuR-Dependent Heme Oxygenase 1 Upregulation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING PROTEIN HUR; MAMMALIAN-CELLS; GENOTOXIC STRESS; RESPONSE ELEMENT; RICH ELEMENTS; TRANSLATION; DEGRADATION; EXPRESSION; ALPHA; CYCLOOXYGENASE-2 AB We previously observed that nitric oxide (NO) exposure increases the stability of mRNAs encoding heme oxygenase 1 (HO-1) and TIEG-1 in human and mouse fibroblasts. Here, we have used microarrays to look broadly for changes in mRNA stability in response to NO treatment. Using human IMR-90 and mouse NIH 3T3 fibroblasts treated with actinomycin D to block de novo transcription, microarray analysis suggested that the stability of the majority of mRNAs was unaffected. Among the mRNAs that were stabilized by NO treatment, seven transcripts were found in both IMR-90 and NIH 3T3 cells (CHIC2, GADD45B, HO-1, PTGS2, RGS2, TIEG, and ID3) and were chosen for further analysis. All seven mRNAs showed at least one hit of a signature motif for the stabilizing RNA-binding protein (RBP) HuR; accordingly, ribonucleoprotein immunoprecipitation analysis revealed that all seven mRNAs associated with HuR. In keeping with a functional role of HuR in the response to NO, a measurable fraction of HuR increased in the cytoplasm following NO treatment. However, among the seven transcripts, only HO-1 mRNA showed a robust increase in the level of its association with HuR following NO treatment. In turn, HO-1 mRNA and protein levels were significantly reduced when HuR levels were silenced in IMR-90 cells, and they were elevated when HuR was overexpressed. In sum, our results indicate that NO stabilizes mRNA subsets in fibroblasts, identify HuR as an RBP implicated in the NO response, reveal that HuR alone is insufficient for stabilizing several mRNAs by NO, and show that HO-1 induction by NO is regulated by HuR. C1 [Rabinovic, Ariel; Demple, Bruce] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02130 USA. [Kuwano, Yuki; Srikantan, Subramanya; Gorospe, Myriam] NIA, RNA Regulat Sect, Lab Cellular & Mol Biol, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Demple, B (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Room 509,Bldg 1,665 Huntington Ave, Boston, MA 02130 USA. EM bdemple@hsph.harvard.edu OI srikantan, subramanya/0000-0003-1810-6519 FU NCI [R01CA082737, T32-CA009078]; National Institute on Aging-Intramural Research Program, National Institutes of Health FX Experimental work at Harvard was supported by NCI grant R01CA082737 ( to B. D.). A. R. was supported by radiation biology training grant NCI T32-CA009078. M. G., S. S., and Y. K. were supported by the National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 60 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2009 VL 29 IS 10 BP 2622 EP 2635 DI 10.1128/MCB.01495-08 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 439ZD UT WOS:000265665900012 PM 19289500 ER PT J AU Callen, E Jankovic, M Wong, N Zha, S Chen, HT Difilippantonio, S Di Virgilio, M Heidkamp, G Alt, FW Nussenzweig, A Nussenzweig, M AF Callen, Elsa Jankovic, Mila Wong, Nancy Zha, Shan Chen, Hua-Tang Difilippantonio, Simone Di Virgilio, Michela Heidkamp, Gordon Alt, Frederick W. Nussenzweig, Andre Nussenzweig, Michel TI Essential Role for DNA-PKcs in DNA Double-Strand Break Repair and Apoptosis in ATM-Deficient Lymphocytes SO MOLECULAR CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; CLASS-SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID; CELL-CYCLE ARREST; ATAXIA-TELANGIECTASIA; B-CELLS; GENOMIC INSTABILITY; IONIZING-RADIATION; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION AB The DNA double-strand break (DSB) repair protein DNA-PKcs and the signal transducer ATM are both activated by DNA breaks and phosphorylate similar substrates in vitro, yet appear to have distinct functions in vivo. Here, we show that ATM and DNA-PKcs have overlapping functions in lymphocytes. Ablation of both kinase activities in cells undergoing immunoglobulin class switch recombination leads to a compound defect in switching and a synergistic increase in chromosomal fragmentation, DNA insertions, and translocations due to aberrant processing of DSBs. These abnormalities are attributed to a compound deficiency in phosphorylation of key proteins required for DNA repair, class switching, and cell death. Notably, both kinases are required for normal levels of p53 phosphorylation in B and T cells and p53-dependent apoptosis. Our experiments reveal a DNA-PKcs-dependent pathway that regulates DNA repair and activation of p53 in the absence of ATM. C1 [Callen, Elsa; Wong, Nancy; Chen, Hua-Tang; Difilippantonio, Simone; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Zha, Shan; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zha, Shan; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Jankovic, Mila; Di Virgilio, Michela; Heidkamp, Gordon; Nussenzweig, Michel] Howard Hughes Med Inst, New York, NY 10065 USA. [Jankovic, Mila; Di Virgilio, Michela; Heidkamp, Gordon; Nussenzweig, Michel] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov; nussen@mall.rockefeller.edu FU NIH; National Cancer Institute; Center for Cancer Research FX We thank Junjie Chen and Anthony Wynshaw-Boris for mice; L. Stapelton for chromosome painting probes; G. Smith for small molecule inhibitors; Jeremy Daniel, Davide Robbiani, Oscar Femandez-Capetillo, and Yair Dorsett for comments on the manuscript; and Rafael Casellas for advice on ShRNA. A.N. is supported by the Intramural Research program of the NIH, National Cancer Institute, Center for Cancer Research. F.W.A. is supported by grants from the NIH. F.W.A. is a Howard Hughes Institute Investigator. M.C.N. is supported by grants from the NIH. M.C.N. is a Howard Hughes Institute Investigator. NR 87 TC 85 Z9 87 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 15 PY 2009 VL 34 IS 3 BP 285 EP 297 DI 10.1016/j.molcel.2009.04.025 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 446TP UT WOS:000266144400004 PM 19450527 ER PT J AU Chang, SE Kenney, MK Loucks, TMJ Ludlow, CL AF Chang, Soo-Eun Kenney, Mary Kay Loucks, Torrey M. J. Ludlow, Christy L. TI Brain activation abnormalities during speech and non-speech in stuttering speakers SO NEUROIMAGE LA English DT Article DE Stuttering; Speech perception; Planning; Production; Non-speech; Functional magnetic resonance imaging (fMRI); Auditory-motor interaction; Forward model ID POSITRON-EMISSION-TOMOGRAPHY; POSTERIOR PARIETAL CORTEX; AUDITORY-CORTEX; MOTOR CONTROL; SYLLABLE PRODUCTION; SENSORIMOTOR INTEGRATION; NEURAL MECHANISMS; FLUENT SPEAKERS; ADULTS; AREAS AB Although stuttering is regarded as a speech-specific disorder, there is a growing body of evidence suggesting that subtle abnormalities in the motor planning and execution of non-speech gestures exist in stuttering individuals. We hypothesized that people who stutter (PWS) would differ from fluent controls in their neural responses during motor planning and execution of both speech and non-speech gestures that had auditory targets. Using fMRI with sparse sampling, separate BOLD responses were measured for perception, planning, and fluent production of speech and non-speech vocal tract gestures. During both speech and non-speech perception and planning, PWS had less activation in the frontal and temporoparietal regions relative to controls. During speech and non-speech production, PWS had less activation than the controls in the left superior temporal gyrus (STG) and the left pre-motor areas (BA 6) but greater activation in the right STG, bilateral Heschl's gyrus (HG), insula, putamen, and precentral motor regions (BA 4). Differences in brain activation patterns between PWS and controls were greatest in females and less apparent in males. In conclusion, similar differences in PWS from the controls were found during speech and non-speech; during perception and planning they had reduced activation while during production they had increased activity in the auditory area on the right and decreased activation in the left sensorimotor regions. These results demonstrated that neural activation differences in PWS are not speech-specific. Published by Elsevier Inc. C1 [Chang, Soo-Eun; Kenney, Mary Kay; Loucks, Torrey M. J.; Ludlow, Christy L.] NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, 10 Ctr Dr MSC 1416 Bldg 10,Room 5D38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-09] NR 75 TC 64 Z9 66 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2009 VL 46 IS 1 BP 201 EP 212 DI 10.1016/j.neuroimage.2009.01.066 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 440TY UT WOS:000265723800022 PM 19401143 ER PT J AU Sayer, JM Louis, JM AF Sayer, Jane M. Louis, John M. TI Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE retroviral protease; aspartic protease; protein structure; calorimetry; kinetics ID VIRUS TYPE-1 PROTEASE; HUMAN-IMMUNODEFICIENCY; CANDIDA-ALBICANS; IN-VITRO; CRYSTAL-STRUCTURE; PLASMODIUM-FALCIPARUM; PROTEINASE-INHIBITORS; THERMODYNAMIC BASIS; DRUG-RESISTANCE; MOLECULAR-BASIS AB The importance of the active site region aspartyl residues 25 and 29 of the mature HIV-1 protease (PR) for the binding of five clinical and three experimental protease inhibitors [symmetric cyclic urea inhibitor DMP323, nonhydrolyzable substrate analog (RPB) and the generic aspartic protease inhibitor acetyl-pepstatin (Ac-PEP)] was assessed by differential scanning calorimetry. Delta T-m values, defined as the difference in T., for a given protein in the presence and absence of inhibitor, for PR with DRV, ATV, SQV, RTV, APV, DMP323, RPB, and Ac-PEP are 22.4, 20.8, 19.3, 15.6, 14.3, 14.7, 8.7, and 6.5 degrees C, respectively. Binding of APV and Ac-PEP is most sensitive to the D25N mutation, as shown by Delta T-m ratios [Delta T-m(PR)/ Delta T-m(PRD25N)] of 35.8 and 16.3, respectively, whereas binding of DMP323 and RPB (Delta T-m ratios of 1-2) is least affected. Binding of the substrate-like inhibitors RPB and Ac-PEP is nearly abolished (Delta T-m(PR)/Delta T-m(PRD29N) >= 44) by the D29N mutation, whereas this mutation only moderately affects binding of the smaller inhibitors (AT. ratios of 1.4-2.2). Of the nine FDA-approved clinical HIV-1 protease inhibitors screened, APV, RTV, and DRV competitively inhibit porcine pepsin with K-i values of 0.3. 0.6, and 2.14 mu M, respectively. DSC results were consistent with this relatively weak binding of APV (Delta T-m 2.7 degrees C) compared with the tight binding of Ac-PEP (Delta T-m >= 17 degrees C). Comparison of superimposed structures of the PR/APV complex with those of PR/Ac-PEP and pepsin/pepstatin A complexes suggests a role for Asp215, Asp32, and Ser219 in pepsin, equivalent to Asp25, Asp25', and Asp29 in PR in the binding and stabilization of the pepsin/APV complex. C1 [Sayer, Jane M.; Louis, John M.] NIDDK, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Louis, JM (reprint author), NIDDK, Chem Phys Lab, NIH, DHHS, Bldg 5,Room B2-29, Bethesda, MD 20892 USA. EM johnl@intra.niddk.nih.gov FU NIDDK; NIH (Intramural Research Program) FX Grant sponsor: NIDDK, NIH (Intramural Research Program). NR 53 TC 11 Z9 11 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD MAY 15 PY 2009 VL 75 IS 3 BP 556 EP 568 DI 10.1002/prot.22271 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 433CJ UT WOS:000265181000004 PM 18951411 ER PT J AU Bhattacharya, S Black, R Bourgeois, L Clemens, J Cravioto, A Deen, JL Dougan, G Glass, R Grais, RF Greco, M Gust, I Holmgren, J Kariuki, S Lambert, PH Liu, MA Longini, I Nair, GB Norrby, R Nossal, GJV Ogra, P Sansonetti, P von Seidlein, L Songane, F Svennerholm, AM Steele, D Walker, R AF Bhattacharya, S. Black, R. Bourgeois, L. Clemens, J. Cravioto, A. Deen, J. L. Dougan, Gordon Glass, R. Grais, R. F. Greco, M. Gust, I. Holmgren, J. Kariuki, S. Lambert, P. -H. Liu, M. A. Longini, I. Nair, G. B. Norrby, R. Nossal, G. J. V. Ogra, P. Sansonetti, P. von Seidlein, L. Songane, F. Svennerholm, A. -M. Steele, D. Walker, R. TI The Cholera Crisis in Africa SO SCIENCE LA English DT Editorial Material ID VACCINATION; VACCINES; ZIMBABWE C1 [Cravioto, A.; Deen, J. L.; von Seidlein, L.] Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Bhattacharya, S.] Indian Council Med Res, New Delhi, India. [Black, R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. [Bourgeois, L.; Steele, D.; Walker, R.] PATH, Enter Vaccine Initiat, Seattle, WA 98107 USA. [Clemens, J.] Int Vaccine Inst, Seoul 151600, South Korea. [Dougan, Gordon] Wellcome Trust Sanger Inst, Cambridge CB10 1RQ, England. [Glass, R.] NIH, Fogarty Inst, Bethesda, MD 20892 USA. [Grais, R. F.] Epictr, FR-75011 Paris, France. [Gust, I.; Nossal, G. J. V.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia. [Gust, I.; Nossal, G. J. V.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Holmgren, J.; Svennerholm, A. -M.] Univ Gothenburg, SE-40530 Gothenburg, Sweden. [Kariuki, S.] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya. [Lambert, P. -H.] Univ Geneva, CH-1211 Geneva 4, Switzerland. [Liu, M. A.] Karolinska Inst, SE-17177 Stockholm, Sweden. [Longini, I.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Longini, I.] Univ Washington, Seattle, WA 98109 USA. [Nair, G. B.] Natl Inst Cholera & Infect Dis, Kolkata 700010, India. [Norrby, R.] Swedish Inst Infect Dis Control, SE-17182 Solna, Sweden. [Ogra, P.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. [Sansonetti, P.] Inst Pasteur, INSERM, U786, Unite Pathogenie Microbienne Mol, FR-75724 Paris 15, France. [Songane, F.] Partnership Maternal Newborn & Child Hlth, CH-1211 Geneva, Switzerland. RP Deen, JL (reprint author), Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. EM jdeen@ivi.int OI Black, Robert/0000-0001-9926-7984 NR 16 TC 23 Z9 24 U1 1 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 15 PY 2009 VL 324 IS 5929 BP 885 EP 885 DI 10.1126/science.1173890 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KD UT WOS:000266048800018 PM 19443768 ER PT J AU Tahiliani, M Koh, KP Shen, YH Pastor, WA Bandukwala, H Brudno, Y Agarwal, S Iyer, LM Liu, DR Aravind, L Rao, A AF Tahiliani, Mamta Koh, Kian Peng Shen, Yinghua Pastor, William A. Bandukwala, Hozefa Brudno, Yevgeny Agarwal, Suneet Iyer, Lakshminarayan M. Liu, David R. Aravind, L. Rao, Anjana TI Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1 SO SCIENCE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GLYCOSYLASE ACTIVITY; CXXC DOMAIN; BASE-J; DEMETHYLATION; CYTOSINE; METHYLATION; PROTEIN; METHYLTRANSFERASE; T(10/11)(Q22,Q23) AB DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC. C1 [Shen, Yinghua; Brudno, Yevgeny; Liu, David R.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Shen, Yinghua; Brudno, Yevgeny; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Tahiliani, Mamta; Koh, Kian Peng; Pastor, William A.; Bandukwala, Hozefa; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tahiliani, Mamta; Koh, Kian Peng; Pastor, William A.; Bandukwala, Hozefa; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. [Agarwal, Suneet] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Agarwal, Suneet] Dana Farber Canc Inst, Boston, MA 02115 USA. [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu; aravind@ncbi.nlm.nih.gov; arao@idi.harvard.edu RI Waha, Andreas/J-2950-2014 FU NIH [AI44432, K08 HL089150]; a Scholar Award from the Juvenile Diabetes Research Foundation; Harvard Stem Cell Institute [Seed]; Howard Hughes Medical Institute; NIH/NIGMS [R01GM065865]; American Heart Association postdoctoral fellowship; National Library of Medicine, NIH; Lady Tata Memorial postdoctoral fellowship; NSF Graduate Fellowships; Department of Defense graduate fellowship FX We thank K. Kreuzer for the gift of the T4 phage and E. coli ER1656 and CR63; Charles Richardson, Udi Qimron, and Ben Beauchamp for advice and assistance in culturing T4 phage; Melissa Call for advice on production of recombinant proteins in insect cells; and Patrick Hogan for many helpful discussions. This work was supported by NIH grant AI44432, a Scholar Award from the Juvenile Diabetes Research Foundation, and a Seed grant from the Harvard Stem Cell Institute (to A.R.); Howard Hughes Medical Institute and NIH/NIGMS (R01GM065865) funding (to D.R.L.); an American Heart Association postdoctoral fellowship (to K.P.K.); intramural funds of the National Library of Medicine, NIH (to L.A. and L.M.I.); a Lady Tata Memorial postdoctoral fellowship (to H.B.); NIH award K08 HL089150 (to S.A.); NSF Graduate Fellowships (to W.A.P. and Y.B.); and a Department of Defense graduate fellowship (to W.A.P.). NR 33 TC 2102 Z9 2172 U1 36 U2 318 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 15 PY 2009 VL 324 IS 5929 BP 930 EP 935 DI 10.1126/science.1170116 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KD UT WOS:000266048800037 PM 19372391 ER PT J AU Fan, HY Liu, ZL Shimada, M Sterneck, E Johnson, PF Hedrick, SM Richards, JS AF Fan, Heng-Yu Liu, Zhilin Shimada, Masayuki Sterneck, Esta Johnson, Peter F. Hedrick, Stephen M. Richards, JoAnne S. TI MAPK3/1 (ERK1/2) in Ovarian Granulosa Cells Are Essential for Female Fertility SO SCIENCE LA English DT Article ID C/EBP-BETA; CUMULUS EXPANSION; KNOCKOUT MICE; MOUSE; EXPRESSION; OVULATION; FOLLICLE; PHOSPHORYLATION; COMMUNICATION; ACTIVATION AB A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Because the signaling molecules RAS and ERK1/2 ( extracellular signal-regulated kinases 1 and 2) are activated by an LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBPb (CCAAT/Enhancer-binding protein-beta) is a critical downstream mediator of ERK1/2 activation. Thus, ERK1/2 and C/EBPb constitute an in vivo LH-regulated signaling pathway that controls ovulation- and luteinization-related events. C1 [Fan, Heng-Yu; Liu, Zhilin; Richards, JoAnne S.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Shimada, Masayuki] Hiroshima Univ, Grad Sch Biosphere Sci, Dept Appl Anim Sci, Higashihiroshima 7398528, Japan. [Sterneck, Esta] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21702 USA. [Johnson, Peter F.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Hedrick, Stephen M.] Univ Calif San Diego, Dept Cell & Mol Biol, La Jolla, CA 92093 USA. [Hedrick, Stephen M.] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA. RP Richards, JS (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM joanner@bcm.edu RI Johnson, Peter/A-1940-2012; Shimada, Masayuki/Q-3673-2016 OI Johnson, Peter/0000-0002-4145-4725; Shimada, Masayuki/0000-0002-6500-2088 FU NIH [NIH-HD16229, NIH-HD07495, NIH-HD07165]; Project II; Japan Society for the Promotion of Science [18688016]; Intramural Research Program of NIH; National Cancer Institute, Center for Cancer Research FX We thank J. Pouyssegur and J. Shao for providing Erk1 mice and adenoviral vector of C/EBPSS, respectively. This work was supported by NIH grants NIH HD16229, NIH HD07495, Project II J.S.R., Grant in Aid for Scientific Research No. 18688016 from the Japan Society for the Promotion of Science M.S., Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research P.F.J. and E.S., and NIH Postdoctoral Training Grant NIH HD07165 H.Y.F. The Gene Expression Omnibus accession number for microarray data is GSE15135. NR 18 TC 227 Z9 234 U1 2 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 15 PY 2009 VL 324 IS 5929 BP 938 EP 941 DI 10.1126/science.1171396 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 445KD UT WOS:000266048800039 PM 19443782 ER PT J AU Carson, KR Evens, AM Richey, EA Habermann, TM Focosi, D Seymour, JF Laubach, J Bawn, SD Gordon, LI Winter, JN Furman, RR Vose, JM Zelenetz, AD Mamtani, R Raisch, DW Dorshimer, GW Rosen, ST Muro, K Gottardi-Littell, NR Talley, RL Sartor, O Green, D Major, EO Bennett, CL AF Carson, Kenneth R. Evens, Andrew M. Richey, Elizabeth A. Habermann, Thomas M. Focosi, Daniele Seymour, John F. Laubach, Jacob Bawn, Susie D. Gordon, Leo I. Winter, Jane N. Furman, Richard R. Vose, Julie M. Zelenetz, Andrew D. Mamtani, Ronac Raisch, Dennis W. Dorshimer, Gary W. Rosen, Steven T. Muro, Kenji Gottardi-Littell, Numa R. Talley, Robert L. Sartor, Oliver Green, David Major, Eugene O. Bennett, Charles L. TI Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project SO BLOOD LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol ID B-CELL LYMPHOMA; IDIOPATHIC THROMBOCYTOPENIC PURPURA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHEMOTHERAPY PLUS RITUXIMAB; MULTIPLE-SCLEROSIS PATIENTS; OF-THE-LITERATURE; JC VIRUS VIREMIA; ANTIBODY NATALIZUMAB; FOLLICULAR LYMPHOMA; INFECTED PATIENTS AB Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons. (Blood. 2009;113:4834-4840) C1 [Evens, Andrew M.; Richey, Elizabeth A.; Gordon, Leo I.; Winter, Jane N.; Rosen, Steven T.; Green, David; Bennett, Charles L.] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. [Carson, Kenneth R.] Washington Univ, Sch Med, Siteman Comprehens Canc Ctr, St Louis, MO USA. [Evens, Andrew M.; Gordon, Leo I.; Winter, Jane N.; Rosen, Steven T.; Green, David; Bennett, Charles L.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Habermann, Thomas M.] Mayo Clin, Coll Med, Dept Hematol, Rochester, MN USA. [Focosi, Daniele] Univ Pisa, Div Hematol, Pisa, Italy. [Seymour, John F.] Peter MacCallum Canc Ctr, Div Haematol & Med Oncol, Melbourne, Australia. [Laubach, Jacob] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bawn, Susie D.] Stanford Univ, Sch Med, Div Hematol Oncol, Stanford, CA 94305 USA. [Furman, Richard R.; Zelenetz, Andrew D.; Mamtani, Ronac] New York Presbyterian Hosp, Cornell Med Ctr, Div Hematol Oncol, New York, NY USA. [Vose, Julie M.] Univ Nebraska, Med Ctr, Hematol Oncol Sect, Omaha, NE USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, New York, NY 10021 USA. [Raisch, Dennis W.] Univ New Mexico, Vet Adm Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM 87131 USA. [Dorshimer, Gary W.] Univ Penn Hlth Syst, Penn Hosp, Philadelphia, PA USA. [Muro, Kenji] Northwestern Univ, Dept Neurol Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Gottardi-Littell, Numa R.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Talley, Robert L.] Kansas City Canc Ctr, Kansas City, MO USA. [Sartor, Oliver] Tulane Med Sch, New Orleans, LA USA. [Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. [Bennett, Charles L.] Jesse Brown VAMC, Vet Adm Ctr Management Complex Chron Condit, Chicago, IL USA. RP Bennett, CL (reprint author), Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, 710 N Fairbanks Ct,Olson Pavil,Suite 8-250, Chicago, IL 60611 USA. EM cbenne@northwestern.edu OI Zelenetz, Andrew/0000-0003-1403-6883; Focosi, Daniele/0000-0001-8811-195X; Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [1R01 CA125077-01A1, R01 CA125077] NR 68 TC 465 Z9 475 U1 9 U2 21 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 14 PY 2009 VL 113 IS 20 BP 4834 EP 4840 DI 10.1182/blood-2008-10-186999 PG 7 WC Hematology SC Hematology GA 445ZT UT WOS:000266090700007 PM 19264918 ER PT J AU Karp, JE Flatten, K Feldman, EJ Greer, JM Loegering, DA Ricklis, RM Morris, LE Ritchie, E Smith, BD Ironside, V Talbott, T Roboz, G Le, SB Meng, XW Schneider, PA Dai, NT Adjei, AA Gore, SD Levis, MJ Wright, JJ Garrett-Mayer, E Kaufmann, SH AF Karp, Judith E. Flatten, Karen Feldman, Eric J. Greer, Jacqueline M. Loegering, David A. Ricklis, Rebecca M. Morris, Lawrence E. Ritchie, Ellen Smith, B. Douglas Ironside, Valerie Talbott, Timothy Roboz, Gail Le, Son B. Meng, Xue Wei Schneider, Paula A. Dai, Nga T. Adjei, Alex A. Gore, Steven D. Levis, Mark J. Wright, John J. Garrett-Mayer, Elizabeth Kaufmann, Scott H. TI Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; FARNESYL TRANSFERASE INHIBITOR; RISK MYELODYSPLASTIC SYNDROME; COUNCIL AML11 TRIAL; INDUCED APOPTOSIS; HEMATOLOGIC MALIGNANCIES; IN-VITRO; INTENSIVE CHEMOTHERAPY; TREATMENT OUTCOMES; CRITICAL TARGET AB The farnesyltransferase inhibitor tipifarnib exhibits modest activity against acute myelogenous leukemia. To build on these results, we examined the effect of combining tipifarnib with other agents. Tipifarnib inhibited signaling downstream of the farnesylated small G protein Rheb and synergistically enhanced etoposide-induced antiproliferative effects in lymphohematopoietic cell lines and acute myelogenous leukemia isolates. We subsequently conducted a phase 1 trial of tipifarnib plus etoposide in adults over 70 years of age who were not candidates for conventional therapy. A total of 84 patients (median age, 77 years) received 224 cycles of oral tipifarnib (300-600 mg twice daily for 14 or 21 days) plus oral etoposide (100-200 mg daily on days 1-3 and 8-10). Dose-limiting toxicities occurred with 21-day tipifarnib. Complete remissions were achieved in 16 of 54 (30%) receiving 14-day tipifarnib versus 5 of 30 (17%) receiving 21-day tipifarnib. Complete remissions occurred in 50% of two 14-day tipifarnib cohorts: 3A (tipifarnib 600, etoposide 100) and 8A (tipifarnib 400, etoposide 200). In vivo, tipifarnib plus etoposide decreased ribosomal S6 protein phosphorylation and increased histone H2AX phosphorylation and apoptosis. Tipifarnib plus etoposide is a promising orally bioavailable regimen that warrants further evaluation in elderly adults who are not candidates for conventional induction chemotherapy. These clinical studies are registered at www.clinicaltrials.gov as #NCT00112853. (Blood. 2009;113:4841-4852) C1 [Karp, Judith E.; Greer, Jacqueline M.; Ricklis, Rebecca M.; Smith, B. Douglas; Ironside, Valerie; Gore, Steven D.; Levis, Mark J.] Johns Hopkins Sidney Kimmel Canc Ctr, Div Hematol Malignancies, Baltimore, MD USA. [Flatten, Karen; Loegering, David A.; Le, Son B.; Meng, Xue Wei; Schneider, Paula A.; Dai, Nga T.; Adjei, Alex A.; Kaufmann, Scott H.] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA. [Feldman, Eric J.; Ritchie, Ellen; Talbott, Timothy; Roboz, Gail] New York Presbyterian Hosp, Cornell Med Ctr, Dept Hematol Oncol, New York, NY USA. [Morris, Lawrence E.] Bone Marrow Transplant Grp Georgia, Atlanta, GA USA. [Wright, John J.] NIH, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC USA. RP Karp, JE (reprint author), Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,CRB 1 Rm 289, Baltimore, MD 21231 USA. EM jkarp2@jhmi.edu FU NCI [U01 CA70095]; NCI Translational Research Initiative [24XS126]; NCI Cancer Center [2P30 CA06973-44]; National Center for Research Resources [M01-RR0052, R01 CA73709, R01 CA127433]; Leukemia & Lymphoma Society Translational Research Project [6047-08] FX The authors thank the Johns Hopkins Sidney Kimmel Cancer Center nursing staff for superb medical care, and the patients and families, without whose partnership we could never have conducted the trial and from whom we have learned critical information that will help us to improve the treatment of these diseases. This work was supported in part by NCI (Cooperative Agreement U01 CA70095; J. E. K.), NCI Translational Research Initiative (contract 24XS126; J. E. K.), NCI Cancer Center (support grant 2P30 CA06973-44), National Center for Research Resources (grants M01-RR0052, R01 CA73709, and R01 CA127433), the Leukemia & Lymphoma Society Translational Research Project (White Plains, NY; grant 6047-08; S. H. K., J. E. K.), and philanthropic funds from Dr Robert Fischell in memory of his late wife Marian (J. E. K.). NR 76 TC 42 Z9 42 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 14 PY 2009 VL 113 IS 20 BP 4841 EP 4852 DI 10.1182/blood-2008-08-172726 PG 12 WC Hematology SC Hematology GA 445ZT UT WOS:000266090700008 PM 19109557 ER PT J AU Landgren, O Gilbert, ES Rizzo, JD Socie, G Banks, PM Sobocinski, KA Horowitz, MM Jaffe, ES Kingma, DW Travis, LB Flowers, ME Martin, PJ Deeg, HJ Curtis, RE AF Landgren, Ola Gilbert, Ethel S. Rizzo, J. Douglas Socie, Gerard Banks, Peter M. Sobocinski, Kathleen A. Horowitz, Mary M. Jaffe, Elaine S. Kingma, Douglas W. Travis, Lois B. Flowers, Mary E. Martin, Paul J. Deeg, H. Joachim Curtis, Rochelle E. TI Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; VERSUS-HOST-DISEASE; HEMATOLOGIC MALIGNANCIES; IMMUNE RECONSTITUTION; DEPLETED MARROW; LEUKEMIA; GRAFTS; AGE AB We evaluated 26 901 patients who underwent allogeneic hematopoietic cell transplantation (HCT) at 271 centers worldwide to define patterns of posttransplantation lymphoproliferative disorders (PTLDs). PTLDs developed in 127 recipients, with 105 (83%) cases occurring within 1 year after transplantation. In multivariate analyses, we confirmed that PTLD risks were strongly associated (P <.001) with T-cell depletion of the donor marrow, antithymocyte globulin (ATG) use, and unrelated or HLA-mismatched grafts (URD/HLA mismatch). Significant associations were also confirmed for acute and chronic graft-versus-host disease. The increased risk associated with URD/HLA-mismatched donors (RR = 3.8) was limited to patients with T-cell depletion or ATG use (P = .004). New findings were elevated risks for age 50 years or older at transplantation (RR = 5.1; P <.001) and second transplantation (RR = 3.5; P <.001). Lower risks were found for T-cell depletion methods that remove both T and B cells (alemtuzumab and elutriation, RR = 3.1; P = .025) compared with other methods (RR = 9.4; P = .005 for difference). The cumulative incidence of PTLDs was low (0.2%) among 21 686 patients with no major risk factors, but increased to 1.1%, 3.6%, and 8.1% with 1, 2, and more than 3 major risk factors, respectively. Our findings identify subgroups of patients who underwent allogeneic HCT at elevated risk of PTLDs for whom prospective monitoring of Epstein-Barr virus activation and early treatment intervention may be particularly beneficial. (Blood. 2009; 113: 4992-5001) C1 [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv HHS, Bethesda, MD 20892 USA. [Landgren, Ola; Gilbert, Ethel S.; Curtis, Rochelle E.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv HHS, NIH, Bethesda, MD 20892 USA. [Rizzo, J. Douglas; Sobocinski, Kathleen A.; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Socie, Gerard] Hosp St Louis, Paris, France. [Banks, Peter M.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Jaffe, Elaine S.; Kingma, Douglas W.] NCI, Pathol Lab, Ctr Canc Res, NIH,HHS, Bethesda, MD 20892 USA. [Travis, Lois B.] Univ Rochester, Dept Radiat Oncol, Rochester, NY 14627 USA. [Flowers, Mary E.; Martin, Paul J.; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Landgren, O (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv HHS, 9000 Rockville Pike,Bldg 10,Rm 13N240F, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU NCI [CP-51027, CP-51028, P01-HL36444, P01-CA18029, P01CA102542, P01-CA15704]; Intramural Research Program of the NIH; Public Health Service [U24-CA76518]; National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute; Office of Naval Research; Health Services Research Administration [K23 CA82350-05]; Abbott Laboratories; Aetna; American International Group; American Red Cross; Amgen; Medical College of Wisconsin; AnorMED; Astellas Pharma US; Baxter International; Berlex Laboratories; Biogen IDEC; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bristol-Myers Squibb Company; BRT Laboratories; Cangene; Celgene; CellGenix; Cell Therapeutics; CelMed Biosciences; Cylex; Cytonome; CytoTherm; DOR BioPharma; Dynal Biotech; Invitrogen Company; Enzon Pharmaceuticals; Gambro BCT; Gamida Cell; Genzyme; Gift of Life Bone Marrow Foundation; GlaxoSmithKline; Histogenetics; HKS Medical Information Systems; Kirin Brewery; Merck Company; The Medical College of Wisconsin; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA; Miltenyi Biotec; MultiPlan; National Marrow Donor Program; Nature Publishing Group; Novartis Pharmaceuticals; Osiris Therapeutics; Pall Medical; Pfizer; Pharmion; PDL BioPharma; Roche Laboratories; Sanofi- aventis; Schering Plough; StemCyte; StemSoft Software; SuperGen; Sysmex; The Marrow Foundation; THERAKOS; University of Colorado Cord Blood Bank; ViaCell; ViraCor Laboratories; Wellpoint; Zelos Therapeutics FX The authors are indebted to the physicians and data professionals at participating transplant centers who contributed high-quality data to this study. We are especially grateful to Dr Catherine Metayer from the University of California, Berkeley, for detailed data review and statistical analyses for the case-control study. We thank Gary Schoch from FHCRC, Seattle, and Diane Knutson and Sharon Nell from the CIBMTR, Milwaukee, for support in data collection. We acknowledge Linda Kaufman, Kathy Chimes, and Diane Fuchs from Westat (Rockville, MD) for coordination of field studies, and Nathan Appel, David Hacker, Heather Bath, and George Geise from Information Management Services (Silver Spring, MD) for computing support.; This research is supported by contract nos. CP-51027 and CP-51028 from the NCI; and by the Intramural Research Program of the NIH and the NCI. The FHCRC investigators are supported by grants P01-HL36444, P01-CA18029, P01CA102542, and P01-CA15704 from the NIH. The CIBMTR is supported by Public Health Service Grant U24-CA76518 from the NCI, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Services Research Administration (HHS); K23 CA82350-05 grant from the NIH; and grants from Abbott Laboratories; Aetna; American International Group; American Red Cross; Amgen; anonymous donation to the Medical College of Wisconsin; AnorMED; Astellas Pharma US; Baxter International; Berlex Laboratories; Biogen IDEC; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bristol-Myers Squibb Company; BRT Laboratories; Cangene; Celgene; CellGenix; Cell Therapeutics; CelMed Biosciences; Cylex; Cytonome; CytoTherm; DOR BioPharma; Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals; Gambro BCT; Gamida Cell; Genzyme; Gift of Life Bone Marrow Foundation; GlaxoSmithKline; Histogenetics; HKS Medical Information Systems; Kirin Brewery; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA; Miltenyi Biotec; MultiPlan; National Marrow Donor Program; Nature Publishing Group; Novartis Pharmaceuticals; Osiris Therapeutics; Pall Medical; Pfizer; Pharmion; PDL BioPharma; Roche Laboratories; Sanofi- aventis; Schering Plough; StemCyte; StemSoft Software; SuperGen; Sysmex; The Marrow Foundation; THERAKOS; University of Colorado Cord Blood Bank; ViaCell; ViraCor Laboratories; Wellpoint; and Zelos Therapeutics.; The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the of the Navy, the Department of Defense, or any other agency of the US government. NR 39 TC 150 Z9 162 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 14 PY 2009 VL 113 IS 20 BP 4992 EP 5001 DI 10.1182/blood-2008-09-178046 PG 10 WC Hematology SC Hematology GA 445ZT UT WOS:000266090700026 PM 19264919 ER PT J AU Capitini, CM Herby, S Milliron, M Anver, MR Mackall, CL Fry, TJ AF Capitini, Christian M. Herby, Sarah Milliron, Matthew Anver, Miriam R. Mackall, Crystal L. Fry, Terry J. TI Bone marrow deficient in IFN-gamma signaling selectively reverses GVHD-associated immunosuppression and enhances a tumor-specific GVT effect SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; INTERFERON-GAMMA; T-CELLS; IMMUNE RECONSTITUTION; STEM-CELLS; NK CELLS; GRAFT; TRANSPLANTATION; IMMUNOTHERAPY; VACCINES AB Vaccine-based expansion of T cells is one approach to enhance the graft-versus-tumor effect of allogeneic bone marrow transplantation (BMT), but the complex immunobiology of the allogeneic environment on responses to tumor vaccines has not been well characterized. We hypothesized that subclinical graft-versus-host disease (GVHD) impairs immunity, but modulation of gamma interferon (IFN-gamma) signaling could reverse this effect. Dendritic cell vaccines and donor lymphocyte infusions (DLIs) were incorporated into a minor histocompatibility antigen-mismatched, T cell-depleted, allogeneic BMT mouse model. Animals were then challenged with H-Y expressing tumors. CD4(+) and CD8(+) responses to H-Y were diminished in vaccinated allogeneic versus syngeneic BMT recipients with DLI doses below the threshold for clinical GVHD, especially in thymectomized hosts. IFN-gamma receptor 1-deficient (IFN-gamma R1(-/-)) T cells cannot cause GVHD but also have diminished vaccine responses. Remarkably, IFN-gamma R1(-/-) bone marrow abrogates GVHD, allowing higher DLI doses to be tolerated, but improves vaccine responses and tumor protection. We conclude that tumor vaccines administered after allogeneic BMT can augment graft-versus-tumor if GVHD is avoided and that prevention of IFN-gamma signaling on donor bone marrow is an effective approach to preventing GVHD while preserving immunocompetence. (Blood. 2009; 113: 5002-5009) C1 [Capitini, Christian M.; Herby, Sarah; Milliron, Matthew; Mackall, Crystal L.; Fry, Terry J.] NCI, Immunol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Anver, Miriam R.] NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp SAIC Frederick, NIH, Frederick, MD 21701 USA. [Fry, Terry J.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. RP Capitini, CM (reprint author), NCI, Immunol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Rm 1W-5832, Bethesda, MD 20892 USA. EM capitinic@mail.nih.gov OI Capitini, Christian/0000-0002-2276-6731 FU National Cancer Institute [HHSN261200800001E]; Children's Cancer Foundation FX The authors thank Richard Childs and Daniel Fowler for their critical review of the data and manuscript drafts.; The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.; This work was supported by intramural research funds at the National Cancer Institute (C. L. M.), the Children's Cancer Foundation (T. J. F.), and in part with federal funds from the NCI, NIH, funded by NCI contract no. HHSN261200800001E (M. R. A.). NR 40 TC 16 Z9 17 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 14 PY 2009 VL 113 IS 20 BP 5002 EP 5009 DI 10.1182/blood-2008-11-187385 PG 8 WC Hematology SC Hematology GA 445ZT UT WOS:000266090700027 PM 19258593 ER PT J AU Han, Q Robinson, H Cai, T Tagle, DA Li, JY AF Han, Qian Robinson, Howard Cai, Tao Tagle, Danilo A. Li, Jianyong TI Structural Insight into the Inhibition of Human Kynurenine Aminotransferase I/Glutamine Transaminase K SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE-RATS; EXCITATORY AMINO-ACIDS; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURES; TRYPTOPHAN DEGRADATION; SYNAPTIC-TRANSMISSION; HUNTINGTONS-DISEASE; NICOTINIC RECEPTORS; QUINOLINIC ACID; DRUG TARGET AB Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of kynurenic acid, a neuroactive compound. Here, we report three high-resolution crystal structures (1.50-1.55 angstrom) of hKAT I that are in complex with glycerol and each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because Tris is able to occupy the substrate binding position, we speculate that this may be the basis for hKAT I inhibition. Furthermore, the hKAT/IAC complex structure reveals that the binding moieties of the inhibitor are its indole ring and a carboxyl group. Six chemicals with both binding moieties were tested for their ability to inhibit hKAT I activity; 3-indolepropionic acid and DL-indole-3-lactic acid demonstrated the highest level of inhibition, and as they cannot be considered as substrates of the enzyme, these two inhibitors are promising candidates for future study. Perhaps even more significantly, we report the discovery of two different ligands located simultaneously in the hKAT I active center for the first time. C1 [Han, Qian; Li, Jianyong] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. [Robinson, Howard] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. [Cai, Tao] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. [Tagle, Danilo A.] NINDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. RP Han, Q (reprint author), Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. EM qianhan@vt.edu RI Han, Qian/J-8696-2014 OI Han, Qian/0000-0001-6245-5252 FU National Synchrotron Light Source; Brookhaven National Laboratory; Intramural Research Program FX This work was carried out in part at the National Synchrotron Light Source, Brookhaven National Laboratory, and supported in part by the Intramural Research Program of the institutes of NIDCR and NINDS at NIH. We are grateful to Elizabeth Watson and Graham Richardson (Dr. Jianyong Li's laboratory, Department-of Biochemistry, Virginia Tech) for critical reading of this paper. NR 57 TC 20 Z9 23 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 14 PY 2009 VL 52 IS 9 BP 2786 EP 2793 DI 10.1021/jm9000874 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 443LP UT WOS:000265911800016 PM 19338303 ER PT J AU Grillet, N Xiong, W Reynolds, A Kazmierczak, P Sato, T Lillo, C Dumont, RA Hintermann, E Sczaniecka, A Schwander, M Williams, D Kachar, B Gillespie, PG Muller, U AF Grillet, Nicolas Xiong, Wei Reynolds, Anna Kazmierczak, Piotr Sato, Takashi Lillo, Concepcion Dumont, Rachel A. Hintermann, Edith Sczaniecka, Anna Schwander, Martin Williams, David Kachar, Bechara Gillespie, Peter G. Mueller, Ulrich TI Harmonin Mutations Cause Mechanotransduction Defects in Cochlear Hair Cells SO NEURON LA English DT Article ID SYNDROME TYPE 1D; SYNDROME TYPE 1F; USHER-SYNDROME; RECESSIVE DEAFNESS; TIP-LINK; SENSORY TRANSDUCTION; PROTOCADHERIN GENE; ALLELIC MUTATIONS; FAST ADAPTATION; CADHERIN GENE AB In hair cells, mechanotransduction channels are gated by tip links, the extracellular filaments that consist of cadherin 23 (CDH23) and protocadherin 15 (PCDH15) and connect the stereocilia of each hair cell. However, which molecules mediate cadherin function at tip links is not known. Here we show that the PDZ-domain protein harmonin is a component of the upper tip-link density (UTLD), where CDH23 inserts into the stereociliary membrane. Harmonin domains that mediate interactions with CDH23 and F-actin control harmonin localization in stereocilia and are necessary for normal hearing. In mice expressing a mutant harmonin protein that prevents UTLD formation, the sensitivity of hair bundles to mechanical stimulation is reduced. We conclude that harmonin is a UTLD component and contributes to establishing the sensitivity of mechanotransduction channels to displacement. C1 [Grillet, Nicolas; Xiong, Wei; Reynolds, Anna; Kazmierczak, Piotr; Hintermann, Edith; Sczaniecka, Anna; Schwander, Martin; Mueller, Ulrich] Scripps Res Inst, Inst Childhood & Neglected Dis, Dept Cell Biol, La Jolla, CA 92037 USA. [Sato, Takashi; Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA. [Lillo, Concepcion; Williams, David] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. [Lillo, Concepcion; Williams, David] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Dept Neurobiol, Los Angeles, CA 90024 USA. [Dumont, Rachel A.; Gillespie, Peter G.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr & Vollum Inst, Portland, OR 97239 USA. RP Muller, U (reprint author), Scripps Res Inst, Inst Childhood & Neglected Dis, Dept Cell Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM umueller@scripps.edu RI Wang, Shirong/G-1698-2011; 2009, Secribsal/A-1266-2012; Xiong, Wei/A-6170-2012; Lillo, Concepcion/A-6321-2009; OI Lillo, Concepcion/0000-0001-5814-9826; Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIH [DC005969, DC007704, EYE07042, DC002368]; Skaggs Institute for Chemical Biology; NHMRC (Australia) [148939]; Bruce Ford and Anne Smith Bundy Foundation FX We thank Anthony Ricci for help with electrophysiology and for comments on the manuscript; C. Ramos, G. Martin, and S. Kupriyanov for assistance in generating mice; and K. Spencer, M. Wood, and T. Fassel for help with microscopy and EM. This work was funded by NIH grants DC005969, DC007704 (U. M.), EYE07042 (D.W,), and DC002368 (P.G.); the Skaggs Institute for Chemical Biology (U.M.); a Jules and Doris Stein RPB professorship (D.W.); a C.J. Martin fellowship (#148939) NHMRC (Australia) (A.R.); and a fellowship from the Bruce Ford and Anne Smith Bundy Foundation (A.R. and W.X). NR 46 TC 64 Z9 66 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 14 PY 2009 VL 62 IS 3 BP 375 EP 387 DI 10.1016/j.neuron.2009.04.006 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 446UG UT WOS:000266146100009 PM 19447093 ER PT J AU Pinsky, PF AF Pinsky, Paul F. TI Antioxidant Supplementation and Cancer Prevention SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov NR 4 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 13 PY 2009 VL 301 IS 18 BP 1878 EP 1878 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 444JX UT WOS:000265978400016 PM 19436011 ER PT J AU Volkow, ND Chandler, RK Fletcher, BW AF Volkow, Nora D. Chandler, Redonna K. Fletcher, Bennett W. TI Drug Addiction as a Brain Disorder or Disease Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Volkow, Nora D.; Chandler, Redonna K.; Fletcher, Bennett W.] NIDA, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 13 PY 2009 VL 301 IS 18 BP 1881 EP 1882 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 444JX UT WOS:000265978400023 ER PT J AU Zhao, XR Strong, R Zhang, J Sun, GH Tsien, JZ Cui, ZZ Grotta, JC Aronowski, J AF Zhao, Xiurong Strong, Roger Zhang, Jie Sun, Guanghua Tsien, Joe Z. Cui, Zhenzhong Grotta, James C. Aronowski, Jaroslaw TI Neuronal PPAR gamma Deficiency Increases Susceptibility to Brain Damage after Cerebral Ischemia SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; TRANSIENT FOCAL ISCHEMIA; INTRACEREBRAL HEMORRHAGE TREATMENT; CAUSES INSULIN-RESISTANCE; DEPENDENT PROTEIN-KINASE; EXPERIMENTAL STROKE; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); 15D-PROSTAGLANDIN J(2); DEVELOPMENTAL-CHANGES; GENE-EXPRESSION AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a role in regulating a myriad of biological processes in virtually all brain cell types, including neurons. We and others have reported recently that drugs which activate PPAR gamma are effective in reducing damage to brain in distinct models of brain disease, including ischemia. However, the cell type responsible for PPAR gamma-mediated protection has not been established. In response to ischemia, PPAR gamma gene is robustly upregulated in neurons, suggesting that neuronal PPAR gamma may be a primary target for PPAR gamma-agonist-mediated neuroprotection. To understand the contribution of neuronal PPAR gamma to ischemic injury, we generated conditional neuron-specific PPAR gamma knock-out mice (N-PPAR gamma-KO). These mice are viable and appeared to be normal with respect to their gross behavior and brain anatomy. However, neuronal PPAR gamma deficiency caused these mice to experience significantly more brain damage and oxidative stress in response to middle cerebral artery occlusion. The primary cortical neurons harvested from N-PPAR gamma-KO mice, but not astroglia, exposed to ischemia in vitro demonstrated more damage and a reduced expression of numerous key gene products that could explain increased vulnerability, including SOD1 (superoxide dismutase 1), catalase, glutathione S-transferase, uncoupling protein-1, or transcription factor liver X receptor-alpha. Also, PPAR gamma agonist-based neuroprotective effect was lost in neurons from N-PPAR gamma neurons. Therefore, we conclude that PPAR gamma in neurons play an essential protective function and that PPAR gamma agonists may have utility in neuronal self-defense, in addition to their well established anti-inflammatory effect. C1 [Strong, Roger; Zhang, Jie; Sun, Guanghua; Grotta, James C.; Aronowski, Jaroslaw] Univ Texas Houston, Sch Med, Dept Neurol, Stroke Program, Houston, TX 77030 USA. [Cui, Zhenzhong] NIMH, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA. [Tsien, Joe Z.] Med Coll Georgia, Brain & Behav Discovery Inst, Augusta, GA 30912 USA. RP Aronowski, J (reprint author), Univ Texas Houston, Sch Med, Dept Neurol, Stroke Program, Houston, TX 77030 USA. EM J.Aronowski@uth.tmc.edu FU National Institutes of Health-National Institute of Neurological Disorders and Stroke [R01NS052791, 1R21NS057284] FX This project was supported by National Institutes of Health-National Institute of Neurological Disorders and Stroke Grants R01NS052791 and 1R21NS057284. NR 65 TC 83 Z9 97 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 13 PY 2009 VL 29 IS 19 BP 6186 EP 6195 DI 10.1523/JNEUROSCI.5857-08.2009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 445HU UT WOS:000266042700016 PM 19439596 ER PT J AU Sarin, H Kanevsky, AS Fung, SH Butman, JA Cox, RW Glen, D Reynolds, R Auh, S AF Sarin, Hemant Kanevsky, Ariel S. Fung, Steve H. Butman, John A. Cox, Robert W. Glen, Daniel Reynolds, Richard Auh, Sungyoung TI Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID CONVERTING-ENZYME-INHIBITION; GADOLINIUM-DTPA COMPLEX; TO-TISSUE TRANSPORT; BLOOD-BRAIN; CEREPORT RMP-7; NITRIC-OXIDE; GD-DTPA; QUANTITATIVE MEASUREMENT; CHEMOTHERAPEUTIC-AGENTS; VASCULAR-PERMEABILITY AB Background: The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods: Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results: The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. Conclusion: Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature. C1 [Sarin, Hemant] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Sarin, Hemant; Kanevsky, Ariel S.; Butman, John A.] NIH, Radiol & Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. [Fung, Steve H.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Cox, Robert W.; Glen, Daniel; Reynolds, Richard] NIMH, Bethesda, MD 20892 USA. [Auh, Sungyoung] NINDS, NIH, Bethesda, MD 20892 USA. RP Sarin, H (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. EM sarinh@mail.nih.gov; kanevskya@cc.nih.gov; SFUNG@PARTNERS.ORG; JButmanA@cc.nih.gov; robertcox@mail.nih.gov; glend@mail.nih.gov; reynoldr@mail.nih.gov; auhs@ninds.nih.gov RI Butman, John/A-2694-2008; Butman, John/J-2780-2013; OI Butman, John/0000-0002-1547-9195; Fung, Steve/0000-0002-1177-682X FU National Institute of Biomedical Imaging Bioengineering (NIBIB); Radiology and Imaging Sciences Program (CC) FX This study was funded by the National Institute of Biomedical Imaging Bioengineering (NIBIB) and the Radiology and Imaging Sciences Program (CC). We thank Dr. Matthew Hall for useful discussions. NR 65 TC 7 Z9 7 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 13 PY 2009 VL 7 AR 33 DI 10.1186/1479-5876-7-33 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 461CA UT WOS:000267240800001 PM 19439100 ER PT J AU Cook, NL Ayanian, JZ Orav, EJ Hicks, LS AF Cook, Nakela L. Ayanian, John Z. Orav, E. John Hicks, Leroi S. TI Differences in Specialist Consultations for Cardiovascular Disease by Race, Ethnicity, Gender, Insurance Status, and Site of Primary Care SO CIRCULATION LA English DT Article DE coronary disease; healthcare disparities; heart failure; quality of health care ID COMMUNITY-HEALTH CENTERS; QUALITY-OF-CARE; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; HEART-FAILURE; ELDERLY-PATIENTS; PHYSICIAN SPECIALTY; RACIAL-DIFFERENCES; OUTCOMES; DISPARITIES AB Background-Consultation with cardiologists may improve the quality of ambulatory care and reduce disparities for patients with heart disease. We assessed the use of cardiology consultations and the associated quality by race/ethnicity, gender, insurance status, and site of care. Methods and Results-In a retrospective cohort, we examined electronic records of 9761 adults with coronary artery disease or congestive heart failure (CHF) receiving primary care at practices affiliated with 2 academic medical centers during 2000 to 2005. During this period, 79.6% of patients with coronary artery disease and 90.3% of patients with CHF had a cardiology consultation. In multivariate analyses, women were less likely to receive a consultation than men for both conditions (coronary artery disease: hazard ratio, 0.89; 95% CI, 0.85 to 0.93; CHF: hazard ratio, 0.93; 95% CI, 0.87 to 0.99). Women also had 15% fewer follow-up consultations than men (P < 0.001). Similarly, patients at community health centers were less likely to receive a consultation (coronary artery disease: hazard ratio, 0.79; 95% CI, 0.74 to 0.84; CHF: hazard ratio, 0.77; 95% CI: 0.71 to 0.84) and had 20% fewer follow-up consultations (P < 0.001) relative to those at hospital-based practices. Black and Hispanic patients with CHF had 13% fewer follow-up consultations than white patients (P = 0.01 and P = 0.04, respectively). In adjusted analyses, consultation was associated with better processes of care compared with no consultation (P < 0.001), particularly for women (P < 0.001 for interaction between consultation and gender). Conclusions-Among ambulatory patients with coronary artery disease or CHF, women and those at community health centers have less access to cardiologists. Consultation is associated with better quality of care and narrows the gender gap in quality. (Circulation. 2009; 119: 2463-2470.) C1 [Cook, Nakela L.] NHLBI, Bethesda, MD 20892 USA. [Hicks, Leroi S.] Brigham & Womens Hosp, Ctr Community Hlth & Hlth Equ, Boston, MA 02115 USA. [Ayanian, John Z.; Orav, E. John; Hicks, Leroi S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Ayanian, John Z.; Hicks, Leroi S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Cook, NL (reprint author), NHLBI, Rockledge 2,Suite 10018,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM cookn2@nhlbi.nih.gov FU Agency for Healthcare Research and Quality [5 T32 HS000020-21] FX Dr Cook was supported by an institutional National Research Service Award from the Agency for Healthcare Research and Quality (5 T32 HS000020-21) during the conduct of this research. NR 37 TC 36 Z9 38 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 12 PY 2009 VL 119 IS 18 BP 2463 EP U76 DI 10.1161/CIRCULATIONAHA.108.825133 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 444WP UT WOS:000266011500007 PM 19398667 ER PT J AU Marietta, C Thompson, LH Lamerdin, JE Brooks, PJ AF Marietta, Cheryl Thompson, Larry H. Lamerdin, Jane E. Brooks, P. J. TI Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: Implications for alcohol-related carcinogenesis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Fanconi anemia; Breast cancer; Esophagus; Alcohol ID DNA CROSS-LINKS; FANCONI-ANEMIA; DAMAGE RESPONSE; ALDEHYDE DEHYDROGENASE-2; POLYMERASE-KAPPA; HEAVY DRINKERS; CANCER-RISK; ADDUCTS; REPAIR; CROTONALDEHYDE AB According to a recent IARC Working Group report, alcohol consumption is causally related to an increased risk of cancer of the upper aerodigestive tract, liver, colorectum, and female breast [R. Baan, K. Straif, Y. Grosse, B. Secretan, F. EI Chissassi, V. Bouvard, A. Altieri, V. Cogliano, Carcinogenicity of alcoholic beverages, Lancet Oncol. 8 (2007) 292-293]. Several lines of evidence indicate that acetalclehyde (AA), the first product of alcohol metabolism, plays a very important role in alcohol-related carcinogenesis, particularly in the esophagus. We previously proposed a model for alcohol-related carcinogenesis in which AA, generated from alcohol metabolism, reacts in cells to generate DNA lesions that form interstrand crosslinks (ICLs) [J.A. Theruvathu, P. Jaruga, R.G. Nath, M. Dizdaroglu, P.J. Brooks, Polyamines stimulate the formation of mutagenic 1, N2-propanodeoxyguanosine adducts from acetalclehyde. Nucleic Acids Res. 33 (2005) 3513-3520]. Since the Fanconi anemia-breast cancer associated (FANC-BRCA) DNA damage response network plays a crucial role in protecting cells against ICLs, in the present work we tested this hypothesis by exposing cells to AA and monitoring activation of this network. We found that AA exposure results in a concentration-dependent increase in FANCD2 monoubiquitination, which is dependent upon the FANC core complex. AA also stimulated BRCA1 phosphorylation at Ser1524 and increased the level of gamma H2AX, with both modifications occurring in a dose-dependent manner. However, AA did not detectably increase the levels of hyperphosphorylated RPA34, a marker of single-stranded DNA exposure at replication forks. These results provide the initial description of the AA-DNA damage response, which is qualitatively similar to the cellular response to mitomycin C, a known DNA crosslinking agent. We discuss the mechanistic implications of these results, as well as their possible relationship to alcohol-related carcinogenesis in different human tissues. (c) 2009 Published by Elsevier B.V. C1 [Marietta, Cheryl; Brooks, P. J.] NIAAA, Mol Neurobiol Sect, Neurogenet Lab, Rockville, MD 20852 USA. [Thompson, Larry H.; Lamerdin, Jane E.] Lawrence Livermore Natl Lab, Biosci & Biotechnol Div, Livermore, CA 94551 USA. [Lamerdin, Jane E.] Odyssey Thera Inc, San Ramon, CA USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, 5625 Fishers Lane,Room 3S32, Rockville, MD 20852 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z01 AA000083-14] NR 51 TC 26 Z9 27 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 12 PY 2009 VL 664 IS 1-2 BP 77 EP 83 DI 10.1016/j.mrfmmm.2009.03.011 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 449XM UT WOS:000266364100011 PM 19428384 ER PT J AU Barbey, AK Krueger, F Grafman, J AF Barbey, Aron K. Krueger, Frank Grafman, Jordan TI Structured event complexes in the medial prefrontal cortex support counterfactual representations for future planning SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE structured event complexes; prefrontal cortex; counterfactual reasoning; planning; prediction; event knowledge ID ANTERIOR CINGULATE CORTEX; GRASP REPRESENTATIONS; MEMORY; KNOWLEDGE; SYSTEMS; REGRET; HIPPOCAMPUS; THINKING; HUMANS; BRAIN AB We propose that counterfactual representations for reasoning about the past or predicting the future depend on structured event complexes (SECs) in the human prefrontal cortex (PFC; 'What would happen if X were performed in the past or enacted in the future?'). We identify three major categories of counterfactual thought (concerning action versus inaction, the self versus other and upward versus downward thinking) and propose that each form of inference recruits SEC representations in distinct regions of the medial PFC. We develop a process model of the regulatory functions these representations serve and draw conclusions about the importance of SECs for explaining the past and predicting the future. C1 [Barbey, Aron K.; Krueger, Frank; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Barbey, Aron K.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Barbey, Aron/L-7312-2015; OI Barbey, Aron/0000-0002-6092-0912; Grafman, Jordan H./0000-0001-8645-4457 FU NINDS FX The authors are supported by the NINDS Intramural Research Program. NR 75 TC 50 Z9 50 U1 3 U2 9 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD MAY 12 PY 2009 VL 364 IS 1521 BP 1291 EP 1300 DI 10.1098/rstb.2008.0315 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 425UE UT WOS:000264662000013 PM 19528010 ER PT J AU SanGiovanni, JP Arking, DE Iyengar, SK Elashoff, M Clemons, TE Reed, GF Henning, AK Sivakumaran, TA Xu, XM Dewan, A Agron, E Rochtchina, E Sue, CM Wang, JJ Mitchell, P Hoh, J Francis, PJ Klein, ML Chew, EY Chakravarti, A AF SanGiovanni, John Paul Arking, Dan E. Iyengar, Sudha K. Elashoff, Michael Clemons, Traci E. Reed, George F. Henning, Alice K. Sivakumaran, Theru A. Xu, Xuming DeWan, Andrew Agron, Elvira Rochtchina, Elena Sue, Carolyn M. Wang, Jie Jin Mitchell, Paul Hoh, Josephine Francis, Peter J. Klein, Michael L. Chew, Emily Y. Chakravarti, Aravinda TI Mitochondrial DNA Variants of Respiratory Complex I that Uniquely Characterize Haplogroup T2 Are Associated with Increased Risk of Age-Related Macular Degeneration SO PLOS ONE LA English DT Article AB Background: Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts. Methodology/Prinicipal Findings: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6). We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II) and in 56 cases and 246 controls from the 10-year study (Stage III). People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36-4.80, P <= 0.004) after considering the totality of evidence. Findings persisted after considering the impact of AMD-associated variants A69S and Y402H (OR = 5.19, 95%CI 1.19-22.69, P <= 0.029). Conclusion: Loci defining the mtDNA T2 haplogroup and Complex I are reasonable targets for novel functional analyses and therapeutic research in AMD. RP SanGiovanni, JP (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM jpsangio@post.harvard.edu RI Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014 OI Wang, Jie Jin/0000-0001-9491-4898; FU Intramural NIH HHS [Z99 EY999999, ZIA EY000489-01]; NEI NIH HHS [01-EY-0-2127, EY015810, R01 EY012203, R01 EY015771, R01 EY015810, R01-EY12203, R01EY015771] NR 30 TC 46 Z9 48 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 12 PY 2009 VL 4 IS 5 AR e5508 DI 10.1371/journal.pone.0005508 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 444VZ UT WOS:000266009800006 PM 19434233 ER PT J AU Lou, H Yeager, M Li, HC Bosquet, JG Hayes, RB Orr, N Yu, K Hutchinson, A Jacobs, KB Kraft, P Wacholder, S Chatterjee, N Feigelson, HS Thun, MJ Diver, WR Albanes, D Virtamo, J Weinstein, S Ma, J Gaziano, JM Stampfer, M Schumacher, FR Giovannucci, E Cancel-Tassin, G Cussenot, O Valeri, A Andriole, GL Crawford, ED Anderson, SK Tucker, M Hoover, RN Fraumeni, JF Thomas, G Hunter, DJ Dean, M Chanock, SJ AF Lou, Hong Yeager, Meredith Li, Hongchuan Bosquet, Jesus Gonzalez Hayes, Richard B. Orr, Nick Yu, Kai Hutchinson, Amy Jacobs, Kevin B. Kraft, Peter Wacholder, Sholom Chatterjee, Nilanjan Feigelson, Heather Spencer Thun, Michael J. Diver, W. Ryan Albanes, Demetrius Virtamo, Jarmo Weinstein, Stephanie Ma, Jing Gaziano, J. Michael Stampfer, Meir Schumacher, Fredrick R. Giovannucci, Edward Cancel-Tassin, Geraldine Cussenot, Olivier Valeri, Antoine Andriole, Gerald L. Crawford, E. David Anderson, Stephen K. Tucker, Margaret Hoover, Robert N. Fraumeni, Joseph F., Jr. Thomas, Gilles Hunter, David J. Dean, Michael Chanock, Stephen J. TI Fine mapping and functional analysis of a common variant in MSMB on chromosome 10q11.2 associated with prostate cancer susceptibility SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genome-wide association studies; prostate cancer genetics; CREB transcription factor ID GENOME-WIDE ASSOCIATION; RADICAL PROSTATECTOMY; RISK LOCUS; PROTEIN; EXPRESSION; 8Q24; POLYMORPHISMS; EPIDEMIOLOGY; SEQUENCE; DISEASE AB Two recent genome-wide association studies have independently identified a prostate cancer susceptibility locus on chromosome 10q11.2. The most significant single-nucleotide polymorphism (SNP) marker reported, rs10993994, is 57 bp centromeric of the first exon of the MSMB gene, which encodes beta-microseminoprotein (prostatic secretory protein 94). In this study, a fine-mapping analysis using HapMap SNPs was conducted across a approximate to 65-kb region (chr10: 51168330-51234020) flanking rs10993994 with 13 tag SNPs in 6,118 prostate cancer cases and 6,105 controls of European origin from the Cancer Genetic Markers of Susceptibility (CGEMS) project. rs10993994 remained the most strongly associated marker with prostate cancer risk [P = 8.8 x 10(-18); heterozygous odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.11-1.30; homozygous OR = 1.64, 95% CI: 1.47-1.86 for the adjusted genotype test with 2 df]. In follow-up functional analyses, the T variant of rs10993994 significantly affected expression of in vitro luciferase reporter constructs. In electrophoretic mobility shift assays, the C allele of rs10993994 preferentially binds to the CREB transcription factor. Analysis of tumor cell lines with a CC or CT genotype revealed a high level of MSMB gene expression compared with cell lines with a TT genotype. These findings were specific to the alleles of rs10993994 and were not observed for other SNPs determined by sequence analysis of the proximal promoter. Together, our mapping study and functional analyses implicate regulation of expression of MSMB as a plausible mechanism accounting for the association identified at this locus. Further investigation is warranted to determine whether rs10993994 alone or in combination with additional variants contributes to prostate cancer susceptibility. C1 [Yeager, Meredith; Bosquet, Jesus Gonzalez; Hayes, Richard B.; Orr, Nick; Yu, Kai; Hutchinson, Amy; Wacholder, Sholom; Chatterjee, Nilanjan; Albanes, Demetrius; Weinstein, Stephanie; Tucker, Margaret; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Lou, Hong; Li, Hongchuan; Anderson, Stephen K.; Dean, Michael] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Lou, Hong; Yeager, Meredith; Hutchinson, Amy] NCI, Core Genotyping Facil, Adv Technol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Jacobs, Kevin B.; Thomas, Gilles] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. [Kraft, Peter; Schumacher, Fredrick R.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Feigelson, Heather Spencer; Thun, Michael J.; Diver, W. Ryan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Ma, Jing; Stampfer, Meir; Schumacher, Fredrick R.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FIN-00300 Helsinki, Finland. [Gaziano, J. Michael] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Med, Div Aging, Brigham & Womens Hosp, Boston, MA 02115 USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] Hop Tenon, AP HP, Ctr Rech Pathol Prostat, F-75970 Paris, France. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63108 USA. [Crawford, E. David] Univ Colorado Denver & Hlth Sci Ctr, Dept Surg, Denver, CO 80204 USA. RP Fraumeni, JF (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM fraumenj@mail.nih.gov RI Anderson, Stephen/B-1727-2012; Dean, Michael/G-8172-2012; Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015; OI Anderson, Stephen/0000-0002-7856-4266; Dean, Michael/0000-0003-2234-0631; Hayes, Richard/0000-0002-0918-661X; Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU NCI NIH HHS [R01 CA097193] NR 27 TC 61 Z9 64 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2009 VL 106 IS 19 BP 7933 EP 7938 DI 10.1073/pnas.0902104106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RG UT WOS:000266208900047 PM 19383797 ER PT J AU Robbins, JB Kubler-Kielb, J Vinogradov, E Mocca, C Pozsgay, V Shiloach, J Schneerson, R AF Robbins, John B. Kubler-Kielb, Joanna Vinogradov, Evguenii Mocca, Christopher Pozsgay, Vince Shiloach, Joseph Schneerson, Rachel TI Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lipopolysaccharide; glycoconjugate; vaccine; Kdo; IgG ID DYSENTERIAE TYPE-1; FLEXNERI TYPE-2A; POLYSACCHARIDE; LIPOPOLYSACCHARIDES; ANTIBODIES; VACCINES; CHILDREN AB Shigellosis, an enteric disease, is on the World Health Organization's priority prevention list. In one study, the Shigella sonnei O-specific polysaccharide (O-SP)-protein conjugate showed 72% protection against disease in Israeli army recruits exposed to high rates (8-14%) of infection. The protection was related to vaccine-induced IgG anti-O-SP levels. Synthetic oligosaccharides of Shigella dysenteriae type 1, bound by their reducing ends to a carrier protein ("sun''-type configuration), induced significantly higher antibody levels than the native O-SP bound to protein by multiple-point attachments ("lattice''-type configuration). Attempts to synthesize the S. sonnei O-SP based oligosaccharides were not successful. Here, we describe the isolation, characterization, and conjugation of low-molecular-mass O-SP-core (O-SPC) fragments. The O-SPC fragments were bound by their reducing ends similar to the preparation of the synthetic S. dysenteriae type 1 conjugates. The O-SPC conjugates used oxime linkages between the terminal Kdo residues at the reducing ends of the S. sonnei saccharides and aminooxy linkers bound to BSA or a recombinant diphtheria toxin. The coupling reaction was carried out at a neutral pH and room temperature. IgG antibody levels induced in young outbred mice by the S. sonnei O-SPC conjugates were significantly higher then those elicited by the O-SP conjugates. Accordingly, we propose to evaluate clinically these conjugates. C1 [Robbins, John B.; Kubler-Kielb, Joanna; Mocca, Christopher; Pozsgay, Vince; Schneerson, Rachel] NICHHD, NIH, Bethesda, MD 20892 USA. [Vinogradov, Evguenii] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. [Shiloach, Joseph] NIAID, NIH, Bethesda, MD 20892 USA. RP Robbins, JB (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM robbinsjo@mail.nih.gov FU National Institutes of Health; National Institute of Child Health and Human Development FX We thank Dr. Vince Pozsgay (National Institutes of Health, Bethesda, MD) for providing the O-(3- thiopropyl) hydroxylamine linker, Dr. Joseph Shiloach (National Institutes of Health, Bethesda, MD) for providing rDT; Dr. Bruce Coxon for assessing sample purities by NMR; Chunyan Guo for technical assistance; and Dr. Arthur Karpas for statistical analyses and manuscript review. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development. NR 21 TC 36 Z9 36 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2009 VL 106 IS 19 BP 7974 EP 7978 DI 10.1073/pnas.0900891106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RG UT WOS:000266208900054 PM 19346477 ER PT J AU Nishimura, Y Sadjadpour, R Mattapallil, JJ Igarashi, T Lee, W Buckler-White, A Roederer, M Chun, TW Martin, MA AF Nishimura, Yoshiaki Sadjadpour, Reza Mattapallil, Joseph J. Igarashi, Tatsuhiko Lee, Wendy Buckler-White, Alicia Roederer, Mario Chun, Tae-Wook Martin, Malcolm A. TI High frequencies of resting CD4(+) T cells containing integrated viral DNA are found in rhesus macaques during acute lentivirus infections SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV; integration; simian immunodeficiency virus; simian/human immunodeficiency virus ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; TYPE-1 DNA; REVERSE TRANSCRIPTION; GENE-EXPRESSION; LYMPHOID-TISSUE; REPLICATION; LYMPHOCYTES; MEMORY AB We and others have reported that the vast majority of virus-producing CD4(+) T cells during the acute infection of rhesus macaques with simian immunodeficiency virus (SIV) or CXCR4 (X4)-using simian/human immunodeficiency viruses (SHIVs) exhibited a nonactivated phenotype. These findings have been extended to show that resting CD4(+) T lymphocytes collected from SIV-or X4-SHIV-infected animals during the first 10 days of infection continue to release virus ex vivo. Furthermore, we observed high frequencies of integrated viral DNA (up to 5.1 x 104 DNA copies per 105 cells) in circulating resting CD4(+) T cells during the first 10 days of the infection. Integration of SIV DNA was detected only in memory CD4(+) T cells and SHIVs preferentially integrated into resting naive CD4(+) T cells. Taken together, these results show that during the acute infection large numbers of resting CD4(+) T cells carry integrated nonhuman primate lentiviral DNA and are the major source of progeny virions irrespective of coreceptor usage. Prompt and sustained interventions are therefore required to block the rapid systemic dissemination of virus and prevent an otherwise fatal clinical outcome. C1 [Nishimura, Yoshiaki; Sadjadpour, Reza; Igarashi, Tatsuhiko; Lee, Wendy; Buckler-White, Alicia; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Mattapallil, Joseph J.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Chun, Tae-Wook] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. EM malm@nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX We thank Rahel Petros, Joseph Mckennan, Dhirenkumar Patel, and Dr. Boris Skopets for diligently assisting in the care and maintenance of our animals; Robin Kruthers and Ranjini Iyengar for determining viral RNA levels; Charles Buckler for arranging and scheduling animal experiments; and Ronald C. Desrosiers (Harvard Medical School, Boston) for providing molecular clones of SIVmac239 and SIVmac316. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 39 TC 20 Z9 20 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 12 PY 2009 VL 106 IS 19 BP 8015 EP 8020 DI 10.1073/pnas.0903022106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 447RG UT WOS:000266208900061 PM 19416840 ER PT J AU Wright, JT Probstfield, JL Cushman, WC Pressel, SL Cutler, JA Davis, BR Einhorn, PT Rahman, M Whelton, PK Ford, CE Haywood, LJ Margolis, KL Oparil, S Black, HR Alderman, MH AF Wright, Jackson T., Jr. Probstfield, Jeffrey L. Cushman, William C. Pressel, Sara L. Cutler, Jeffrey A. Davis, Barry R. Einhorn, Paula T. Rahman, Mahboob Whelton, Paul K. Ford, Charles E. Haywood, L. Julian Margolis, Karen L. Oparil, Suzanne Black, Henry R. Alderman, Michael H. CA ALLHAT Collaborative Res Grp TI ALLHAT Findings Revisited in the Context of Subsequent Analyses, Other Trials, and Meta-analyses SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; CONVERTING-ENZYME-INHIBITOR; CALCIUM-CHANNEL BLOCKER; PROSPECTIVELY-DESIGNED OVERVIEWS; ISOLATED SYSTOLIC HYPERTENSION; BLOOD-PRESSURE REDUCTION; ANTIHYPERTENSIVE DRUG-TREATMENT; MAJOR CARDIOVASCULAR EVENTS; HIGH-RISK PATIENTS AB The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is reevaluated considering information from new clinical trials, meta-analyses, and recent subgroup and explanatory analyses from ALLHAT, especially those regarding heart failure (HF) and the association of drug treatment with new-onset diabetes mellitus (DM) and its cardiovascular disease (CVD) consequences. Chlorthalidone was superior to (1) doxazosin mesylate in preventing combined CVD (CCVD)(risk ratio [RR], 1.20; 95% confidence interval [CI], 1.13-1.27), especially HF (RR, 1.80; 95% CI, 1.40-2.22) and stroke (RR, 1.26; 95% CI, 1.10-1.46); ( 2) lisinopril in preventing CCVD (RR, 1.10; 95% CI, 1.05-1.16), including stroke ( in black persons only) and HF (RR, 1.20; 95% CI, 1.09-1.34); and ( 3) amlodipine besylate in preventing HF, overall (by 28%) and in hospitalized or fatal cases (by 26%). Central independent blinded reassessment of HF hospitalizations confirmed each comparison. Results were consistent by age, sex, race ( except for stroke and CCVD), DM status, metabolic syndrome status, and renal function level. Neither amlodipine nor lisinopril was superior to chlorthalidone in preventing end-stage renal disease overall, by DM status, or by renal function level. In the chlorthalidone arm, new-onset DM was not significantly associated with CCVD (RR, 0.96; 95% CI, 0.88-2.42). Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither alpha-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF, and new-onset DM associated with thiazides does not increase CVD outcomes. Arch Intern Med. 2009;169(9):832-842 C1 [Wright, Jackson T., Jr.; Rahman, Mahboob] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Probstfield, Jeffrey L.] Univ Washington, Clin Trial Serv Unit, Seattle, WA 98195 USA. [Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA. [Pressel, Sara L.] Univ Texas Houston Hlth Sci Ctr, Sch Publ Hlth, Allhat Clin Trials Ctr, Houston, TX 77030 USA. [Cutler, Jeffrey A.; Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA. [Whelton, Paul K.] Loyola Univ, Med Ctr & Hlth Syst, Maywood, IL 60153 USA. [Haywood, L. Julian] Univ So Calif, Med Ctr, Los Angeles, CA USA. [Margolis, Karen L.] Hlth Partners Res Fdn, Minneapolis, MN USA. [Oparil, Suzanne] Univ Alabama Birmingham, Birmingham, AL USA. [Black, Henry R.] NYU, Sch Med, New York, NY 10003 USA. [Alderman, Michael H.] Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. RP Pressel, SL (reprint author), Univ Texas Houston Hlth Sci Ctr, Sch Publ Hlth, Allhat Clin Trials Ctr, 1200 Herman Pressler St,Ste 801, Houston, TX 77030 USA. EM Sara.L.Pressel@uth.tmc.edu FU NHLBI NIH HHS [N01 HC 35130, N01 HC035130, N01HC35130] NR 62 TC 56 Z9 57 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 11 PY 2009 VL 169 IS 9 BP 832 EP 842 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 444PX UT WOS:000265994000003 PM 19433694 ER PT J AU Cherkin, DC Sherman, KJ Avins, AL Erro, JH Ichikawa, L Barlow, WE Delaney, K Hawkes, R Hamilton, L Pressman, A Khalsa, PS Deyo, RA AF Cherkin, Daniel C. Sherman, Karen J. Avins, Andrew L. Erro, Janet H. Ichikawa, Laura Barlow, William E. Delaney, Kristin Hawkes, Rene Hamilton, Luisa Pressman, Alice Khalsa, Partap S. Deyo, Richard A. TI A Randomized Trial Comparing Acupuncture, Simulated Acupuncture, and Usual Care for Chronic Low Back Pain SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 9th International Forum for Primary Care Research on Low Back Pain CY OCT 06, 2007 CL Mallorca, SPAIN ID EXPENDITURES; PATTERNS; EFFICACY; OUTCOMES AB Background: Acupuncture is a popular complementary and alternative treatment for chronic back pain. Recent European trials suggest similar short-term benefits from real and sham acupuncture needling. This trial addresses the importance of needle placement and skin penetration in eliciting acupuncture effects for patients with chronic low back pain. Methods: A total of 638 adults with chronic mechanical low back pain were randomized to individualized acupuncture, standardized acupuncture, simulated acupuncture, or usual care. Ten treatments were provided over 7 weeks by experienced acupuncturists. The primary outcomes were back-related dysfunction (Roland-Morris Disability Questionnaire score; range, 0-23) and symptom bothersomeness (0-10 scale). Outcomes were assessed at baseline and after 8, 26, and 52 weeks. Results: At 8 weeks, mean dysfunction scores for the individualized, standardized, and simulated acupuncture groups improved by 4.4, 4.5, and 4.4 points, respectively, compared with 2.1 points for those receiving usual care (P < .001). Participants receiving real or simulated acupuncture were more likely than those receiving usual care to experience clinically meaningful improvements on the dysfunction scale (60% vs 39%; P < .001). Symptoms improved by 1.6 to 1.9 points in the treatment groups compared with 0.7 points in the usual care group (P < .001). After 1 year, participants in the treatment groups were more likely than those receiving usual care to experience clinically meaningful improvements in dysfunction (59% to 65% vs 50%, respectively; P=.02) but not in symptoms (P > .05). Conclusions: Although acupuncture was found effective for chronic low back pain, tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits. These findings raise questions about acupuncture's purported mechanisms of action. It remains unclear whether acupuncture or our simulated method of acupuncture provide physiologically important stimulation or represent placebo or nonspecific effects. C1 [Cherkin, Daniel C.; Sherman, Karen J.; Erro, Janet H.; Ichikawa, Laura; Barlow, William E.; Delaney, Kristin; Hawkes, Rene] Ctr Hlth Studies, Seattle, WA 98101 USA. [Avins, Andrew L.; Hamilton, Luisa; Pressman, Alice] No Calif Kaiser Permanente, Div Res, Oakland, CA USA. [Barlow, William E.] Canc Res & Biostat, Seattle, WA USA. [Khalsa, Partap S.] Natl Ctr Complementary & Alternat Med, Div Extramural Res & Training, NIH, Bethesda, MD USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. RP Cherkin, DC (reprint author), Ctr Hlth Studies, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. EM cherkin.d@ghc.org FU Intramural NIH HHS [Z99 AT999999]; NCCIH NIH HHS [U01 AT 001110, U01 AT001110, U01 AT001110-01A1] NR 39 TC 178 Z9 190 U1 4 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 11 PY 2009 VL 169 IS 9 BP 858 EP 866 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 444PX UT WOS:000265994000006 PM 19433697 ER PT J AU Chakraborty, T Perlot, T Subrahmanyam, R Jani, A Goff, PH Zhang, Y Ivanova, I Alt, FW Sen, R AF Chakraborty, Tirtha Perlot, Thomas Subrahmanyam, Ramesh Jani, Anant Goff, Peter H. Zhang, Yu Ivanova, Irina Alt, Frederick W. Sen, Ranjan TI A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BETA-GLOBIN LOCUS; RECEPTOR-GENE REARRANGEMENT; MOUSE IGH LOCUS; HISTONE ACETYLATION; CONTROL REGION; V(D)J RECOMBINATION; CORE REGION; CHROMATIN; METHYLATION; MU AB A tissue-specific transcriptional enhancer, E mu, has been implicated in developmentally regulated recombination and transcription of the immunoglobulin heavy chain (IgH) gene locus. We demonstrate that deleting 220 nucleotides that constitute the core E. results in partially active locus, characterized by reduced histone acetylation, chromatin remodeling, transcription, and recombination, whereas other hallmarks of tissue-specific locus activation, such as loss of H3K9 dimethylation or gain of H3K4 dimethylation, are less affected. These observations define E mu-independent and E mu-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression. C1 [Chakraborty, Tirtha; Subrahmanyam, Ramesh; Ivanova, Irina; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Jani, Anant] Yale Univ, Sch Med, Program Immunol, New Haven, CT 06510 USA. [Perlot, Thomas] Univ Vienna, A-1010 Vienna, Austria. [Perlot, Thomas; Goff, Peter H.; Zhang, Yu; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Perlot, Thomas; Goff, Peter H.; Zhang, Yu; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. RP Sen, R (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM rs465z@nih.gov RI Subrahmanyam, Ramesh/K-5503-2012 FU National Institutes of Health [AI2047]; Intramural Research Program of the National Institute on Aging (Baltimore, MD) FX T. Perlot is supported by a Boehringer Ingelheim Fonds PhD scholarship. F. W. Alt is an investigator of the Howard Hughes Medical Institute. This work was supported by National Institutes of Health grant AI2047 (to F. W. Alt) and by the Intramural Research Program of the National Institute on Aging (Baltimore, MD). The authors have no conflicting financial interests. NR 35 TC 30 Z9 31 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 11 PY 2009 VL 206 IS 5 BP 1019 EP 1027 DI 10.1084/jem.20081621 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444WB UT WOS:000266010000009 PM 19414554 ER PT J AU Keele, BF Li, H Learn, GH Hraber, P Giorgi, EE Grayson, T Sun, CX Chen, YL Yeh, WW Letvin, NL Mascola, JR Nabel, GJ Haynes, BF Bhattacharya, T Perelson, AS Korber, BT Hahn, BH Shaw, GM AF Keele, Brandon F. Li, Hui Learn, Gerald H. Hraber, Peter Giorgi, Elena E. Grayson, Truman Sun, Chuanxi Chen, Yalu Yeh, Wendy W. Letvin, Norman L. Mascola, John R. Nabel, Gary J. Haynes, Barton F. Bhattacharya, Tanmoy Perelson, Alan S. Korber, Bette T. Hahn, Beatrice H. Shaw, George M. TI Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; GASTROINTESTINAL-TRACT; HETEROSEXUAL TRANSMISSION; TYPE-1 TRANSMISSION; NONHUMAN-PRIMATES; VIRAL LOAD; MULTIPLE; SIV; DIVERSITY AB We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences ( median of 48 per animal) were determined from plasma virion RNA 1-5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1-5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research. C1 [Keele, Brandon F.; Li, Hui; Learn, Gerald H.; Grayson, Truman; Sun, Chuanxi; Chen, Yalu; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Birmingham, AL 35223 USA. [Hraber, Peter; Giorgi, Elena E.; Bhattacharya, Tanmoy; Perelson, Alan S.; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Bhattacharya, Tanmoy; Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA. [Giorgi, Elena E.] Univ Massachusetts, Amherst, MA 01002 USA. [Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Letvin, Norman L.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Yeh, Wendy W.; Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02115 USA. RP Shaw, GM (reprint author), Univ Alabama, Birmingham, AL 35223 USA. EM gshaw@uab.edu RI Bhattacharya, Tanmoy/J-8956-2013; OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897 FU Center for HIV/AIDS Vaccine Immunology; National Institutes of Health [AI67854, AI27767]; Bill and Melinda Gates Foundation [37874]; American Foundation for AIDS Research [106997-3] FX This work was supported by the Center for HIV/AIDS Vaccine Immunology and by grants from the National Institutes of Health (AI67854 and AI27767), the Bill and Melinda Gates Foundation (# 37874), and the American Foundation for AIDS Research (106997-3). NR 66 TC 200 Z9 200 U1 1 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 11 PY 2009 VL 206 IS 5 BP 1117 EP 1134 DI 10.1084/jem.20082831 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444WB UT WOS:000266010000017 PM 19414559 ER PT J AU Robison, LL Armstrong, GT Boice, JD Chow, EJ Davies, SM Donaldson, SS Green, DM Hammond, S Meadows, AT Mertens, AC Mulvihill, JJ Nathan, PC Neglia, JP Packer, RJ Rajaraman, P Sklar, CA Stovall, M Strong, LC Yasui, Y Zeltzer, LK AF Robison, Leslie L. Armstrong, Gregory T. Boice, John D. Chow, Eric J. Davies, Stella M. Donaldson, Sarah S. Green, Daniel M. Hammond, Sue Meadows, Anna T. Mertens, Ann C. Mulvihill, John J. Nathan, Paul C. Neglia, Joseph P. Packer, Roger J. Rajaraman, Preetha Sklar, Charles A. Stovall, Marilyn Strong, Louise C. Yasui, Yutaka Zeltzer, Lonnie K. TI The Childhood Cancer Survivor Study: A National Cancer Institute-Supported Resource for Outcome and Intervention Research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; QUALITY-OF-LIFE; BODY-MASS-INDEX; ADULT SURVIVORS; ADOLESCENT CANCER; 5-YEAR SURVIVORS; GROWTH-HORMONE; HODGKINS-DISEASE; HEALTH-CARE AB Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors. C1 [Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. Natl Canc Inst, Int Epidemiol Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. OH State Univ, Sch Med, Dept Pathol, Columbus, OH USA. Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Canc Genet, Houston, TX 77030 USA. Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada. Univ Alberta, Sch Publ Hlth, Dept Publ Hlth Sci, Edmonton, AB, Canada. RP Robison, LL (reprint author), St Jude Childrens Hosp, Dept Epidemiol & Canc Control, 262 Danny Thomas Pl,Mail Stop 735, Memphis, TN 38105 USA. EM les.robison@stjude.org RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [U24 CA055727, U24 CA 55727] NR 103 TC 242 Z9 244 U1 2 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2009 VL 27 IS 14 BP 2308 EP 2318 DI 10.1200/JCO.2009.22.3339 PG 11 WC Oncology SC Oncology GA 447MM UT WOS:000266195200002 PM 19364948 ER PT J AU Meadows, AT Friedman, DL Neglia, JP Mertens, AC Donaldson, SS Stovall, M Hammond, S Yasui, Y Inskip, PD AF Meadows, Anna T. Friedman, Debra L. Neglia, Joseph P. Mertens, Ann C. Donaldson, Sarah S. Stovall, Marilyn Hammond, Sue Yasui, Yutaka Inskip, Peter D. TI Second Neoplasms in Survivors of Childhood Cancer: Findings From the Childhood Cancer Survivor Study Cohort SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MALIGNANT NEOPLASMS; FOLLOW-UP; 5-YEAR SURVIVORS; NONMELANOMA SKIN; HODGKIN-DISEASE; THYROID-CANCER; BREAST-CANCER; RISK; CHILDREN AB Purpose To review the reports of subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort that were made through January 1, 2006, and published before July 31, 2008, and to discuss the host-, disease-, and therapy-related risk factors associated with SNs. Patients and Methods SNs were ascertained by survivor self-reports and subsequently confirmed by pathology findings or medical record review. Cumulative incidence of SNs and standardized incidence ratios for second malignant neoplasms (SMNs) were calculated. The impact of host-, disease-, and therapy-related risk factors was evaluated by Poisson regression. Results Among 14,358 cohort members, 730 reported 802 SMNs (excluding nonmelanoma skin cancers). This represents a 2.3-fold increase in the number of SMNs over that reported in the first comprehensive analysis of SMNs in the CCSS cohort, which was done 7 years ago. In addition, 66 cases of meningioma and 1,007 cases of nonmelanoma skin cancer were diagnosed. The 30-year cumulative incidence of SMNs was 9.3% and that of nonmelanoma skin cancer was 6.9%. Risk of SNs remains elevated for more than 20 years of follow-up for all primary childhood cancer diagnoses. In multivariate analyses, risks differ by SN subtype, but include radiotherapy, age at diagnosis, sex, family history of cancer, and primary childhood cancer diagnosis. Female survivors whose primary childhood cancer diagnosis was Hodgkin's lymphoma or sarcoma and who received radiotherapy are at particularly increased risk. Analyses of risk associated with radiotherapy demonstrated different dose-response curves for specific SNs. Conclusion Childhood cancer survivors are at a substantial and increasing risk for SNs, including nonmelanoma skin cancer and meningiomas. Health care professionals should understand the magnitude of these risks to provide individuals with appropriate counseling and follow-up. C1 [Meadows, Anna T.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Vanderbilt Univ, Nashville, TN USA. Univ Minnesota, Minneapolis, MN USA. Emory Univ, Atlanta, GA 30322 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Hammond Univ Alberta, Edmonton, AB, Canada. Natl Canc Inst, Rockville, MD USA. RP Meadows, AT (reprint author), Childrens Hosp Philadelphia, 34th St & Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM meadows@chop.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [U24 CA055727, U24 CA55727] NR 35 TC 202 Z9 203 U1 3 U2 15 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2009 VL 27 IS 14 BP 2356 EP 2362 DI 10.1200/JCO.2008.21.1920 PG 7 WC Oncology SC Oncology GA 447MM UT WOS:000266195200006 PM 19255307 ER PT J AU Davis, KL Gray, ES Moore, PL Decker, JM Salomon, A Montefiori, DC Graham, BS Keefer, MC Pinter, A Morris, L Hahn, BH Shaw, GM AF Davis, Katie L. Gray, Elin S. Moore, Penny L. Decker, Julie M. Salomon, Aidy Montefiori, David C. Graham, Barney S. Keefer, Michael C. Pinter, Abraham Morris, Lynn Hahn, Beatrice H. Shaw, George M. TI High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination SO VIROLOGY LA English DT Article DE HIV-1; HIV-2; Variable loop 3; Neutralizing antibodies; Acute HIV-1 infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBTYPE-C INFECTION; MONOCLONAL-ANTIBODIES; TYPE-1 ENVELOPE; CLADE-A; GP120; DOMAINS; RESPONSES; EPITOPES; SEQUENCE AB Identifying the earliest neutralizing antibody specificities that are elicited following infection or vaccination by HIV-1 is an important objective of current HIV/AIDS vaccine research. We have shown previously that transplantation of HIV-1 V3 epitopes into an HIV-2 envelope (Env) scaffold provides a sensitive and specific means to detect and quantify HIV-1 V3 epitope specific neutralizing antibodies (Nabs) in human sera. Here, we employ this HIV-2/HIV-1 V3 scaffolding strategy to study the kinetics of development and breadth of V3-specific Nabs in longitudinal sera from individuals acutely infected with clade C or clade B HIV-1 and in human Subjects immunized with clade B HIV-1 immunogens. HIV-2/HIV-1 chimeras containing V3 sequences matched to virus type (HIV-2 or HIV-1), subtype (clade B or C), or strain (autologous or heterologous) were used as test reagents. We found that by 3-8 weeks post infection, 12 of 14 clade C subjects had a median IC(50) V3-specific Nab titer of 1:700 against chimeric viruses containing a heterologous clade C V3. By 5 months post-infection, all 14 subjects were positive for V3-specific Nabs with median titers of 1:8000 against heterologous clade C V3 and 1:1300 against clade B V3. Two acutely infected clade B patients developed heterologous clade B V3-specific Nabs at titers of 1:300 and 1:1800 by 13 weeks of infection and 1:5000 and 1:11000 by 7 months of infection. Titers were not different against chimeras containing autologous clade B V3 sequences. Each of 10 uninfected normal human volunteers who were immunized with clade B HIV-1 Env immunogens, but none of five sham immunized control subjects, developed V3-specific Nabs titers as high as 1:3000 (median 1: 1300; range 1:700-1:3000). None of the HIV-1 infected or vaccinated subjects had antibodies that neutralized primary HIV-1 virus strains. These results indicate that high-titer, broadly reactive V3-specific antibodies are among the first to be elicited during acute and early HIV-1 infection and following vaccination but these antibodies lack neutralizing potency against primary HIV-1 viruses, which effectively shield V3 from antibody binding to the functional Env trimer. (C) 2009 Elsevier Inc. All rights reserved. C1 [Decker, Julie M.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Davis, Katie L.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Gray, Elin S.; Moore, Penny L.; Morris, Lynn] Natl Inst Communicable Dis, AIDS Virus Res Unit, Johannesburg, South Africa. [Salomon, Aidy; Pinter, Abraham] Publ Hlth Res Inst, Newark, NJ 07103 USA. [Salomon, Aidy; Pinter, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Keefer, Michael C.] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. RP Shaw, GM (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA. EM gshaw@uab.edu OI Moore, Penny/0000-0001-8719-4028; , Lynn/0000-0003-3961-7828; Gray, Elin/0000-0002-8613-3570 FU Bill and Melinda Gates Foundation [37874, 38619, 38631]; NIH [AI 67854, AI 27767, AI 46238, U01 AI-46747] FX we thank the CAPRISA leadership, S. S. Abdool Karim, K. Mlisana, and C. Williamson, as well as the clinical and laboratory staff at CAPRISA for serum specimens; L. Corey and J. McElrath for providing HVTN Protocol 203 serum specimens; S. Meleth and H. Kuo for statistical analysis; D. Edwards for technical assistance; and the clinical and sequencing cores of the UAB Center for AIDS Research. This work served as partial fulfillment of the requirements for the Ph. D. degree for K.L. Davis and was supported by grants from the Bill and Melinda Gates Foundation (#37874, #38619, #38631) and the NIH (AI 67854, AI 27767, AI 46238, and U01 AI-46747). NR 42 TC 50 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 2009 VL 387 IS 2 BP 414 EP 426 DI 10.1016/j.virol.2009.02.022 PG 13 WC Virology SC Virology GA 439YF UT WOS:000265663100020 PM 19298995 ER PT J AU Shannon, JG Cockrell, DC Takahashi, K Stahl, GL Heinzen, RA AF Shannon, Jeffrey G. Cockrell, Diane C. Takahashi, Kazue Stahl, Gregory L. Heinzen, Robert A. TI Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent SO BMC IMMUNOLOGY LA English DT Article ID Q-FEVER; RELAPSING FEVER; DENDRITIC CELLS; DEFICIENT MICE; INFECTION; MACROPHAGES; CLEARANCE; LIPOPOLYSACCHARIDE; MECHANISMS; GENERATION AB Background: The obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonosis Q fever. The intracellular niche of C. burnetii has led to the assumption that cell-mediated immunity is the most important immune component for protection against this pathogen. However, passive immunization with immune serum can protect naive animals from challenge with virulent C. burnetii, indicating a role for antibody (Ab) in protection. The mechanism of this Ab-mediated protection is unknown. Therefore, we conducted a study to determine whether Fc receptors (FcR) or complement contribute to Ab-mediated immunity (AMI) to C. burnetii. Results: Virulent C. burnetii infects and replicates within human dendritic cells (DC) without inducing their maturation or activation. We investigated the effects of Ab opsonized C. burnetii on human monocyte-derived and murine bone marrow-derived DC. Infection of DC with Ab-opsonized C. burnetii resulted in increased expression of maturation markers and inflammatory cytokine production. Bacteria that had been incubated with naive serum had minimal effect on DC, similar to virulent C. burnetii alone. The effect of Ab opsonized C. burnetii on DC was FcR dependent as evidenced by a reduced response of DC from FcR knockout (FcR k/o) compared to C57Bl/6 (B6) mice. To address the potential role of FcR in Ab-mediated protection in vivo, we compared the response of passively immunized FcR k/o mice to the B6 controls. Interestingly, we found that FcR are not essential for AMI to C. burnetii in vivo. We subsequently examined the role of complement in AMI by passively immunizing and challenging several different strains of complement-deficient mice and found that AMI to C. burnetii is also complement-independent. Conclusion: Despite our data showing FcR-dependent stimulation of DC in vitro, Ab-mediated immunity to C. burnetii in vivo is FcR-independent. We also found that passive immunity to this pathogen is independent of complement. C1 [Shannon, Jeffrey G.; Cockrell, Diane C.; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH,Coxiella Pathogenesis Sect, Hamilton, MT 59840 USA. [Stahl, Gregory L.] Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med,Sch Med, Boston, MA 02115 USA. [Takahashi, Kazue] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Lab Dev Immunol, Boston, MA USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH,Coxiella Pathogenesis Sect, Hamilton, MT 59840 USA. EM jshannon@niaid.nih.gov; dcockrell@niaid.nih.gov; ktakahashi1@partners.org; gstahl@zeus.bwh.harvard.edu; rheinzen@niaid.nih.gov RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 FU Intramural Research Program of the National Institutes of Health [AI052343, HL56068, HL52886, DE016191, DE017821]; National Institute of Allergy and Infectious Diseases FX We thank Shelly Robertson and Harlan Caldwell for critical review of the manuscript and Gary Hettrick and Anita Mora for graphic illustrations. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (J.G.S., D.C.C, and R.A.H.), NIH grant AI052343 (K.T.), and NIH grants HL56068, HL52886, DE016191 and DE017821 (G.A.S.). NR 35 TC 19 Z9 20 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD MAY 8 PY 2009 VL 10 AR 26 DI 10.1186/1471-2172-10-26 PG 8 WC Immunology SC Immunology GA 454PP UT WOS:000266695000002 PM 19426498 ER PT J AU Duncan, CG Leary, RJ Lin, JCH Cummins, J Di, CH Schaefer, CF Wang, TL Riggins, GJ Edwards, J Bigner, D Kopelovich, L Vogelstein, B Kinzler, KW Velculescu, VE Yan, H AF Duncan, Christopher G. Leary, Rebecca J. Lin, Jimmy Cheng-Ho Cummins, Jordan Di, Chunhui Schaefer, Carl F. Wang, Tian-Li Riggins, Gregory J. Edwards, Jennifer Bigner, Darell Kopelovich, Levy Vogelstein, Bert Kinzler, Kenneth W. Velculescu, Victor E. Yan, Hai TI Identification of microbial DNA in human cancer SO BMC MEDICAL GENOMICS LA English DT Article ID UNRECOGNIZED PATHOGENS; SEARCH; SEQUENCES; TRANSCRIPTOME; SUBTRACTION; CARCINOMA; DATABASE; GENOMES; TUMOR AB Background: Microorganisms have been associated with many types of human diseases; however, a significant number of clinically important microbial pathogens remain to be discovered. Methods: We have developed a genome-wide approach, called Digital Karyotyping Microbe Identification (DK-MICROBE), to identify genomic DNA of bacteria and viruses in human disease tissues. This method involves the generation of an experimental DNA tag library through Digital Karyotyping (DK) followed by analysis of the tag sequences for the presence of microbial DNA content using a compiled microbial DNA virtual tag library. Results: To validate this technology and to identify pathogens that may be associated with human cancer pathogenesis, we used DK-MICROBE to determine the presence of microbial DNA in 58 human tumor samples, including brain, ovarian, and colorectal cancers. We detected DNA from Human herpesvirus 6 (HHV-6) in a DK library of a colorectal cancer liver metastasis and in normal tissue from the same patient. Conclusion: DK-MICROBE can identify previously unknown infectious agents in human tumors, and is now available for further applications for the identification of pathogen DNA in human cancer and other diseases. C1 [Duncan, Christopher G.; Di, Chunhui; Bigner, Darell; Yan, Hai] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Pathol,Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. [Leary, Rebecca J.; Lin, Jimmy Cheng-Ho; Cummins, Jordan; Wang, Tian-Li; Vogelstein, Bert; Kinzler, Kenneth W.; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. [Leary, Rebecca J.; Lin, Jimmy Cheng-Ho; Cummins, Jordan; Wang, Tian-Li; Vogelstein, Bert; Kinzler, Kenneth W.; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA. [Schaefer, Carl F.] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. [Riggins, Gregory J.; Edwards, Jennifer] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21231 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Yan, H (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Dept Pathol,Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. EM chris.duncan@duke.edu; rleary1@jhmi.edu; jimmy.lin@jhmi.edu; jordanmcummins@gmail.com; di.chunhui@duke.edu; schaefec@mail.nih.gov; tlw@welch.jhu.edu; griggin1@jhmi.edu; jennifer.b.edwards@gmail.com; bigne001@mc.duke.edu; kopelovl@mail.nih.gov; bertvog@gmail.com; kinzlke@jhmi.edu; velculescu@jhmi.edu; hai.yan@duke.edu FU Pediatric Brain Tumor Foundation Institute at Duke; Damon Runyon Foundation Scholar Award; Southeastern Brain Tumor Foundation Research Grant; Alex's Lemonade Stand Foundation Innovation Award; V Foundation Cancer Research; NIH [R01CA118822, R01CA121113, NS20023-21, NS052507, R37CA11898-34, R37 CA 011898-38]; Brain Tumor Specialized Programs of Research Excellence [5P20CA096890-02]; Duke Comprehensive Cancer Center [2P30CA14236]; Accelerate Brain Tumor Cure Foundation; National Cancer Center, NINDS [5P50 NS20023-25]; NIH SPORE [5P50 CA108786-4]; NCI [HHSN261200433002C]; Pew Charitable Trusts FX This work was supported by The Pediatric Brain Tumor Foundation Institute at Duke; a Damon Runyon Foundation Scholar Award; a Southeastern Brain Tumor Foundation Research Grant; an Alex's Lemonade Stand Foundation Innovation Award; a V Foundation Cancer Research Grant; NIH Grants R01CA118822, R01CA121113, NS20023-21, NS052507 and R37CA11898-34; Brain Tumor Specialized Programs of Research Excellence 5P20CA096890-02; Duke Comprehensive Cancer Center Support Grant 2P30CA14236; and grants from the Accelerate Brain Tumor Cure Foundation and the National Cancer Center, NINDS Grant 5P50 NS20023-25, NIH SPORE Grant 5P50 CA108786-4, NIH Merit Award R37 CA 011898-38, NCI Division of Cancer Prevention contract HHSN261200433002C, and The Pew Charitable Trusts. NR 34 TC 13 Z9 15 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD MAY 8 PY 2009 VL 2 AR 22 DI 10.1186/1755-8794-2-22 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 532VD UT WOS:000272777300001 PM 19426505 ER PT J AU Wolf, R Voscopoulos, C Winston, J Dharamsi, A Goldsmith, P Gunsior, M Vonderhaar, BK Olson, M Watson, PH Yuspa, SH AF Wolf, Ronald Voscopoulos, Christopher Winston, Jason Dharamsi, Alif Goldsmith, Paul Gunsior, Michele Vonderhaar, Barbara K. Olson, Melanie Watson, Peter H. Yuspa, Stuart H. TI Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer SO CANCER LETTERS LA English DT Article DE Mammary cancer; Calcium binding proteins; S100; Psoriasis; Myoepithelial cells ID PSORIASIN S100A7 EXPRESSION; MESSENGER-RNA; IN-SITU; PROGRESSION; SKIN; CARCINOMA; RECEPTOR; CELLS; JAB1 AB Human S100A7 (psoriasin) is considered a marker for specific stages of breast cancer. hS100A15 is almost identical to hS100A7 and difficult to discriminate. We developed specific probes to distinguish hS100A7 and hS100A15, and demonstrate their differential distribution in normal breast tissue. Further, hS100A7 and S100A15 transcripts are elevated in ER/PR negative breast cancers, but hS100A15 protein is detected in all cancer specimens while hS100A7 protein is sporadically expressed. The differential regulation, expression and distribution of hS100A7 and hS100A15 and their reported distinct functions are compelling reasons to discriminate among these proteins in normal breast and breast cancers. Published by Elsevier Ireland Ltd. C1 [Wolf, Ronald; Voscopoulos, Christopher; Winston, Jason; Dharamsi, Alif; Yuspa, Stuart H.] NCI, NIH, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Goldsmith, Paul; Gunsior, Michele] NCI, NIH, Antibody & Prot Purificat Unit, Ctr Canc Res, Bethesda, MD 20892 USA. [Vonderhaar, Barbara K.] NCI, NIH, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Olson, Melanie; Watson, Peter H.] BC Canc Agcy, Deeley Res Ctr, Victoria, BC, Canada. RP Yuspa, SH (reprint author), NCI, NIH, Lab Canc Biol & Genet, Ctr Canc Res, 37 Convent Dr,MSC 4255,Bldg 37,Room 4068A, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research; German Research Foundation (DFG); Emmy-Noether Program [Wo 843/2-1] FX We thank Dr. Akira Oshima for histological evaluation. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Ronald Wolf is funded by the German Research Foundation (DFG), Emmy-Noether Program (Wo 843/2-1). NR 20 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 8 PY 2009 VL 277 IS 1 BP 101 EP 107 DI 10.1016/j.canlet.2008.11.032 PG 7 WC Oncology SC Oncology GA 432DT UT WOS:000265114400012 PM 19136201 ER PT J AU Son, MJ Woolard, K Nam, DH Lee, J Fine, HA AF Son, Myung Jin Woolard, Kevin Nam, Do-Hyun Lee, Jeongwu Fine, Howard A. TI SSEA-1 Is an Enrichment Marker for Tumor-Initiating Cells in Human Glioblastoma SO CELL STEM CELL LA English DT Article ID CANCER STEM-CELLS; NERVOUS-SYSTEM; PROGENITOR CELLS; CD133; BRAIN; PROTEIN; GLIOMA; IDENTIFICATION; ANTIGEN; GROWTH AB CD133+ populations of human glioblastoma multi-forme (GBM) cells are reportedly enriched for tumor stem cells (TSCs) or tumor-initiating cells (TICs). Approximately 40% of freshly isolated GBM specimens, however, do not contain CD133+ tumor cells, raising the possibility that CD133 may not be a universal enrichment marker for GBM TSCs/TiCs. Here we demonstrate that stage-specific embryonic antigen 1(SSEA-1/LeX)+ GBM cells fulfill the functional criteria for TSC/TIC, since (1) SSEA-1+ cells are highly tumorigenic in vivo, unlike SSEA-1-cells; (2) SSEA-1+ cells can give rise to both SSEA-1+ and SSEA-1-cells, thereby establishing a cellular hierarchy; and (3) SSEA-1+ cells have self-renewal and multilineage differentiation potentials. A distinct subpopulation of SSEA-1+ cells was present in all but one of the primary GBMsexamined (n = 24), and most CD133+ tumor cells were also SSEA-1+, suggesting that SSEA-1 may be a general TSC/TIC enrichment marker in human GBMs. C1 [Son, Myung Jin; Woolard, Kevin; Lee, Jeongwu; Fine, Howard A.] NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. [Nam, Do-Hyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurosurg, Seoul 135710, South Korea. RP Lee, J (reprint author), NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. EM leejeo@mail.nih.gov; hfine@mail.nih.gov RI Nam, Do Hyun/C-9656-2011 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; NINDS FACS Facility; NINDS Light Imaging Facility FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Dr. Dragan Maric (NINDS FACS Facility) for his valuable contributions to this work. We also thank Dr. Carolyn Smith (NINDS Light Imaging Facility) and Dr. Hong Sug Kim for their valuable contributions to this work. NR 53 TC 313 Z9 319 U1 3 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 8 PY 2009 VL 4 IS 5 BP 440 EP 452 DI 10.1016/j.stem.2009.03.003 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 445SF UT WOS:000266071100012 PM 19427293 ER PT J AU Hanover, JA Love, DC Prinz, WA AF Hanover, John A. Love, Dona C. Prinz, William A. TI Calmodulin-driven Nuclear Entry: Trigger for Sex Determination and Terminal Differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID HELIX TRANSCRIPTION FACTORS; TRANSPORT IN-VIVO; PROTEIN IMPORT; LOCALIZATION SIGNALS; CALCIUM/CALMODULIN INHIBITION; NUCLEOCYTOPLASMIC TRANSPORT; REVERSING MUTATIONS; CALCIUM REGULATION; FACTOR SEF2-1/E2-2; BINDING-PROTEIN AB We originally proposed that Ca(2+)-calmodulin mediates a novel nuclear entry pathway distinct from the canonic Ran-dependent pathway (Sweitzer, T. D., and Hanover, J. A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 14574-14579). Although seemingly redundant, Ca(2+)-calmodulin-driven nuclear entry is now known to facilitate nuclear delivery of architectural transcription factors to chromatin. Intriguingly, defects in calmodulin-driven nuclear import of the transcription factors SRY and SOX9 in Sertoli cells lead to human sex reversal diseases with altered male gonad development. Calmodulin-triggered nuclear entry is an evolutionarily ancient feature of eukaryotes observed from yeast to man. Ca(2+)-calmodulin-triggered nuclear entry of key architectural transcription factors is a potentially key epigenetic regulator of terminal differentiation in response to cell signaling. C1 [Hanover, John A.; Love, Dona C.; Prinz, William A.] NIDDK, Lab Cell Biochem & Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. EM jah@helix.nih.gov NR 63 TC 25 Z9 25 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 12593 EP 12597 DI 10.1074/jbc.R800076200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300002 PM 19126540 ER PT J AU Salgado, MT Nagababu, E Rifkind, JM AF Salgado, Maria T. Nagababu, Enika Rifkind, Joseph M. TI Quantification of Intermediates Formed during the Reduction of Nitrite by Deoxyhemoglobin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-NITROSOHEMOGLOBIN; HUMAN CIRCULATION; VASCULAR CONTROL; RED-CELL; OXIDE; HEMOGLOBIN; MECHANISM; BLOOD; NO; NITROSYLATION AB Nitric oxide (NO) plays a crucial role in human physiology by regulating vascular tone and blood flow. The short life-span of NO in blood requires a mechanism to retain NO bioactivity in the circulation. Recent studies have suggested a mechanism involving the reduction of nitrite back to NO by deoxyhemoglobin in RBCs. A role for RBCs in transporting NO must, however, bypass the scavenging of NO in RBCs by hemoglobin. To understand how the nitrite reaction can deliver bioactive NO to the vasculature, we have studied the intermediates formed during the reaction. A reliable measure of the total concentration of heme-associated nitrite/NO intermediates formed was provided by combining filtration to measure free nitrite by chemiluminescence and electron paramagnetic resonance to measure the final product Hb(II)NO. By modifying the chemiluminescence method used to detect NO, we have been able to identify two intermediates: 1) a heme-associated nitrite complex that is released as NO in acid solution in the presence of ascorbate and 2) an intermediate that releases NO at neutral pH in the presence of ferricyanide when reacted with an Fe(III) ligand like azide. This species designated as "Hb(II)NO(+)reversible arrow Hb(III)NO" has properties of both isomeric forms resulting in a slower NO dissociation rate and much higher stability than Hb(III)NO, but provides a potential source for bioactive NO, which can be released from the RBC. This detailed analysis of the nitrite reaction with deoxyHb provides important insights into the mechanism for nitrite induced vasodilation by RBCs. C1 [Salgado, Maria T.; Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), 251 Bayview Blvd,Rm 05B129, Baltimore, MD 21224 USA. EM rifkindj@mail.nih.gov FU National Institutes of Health NIA Intramural Research Program FX This work was supported, in whole or in part, by the National Institutes of Health NIA Intramural Research Program. NR 31 TC 30 Z9 30 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 12710 EP 12718 DI 10.1074/jbc.M808647200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300015 PM 19270306 ER PT J AU Panchal, RG Ulrich, RL Bradfute, SB Lane, D Ruthel, G Kenny, TA Iversen, PL Anderson, AO Gussio, R Raschke, WC Bavari, S AF Panchal, Rekha G. Ulrich, Ricky L. Bradfute, Steven B. Lane, Douglas Ruthel, Gordon Kenny, Tara A. Iversen, Patrick L. Anderson, Arthur O. Gussio, Rick Raschke, William C. Bavari, Sina TI Reduced Expression of CD45 Protein-tyrosine Phosphatase Provides Protection against Anthrax Pathogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; LETHAL TOXIN; BACTERIAL PATHOGENS; SIGNALING PATHWAYS; DENDRITIC CELLS; HUMAN-DISEASE; MACROPHAGES; INHIBITORS; SPORES; KINASE AB The modulation of cellular processes by small molecule inhibitors, gene inactivation, or targeted knockdown strategies combined with phenotypic screens are powerful approaches to delineate complex cellular pathways and to identify key players involved in disease pathogenesis. Using chemical genetic screening, we tested a library of known phosphatase inhibitors and identified several compounds that protected Bacillus anthracis infected macrophages from cell death. The most potent compound was assayed against a panel of sixteen different phosphatases of which CD45 was found to be most sensitive to inhibition. Testing of a known CD45 inhibitor and antisense phosphorodiamidate morpholino oligomers targeting CD45 also protected B. anthracis-infected macrophages from cell death. However, reduced CD45 expression did not protect anthrax lethal toxin ( LT) treated macrophages, suggesting that the pathogen and independently added LT may signal through distinct pathways. Subsequent, in vivo studies with both gene-targeted knockdown of CD45 and genetically engineered mice expressing reduced levels of CD45 resulted in protection of mice after infection with the virulent Ames B. anthracis. Intermediate levels of CD45 expression were critical for the protection, as mice expressing normal levels of CD45 or disrupted CD45 phosphatase activity or no CD45 all succumbed to this pathogen. Mechanism-based studies suggest that the protection provided by reduced CD45 levels results from regulated immune cell homeostasis that may diminish the impact of apoptosis during the infection. To date, this is the first report demonstrating that reduced levels of host phosphatase CD45 modulate anthrax pathogenesis. C1 [Panchal, Rekha G.; Ulrich, Ricky L.; Bradfute, Steven B.; Ruthel, Gordon; Anderson, Arthur O.; Bavari, Sina] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Lane, Douglas; Kenny, Tara A.] NCI, NIH, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. [Iversen, Patrick L.] AVI BioPharma Inc, Corvallis, OR 97333 USA. [Gussio, Rick] NCI, NIH, Target Struct Based Drug Discovery Grp, Informat Technol Branch,Dev Therapeut Program, Frederick, MD 21702 USA. [Raschke, William C.] Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. [Raschke, William C.] Virogenics Inc, Del Mar, CA 92014 USA. RP Panchal, RG (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Ft Detrick, MD 21702 USA. EM rekha.panchal@amedd.army.mil; sina.bavari@amedd.army.mil FU National Institutes of Health [N01-CO-12400, R43 A1055102]; Defense Threat Reduction Agency; NIAID; Developmental Therapeutics Program; Division of Cancer Treatment and Diagnosis of the NCI FX This work was supported, in whole or in part, by National Institutes of Health Grant N01-CO-12400, by the Defense Threat Reduction Agency (to S. B. and R. G. P.), the NIAID, National Institutes of Health Grant R43 A1055102 (to W. C. R.), and by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the NCI, National Institutes of Health. NR 56 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 12874 EP 12885 DI 10.1074/jbc.M809633200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300033 PM 19269962 ER PT J AU Qiu, ZJ Dyer, KD Xie, ZH Radinger, M Rosenberg, HF AF Qiu, Zhijun Dyer, Kimberly D. Xie, Zhihui Radinger, Madeleine Rosenberg, Helene F. TI GATA Transcription Factors Regulate the Expression of the Human Eosinophil-derived Neurotoxin (RNase 2) Gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-CELL LINE; INTRONIC ENHANCER; CATIONIC PROTEIN; RIBONUCLEASE GENES; RNS2 GENE; PROMOTER; FAMILY; DIFFERENTIATION; EVOLUTION; SEQUENCE AB The transcription factors GATA-1 and GATA-2 have been implicated in promoting differentiation of eosinophilic leukocytes. In this study, we examined the roles of GATA-1 and GATA-2 in activating transcription of the secretory ribonuclease, the eosinophil- derived neurotoxin (EDN/RNase 2). Augmented expression of both GATA-1 and GATA-2 was detected in eosinophil promyelocyte HL-60 clone 15 cells in response to biochemical differentiation with butyric acid. Deletion or mutation of one or both of the two consensus GATA-binding sites in the extended 1000-bp 5' promoter of the EDN gene resulted in profound reduction in reporter gene activity. Antibody-augmented electrophoretic mobility shift and chromatin immunoprecipitation analyses indicate that GATA-1 and GATA-2 proteins bind to both functional GATA consensus sequences in the EDN promoter. Interestingly, RNA silencing of GATA-1 alone had no impact on EDN expression; silencing of GATA-2 resulted in diminished expression of EDN, and also diminished expression of GATA-1 in both butyric acid-induced HL-60 clone 15 cells and in differentiating human eosinophils derived from CD34(+) hematopoietic progenitors. Likewise, overexpression of GATA-2 in uninduced HL-60 clone 15 cells resulted in augmented transcription of both EDN and GATA-1. Taken together, our data suggest that GATA-2 functions directly via interactions with the EDN promoter and also indirectly, via its ability to regulate the expression of GATA-1 in differentiating eosinophils and eosinophil cell lines. C1 [Qiu, Zhijun; Dyer, Kimberly D.; Xie, Zhihui; Radinger, Madeleine; Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU National Institutes of Health [AI00941, AI00942] FX This work was supported, in whole or in part, by National Institutes of Health Grants AI00941 and AI00942 NIAID (Division of Intramural Research). NR 49 TC 13 Z9 14 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 13099 EP 13109 DI 10.1074/jbc.M807307200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300057 PM 19279013 ER PT J AU Weisz, A Mazzola, EP Ito, Y AF Weisz, Adrian Mazzola, Eugene P. Ito, Yoichiro TI Preparative separation of di- and trisulfonated components of Quinoline Yellow using affinity-ligand pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 5th International Conference on Countercurrent Chromatography CY JUL 26-29, 2008 CL Rio de Janeiro, BRAZIL DE Counter-current chromatography; pH-zone-refining CCC; Quinoline Yellow; D&C Yellow No. 10; Sulfonic acids; Disulfonic acids; Trisulfonic acid; Isomers; Ligand; Dyes; NMR ID TANDEM MASS-SPECTROMETRY; ACIDS; PURIFICATION AB Four positionally isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dionedisulfonic acids (SA) and one triSA, components of the color additive Quinoline Yellow (QY, Color Index No. 47005), were isolated from the dye mixture by affinity-ligand pH-zone-refining counter-current chromatography (CCC) through complementary use of ion-exchange and ion-pair reagents as the ligand. The added ligands facilitated the partitioning oft lie very polar polysulfonated components into the organic stationary phase of the two-phase solvent systems that consisted of isoamyl alcohol-methyl tert-butyl ether-acetonitrile-water (3:5:1 :7).(3:4: 1:7) or (3:11:5). Thus. separation of a 5-g portion Of QY using Sulfuric acid as the retainer and dodecylanime as the ligand (an ion-exchange reagent, 20% in the stationary phase), resulted in 1.21 g of 6',5-diSA and 1.69 g of 6',8',5-triSA, both of over 99% purity. A minor component, 8',4-diSA, not previously reported was also obtained (4.8 mg of over 94% purity) through a similar separation of a different batch Of QY using hydrochloric acid as the retainer and 10% dodecylamine as the ligand in the stationary phase. Two components that co-eluted (0.55 g) in the 5 g separation were separated when trifluoroacetic acid was used as the retainer and tetrabutylammonium hydroxide (an ion-pair reagent) as the ligand. The separation resulted in 20.7 mg of 6',4-diSA, not previously reported, and 111.8 mg of 8'.5-diSA, both of over 98% purity. The isolated Compounds were characterized by high-resolution mass spectrometry and proton nuclear magnetic resonance with correlated spectroscopy assignments. Published by Elsevier B.V. C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [Z99 HL999999] NR 26 TC 18 Z9 20 U1 5 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 8 PY 2009 VL 1216 IS 19 BP 4161 EP 4168 DI 10.1016/j.chroma.2009.02.064 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 444BU UT WOS:000265955900005 PM 19281993 ER PT J AU Ito, Y Clary, R Powell, J Knight, M Finn, TM AF Ito, Y. Clary, R. Powell, J. Knight, M. Finn, T. M. TI Improved spiral tube assembly for high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 5th International Conference on Countercurrent Chromatography CY JUL 26-29, 2008 CL Rio de Janeiro, BRAZIL DE Spiral tube support assembly; High-speed counter-current chromatography; Separation of proteins and peptides; Polymer phase system (TPAS) AB The original spiral tube support (STS) assembly is improved by changing the shape of the tubing, with I cm presses perpendicularly along the length. This modification interrupts the laminar flow of the mobile phase. The tubing in the four return grooves to the center of the rotor is flattened by a specially made pressing tool to increase the number of spiral layers and decrease the dead space Volume, thus increasing the column efficiency. The performance of this spiral tube assembly was tested in separations of dipeptides and proteins with Suitable polar two-phase solvent systems. The results revealed that the present system yields high partition efficiency with a satisfactory level of stationary phase retention in a short elution time. The present high-speed counter-current chromatographic (HSCCC) system will be efficiently applied to a broad spectrum of two-phase solvent systems including aqueous-aqueous polymer phase systems (TPAS) which are used for separation of biopolymers such as proteins and nucleic acids. Published by Elsevier B.V. C1 [Ito, Y.] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Knight, M.; Finn, T. M.] CC Biotech LLC, Rockville, MD 20850 USA. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov OI Knight, Martha/0000-0003-4863-8858 FU Intramural NIH HHS [Z99 HL999999] NR 7 TC 26 Z9 26 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 8 PY 2009 VL 1216 IS 19 BP 4193 EP 4200 DI 10.1016/j.chroma.2008.10.126 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 444BU UT WOS:000265955900010 PM 19062024 ER PT J AU Baldermann, S Fleischmann, P Bolten, M Watanabe, N Winterhalter, P Ito, Y AF Baldermann, Susanne Fleischmann, Peter Bolten, Mareike Watanabe, Naoharu Winterhalter, Peter Ito, Yoichiro TI Centrifugal precipitation chromatography, a powerful technique for the isolation of active enzymes from tea leaves (Camellia sinensis) SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 5th International Conference on Countercurrent Chromatography CY JUL 26-29, 2008 CL Rio de Janeiro, BRAZIL DE Centrifugal precipitation chromatography; CCD; Carotenoid cleavage; Tea; Camellia sinensis ID CAROTENOID CLEAVAGE DIOXYGENASE; FUNCTIONAL-CHARACTERIZATION; AMMONIUM-SULFATE; FRACTIONATION; IDENTIFICATION; PIGMENTS AB Centrifugal precipitation chromatography was developed approximately 10 years ago. In contrast to other counter-current chromatographic techniques, the centrifugal precipitation chromatography system is operated With two Mutually miscible Solutions separated by a cut-off membrane. Centrifugal precipitation chromatography was firstly introduced for the separation of proteins using all ammonium sulfate gradient. In this study we describe a novel approach using solvent-based protein precipitation for the isolation of active plant enzymes from tea leaves (Camellia sinensis) by centrifugal precipitation chromatography. We developed a gradient based oil acetone and Tris-buffer, because the biological activity of carotenases in tea leaves cannot be preserved in the presence of ammonium sulfate. Parameters Such as the critical solvent concentration, flow rate, buffer concentration, and sample load were determined and/or optimized. Subsequently, the newly developed separation protocol was successfully used for the isolation Of active carotenoid cleavage enzymes from tea leaves. The isolated enzymes showed high enzymatic activities and purities and could be directly used for enzymatic assays and structure elucidation. (C) 2009 Elsevier B.V. All rights reserved. C1 [Baldermann, Susanne; Watanabe, Naoharu] Shizuoka Univ, Grad Sch Sci & Technol, Integrated Biosci Sect, Suruga Ku, Shizuoka 4228529, Japan. [Baldermann, Susanne; Fleischmann, Peter; Bolten, Mareike; Winterhalter, Peter] Tech Univ Carolo Wilhelmina Braunschweig, Inst Food Chem, D-38106 Braunschweig, Germany. [Ito, Yoichiro] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Baldermann, S (reprint author), Shizuoka Univ, Grad Sch Sci & Technol, Integrated Biosci Sect, Suruga Ku, 836 Ohya, Shizuoka 4228529, Japan. EM s.baldermann@tu-bs.de RI Baldermann, Susanne/C-4292-2014 OI Baldermann, Susanne/0000-0002-1501-4320 FU Intramural NIH HHS [Z01 HL001047-09] NR 23 TC 6 Z9 6 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 8 PY 2009 VL 1216 IS 19 BP 4263 EP 4267 DI 10.1016/j.chroma.2009.01.102 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 444BU UT WOS:000265955900020 PM 19233373 ER PT J AU Wei, Y Xie, QQ Dong, WT Ito, Y AF Wei, Yun Xie, Qianqian Dong, Wanting Ito, Yoichiro TI Separation of epigallocatechin and flavonoids from Hypericum perforatum L. by high-speed counter-current chromatography and preparative high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 5th International Conference on Countercurrent Chromatography CY JUL 26-29, 2008 CL Rio de Janeiro, BRAZIL DE High-speed counter-current chromatography; Preparative high-performance liquid chromatography; Hypericum perforatum L.; Flavonoids; Epigallocatechin ID CONSTITUENTS AB High-speed counter-current chromatography (HSCCC) and preparative high-performance liquid chromatography (prep-HPLC) were successively used for the separation of epigallocatechin and flavonoids from Hypericum perforatum L. The two-phase solvent system composed of ethyl acetate-methanol-water (10:1:10, v/v) was used for HSCCC. About 900 mg of the crude extract was separated by HSCCC, yielding 7.8 mg of quercitrin at a purity of over 97%, 12.6 mg of quercetin at a purity of over 93%, and 38.9 mg of a mixture of hyperoside, isoquercitrin and miquelianin constituting over 97% of the fraction. A mixture of epigallocatechin arid avicularin pooled from three HSCCC runs, a total amount of 54.3 mg, was further separated by prep-HPLC yielding 23.4 mg of epigallocatechin and 15.3 mg of avicularin each at a purity of over 97%. (C) 2008 Elsevier B.V. All rights reserved. C1 [Wei, Yun; Xie, Qianqian; Dong, Wanting] Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, Beijing 100029, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Wei, Y (reprint author), Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, 15 Beisanhuan E Rd, Beijing 100029, Peoples R China. EM weiyun@mail.buct.edu.cn FU Intramural NIH HHS [Z99 HL999999] NR 14 TC 42 Z9 46 U1 0 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 8 PY 2009 VL 1216 IS 19 BP 4313 EP 4318 DI 10.1016/j.chroma.2008.12.056 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 444BU UT WOS:000265955900028 PM 19150073 ER PT J AU Beilhartz, GL Wendeler, M Baichoo, N Rausch, J Le Grice, S Gotte, M AF Beilhartz, Greg L. Wendeler, Michaela Baichoo, Noel Rausch, Jason Le Grice, Stuart Goette, Matthias TI HIV-1 Reverse Transcriptase Can Simultaneously Engage Its DNA/RNA Substrate at Both DNA Polymerase and RNase H Active Sites: Implications for RNase H Inhibition SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV; reverse transcriptase; RNase H; drug resistance; inhibitors ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNNATURAL AMINO-ACIDS; RIBONUCLEASE-H; CRYSTAL-STRUCTURE; CLEAVAGE SPECIFICITY; DRUG-RESISTANCE; RATCHET MODEL; PRIMER; TRANSLOCATION; MECHANISM AB Reverse transcriptase of the human immunodeficiency virus possesses DNA polymerase and ribonuclease (RNase) H activities. Although the nucleic acid binding cleft separating these domains can accommodate structually diverse duplexes, it is currently unknown whether regular DNA/RNA hybrids can simultaneously contact both active sites. In this study, we demonstrate that ligands capable of trapping the T-end of the primer at the polymerase active site affect the specificity of RNase H cleavage without altering the efficiency of the reaction. Experiments under single-turnover Conditions reveal that complexes with a bound nucleotide substrate show specific RNase H cleavage at template position -18, while complexes with the pyrophosphate analogue foscarnet show a specific cut at position -19. This pattern is indicative of post-translocated and pre-translocated conformations. The data are inconsistent with models postulating that the substrate toggles between both active sites, such that the primer 3'-terminus is disengaged from the polymerase active site when the template is in contact with the RNase H active site. In contrast, our findings provide strong evidence to suggest that the nucleic acid substrate can engage both active sites at the same time. As a consequence, the bound and intact DNA/RNA hybrid can restrict access of RNase H active site inhibitors. We have mapped the binding site of the recently discovered inhibitor beta-thujaplicinol between the RNase H active site and Y501 of the RNase H primer grip, and have shown that the inhibitor is unable to bind to a preformed reverse transcriptase-DNA/RNA complex. In conclusion, the bound nucleic acid substrate and in turn, active DNA synthesis can represent an obstacle to RNase H inhibition with compounds that bind to the RNase H active site. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Beilhartz, Greg L.; Goette, Matthias] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. [Wendeler, Michaela; Baichoo, Noel; Rausch, Jason; Le Grice, Stuart] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Gotte, M (reprint author), McGill Univ, Dept Microbiol & Immunol, Duff Med Bldg D-6,3775 Univ St, Montreal, PQ H3A 2B4, Canada. EM matthias.gotte@mcgill.ca FU Canadian Association; Canadian Institutes of Health Research; Center for Cancer Research, National Cancer Center, National Institutes of Health FX The authors would like to thank Suzanne McCormick and Jennifer T. Miller for excellent technical assistance. This; work was funded by a grant from the Canadian Association for AIDS Research to M. G. M.G. was the recipient of a national career award from the Canadian Institutes of Health Research. S. L.G. was supported by the intramural research program of the Center for Cancer Research, National Cancer Center, National Institutes of Health. NR 48 TC 39 Z9 40 U1 1 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 8 PY 2009 VL 388 IS 3 BP 462 EP 474 DI 10.1016/j.jmb.2009.03.025 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 447GD UT WOS:000266178700004 PM 19289131 ER PT J AU Bhaumik, P Xiao, HG Parr, CL Kiso, Y Gustchina, A Yada, RY Wlodawer, A AF Bhaumik, Prasenjit Xiao, Huogen Parr, Charity L. Kiso, Yoshiaki Gustchina, Alla Yada, Rickey Y. Wlodawer, Alexander TI Crystal Structures of the Histo-Aspartic Protease (HAP) from Plasmodium falciparum SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE aspartic proteases; inhibitor binding; crystal structure ID HYDROXYMETHYLCARBONYL HMC ISOSTERE; VIRUS TYPE-1 PROTEASE; ACTIVE-SITE; PLASMEPSIN-II; MOLECULAR REPLACEMENT; MACROMOLECULAR STRUCTURES; HISTOASPARTIC PROTEASE; MAXIMUM-LIKELIHOOD; MALARIA PARASITE; CATALYTIC SITE AB The structures of recombinant histo-aspartic protease (HAP) from malariacausing parasite Plasmodium falciparum as apoenzyme and in complex with two inhibitors, pepstatin A and KNI-10006, were solved at 2.5-, 3.3-, and 3.05-angstrom resolutions, respectively. In the apoenzyme crystals, HAP forms a tight dimer not seen previously in any aspartic protease. The interactions between the monomers affect the conformation of two flexible loops, the functionally important "flap" (residues 70-83) and its structural equivalent in the C-terminal domain (residues 238-245), as well as the orientation of helix 225-235. The flap is found in an open conformation in the apoenzyme. Unexpectedly, the active site of the apoenzyme contains a zinc ion tightly bound to His32 and Asp215 from one monomer and to Glu278A from the other monomer, with the coordination of Zn resembling that seen in metalloproteases. The flap is closed in the structure of the pepstatin A complex, whereas it is open in the complex with KNI-10006. Although the binding mode of pepstatin A is significantly different from that in other pepsin-like aspartic proteases, its location in the active site makes unlikely the previously proposed hypothesis that HAP is a serine protease. The binding mode of KNI-10006 is unusual compared with the binding of other inhibitors from the KNI series to aspartic proteases. The novel features of the HAP active site could facilitate design of specific inhibitors used in the development of antimalarial drugs. Published by Elsevier Ltd. C1 [Bhaumik, Prasenjit; Gustchina, Alla; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Xiao, Huogen; Parr, Charity L.; Yada, Rickey Y.] Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada. [Kiso, Yoshiaki] Kyoto Pharmaceut Univ, Dept Med Chem, Ctr Frontier Res Med Sci, Yamashina Ku, Kyoto 6078412, Japan. RP Gustchina, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM alla@ncifcrf.gov RI Yada, Rickey/A-8289-2013 FU U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [31-109-Eng-38]; Natural Sciences and Engineering Research Council of Canada FX Diffraction data were collected at the SER-CAT beamline 22-ID, located at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38. This project was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Financial support from the Natural Sciences and Engineering Research Council of Canada and that from the Canada Research Chairs NR 58 TC 24 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 8 PY 2009 VL 388 IS 3 BP 520 EP 540 DI 10.1016/j.jmb.2009.03.011 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 447GD UT WOS:000266178700008 PM 19285084 ER PT J AU Zhang, J Jima, DD Jacobs, C Fischer, R Gottwein, E Huang, G Lugar, PL Lagoo, AS Rizzieri, DA Friedman, DR Weinberg, JB Lipsky, PE Dave, SS AF Zhang, Jenny Jima, Dereje D. Jacobs, Cassandra Fischer, Randy Gottwein, Eva Huang, Grace Lugar, Patricia L. Lagoo, Anand S. Rizzieri, David A. Friedman, Daphne R. Weinberg, J. Brice Lipsky, Peter E. Dave, Sandeep S. TI Patterns of microRNA expression characterize stages of human B-cell differentiation SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; BURKITTS-LYMPHOMA; PROTEIN-SYNTHESIS; BLIMP-1; PROLIFERATION; MICROARRAY; PREDICTION; PROFILES AB Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells. (Blood. 2009;113:4586-4594) C1 [Zhang, Jenny; Jima, Dereje D.; Jacobs, Cassandra; Huang, Grace; Dave, Sandeep S.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA. [Fischer, Randy; Lugar, Patricia L.; Lipsky, Peter E.] NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. [Gottwein, Eva] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Gottwein, Eva] Duke Univ, Ctr Virol, Durham, NC 27710 USA. [Lugar, Patricia L.; Rizzieri, David A.; Friedman, Daphne R.; Weinberg, J. Brice; Dave, Sandeep S.] Duke Univ, Dept Med, Durham, NC 27710 USA. [Lagoo, Anand S.] Duke Univ, Dept Pathol, Durham, NC 27710 USA. RP Dave, SS (reprint author), Duke Univ, Duke Inst Genome Sci & Policy, 101 Sci Dr,Box 3382, Durham, NC 27710 USA. EM sandeep.dave@duke.edu FU Doris Duke Charitable Foundation (New York, NY); National Institutes of Health [K12]; Duke Cancer Center Development FX S. S. D. was supported by the Doris Duke Charitable Foundation (New York, NY), National Institutes of Health grant K12, and a Duke Cancer Center Development Grant. We thank Dr Joseph Nevins for a critical review of the manuscript, and Laszlo Jakoi and Chaitanya Acharya for technical assistance. We also thank Wayne Terrell and Dr Raj Dash for assistance with pathology specimens, and Tri-Tin Le (Applied Biosystems), Chris Miller (Applied Biosystems), and John Alexandrou (Exiqon) for advice and technical support. NR 50 TC 132 Z9 142 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 7 PY 2009 VL 113 IS 19 BP 4586 EP 4594 DI 10.1182/blood-2008-09-178186 PG 9 WC Hematology SC Hematology GA 443LC UT WOS:000265910300021 PM 19202128 ER PT J AU Lucas, DM Edwards, RB Lozanski, G West, DA Shin, JD Vargo, MA Davis, ME Rozewski, DM Johnson, AJ Su, BN Goettl, VM Heerema, NA Lin, TS Lehman, A Zhang, XL Jarjoura, D Newman, DJ Byrd, JC Kinghorn, AD Grever, MR AF Lucas, David M. Edwards, Ryan B. Lozanski, Gerard West, Derek A. Shin, Jungook D. Vargo, Melissa A. Davis, Melanie E. Rozewski, Darlene M. Johnson, Amy J. Su, Bao-Ning Goettl, Virginia M. Heerema, Nyla A. Lin, Thomas S. Lehman, Amy Zhang, Xiaoli Jarjoura, David Newman, David J. Byrd, John C. Kinghorn, A. Douglas Grever, Michael R. TI The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo SO BLOOD LA English DT Article ID ROCAGLAMIDE DERIVATIVES; HISTONE DEACETYLASE; MULTIPLE-MYELOMA; DOWN-REGULATION; BCL-2 FAMILY; T-CELLS; APOPTOSIS; MCL-1; PROTEIN; FLAVOPIRIDOL AB Therapeutic options for advanced B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are limited. Available treatments can also deplete T lymphocytes, leaving patients at risk of life-threatening infections. In the National Cancer Institute cell line screen, the structurally unique natural product silvestrol produces an unusual pattern of cytotoxicity that suggests activity in leukemia and selectivity for B cells. We investigated silvestrol efficacy using primary human B-leukemia cells, established B-leukemia cell lines, and animal models. In CLL cells, silvestrol LC(50) (concentration lethal to 50%) is 6.9 nM at 72 hours. At this concentration, there is no difference in sensitivity of cells from patients with or without the del( 17p13.1) abnormality. In isolated cells and whole blood, silvestrol is more cytotoxic toward B cells than T cells. Silvestrol causes early reduction in Mcl-1 expression due to translational inhibition with subsequent mitochondrial damage, as evidenced by reactive oxygen species generation and membrane depolarization. In vivo, silvestrol causes significant B-cell reduction in E mu-Tcl-1 transgenic mice and significantly extends survival of 697 xenograft severe combined immunodeficient (SCID) mice without discernible toxicity. These data indicate silvestrol has efficacy against B cells in vitro and in vivo and identify translational inhibition as a potential therapeutic target in B-cell leukemias. (Blood. 2009;113:4656-4666) C1 [Lucas, David M.; Edwards, Ryan B.; West, Derek A.; Shin, Jungook D.; Vargo, Melissa A.; Davis, Melanie E.; Rozewski, Darlene M.; Johnson, Amy J.; Goettl, Virginia M.; Lin, Thomas S.; Byrd, John C.; Grever, Michael R.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Lozanski, Gerard; Heerema, Nyla A.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Su, Bao-Ning; Byrd, John C.; Kinghorn, A. Douglas] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. [Lehman, Amy; Zhang, Xiaoli; Jarjoura, David] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. [Newman, David J.] NCI, Nat Prod Branch, Frederick, MD 21701 USA. RP Lucas, DM (reprint author), OSUCCC Bldg,Rm 455,410 W 12th Ave, Columbus, OH 43210 USA. EM david.lucas@osumc.edu RI Johnson, Amy/A-5662-2009; Lucas, David/E-3555-2011; OI Kinghorn, A. Douglas/0000-0002-6647-8707 FU CLL Global Research Foundation (Houston, TX) [NCI (P01 CA081534)]; American Cancer Society (Atlanta, GA; Institutional Research Grant); Samuel Waxman Cancer Research Foundation (New York, NY); Leukemia & Lymphoma Society (White Plains, NY); Warren Brown Foundation (Columbus, OH); National Cooperative Drug Discovery Group [CA52956, CA125066] FX This work was supported in part by the NCI (P01 CA081534), the CLL Global Research Foundation (Houston, TX), the American Cancer Society (Atlanta, GA; Institutional Research Grant), the Samuel Waxman Cancer Research Foundation (New York, NY), the Leukemia & Lymphoma Society (White Plains, NY), and the D. Warren Brown Foundation (Columbus, OH). Silvestrol was provided through a National Cooperative Drug Discovery Group (CA52956) and NCI P01 (CA125066; A. D. K.). NR 57 TC 91 Z9 91 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 7 PY 2009 VL 113 IS 19 BP 4656 EP 4666 DI 10.1182/blood-2008-09-175430 PG 11 WC Hematology SC Hematology GA 443LC UT WOS:000265910300028 PM 19190247 ER PT J AU Brander, C Marincola, FM AF Brander, Christian Marincola, Francesco M. TI AAAS joins the Translational Medicine family SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material AB The AAAS has announced the launch of Science Translational Medicine. This is further and critical recognition of this discipline and we are deeply gratified that translational medicine has risen to the level of recognition by one of the world's most prestigious scientific organizations. We believe that Science Translational Medicine will provide another valuable venue for the rapid and broad dissemination of important articles in the field and contribute to enhancing the effectiveness of translational medicine overall. It has been almost six years since we launched the Journal of Translational Medicine as an open-access journal with Biomed Central [1]. At the beginning, we faced the inevitable skepticism and received several inquires among others also from Science reporters questioning both the significance of translational medicine in today's biomedical world and the need for a new journal dedicated to it. C1 [Brander, Christian] Hosp Univ Germans Trias & Pujol, Fundacio IrsiCaixa, Lab Retrovirol, Badalona 08916, Spain. [Brander, Christian] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. [Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. RP Brander, C (reprint author), Hosp Univ Germans Trias & Pujol, Fundacio IrsiCaixa, Lab Retrovirol, Ctra Canyet S-N, Badalona 08916, Spain. EM cbrander@irsicaixa.es; fmarincola@mail.cc.nih.gov OI Brander, Christian/0000-0002-0548-5778 NR 7 TC 2 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 7 PY 2009 VL 7 AR 32 DI 10.1186/1479-5876-7-32 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 447BK UT WOS:000266166400001 PM 19422684 ER PT J AU Nienborg, H Cumming, BG AF Nienborg, Hendrikje Cumming, Bruce G. TI Decision-related activity in sensory neurons reflects more than a neuron's causal effect SO NATURE LA English DT Article ID EARLY VISUAL-CORTEX; PERCEPTUAL DECISION; TASK STRATEGY; V2 NEURONS; AREA MT; CHOICE; RESPONSES; DISCRIMINATION; REPRESENTATION; VARIABILITY AB During perceptual decisions, the activity of sensory neurons correlates with a subject's percept, even when the physical stimulus is identical(1-9). The origin of this correlation is unknown. Current theory proposes a causal effect of noise in sensory neurons on perceptual decisions(10-12), but the correlation could result from different brain states associated with the perceptual choice(13) (a top-down explanation). These two schemes have very different implications for the role of sensory neurons in forming decisions(14). Here we use white-noise analysis(15) to measure tuning functions of V2 neurons associated with choice and simultaneously measure how the variation in the stimulus affects the subjects' (two macaques) perceptual decisions(16-18). In causal models, stronger effects of the stimulus upon decisions, mediated by sensory neurons, are associated with stronger choice-related activity. However, we find that over the time course of the trial these measures change in different directions-at odds with causal models. An analysis of the effect of reward size also supports this conclusion. Finally, we find that choice is associated with changes in neuronal gain that are incompatible with causal models. All three results are readily explained if choice is associated with changes in neuronal gain caused by top-down phenomena that closely resemble attention(19). We conclude that top-down processes contribute to choice-related activity. Thus, even forming simple sensory decisions involves complex interactions between cognitive processes and sensory neurons. C1 [Nienborg, Hendrikje; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nienborg, H (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM hnienb@gmail.com FU US National Institutes of Health; National Eye Institute FX This research was supported by the Intramural Research Program of the US National Institutes of Health, National Eye Institute. We are grateful to J.A. Movshon and M. Shadlen for discussions and to the members of the Laboratory of Sensorimotor Research for comments on an earlier version of this manuscript. We also thank D. Parker and B. Nagy for excellent animal care. NR 31 TC 121 Z9 122 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 89 EP U93 DI 10.1038/nature07821 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300035 PM 19270683 ER PT J AU He, LM Xue, L Xu, JH McNeil, BD Bai, L Melicoff, E Adachi, R Wu, LG AF He, Liming Xue, Lei Xu, Jianhua McNeil, Benjamin D. Bai, Li Melicoff, Ernestina Adachi, Roberto Wu, Ling-Gang TI Compound vesicle fusion increases quantal size and potentiates synaptic transmission SO NATURE LA English DT Article ID MULTIVESICULAR RELEASE; POSTTETANIC POTENTIATION; TRANSMITTER RELEASE; RIBBON SYNAPSE; RAT CALYX; 2 MODES; EXOCYTOSIS; NEURONS; ENDOCYTOSIS; CAPACITANCE AB Exocytosis at synapses involves fusion between vesicles and the plasma membrane(1). Although compound fusion between vesicles(2,3) was proposed to occur at ribbon-type synapses(4,5), whether it exists, how it is mediated, and what role it plays at conventional synapses remain unclear. Here we report the existence of compound fusion, its underlying mechanism, and its role at a nerve terminal containing conventional active zones in rats and mice. We found that high potassium application and high frequency firing induced giant capacitance up-steps, reflecting exocytosis of vesicles larger than regular ones, followed by giant down-steps, reflecting bulk endocytosis. These intense stimuli also induced giant vesicle-like structures, as observed with electron microscopy, and giant miniature excitatory postsynaptic currents (mEPSCs), reflecting more transmitter release. Calcium and its sensor for vesicle fusion, synaptotagmin, were required for these giant events. After high frequency firing, calcium/synaptotagmin-dependent mEPSC size increase was paralleled by calcium/synaptotagmin-dependent post-tetanic potentiation. These results suggest a new route of exocytosis and endocytosis composed of three steps. First, calcium/synaptotagmin mediates compound fusion between vesicles. Second, exocytosis of compound vesicles increases quantal size, which increases synaptic strength and contributes to the generation of post-tetanic potentiation. Third, exocytosed compound vesicles are retrieved via bulk endocytosis. We suggest that this vesicle cycling route be included in models of synapses in which only vesicle fusion with the plasma membrane is considered(1). C1 [He, Liming; Xue, Lei; Xu, Jianhua; McNeil, Benjamin D.; Bai, Li; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA. [Melicoff, Ernestina; Adachi, Roberto] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Bldg 35,Room 2B 1012, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI Xu, Jianhua/0000-0003-0084-8856; McNeil, Benjamin/0000-0001-7545-3598 FU National Institute of Neurological Disorders and Stroke Intramural Research Program; American Heart Association FX We thank J. Diamond and K. Paradiso for comments on the manuscript, and S. Cheng, R. Azzam and V. Crocker for help in EM. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program (L.-G. W.) and the American Heart Association (R. A.). NR 33 TC 70 Z9 70 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 93 EP U99 DI 10.1038/nature07860 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300036 PM 19279571 ER PT J AU Adams, GB Alley, IR Chung, U Chabner, KT Jeanson, NT Lo Celso, C Marsters, ES Chen, M Weinstein, LS Lin, CP Kronenberg, HM Scadden, DT AF Adams, Gregor B. Alley, Ian R. Chung, Ung-il Chabner, Karissa T. Jeanson, Nathaniel T. Lo Celso, Cristina Marsters, Emily S. Chen, Min Weinstein, Lee S. Lin, Charles P. Kronenberg, Henry M. Scadden, David T. TI Haematopoietic stem cells depend on G alpha(s)-mediated signalling to engraft bone marrow SO NATURE LA English DT Article ID IN-VIVO; CHOLERA-TOXIN; MICE; DIFFERENTIATION; LYMPHOPOIESIS; MYELOPOIESIS; MIGRATION; SELECTINS; CXCR4 AB Haematopoietic stem and progenitor cells (HSPCs) change location during development(1) and circulate in mammals throughout life(2), moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention(3-5). Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory a subunit (G alpha(s)). HSPCs from adult mice deficient in G alpha(s) (G alpha(-/-)(s)) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow microvasculature. If deleted after engraftment, G alpha(s) deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of G alpha(s) affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. G alpha(s) governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency. C1 [Adams, Gregor B.; Alley, Ian R.; Chabner, Karissa T.; Jeanson, Nathaniel T.; Lo Celso, Cristina; Marsters, Emily S.; Scadden, David T.] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Chung, Ung-il; Kronenberg, Henry M.] Harvard Univ, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Lin, Charles P.] Harvard Univ, Sch Med, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Charles P.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adams, Gregor B.; Lo Celso, Cristina; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Scadden, David T.] Harvard Univ, Sch Med, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. [Chen, Min; Weinstein, Lee S.] NIDDKD, Bethesda, MD 20892 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu FU Burroughs Wellcome Fund, Doris Duke Charitable Trust; Harvard Stem Cell Institute; National Institutes of Health FX Financial support for this work was provided by the Burroughs Wellcome Fund, Doris Duke Charitable Trust (D. T. S.), the Harvard Stem Cell Institute (C. P. L.) and the National Institutes of Health (G. B. A., C. P. L., H. M. K., D. T. S.). NR 21 TC 41 Z9 42 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 103 EP U111 DI 10.1038/nature07859 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300038 PM 19322176 ER PT J AU Heintzman, ND Hon, GC Hawkins, RD Kheradpour, P Stark, A Harp, LF Ye, Z Lee, LK Stuart, RK Ching, CW Ching, KA Antosiewicz-Bourget, JE Liu, H Zhang, XM Green, RD Lobanenkov, VV Stewart, R Thomson, JA Crawford, GE Kellis, M Ren, B AF Heintzman, Nathaniel D. Hon, Gary C. Hawkins, R. David Kheradpour, Pouya Stark, Alexander Harp, Lindsey F. Ye, Zhen Lee, Leonard K. Stuart, Rhona K. Ching, Christina W. Ching, Keith A. Antosiewicz-Bourget, Jessica E. Liu, Hui Zhang, Xinmin Green, Roland D. Lobanenkov, Victor V. Stewart, Ron Thomson, James A. Crawford, Gregory E. Kellis, Manolis Ren, Bing TI Histone modifications at human enhancers reflect global cell-type-specific gene expression SO NATURE LA English DT Article ID HUMAN GENOME; BINDING-SITES; TRANSCRIPTION; PROMOTERS; ELEMENTS; SEQUENCE; RECEPTOR; MAP AB The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene(1-3), the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome(4-6). Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression. C1 [Heintzman, Nathaniel D.; Hon, Gary C.; Hawkins, R. David; Harp, Lindsey F.; Ye, Zhen; Lee, Leonard K.; Stuart, Rhona K.; Ching, Christina W.; Ching, Keith A.; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Heintzman, Nathaniel D.] Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA. [Hon, Gary C.] Univ Calif San Diego, Sch Med, Bioinformat Program, La Jolla, CA 92093 USA. [Ren, Bing] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Kheradpour, Pouya; Stark, Alexander; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Stark, Alexander; Kellis, Manolis] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Antosiewicz-Bourget, Jessica E.; Stewart, Ron; Thomson, James A.] Morgridge Inst Res, Madison, WI 53707 USA. [Liu, Hui; Zhang, Xinmin; Green, Roland D.] Roche NimbleGen Inc, Madison, WI 53719 USA. [Lobanenkov, Victor V.] NIAID, Rockville, MD 20852 USA. [Thomson, James A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. [Crawford, Gregory E.] Duke Univ, Dept Pediat, Durham, NC 27708 USA. RP Ren, B (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM biren@ucsd.edu RI Stark, Alexander/D-1473-2012; OI Stark, Alexander/0000-0003-2611-0841; Lobanenkov, Victor/0000-0001-6665-3635; Stuart, Rhona/0000-0001-5916-9693 FU American Cancer Society; NIAID; LICR; NHGRI; NCI; CIRM FX We thank members of the Ren laboratory for comments. This work was supported by funding from American Cancer Society (R. D. H.), NIAID Intramural Research Program (V. V. L.), LICR (B. R.), NHGRI (B. R.), NCI (B. R.) and CIRM (B. R.). NR 25 TC 1087 Z9 1106 U1 9 U2 85 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 108 EP 112 DI 10.1038/nature07829 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300039 PM 19295514 ER PT J AU Saini, P Eyler, DE Green, R Dever, TE AF Saini, Preeti Eyler, Daniel E. Green, Rachel Dever, Thomas E. TI Hypusine-containing protein eIF5A promotes translation elongation SO NATURE LA English DT Article ID SYNTHESIS INITIATION-FACTORS; PEPTIDE-BOND SYNTHESIS; SACCHAROMYCES-CEREVISIAE; DECAY PATHWAY; YEAST; PURIFICATION; PROGRESSION; MECHANISM; MUTANTS; BINDING AB Translation elongation factors facilitate protein synthesis by the ribosome. Previous studies identified two universally conserved translation elongation factors, EF-Tu in bacteria (known as eEF1A in eukaryotes) and EF-G (eEF2), which deliver aminoacyl-tRNAs to the ribosome and promote ribosomal translocation, respectively(1). The factor eIF5A (encoded by HYP2 and ANB1 in Saccharomyces cerevisiae), the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (N(epsilon)-(4-amino-2-hydroxybutyl)lysine)(2), was originally identified based on its ability to stimulate the yield (endpoint) of methionylpuromycin synthesis-a model assay for first peptide bond synthesis thought to report on certain aspects of translation initiation(3,4). Hypusine is required for eIF5A to associate with ribosomes(5,6) and to stimulate methionyl-puromycin synthesis(7). Because eIF5A did not stimulate earlier steps of translation initiation(8), and depletion of eIF5A in yeast only modestly impaired protein synthesis(9), it was proposed that eIF5A function was limited to stimulating synthesis of the first peptide bond or that eIF5A functioned on only a subset of cellular messenger RNAs. However, the precise cellular role of eIF5A is unknown, and the protein has also been linked to mRNA decay, including the nonsense-mediated mRNA decay pathway(10,11), and to nucleocytoplasmic transport(12,13). Here we use molecular genetic and biochemical studies to show that eIF5A promotes translation elongation. Depletion or inactivation of eIF5A in the yeast S. cerevisiae resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF5A might function together with eEF2 to promote ribosomal translocation. Because eIF5A is a structural homologue of the bacterial protein EF-P(14,15), we propose that eIF5A/EF-P is a universally conserved translation elongation factor. C1 [Saini, Preeti; Dever, Thomas E.] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Eyler, Daniel E.; Green, Rachel] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Dever, TE (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678 FU HHMI; NIH; NICHD FX Acknowledgements We thank T. G. Kinzy for providing anti-yeast eEF1A, eEF2 and eEF3 antisera, as well as constructs for the purification of eEF2 and eEF3; J. Lorsch for providing constructs for purification of yeast initiation factors; J. Dinmann for frameshifting reporter vectors, and A. Hinnebusch, T. G. Kinzy, A. Jivotovskaya, D. Shelton, C. Grant, J. Lorsch and members of the Dever and Hinnebusch laboratories for comments and discussion. Salary support provided by HHMI (R. G.) and NIH (D. E. E.). This work was supported in part by the Intramural Research Program of the NIH, NICHD (to T. E. D.). NR 35 TC 185 Z9 194 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 7 PY 2009 VL 459 IS 7243 BP 118 EP U129 DI 10.1038/nature08034 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441WN UT WOS:000265801300041 PM 19424157 ER PT J AU Bockenhauer, D Feather, S Stanescu, HC Bandulik, S Zdebik, AA Reichold, M Tobin, J Lieberer, E Sterner, C Landoure, G Arora, R Sirimanna, T Thompson, D Cross, JH van't Hoff, W Al Masri, O Tullus, K Yeung, S Anikster, Y Klootwijk, E Hubank, M Dillon, MJ Heitzmann, D Arcos-Burgos, M Knepper, MA Dobbie, A Gahl, WA Warth, R Sheridan, E Kleta, R AF Bockenhauer, Detlef Feather, Sally Stanescu, Horia C. Bandulik, Sascha Zdebik, Anselm A. Reichold, Markus Tobin, Jonathan Lieberer, Evelyn Sterner, Christina Landoure, Guida Arora, Ruchi Sirimanna, Tony Thompson, Dorothy Cross, J. Helen van't Hoff, William Al Masri, Omar Tullus, Kjell Yeung, Stella Anikster, Yair Klootwijk, Enriko Hubank, Mike Dillon, Michael J. Heitzmann, Dirk Arcos-Burgos, Mauricio Knepper, Mark A. Dobbie, Angus Gahl, William A. Warth, Richard Sheridan, Eamonn Kleta, Robert TI Epilepsy, Ataxia, Sensorineural Deafness, Tubulopathy, and KCNJ10 Mutations. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DISTAL CONVOLUTED TUBULE; WIDE LINKAGE ANALYSIS; NA-CL COTRANSPORTER; BARTTERS-SYNDROME; K+ CHANNEL; POTASSIUM CHANNEL; BLOOD-PRESSURE; HYPOKALEMIC ALKALOSIS; BASOLATERAL MEMBRANE; KNOCK-OUT AB Background: Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, and a renal salt-losing tubulopathy with normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call the EAST syndrome (the presence of epilepsy, ataxia, sensorineural deafness, and tubulopathy). Methods: Whole-genome linkage analysis was performed in the four affected children in one of the families. Newly identified mutations in a potassium-channel gene were evaluated with the use of a heterologous expression system. Protein expression and function were further investigated in genetically modified mice. Results: Linkage analysis identified a single significant locus on chromosome 1q23.2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney. Sequencing of this candidate gene revealed homozygous missense mutations in affected persons in both families. These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents. Mice with Kcnj10 deletions became dehydrated, with definitive evidence of renal salt wasting. Conclusions: Mutations in KCNJ10 cause a specific disorder, consisting of epilepsy, ataxia, sensorineural deafness, and tubulopathy. Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation. N Engl J Med 2009;360:1960-70. C1 [Bockenhauer, Detlef; Stanescu, Horia C.; Zdebik, Anselm A.; Tobin, Jonathan; Landoure, Guida; Arora, Ruchi; Sirimanna, Tony; Thompson, Dorothy; Cross, J. Helen; van't Hoff, William; Tullus, Kjell; Klootwijk, Enriko; Hubank, Mike; Dillon, Michael J.; Kleta, Robert] UCL, Great Ormond St Hosp, London NW3 2PF, England. [Feather, Sally; Yeung, Stella; Dobbie, Angus; Sheridan, Eamonn] Univ Leeds, Leeds Hosp, Leeds, W Yorkshire, England. [Feather, Sally; Yeung, Stella; Dobbie, Angus; Sheridan, Eamonn] Univ Leeds, Bradford Teaching Hosp, Leeds, W Yorkshire, England. [Stanescu, Horia C.; Landoure, Guida; Anikster, Yair; Klootwijk, Enriko; Arcos-Burgos, Mauricio; Knepper, Mark A.; Gahl, William A.; Kleta, Robert] NIH, Bethesda, MD 20892 USA. [Bandulik, Sascha; Reichold, Markus; Lieberer, Evelyn; Sterner, Christina; Heitzmann, Dirk; Warth, Richard] Univ Regensburg, Inst Physiol, Regensburg, Germany. [Landoure, Guida] Univ Bamako, Dept Neurol, Bamako, Mali. [Al Masri, Omar] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Anikster, Yair] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Arcos-Burgos, Mauricio] Univ Miami, Miami, FL USA. RP Kleta, R (reprint author), UCL, Royal Free Hosp, Ctr Nephrol, Rowland Hill St, London NW3 2PF, England. EM r.kleta@ucl.ac.uk RI Bockenhauer, Detlef/C-5951-2008; Hubank, Michael/C-1837-2008; Warth, Richard/N-7119-2014; Reichold, Markus/J-9933-2015; Bandulik, Sascha/L-7365-2015; OI Bockenhauer, Detlef/0000-0001-5878-941X; Hubank, Michael/0000-0002-2901-0742; Warth, Richard/0000-0001-6084-0659; Thompson, Dorothy/0000-0001-5491-3911 FU Intramural NIH HHS [Z01 HL001285-22, Z99 HL999999, ZIA HL001285-23, ZIA HL001285-24, Z01 HL001285-21] NR 41 TC 208 Z9 213 U1 1 U2 15 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 7 PY 2009 VL 360 IS 19 BP 1960 EP 1970 DI 10.1056/NEJMoa0810276 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 441QN UT WOS:000265784400006 PM 19420365 ER PT J AU Upton, TG Kashemirov, BA McKenna, CE Goodman, MF Prakash, GKS Kultyshev, R Batra, VK Shock, DD Pedersen, LC Beard, WA Wilson, SH AF Upton, Thomas G. Kashemirov, Boris A. McKenna, Charles E. Goodman, Myron F. Prakash, G. K. Surya Kultyshev, Roman Batra, Vinod K. Shock, David D. Pedersen, Lars C. Beard, William A. Wilson, Samuel H. TI alpha,beta-Difluoromethylene Deoxynucleoside 5 '-Triphosphates: A Convenient Synthesis of Useful Probes for DNA Polymerase beta Structure and Function SO ORGANIC LETTERS LA English DT Article ID VIRUS-1 REVERSE-TRANSCRIPTASE; PHOSPHONATE ANALOGS; NUCLEOSIDE TRIPHOSPHATE; PERCHLORYL FLUORIDE; ATP ANALOGS; FIDELITY; ACID; NUCLEOTIDES; SPECIFICITY; DERIVATIVES AB alpha,beta-Difluoromethylene deoxynucleoside 5'-triphosphates (dNTPs, N = A or C) are advantageously obtained via phosphorylation of corresponding dNDP analogues using catalytic ATP, PEP, nucleoside diphosphate kinase, and pyruvate kinase. DNA pol beta K(d) values for the alpha,beta-CF(2) and unmodified dNTPs, alpha,beta-NH dUTP, and the alpha,beta-CH(2) analogues of dATP and dGTP are discussed in relation to the conformations of alpha,beta-CF(2) dTTP versus alpha,beta-NH dUTP bound into the enzyme active site. C1 [Upton, Thomas G.; Kashemirov, Boris A.; McKenna, Charles E.; Goodman, Myron F.; Prakash, G. K. Surya; Kultyshev, Roman] Univ So Calif, Dept Biol & Chem, Los Angeles, CA 90089 USA. [Batra, Vinod K.; Shock, David D.; Pedersen, Lars C.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP McKenna, CE (reprint author), Univ So Calif, Dept Biol & Chem, Los Angeles, CA 90089 USA. EM mckenna@usc.edu RI Upton, Thomas/E-3749-2012 FU NIH [5-U19-CA105010]; National Institute of Environmental Health Sciences FX We thank Dr. Ron New (Mass Spectrometry Facility, University of California, Riverside) for assistance in obtaining high resolution mass spectra of nucleotide analogues, Ms. Keriann Oertell (University of Southern California) for verifying the DNA synthesis background activity in 9 after dual-HPLC purification, and Prof. George L. Kenyon (University of Michigan) for helpful discussions. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and by NIH program project grant 5-U19-CA105010. NR 43 TC 26 Z9 26 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD MAY 7 PY 2009 VL 11 IS 9 BP 1883 EP 1886 DI 10.1021/ol701755k PG 4 WC Chemistry, Organic SC Chemistry GA 438AT UT WOS:000265529000005 PM 19351147 ER PT J AU Xu, SG White, HD Offer, GW Yu, LC AF Xu, Sengen White, Howard D. Offer, Gerald W. Yu, Leepo C. TI Stabilization of Helical Order in the Thick Filaments by Blebbistatin: Further Evidence of Coexisting Multiple Conformations of Myosin SO BIOPHYSICAL JOURNAL LA English DT Article ID ADENOSINE-TRIPHOSPHATE; MOTOR DOMAIN; SKELETAL-MUSCLE; CROSS-BRIDGES; INHIBITION; MECHANISM; STATES; CROSSBRIDGES; DISSOCIATION; SPECIFICITY AB The degree of helical order of the thick filament of mammalian skeletal muscle is highly dependent on temperature and the nature of the ligand. Previously, we showed that there was a close correlation between the conformation of the myosin heads on the surface of the thick filaments and the extent of their helical order. Helical order required the heads to be in the closed conformation. In addition, we showed that, with the same ligand bound at the active site, three conformations of myosin coexisted in equilibrium. Hitherto, however, there was no detectable helical order as measured by x-ray diffraction under the temperatures studied for myosin with MgADP and the nucleotide-free myosin, raising the possibility that the concept of multiple conformations has I mited validity. In this study, blebbistatin was used to stabilize the closed conformation of myosin. The degree of helical order is substantially improved with MgATP at low temperature or with MgADP or in the absence of nucleotide. The thermodynamic parameters of the disorder-order transition and the characteristics of the ordered array were not significantly altered by binding blebbistatin. The simplest explanation is that the binding of blebbistatin increases the proportion of myosin in the closed conformation from being negligible to substantial. These results provide further evidence for the coexistence of multiple conformations of myosin under a wide range of conditions and for the closed conformation being directly coupled to helical order. C1 [Xu, Sengen; Yu, Leepo C.] NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [White, Howard D.] E Virginia Med Sch, Norfolk, VA USA. [Offer, Gerald W.] Univ Bristol, Dept Physiol & Pharmacol, Bristol, Avon, England. RP Yu, LC (reprint author), NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM yule@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health; National Institutes of Health [EB00209, HL040864] FX This research was supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and in part by National Institutes of Health grants (No. EB00209 and HL040864 to H.D.W.). NR 29 TC 14 Z9 14 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY 6 PY 2009 VL 96 IS 9 BP 3673 EP 3681 DI 10.1016/j.bpj.2009.01.049 PG 9 WC Biophysics SC Biophysics GA 450JV UT WOS:000266397700020 PM 19413972 ER PT J AU Mattson, MP Maudsley, S AF Mattson, Mark P. Maudsley, Stuart TI Live Longer sans the AT(1A) Receptor SO CELL METABOLISM LA English DT Editorial Material ID II TYPE-1 RECEPTOR; STRESS AB Excessive activation of the AT(1A) receptor (AT(1A)R) by angiotensin II (Ang II) is implicated in the age-related development of hypertension, diabetes, and kidney disease. AT(1A)R-deficient mice live longer and have lower levels of oxidative stress than wild-type mice (Benigni et al., 2009), suggesting a role for AT(1A)R signaling in the aging process. C1 [Mattson, Mark P.; Maudsley, Stuart] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [ZIA AG000318-04, Z01 AG000314-07] NR 10 TC 9 Z9 9 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 6 PY 2009 VL 9 IS 5 BP 403 EP 405 DI 10.1016/j.cmet.2009.04.002 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 442LC UT WOS:000265841700003 PM 19416709 ER PT J AU Wang, XL Suzuki, R Lee, K Tran, T Gunton, JE Saha, AK Patti, ME Goldfine, A Ruderman, NB Gonzalez, FJ Kahn, CR AF Wang, Xiaohui L. Suzuki, Ryo Lee, Kevin Tran, Thien Gunton, Jenny E. Saha, Asish K. Patti, Mary-Elizabeth Goldfine, Allison Ruderman, Neil B. Gonzalez, Frank J. Kahn, C. Ronald TI Ablation of ARNT/HIF1 beta in Liver Alters Gluconeogenesis, Lipogenic Gene Expression, and Serum Ketones SO CELL METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; HYPOXIA-INDUCIBLE FACTOR-1; ARYL-HYDROCARBON RECEPTOR; HEPATIC GLUCONEOGENESIS; INSULIN-RESISTANCE; LIPID HOMEOSTASIS; MALONYL-COA; PPAR-ALPHA; IN-VIVO; ACID AB We have previously shown that expression of the transcription factor ARNT/HIF1 beta is reduced in islets of humans with type 2 diabetes. We have now found that ARNT is also reduced in livers of diabetics. To study the functional effect of its reduction, we created mice with liver-specific ablation (L-ARNT KO) using ARNT IoxP mice and adenoviral-mediated delivery of Cre. L-ARNT KO mice had normal blood glucose but increased fed insulin levels. These mice also exhibited features of type 2 diabetes with increased hepatic gluconeogenesis, increased lipogenic gene expression, and low serum beta-hydroxybutyrate. These effects appear to be secondary to increased expression of CCAAT/enhancer-binding protein alpha (C/EBP alpha), farnesoid X receptor (FXR), and sterol response element-binding protein 1 c (SREBP-1c) and a reduction in phosphorylation of AMPK without changes in the expression of enzymes in ketogenesis, fatty acid oxidation, or FGF21. These results demonstrate that a deficiency of ARNT action in the liver, coupled with that in beta cells, could contribute to the metabolic phenotype of human type 2 diabetes. C1 [Wang, Xiaohui L.; Suzuki, Ryo; Lee, Kevin; Tran, Thien; Gunton, Jenny E.; Patti, Mary-Elizabeth; Goldfine, Allison; Kahn, C. Ronald] Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Med Ctr, Diabet Unit, Endocrinol Sect, Boston, MA 02118 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Sch Med, Dept Physiol, Boston, MA 02118 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Gunton, Jenny E.] Garvan Inst Med Res, Sydney, NSW, Australia. RP Kahn, CR (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Saha, Asish/0000-0003-1001-5110; Ruderman, Neil/0000-0002-6589-6587 FU Intramural NIH HHS [Z01 BC005708-17]; NHLBI NIH HHS [P01 HL068758, P01HL68758]; NIDDK NIH HHS [R01 DK067509, DK-067509, R01 DK060837, DK-060837] NR 33 TC 42 Z9 42 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 6 PY 2009 VL 9 IS 5 BP 428 EP 439 DI 10.1016/j.cmet.2009.04.001 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 442LC UT WOS:000265841700007 PM 19416713 ER PT J AU Zhang, DL Hughes, RI Ollivierre-Wilson, H Ghosh, MC Rouault, TA AF Zhang, De-Liang Hughes, Robert Im. Ollivierre-Wilson, Hayden Ghosh, Manik C. Rouault, Tracey A. TI A Ferroportin Transcript that Lacks an Iron-Responsive Element Enables Duodenal and Erythroid Precursor Cells to Evade Translational Repression SO CELL METABOLISM LA English DT Article ID REGULATORY PROTEINS; GENE-EXPRESSION; POLYCYTHEMIA MICE; FACTOR GATA-1; HOMEOSTASIS; METABOLISM; HEPCIDIN; TRANSPORTER; ERYTHROPOIESIS; HEMATOPOIESIS AB Ferroportin (FPN1), the sole characterized mammalian iron exporter, has an iron-responsive element (IRE) in its 5' untranslated region, which ensures that its translation is repressed by iron regulatory proteins (IRPs) in iron-deficient conditions to maintain cellular iron content. However, here we demonstrate that duodenal epithelial and erythroid precursor cells utilize an alternative upstream promoter to express a FPN1 transcript, FPN1 13, which lacks the IRE and is not repressed in iron-deficient conditions. The FPN1 B transcript encodes ferroportin with an identical open reading frame and contributes significantly to ferroportin protein expression in erythroid precursors and likely also in the duodenum of iron-starved animals. The identification of FPN1B reveals how FPN1 expression can bypass IRP-dependent repression in intestinal iron uptake, even when cells throughout the body are iron deficient. In erythroid precursor cells, we hypothesize that FPN1 B expression enhances real-time sensing of systemic iron status and facilitates restriction of erythropoiesis in response to low systemic iron. C1 [Zhang, De-Liang; Hughes, Robert Im.; Ollivierre-Wilson, Hayden; Ghosh, Manik C.; Rouault, Tracey A.] NICHHD, Program Mol Med, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Program Mol Med, Bethesda, MD 20892 USA. EM rouault@mail.nih.gov RI Zhang, Deliang/F-7848-2013; OI Zhang, Deliang/0000-0001-9478-5344 FU Intramural NIH HHS [Z01 HD001602-23] NR 40 TC 130 Z9 132 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY 6 PY 2009 VL 9 IS 5 BP 461 EP 473 DI 10.1016/j.cmet.2009.03.006 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 442LC UT WOS:000265841700010 PM 19416716 ER PT J AU Abdelmohsen, K Srikantan, S Yang, XL Lal, A Kim, HH Kuwano, Y Galban, S Becker, KG Kamara, D de Cabo, R Gorospe, M AF Abdelmohsen, Kotb Srikantan, Subramanya Yang, Xiaoling Lal, Ashish Kim, Hyeon Ho Kuwano, Yuki Galban, Stefanie Becker, Kevin G. Kamara, Davida de Cabo, Rafael Gorospe, Myriam TI Ubiquitin-mediated proteolysis of HuR by heat shock SO EMBO JOURNAL LA English DT Article DE post-transcriptional gene regulation; proteasome; protein stability; ribonucleoprotein complex; ubiquitination ID MESSENGER-RNA STABILITY; BINDING PROTEIN HUR; TRANSLATIONAL CONTROL; NUCLEAR IMPORT; STABILIZATION; TURNOVER; EXPRESSION; STRESS; PHOSPHORYLATION; KINASE AB The RNA-binding protein HuR regulates the stability and translation of numerous mRNAs encoding stress-response and proliferative proteins. Although its post-transcriptional influence has been linked primarily to its cytoplasmic translocation, here we report that moderate heat shock (HS) potently reduces HuR levels, thereby altering the expression of HuR target mRNAs. HS did not change HuR mRNA levels or de novo translation, but instead reduced HuR protein stability. Supporting the involvement of the ubiquitin-proteasome system in this process were results showing that (1) HuR was ubiquitinated in vitro and in intact cells, (2) proteasome inhibition increased HuR abundance after HS, and (3) the HuR kinase checkpoint kinase 2 protected against the loss of HuR by HS. Within a central, HS-labile similar to 110-amino-acid region, K182 was found to be essential for HuR ubiquitination and proteolysis as mutant HuR(K182R) was left virtually un-ubiquitinated and was refractory to HS-triggered degradation. Our findings reveal that HS transiently lowers HuR by proteolysis linked to K182 ubiquitination and that HuR reduction enhances cell survival following HS. The EMBO Journal (2009) 28, 1271-1282. doi: 10.1038/emboj.2009.67; Published online 26 March 2009 C1 [Abdelmohsen, Kotb; Srikantan, Subramanya; Yang, Xiaoling; Lal, Ashish; Kim, Hyeon Ho; Kuwano, Yuki; Galban, Stefanie; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. [Abdelmohsen, Kotb; Becker, Kevin G.] NIA, Res Resources Branch, IRP, NIH, Baltimore, MD 21224 USA. [Kamara, Davida; de Cabo, Rafael] NIA, Lab Expt Gerontol, IRP, NIH, Baltimore, MD 21224 USA. [Lal, Ashish] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Lal, Ashish] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Abdelmohsen, K (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov; myriam-gorospe@nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810; Becker, Kevin/0000-0002-6794-6656; , rafael/0000-0003-2830-5693 FU NIA-IRP Program [Z01-AG000511-10]; NIA-IRP, NIH FX We thank MJ Pazin, V Dixit, WH Wood 3rd, B Frank, S Subaran, and FE Indig for their assistance with these studies. HCT116 cells were kindly provided by F Bunz. This research was supported entirely by the NIA-IRP Program Z01-AG000511-10 and by set-aside funds of the NIA-IRP, NIH. NR 55 TC 68 Z9 69 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 6 PY 2009 VL 28 IS 9 BP 1271 EP 1282 DI 10.1038/emboj.2009.67 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 443BK UT WOS:000265885000009 PM 19322201 ER PT J AU Kayagil, TA Bai, O Henriquez, CS Lin, P Furlani, SJ Vorbach, S Hallett, M AF Kayagil, Turan A. Bai, Ou Henriquez, Craig S. Lin, Peter Furlani, Stephen J. Vorbach, Sherry Hallett, Mark TI A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article ID BRAIN-COMPUTER-INTERFACE; MENTAL PROSTHESIS; COMMUNICATION; PERFORMANCE; POTENTIALS AB Background: Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement. Methods: We tested the paradigm with four healthy subjects, none of whom had prior BCI experience. Each subject played a game wherein he or she attempted to move a cursor to a target within a grid while avoiding a trap. We also present supplementary results including one healthy subject using motor imagery, one primary lateral sclerosis (PLS) patient, and one healthy subject using a single EEG channel without Laplacian derivation. Results: For the four healthy subjects using real hand movement, the system provided accurate cursor control with little or no required user training. The average accuracy of the cursor movement was 86.1% (SD 9.8%), which is significantly better than chance (p = 0.0015). The best subject achieved a control accuracy of 96%, with only one incorrect bit classification out of 47. The supplementary results showed that control can be achieved under the respective experimental conditions, but with reduced accuracy. Conclusion: The binary method provides naive subjects with real-time control of a cursor in 2-D using dichotomous classification of synchronous EEG band power readings from a small number of channels during hand movement. The primary strengths of our method are simplicity of hardware and software, and high accuracy when used by untrained subjects. C1 [Kayagil, Turan A.; Bai, Ou; Lin, Peter; Furlani, Stephen J.; Vorbach, Sherry; Hallett, Mark] NINDS, Bethesda, MD 20892 USA. [Kayagil, Turan A.; Henriquez, Craig S.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. [Kayagil, Turan A.] Georgetown Univ, Sch Med, Washington, DC 20057 USA. [Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, Richmond, VA 23284 USA. RP Bai, O (reprint author), NINDS, Bethesda, MD 20892 USA. EM tkayagil@gmail.com; obai@vcu.edu; ch@duke.edu; linpe@ninds.nih.gov; sfur777@hotmail.com; vorbachs@ninds.nih.gov; hallettm@ninds.nih.gov FU Intramural Research Program of the NIH (National Institute of Neurological Disorders and Stroke) FX This research was supported by the Intramural Research Program of the NIH (National Institute of Neurological Disorders and Stroke). We thank Dr. Robert Lutz and the National Institutes of Health Biomedical Engineering Summer Internship Program, which is supported by the National Institute of Biomedical Imaging and Bioengineering. We thank Dr. Mary Kay Floeter for her collaboration on the PLS study. NR 26 TC 12 Z9 12 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD MAY 6 PY 2009 VL 6 AR 14 DI 10.1186/1743-0003-6-14 PG 16 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 455HB UT WOS:000266748100001 PM 19419576 ER PT J AU Robak, LA Venkatesh, K Lee, H Raiker, SJ Duan, Y Lee-Osbourne, J Hofer, T Mage, RG Rader, C Giger, RJ AF Robak, Laurie A. Venkatesh, Karthik Lee, Hakjoo Raiker, Stephen J. Duan, Yuntao Lee-Osbourne, Jane Hofer, Thomas Mage, Rose G. Rader, Christoph Giger, Roman J. TI Molecular Basis of the Interactions of the Nogo-66 Receptor and Its Homolog NgR2 with Myelin-Associated Glycoprotein: Development of NgR(OMNI)-Fc, a Novel Antagonist of CNS Myelin Inhibition SO JOURNAL OF NEUROSCIENCE LA English DT Article ID NEURITE OUTGROWTH INHIBITION; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; ACID BINDING-SITE; AXON REGENERATION; WHITE-MATTER; IB-ALPHA; GROWTH; RECOVERY; DISTINCT AB Myelin-associated glycoprotein (MAG) is a sialic acid-binding Ig-family lectin that functions in neuronal growth inhibition and stabilization of axon-glia interactions. The ectodomain of MAG is comprised of five Ig-like domains and uses neuronal cell-type-specific mechanisms to signal growth inhibition. We show that the first three Ig-like domains of MAG bind with high affinity and in a sialic acid-dependent manner to the Nogo-66 receptor-1 (NgR1) and its homolog NgR2. Domains Ig3-Ig5 of MAG are sufficient to inhibit neurite outgrowth but fail to associate with NgR1 or NgR2. Nogo receptors are sialoglycoproteins comprised of 8.5 canonical leucine-rich repeats (LRR) flanked by LRR N-terminal (NT) and C-terminal (CT)-cap domains. The LRR cluster is connected through a stalk region to a membrane lipid anchor. The CT-cap domain and stalk region of NgR2, but not NgR1, are sufficient for MAG binding, and when expressed in neurons, exhibit constitutive growth inhibitory activity. The LRR cluster of NgR1 supports binding of Nogo-66, OMgp, and MAG. Deletion of disulfide loop Cys(309)-Cys(336) of NgR1 selectively increases its affinity for Nogo-66 and OMgp. A chimeric Nogo receptor variant (NgR(OMNI)) in which Cys(309)-Cys(336) is deleted and followed by a 13 aa MAG-binding motif of the NgR2 stalk, shows superior binding of OMgp, Nogo-66, and MAG compared with wild-type NgR1 or NgR2. Soluble NgR(OMNI) (NgR(OMNI)-Fc) binds strongly to membrane-bound inhibitors and promotes neurite outgrowth on both MAG and CNS myelin substrates. Thus, NgR(OMNI)-Fc may offer therapeutic opportunities following nervous system injury or disease where myelin inhibits neuronal regeneration. C1 [Raiker, Stephen J.; Duan, Yuntao; Giger, Roman J.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Venkatesh, Karthik; Raiker, Stephen J.; Duan, Yuntao; Giger, Roman J.] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mage, Rose G.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Robak, Laurie A.; Lee, Hakjoo; Raiker, Stephen J.; Lee-Osbourne, Jane; Giger, Roman J.] Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Rochester, NY 14642 USA. RP Giger, RJ (reprint author), Univ Michigan, Sch Med, Dept Cell & Dev Biol, 109 Zina Pitcher Pl,3065 BSRB, Ann Arbor, MI 48109 USA. EM rgiger@umich.edu FU National Institutes of Health [T32 NS07489]; National Research Service Award Ruth Kirschstein Fellowship [F31NS049870]; New York State Spinal Cord Injury Research Program; Christopher Reeve and Sam Schmidt Paralysis Foundation; Ellison Medical Foundation; National Alliance for Research on Schizophrenia and Depression; Miriam and Sheldon G. Adelson Medical Foundation; National Institute of Neurological Disorders and Stroke [NS047333] FX This work was supported by National Institutes of Health Training Grant T32 NS07489 (L. R. and K. V.), National Research Service Award Ruth Kirschstein Fellowship F31NS049870 (K. V.), the New York State Spinal Cord Injury Research Program (R. J. G. and C. R.), the Christopher Reeve and Sam Schmidt Paralysis Foundation, the Ellison Medical Foundation, the National Alliance for Research on Schizophrenia and Depression, the Dr. Miriam and Sheldon G. Adelson Medical Foundation's Adelson Program in Neural Repair and Rehabilitation, and National Institute of Neurological Disorders and Stroke Grant NS047333 (R. J. G.). We thank R. Geary, B. Carlin, and J. J. Winters for excellent technical assistance, R. Schnaar for Galgt1 mouse brain tissue, and R. Quarles for anti-MAG B11F7. NR 55 TC 33 Z9 33 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 6 PY 2009 VL 29 IS 18 BP 5768 EP 5783 DI 10.1523/JNEUROSCI.4935-08.2009 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 442GC UT WOS:000265827900008 PM 19420245 ER PT J AU Goldstein, RZ Tomasi, D Alia-Klein, N Carrillo, JH Maloney, T Woicik, PA Wang, RL Telang, F Volkow, ND AF Goldstein, Rita Z. Tomasi, Dardo Alia-Klein, Nelly Carrillo, Jean Honorio Maloney, Thomas Woicik, Patricia A. Wang, Ruiliang Telang, Frank Volkow, Nora D. TI Dopaminergic Response to Drug Words in Cocaine Addiction SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VENTRAL TEGMENTAL AREA; ANTERIOR CINGULATE; GLUTAMATE; CORTEX; CUES; SENSITIVITY; ACTIVATION; STRIATUM; SIGNALS; SEEKING AB When exposed to drug conditioned cues (stimuli associated with the drug), addicted individuals experience an intense desire for the drug, which is associated with increased dopamine cell firing. We hypothesized that drug-related words can trigger activation in the mesencephalon, where dopaminergic cells are located. During functional magnetic resonance imaging (fMRI), 15 individuals with cocaine use disorders and 15 demographically matched healthy control subjects pressed buttons for color of drug-related versus neutral words. Results showed that the drug words, but not neutral words, activated the mesencephalon in the cocaine users only. Further, in the cocaine users only, these increased drug-related mesencephalic responses were associated with enhanced verbal fluency specifically for drug words. Our results for the first time demonstrate fMRI response to drug words in cocaine-addicted individuals in mesencephalic regions as possibly associated with dopaminergic mechanisms and with conditioning to language (in this case drug words). The correlation between the brief verbal fluency test, which can be easily administered (crucial for clinical studies), and fMRI cue reactivity could be used as a biomarker of neurobiological changes in addiction. C1 [Goldstein, Rita Z.; Tomasi, Dardo; Alia-Klein, Nelly; Carrillo, Jean Honorio; Maloney, Thomas; Woicik, Patricia A.; Wang, Ruiliang; Telang, Frank] Brookhaven Natl Lab, Dept Med Res, Ctr Translat Neuroimaging, Upton, NY 11973 USA. [Carrillo, Jean Honorio] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Telang, Frank; Volkow, Nora D.] NIAAA, Rockville, MD 20857 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Dept Med Res, Ctr Translat Neuroimaging, POB 5000, Upton, NY 11973 USA. EM rgoldstein@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU National Institute on Drug Abuse [1R01DA023579, R21DA02062]; General Clinical Research Center [5-MO1-RR-10710] FX This study was supported by grants from the National Institute on Drug Abuse (Grants 1R01DA023579 and R21DA02062 to R. Z. G.) and the General Clinical Research Center (Grant 5-MO1-RR-10710). WethankMuhammadA. Parvaz for help with task administration, Alex Panagopoulos and Dimitris Samaras for help with early data analyses, and Gene-JackWangfor help with medical screens. Wealso thank Sahib S. Khalsa and Steve Berry for help with word selection, matching, and ratings and Suparna Rajaram for help with early task design. NR 44 TC 43 Z9 47 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 6 PY 2009 VL 29 IS 18 BP 6001 EP 6006 DI 10.1523/JNEUROSCI.4247-08.2009 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 442GC UT WOS:000265827900029 PM 19420266 ER PT J AU Ye, WJ Sangaiah, R Degen, DE Gold, A Jayaraj, K Koshlap, KM Boysen, G Williams, J Tomer, KB Mocanu, V Dicheva, N Parker, CE Schaaper, RM Ball, LM AF Ye, Wenjie Sangaiah, R. Degen, Diana E. Gold, Avram Jayaraj, K. Koshlap, Karl M. Boysen, Gunnar Williams, Jason Tomer, Kenneth B. Mocanu, Viorel Dicheva, Nedyalka Parker, Carol E. Schaaper, Roel M. Ball, Louise M. TI Iminohydantoin Lesion Induced in DNA by Peracids and Other Epoxidizing Oxidants SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MITOCHONDRIAL-DNA; GUANINE OXIDATION; PURINE NUCLEOSIDES; TANDEM LESIONS; SIDE REACTIONS; MAJOR PRODUCT; ONE-ELECTRON; DAMAGE; SPIROIMINODIHYDANTOIN; MECHANISM AB The oxidation of guanine to 5-carboxamido-5-formamido-2-iminohydantoin (2-1h) is shown to be a major transformation in the oxidation of the single-stranded DNA 5-mer d(TTGTT) by m-chloroperbenzoic acid (m-CPBA) and dimethyldioxirane (DMDO) as a model for peracid oxidants and in the oxidation of the 5-base pair duplex d[(TTGTT) center dot (AACAA)] with DMDO. 2-1h has not been reported as an oxidative lesion at the level of single/double-stranded DNA or at the nucleoside/nucleotide level. The lesion is stable to DNA digestion and chromatographic purification, suggesting that 2-1h may be a stable biomarker in vivo. The oxidation products have been structurally characterized and the reaction mechanism has been probed by oxidation of the monomeric species dGuo, dGMP, and dGTP. DMDC) selectively oxidizes the guanine moiety of dGuo, dGMP, and dGTP to 2-1h, and both peracetic and m-chloroperbenzoic acids exhibit the same selectivity. The presence of the glycosidic bond results in the stereoselective induction of an asymmetric center at the Spiro carbon to give a mixture of diastereomers, with each diastereomer in equilibrium with a minor conformer through rotation about the formamido C-N bond. Labeling studies with [O-18(2)]-m-CPBA and (H2O)-O-18 to determine the source of the added oxygen atoms have established initial epoxidation of the guanine 4-5 bond with pyrimidine ring contraction by an acyl 1,2-migration of guanine carbonyl C6 to form a transient dehydrodeoxyspiroiminodihydantoin followed by hydrolytic ring-opening of the imidazolone ring. Consistent with the proposed mechanism, no 8-oxoguanine was detected as a product of the oxidations of the oligonucleotides or monomeric species mediated by DMDO or the peracids. The 2-1h base thus appears to be a pathway-specific lesion generated by peracids and possibly other epoxidizing agents and holds promise as a potential biomarker. C1 [Ye, Wenjie; Sangaiah, R.; Degen, Diana E.; Gold, Avram; Jayaraj, K.; Boysen, Gunnar; Ball, Louise M.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Koshlap, Karl M.] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. [Mocanu, Viorel; Dicheva, Nedyalka; Parker, Carol E.] Univ N Carolina, UNC Duke Prote Ctr, Program Mol Biol & Biotechnol, Chapel Hill, NC 27599 USA. [Williams, Jason; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Schaaper, Roel M.] NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Gold, A (reprint author), Univ N Carolina, Dept Environm Sci & Engn, CB7431, Chapel Hill, NC 27599 USA. EM golda@email.unc.edu RI Tomer, Kenneth/E-8018-2013; OI Boysen, Gunnar/0000-0001-8364-9881 FU PHS [P42-ES005948]; NIEHS [ESR30262]; Intramural Research Program of the NIEHS/NIH [Z01 ES050171]; UNC-Duke Proteomics Center FX This work was supported in part by PHS Grant P42-ES005948 and NIEHS Contract ESR30262. K.B.T and J.W. thank the Intramural Research Program of the NIEHS/NIH (Grant Z01 ES050171) for support. The UNC-Duke Proteomics Center was partially funded by a gift from an anonymous donor in honor of Michael Hooker. NR 42 TC 18 Z9 18 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 6 PY 2009 VL 131 IS 17 BP 6114 EP 6123 DI 10.1021/ja8090752 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 441FX UT WOS:000265755800035 PM 19354244 ER PT J AU Turjanski, AG Hummer, G Gutkind, JS AF Gustavo Turjanski, Adrian Hummer, Gerhard Gutkind, J. Silvio TI How Mitogen-Activated Protein Kinases Recognize and Phosphorylate Their Targets: A QM/MM Study SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CYCLIN-DEPENDENT KINASE; MAP KINASES; AB-INITIO; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; ERK2; MECHANISM; PATHWAY; CONFORMATION; BINDING AB Mitogen-activated protein kinase (MAPK) signaling pathways play an essential role in the transduction of environmental stimuli to the nucleus, thereby regulating a variety of cellular processes, including cell proliferation, differentiation, and programmed cell death. The components of the MAPK extracellular activated protein kinase (ERK) cascade represent attractive targets for cancer therapy, as their aberrant activation is a frequent event among highly prevalent human cancers. To understand how MAPKs recognize and phosphorylate their targets is key to unravel their function. However, these events are still poorly understood because of the lack of complex structures of MAPKs with their bound targets in the active site. Here we have modeled the interaction of ERK with a target peptide and analyzed the specificity toward Ser/Thr-Pro motifs. By using a quantum mechanics/molecular mechanics (QM/MM) approach, we propose a mechanism for the phosphoryl transfer catalyzed by ERK that offers new insights into MAPK function. Our results suggest that (1) the proline residue has a role in both specificity and phospho transfer efficiency, (2) the reaction occurs in one step, with ERK2 Asp(147) acting as the catalytic base, (3) a conserved Lys in the kinase superfamily that is usually mutated to check kinase activity strongly stabilizes the transition state, and (4) the reaction mechanism is similar with either one or two Mg(2+) ions in the active site. Taken together, our results provide a detailed description of the molecular events involved in the phosphorylation reaction catalyzed by MAPK and contribute to the general understanding of kinase activity. C1 [Gustavo Turjanski, Adrian; Gutkind, J. Silvio] Natl Inst Dental & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Turjanski, AG (reprint author), Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Inorgan Analit & Quim Fis, Buenos Aires, DF, Argentina. EM adrian@qi.fcen.uba.ar RI Gutkind, J. Silvio/A-1053-2009; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU PEW Latin American Fellow; Intramural Research Programs of NIDCR, NIH; NIDDK, NIH FX Adrian Turjanski was supported as a PEW Latin American Fellow. The authors acknowledge support by the Intramural Research Programs of NIDCR, NIH (A.G.T. and J.S.G.) and NIDDK, NIH (G.H.). NR 55 TC 24 Z9 24 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 6 PY 2009 VL 131 IS 17 BP 6141 EP 6148 DI 10.1021/ja8071995 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 441FX UT WOS:000265755800038 PM 19361221 ER PT J AU Ballard-Barbash, R Hunsberger, S Alciati, MH Blair, SN Goodwin, PJ McTiernan, A Wing, R Schatzkin, A AF Ballard-Barbash, Rachel Hunsberger, Sally Alciati, Marianne H. Blair, Steven N. Goodwin, Pamela J. McTiernan, Anne Wing, Rena Schatzkin, Arthur TI Physical Activity, Weight Control, and Breast Cancer Risk and Survival: Clinical Trial Rationale and Design Considerations SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CORONARY HEART-DISEASE; BODY-MASS INDEX; DIABETES-PREVENTION-PROGRAM; LIFE-STYLE INTERVENTIONS; HEALTHY FOOD CHOICES; ALL-CAUSE MORTALITY; RANDOMIZED-TRIAL; FOLLOW-UP; CARDIORESPIRATORY FITNESS; RECRUITMENT METHODS AB Substantial observational epidemiological evidence exists that physical activity and weight control are associated with decreased risk of postmenopausal breast cancer. Uncertainty remains regarding several aspects of these associations, including the effect of possible confounding factors on these associations. We present the rationale and design for two randomized controlled trials that can help resolve this uncertainty. In a 5-year prevention trial conducted among women at high risk of breast cancer, the primary endpoint would be breast cancer incidence. For a comparable survivorship trial, the primary endpoint would be the disease-free interval and secondary endpoints would be breast cancer recurrence-free interval, second primary breast cancer, and total invasive plus in situ breast cancer. A set of inclusion and exclusion criteria is proposed for both trials. Intervention goals are the same for both trials. Goals for the weight control intervention would be, for women whose body mass index (BMI) is greater than 25 kg/m(2), to lose 10% of body weight and, for women whose BMI is less than or equal to 25 kg/m(2), to avoid weight gain. The goal for the physical activity intervention would be to achieve and maintain regular participation in a moderate-intensity physical activity program for a total of 150-225 minutes over at least 5 days per week. Sample size calculations are based on alternative assumptions about hazard ratio, adherence, follow-up duration, and power and are presented for the primary prevention and survivorship trials. Although both studies could enhance our understanding of breast cancer etiology and benefit public health, practical considerations, including smaller sample size, ease of recruitment, and reduced likelihood of early termination, favor the survivorship trial at this time. C1 [Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hunsberger, Sally] NCI, Biometr Res Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. [Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Alciati, Marianne H.] Susan G Komen Cure, Sci Operat, Dallas, TX USA. [Blair, Steven N.] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. [Goodwin, Pamela J.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, CA USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Wing, Rena] Miriam Hosp, Ctr Behav Med, Providence, RI 02906 USA. [Wing, Rena] Miriam Hosp, Ctr Prevent Med, Providence, RI 02906 USA. [Wing, Rena] Brown Univ, Providence, RI 02912 USA. RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, EPN 4005,Execut Blvd, Bethesda, MD 20892 USA. EM barbashr@mail.nih.gov RI Goodwin, Pamela/K-1477-2013; OI Alciati, Marianne/0000-0001-6294-1090 NR 81 TC 51 Z9 51 U1 1 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 6 PY 2009 VL 101 IS 9 BP 630 EP 643 DI 10.1093/jnci/djp068 PG 14 WC Oncology SC Oncology GA 444AR UT WOS:000265952700007 PM 19401543 ER PT J AU Anderson, WF Sherman, ME Carreon, JD Brinton, LA AF Anderson, William F. Sherman, Mark E. Carreon, J. Daniel Brinton, Louise A. TI Response: Re: Recent Trends in Breast Cancer Among Younger Women in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID RATES C1 [Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Sherman, Mark E.; Carreon, J. Daniel; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Anderson, WF (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 8036, Rockville, MD 20852 USA. EM wanderso@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 7 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 6 PY 2009 VL 101 IS 9 BP 692 EP 693 DI 10.1093/jnci/djp027 PG 2 WC Oncology SC Oncology GA 444AR UT WOS:000265952700016 ER PT J AU Hong, SY Saavedra, JE Keefer, LK Chakrapani, H AF Hong, Sam Y. Saavedra, Joseph E. Keefer, Larry K. Chakrapani, Harinath TI Improved synthesis of V-PYRRO/NO, a liver-selective nitric oxide prodrug, and analogues SO TETRAHEDRON LETTERS LA English DT Article ID INDUCED HEPATOTOXICITY; SECONDARY-AMINES; DONOR; MICE; PROTECTS; APOPTOSIS; TOXICITY; CHEMISTRY AB The reported synthesis of O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate(V-PYRRO/NO), a hepatoprotective agent, was cumbersome and limited by a poor overall yield of 4% from sodium 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (PYRRO/No). We report an improved synthesis of V-PYRRO/NO in two steps with a significantly higher overall yield of 40% from PYRRO/NO. Using this protocol, a number of structural analogues of V-PYRRO/NO were prepared in good yields. Published by Elsevier Ltd. C1 [Hong, Sam Y.; Keefer, Larry K.; Chakrapani, Harinath] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Chakrapani, H (reprint author), NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM chakrah@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural Research Program of the NIH; National Cancer Institute [N01-CO2008-00001]; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as National Cancer Institute contract N01-CO2008-00001 to SAIC. NR 27 TC 6 Z9 6 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 6 PY 2009 VL 50 IS 18 BP 2069 EP 2071 DI 10.1016/j.tetlet.2009.02.103 PG 3 WC Chemistry, Organic SC Chemistry GA 431HS UT WOS:000265052800010 ER PT J AU Wu, HT Kaur, G Griffiths, GL AF Wu, Haitao Kaur, Gurpreet Griffiths, Gary L. TI An improved synthesis of a fluorescent gabapentin-choline conjugate for single molecule detection SO TETRAHEDRON LETTERS LA English DT Article DE Calcium ion channel; Gabapentin; Single molecule detection; Fluorescence imaging ID ACETYLCHOLINE; PHARMACOLOGY AB Voltage-gated calcium ion channels comprise pore-forming alpha(1) and auxiliary alpha(2)delta, beta, and gamma subunits. They are important molecular devices involved in a variety of cell functions. Fluorescently labeled acylcholine analogues are important in studies such as ion channel regulation. Cy3-3-acetylcholine has recently been synthesized for single molecule detection studies; albeit in an extremely low overall yield (0.06%). In this Work, an alternative route to that used in the previous Cy3-3-acetylcholine synthesis was developed with a 90% yield at a significantly lower material cost. Published by Elsevier Ltd. C1 [Wu, Haitao; Kaur, Gurpreet; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. RP Griffiths, GL (reprint author), NHLBI, Imaging Probe Dev Ctr, NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM griffithsgl@mail.nih.gov FU NIH Roadmap for Medical Research Initiative FX This work was supported by the NIH Roadmap for Medical Research Initiative through its establishment of the imaging Probe Development Center, administered by the National Heart, Lung, and Blood Institute. NR 11 TC 8 Z9 8 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 6 PY 2009 VL 50 IS 18 BP 2100 EP 2102 DI 10.1016/j.tetlet.2009.02.125 PG 3 WC Chemistry, Organic SC Chemistry GA 431HS UT WOS:000265052800019 PM 20161233 ER PT J AU Levey, AS Stevens, LA Schmid, CH Zhang, YP Castro, AF Feldman, HI Kusek, JW Eggers, P Van Lente, F Greene, T Coresh, J AF Levey, Andrew S. Stevens, Lesley A. Schmid, Christopher H. Zhang, Yaping (Lucy) Castro, Alejandro F., III Feldman, Harold I. Kusek, John W. Eggers, Paul Van Lente, Frederick Greene, Tom Coresh, Josef CA Chronic Kidney Dis Epidemiology Co TI A New Equation to Estimate Glomerular Filtration Rate SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CHRONIC KIDNEY-DISEASE; COCKCROFT-GAULT EQUATIONS; RENIN-ANGIOTENSIN SYSTEM; SERUM CREATININE VALUES; RENAL-DISEASE; DIABETIC-NEPHROPATHY; PREDICTIVE PERFORMANCE; NATIONAL-HEALTH; DUAL BLOCKADE; CYSTATIN-C AB Background: Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. Objective: To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Design: Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U. S. population for prevalence estimates. Setting: Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. Participants: 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16 032 participants in NHANES. Measurements: GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. Results: In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) ( IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). Limitation: The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. Conclusion: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases. C1 [Levey, Andrew S.; Stevens, Lesley A.; Schmid, Christopher H.; Zhang, Yaping (Lucy)] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Castro, Alejandro F., III; Coresh, Josef] Johns Hopkins Univ, Baltimore, MD USA. [Feldman, Harold I.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Kusek, John W.; Eggers, Paul] NIH, Bethesda, MD 20892 USA. [Van Lente, Frederick] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. RP Levey, AS (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. RI Nelson, Robert/B-1470-2012; OI Schmid, Christopher/0000-0002-0855-5313 FU National Institute of Diabetes and Digestive and Kidney Diseases [UO1 DK 053869, UO1 DK 067651, UO1 DK 35073] FX By grants UO1 DK 053869, UO1 DK 067651, and UO1 DK 35073 as part of a cooperative agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. NR 50 TC 4953 Z9 5157 U1 27 U2 150 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 5 PY 2009 VL 150 IS 9 BP 604 EP 612 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 443IQ UT WOS:000265903800004 PM 19414839 ER PT J AU O'Brien, EP Brooks, BR Thirumalai, D AF O'Brien, Edward P. Brooks, Bernard R. Thirumalai, D. TI Molecular Origin of Constant m-Values, Denatured State Collapse, and Residue-Dependent Transition Midpoints in Globular Proteins SO BIOCHEMISTRY LA English DT Article ID AQUEOUS UREA SOLUTIONS; FREE-ENERGY CHANGES; TRANSFER MODEL; AMINO-ACID; GUANIDINE-HYDROCHLORIDE; LINEAR EXTRAPOLATION; ALPHA-CHYMOTRYPSIN; DYNAMICS METHOD; LATTICE MODELS; SIDE-CHAINS AB Experiments show that for many two-state folders the free energy of the native state, Delta G(ND)([C]) changes linearly as the denaturant concentration, [C], is varied. The slope {m = [d Delta G(ND)([C])]/(d[C])}, is nearly constant. According to the transfer model, the m-value is associated with the difference in the 2 surface area between the native (N) and denatured (D) state, which should be a function of Delta R-g(2), the difference in the square of the radius of gyration between the D and N states. Single-molecule experiments show that the R-g of the structurally heterogeneous denatured state undergoes an equilibrium collapse transition as [C] decreases, which implies m also should be [C]-dependent. We resolve the conundrum between constant m-values and [C]-dependent changes in R-g using molecular simulations of a coarse-grained representation of protein L, and the molecular transfer model, for which the equilibrium folding can be accurately calculated as a function of denaturant (urea) concentration. In agreement with experiment, we find that over a large range of denaturant concentration (>3 M) the m-value is a constant, whereas under strongly renaturing conditions (<3 M), it depends on [C]. The m-value is a constant above [C] > 3 M because the [C]-dependent changes in the surface area of the backbone groups, which make the largest contribution to m, are relatively narrow in the denatured state. The burial of the backbone and hydrophobic side chains gives rise to substantial surface area changes below [C] < 3 M, leading to collapse in the denatured state of protein L. Dissection of the contribution of various amino acids to the total surface area change with [C] shows that both the sequence context and residual structure are important. There are [C]-dependent variations in the surface area for chemically identical groups such as the backbone or Ala. Consequently, the midpoints of transition of individual residues vary significantly (which we call the Holtzer effect) even though global folding can be described as an all-or-none transition. The collapse is specific in nature, resulting in the formation of compact structures with appreciable populations of nativelike secondary structural elements. The collapse transition is driven by the loss of favorable residue-solvent interactions and a concomitant increase in the strength of intrapeptide interactions with a decreasing [C]. The strength of these interactions is nonuniformly distributed throughout the structure of protein L. Certain secondary structure elements have stronger [C]-dependent interactions than others in the denatured state. C1 [O'Brien, Edward P.; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. [O'Brien, Edward P.; Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [O'Brien, Edward P.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. EM thirum@umd.edu RI O'Brien, Edward/C-3587-2015 FU National Science Foundation [05-14056]; Air Force Office of Scientific Research [FA9550-07-1-0098]; National Institutes of Health; National Heart, Lung and Blood Institute FX This work was supported in part by a grant from the National Science Foundation (05-14056) and the Air Force Office of Scientific Research (FA9550-07-1-0098) to D.T., by a National Institutes of Health GPP Biophysics Fellowship to E.P.O., and by the Intramural Research Program of the National Heart, Lung and Blood Institute. NR 65 TC 25 Z9 25 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 5 PY 2009 VL 48 IS 17 BP 3743 EP 3754 DI 10.1021/bi8021119 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 438AR UT WOS:000265528800006 PM 19278261 ER PT J AU Gohlke, JM Thomas, R Zhang, YQ Rosenstein, MC Davis, AP Murphy, C Becker, KG Mattingly, CJ Portier, CJ AF Gohlke, Julia M. Thomas, Reuben Zhang, Yonqing Rosenstein, Michael C. Davis, Allan P. Murphy, Cynthia Becker, Kevin G. Mattingly, Carolyn J. Portier, Christopher J. TI Genetic and environmental pathways to complex diseases SO BMC SYSTEMS BIOLOGY LA English DT Article ID INFLAMMATION-RELATED GENES; EXPRESSION PROFILES; SYSTEMATIC METAANALYSES; INTERACTION NETWORKS; RETINOIC ACID; PPAR-GAMMA; GENOME; OBESITY; DATABASE; RISK AB Background: Pathogenesis of complex diseases involves the integration of genetic and environmental factors over time, making it particularly difficult to tease apart relationships between phenotype, genotype, and environmental factors using traditional experimental approaches. Results: Using gene-centered databases, we have developed a network of complex diseases and environmental factors through the identification of key molecular pathways associated with both genetic and environmental contributions. Comparison with known chemical disease relationships and analysis of transcriptional regulation from gene expression datasets for several environmental factors and phenotypes clustered in a metabolic syndrome and neuropsychiatric subnetwork supports our network hypotheses. This analysis identifies natural and synthetic retinoids, antipsychotic medications, Omega 3 fatty acids, and pyrethroid pesticides as potential environmental modulators of metabolic syndrome phenotypes through PPAR and adipocytokine signaling and organophosphate pesticides as potential environmental modulators of neuropsychiatric phenotypes. Conclusion: Identification of key regulatory pathways that integrate genetic and environmental modulators define disease associated targets that will allow for efficient screening of large numbers of environmental factors, screening that could set priorities for further research and guide public health decisions. C1 [Gohlke, Julia M.; Thomas, Reuben; Portier, Christopher J.] Natl Inst Environm Hlth Sci, Environm Syst Biol Grp, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Zhang, Yonqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. [Rosenstein, Michael C.; Davis, Allan P.; Murphy, Cynthia; Mattingly, Carolyn J.] Mt Desert Isl Biol Lab, Dept Bioinformat, Salsbury Cove, ME 04672 USA. RP Portier, CJ (reprint author), Natl Inst Environm Hlth Sci, Environm Syst Biol Grp, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. EM gohlkej@niehs.nih.gov; thomasr3@niehs.nih.gov; zhangyon@grc.nia.nih.gov; mcr@mdibl.org; apdavis@mdibl.org; cmurphy@mdibl.org; beckerk@grc.nia.nih.gov; cmattin@mdibl.org; portier@niehs.nih.gov RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Gohlke, Julia/0000-0002-6984-2893; Becker, Kevin/0000-0002-6794-6656 FU NIH, National Institute of Environmental Health Sciences; National Institute of Aging; NIEHS [5R01ES014065-02] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (J.G., R.T., C.P.) and National Institute of Aging (Y.Z., K.B.) as well as NIEHS extramural funding under grant 5R01ES014065-02 ( M. R., A.D., C.M. and C.J.M.). NR 78 TC 40 Z9 40 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD MAY 5 PY 2009 VL 3 AR 46 DI 10.1186/1752-0509-3-46 PG 15 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 444TA UT WOS:000266002100001 PM 19416532 ER PT J AU Miao, CL Chen, SG Macedo, R Lai, SH Liu, K Li, DB Wasserman, BA Vogel-Clausen, J Lima, JAC Bluemke, DA AF Miao, Cuilian Chen, Shaoguang Macedo, Robson Lai, Shenghan Liu, Kiang Li, Debiao Wasserman, Bruce A. Vogel-Clausen, Jens Lima, Joao A. C. Bluemke, David A. TI Positive Remodeling of the Coronary Arteries Detected by Magnetic Resonance Imaging in an Asymptomatic Population MESA (Multi-Ethnic Study of Atherosclerosis) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE subclinical atherosclerosis; magnetic resonance imaging; coronary artery disease; plaque ID VESSEL WALL; IN-VIVO; INTRAVASCULAR ULTRASOUND; COMPENSATORY ENLARGEMENT; COMPUTED-TOMOGRAPHY; PLAQUE; MRI; INDIVIDUALS; ENDOTHELIUM; THERAPY AB Objectives The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall magnetic resonance imaging (MRI) in an asymptomatic population-based cohort. Background In early atherosclerosis, compensatory enlargement of both the outer wall of the vessel as well as the lumen, termed compensatory enlargement or positive remodeling, occurs before luminal narrowing. Methods One hundred seventy-nine participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial were evaluated using black-blood coronary wall MRI. Coronary cross-sectional area (vessel size), lumen area, and mean wall thickness of the proximal coronary arteries were measured. Results Men had a greater vessel size, lumen area, and mean wall thickness than women (38.3 +/- 11.3 mm(2) vs. 32.6 +/- 9.4 mm(2), 6.7 +/- 3.2 mm(2) vs. 5.3 +/- 2.4 mm(2), and 2.0 +/- 0.3 mm vs. 1.9 +/- 0.3 mm, respectively, p < 0.05). No significant coronary artery narrowing was present by magnetic resonance angiography. Overall, coronary vessel size increased 25.9 mm(2) per millimeter increase in coronary wall thickness, whereas lumen area increased only slightly at 3.1 mm(2) for every millimeter increase in wall thickness (difference in slopes, p < 0.0001). Adjusting for age and sex, participants with an Agatston score > 0 were more likely to have wall thickness > 2.0 mm (odds ratio: 2.0, 95% confidence interval: 1.01 to 3.84). Conclusions Coronary wall MRI detected positive arterial remodeling in asymptomatic men and women with subclinical atherosclerosis. (J Am Coll Cardiol 2009; 53: 1708-15) (C) 2009 by the American College of Cardiology Foundation C1 [Miao, Cuilian; Macedo, Robson; Wasserman, Bruce A.; Vogel-Clausen, Jens; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA. [Chen, Shaoguang; Lai, Shenghan] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Liu, Kiang] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. [Li, Debiao] Northwestern Univ, Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), Johns Hopkins Univ Hosp, MRI Room 143 Nelson Basement,600 N Wolfe St, Baltimore, MD 21287 USA. EM dbluemke@jhmi.edu RI Li, Debiao/B-7622-2009; OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [R01 HL78909, N01-HC95159, N01-HC-95169] FX This research was supported by R01 HL78909 and contracts N01-HC95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. Paul Schoenhagen, MD, served as Guest Editor for this article. NR 27 TC 66 Z9 71 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 5 PY 2009 VL 53 IS 18 BP 1708 EP 1715 DI 10.1016/j.jacc.2008.12.063 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 439LL UT WOS:000265628500012 PM 19406347 ER PT J AU Copenhaver, BR Shin, J Warach, S Butman, JA Saver, JL Kidwell, CS AF Copenhaver, B. R. Shin, J. Warach, S. Butman, J. A. Saver, J. L. Kidwell, C. S. TI Gradient echo MRI Implementation of a training tutorial for intracranial hemorrhage diagnosis SO NEUROLOGY LA English DT Article ID ACUTE STROKE; THROMBOLYTIC THERAPY; COMPUTED-TOMOGRAPHY; ISCHEMIC-STROKE; CT; DISEASE; HEME AB Background: Recent studies have demonstrated that gradient echo (GRE) MRI sequences are as accurate as CT for the detection of intracerebral hemorrhage (ICH) in the context of acute stroke. However, many physicians who currently read acute stroke imaging studies may be unfamiliar with interpretation of GRE images. Methods: An NIH Web-based training program was developed including a pretest, tutorial, and posttest. Physicians involved in the care of acute stroke patients were encouraged to participate. The tutorial covered acute, chronic, and mimic hemorrhages as they appear on CT, diffusion-weighted imaging, and GRE sequences. Ability of users to identify ICH presence, type, and age on GRE was compared from the pretest to posttest timepoint. Results: A total of 104 users completed the tutorial. Specialties represented included general radiology (42%), general neurology (16%), neuroradiology (15%), stroke neurology (14%), emergency medicine (1%), and other (12%). Median overall score improved pretest to posttest from 66.7% to 83.3%, p < 0.001. Improvement by category was as follows: acute ICH, 66.7%-100%, p < 0.001; chronic ICH, 33.3%-66.7%, p < 0.001; ICH negatives/mimics, 100%-100%, p = 0.787. Sensitivity for identification of acute hemorrhage improved from 68.2% to 96.4%. Conclusions: Physicians involved in acute stroke care achieved significant improvement in gradient echo ( GRE) hemorrhage interpretation after completing the NIH GRE MRI tutorial. This indicates that a Web-based tutorial may be a viable option for the widespread education of physicians to achieve an acceptable level of diagnostic accuracy at reading GRE MRI, thus enabling confident acute stroke treatment decisions. Neurology (R) 2009;72:1576-1581 C1 [Copenhaver, B. R.; Kidwell, C. S.] Georgetown Univ, Dept Neurol, Washington, DC USA. [Shin, J.; Saver, J. L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Warach, S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Butman, J. A.] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Kidwell, CS (reprint author), 4000 Reservoir Rd,Bldg D,Suite 150, Washington, DC 20007 USA. EM ck256@georgetown.edu RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195; Saver, Jeffrey/0000-0001-9141-2251 FU Intramural NIH HHS; NINDS NIH HHS [P50 NS044378, P50 NS044378-069011] NR 12 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 5 PY 2009 VL 72 IS 18 BP 1576 EP 1581 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 441PZ UT WOS:000265782600008 PM 19414724 ER PT J AU Wolf, YI Novichkov, PS Karev, GP Koonin, EV Lipman, DJ AF Wolf, Yuri I. Novichkov, Pavel S. Karev, Georgy P. Koonin, Eugene V. Lipman, David J. TI The universal distribution of evolutionary rates of genes and distinct characteristics of eukaryotic genes of different apparent ages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene age; gene expression; genome evolution; intron density ID PROTEIN EVOLUTION; INVERSE RELATIONSHIP; SEQUENCE EVOLUTION; MAMMALIAN GENES; PSI-BLAST; GENOME; DATABASE; DISPENSABILITY; DIVERGENCE; EXPRESSION AB The evolutionary rates of protein-coding genes in an organism span, approximately, 3 orders of magnitude and show a universal, approximately log-normal distribution in a broad variety of species from prokaryotes to mammals. This universal distribution implies a steady-state process, with identical distributions of evolutionary rates among genes that are gained and genes that are lost. A mathematical model of such process is developed under the single assumption of the constancy of the distributions of the propensities for gene loss (PGL). This model predicts that genes of different ages, that is, genes with homologs detectable at different phylogenetic depths, substantially differ in those variables that correlate with PGL. We computationally partition protein-coding genes from humans, flies, and Aspergillus fungus into age classes, and show that genes of different ages retain the universal log-normal distribution of evolutionary rates, with a shift toward higher rates in "younger'' classes but also with a substantial overlap. The only exception involves human primate-specific genes that show a heavy tail of rapidly evolving genes, probably owing to gene annotation artifacts. As predicted, the gene age classes differ in characteristics correlated with PGL. Compared with "young'' genes (e.g., mammal-specific human ones), "old'' genes (e.g., eukaryote-specific), on average, are longer, are expressed at a higher level, possess a higher intron density, evolve slower on the short time scale, and are subject to stronger purifying selection. Thus, genome evolution fits a simple model with approximately uniform rates of gene gain and loss, without major bursts of genomic innovation. C1 [Wolf, Yuri I.; Karev, Georgy P.; Koonin, Eugene V.; Lipman, David J.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Novichkov, Pavel S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. RP Lipman, DJ (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM lipman@ncbi.nlm.nih.gov FU Department of Health and Human Services (National Library of Medicine, National Institutes of Health) FX We thank Liran Carmel for valuable help with the expression data and useful discussions of the statistical analysis and Josh Cherry for critical reading of the manuscript. This work was supported by the Department of Health and Human Services (National Library of Medicine, National Institutes of Health). NR 64 TC 98 Z9 100 U1 0 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7273 EP 7280 DI 10.1073/pnas.0901808106 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600004 PM 19351897 ER PT J AU Dikeakos, JD Di Lello, P Lacombe, MJ Ghirlando, R Legault, P Reudelhuber, TL Omichinski, JG AF Dikeakos, Jimmy D. Di Lello, Paola Lacombe, Marie-Josee Ghirlando, Rodolfo Legault, Pascale Reudelhuber, Timothy L. Omichinski, James G. TI Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NMR; prohormone convertases ID C-13-LABELED PROTEINS; IMPROVED SENSITIVITY; REGULATED PATHWAY; NMR EXPERIMENTS; ALPHA-HELIX; J COUPLINGS; SPECTROSCOPY; PROPROTEIN; SEQUENCE; SYSTEM AB Several peptide hormones are initially synthesized as inactive precursors. It is only on entry of these prohormones and their processing proteases into dense core secretory granules (DCSGs) that the precursors are cleaved to generate their active forms. Prohormone convertase (PC)1/3 is a processing protease that is targeted to DCSGs. The signal for targeting PC1/3 to DCSGs resides in its carboxy-terminal tail (PC1/3(617-753)), where 3 regions (PC1/3(617-625), PC1/3(665-682), and PC1/3(711-753)) are known to aid in sorting and membrane association. In this article, we have determined a high-resolution structure of the extreme carboxy-terminal sorting domain, PC1/3(711-753) in micelles by NMR spectroscopy. PC1/3(711-753) contains 2 alpha helices located between residues 722-728 and 738-750. Functional assays demonstrate that the second helix (PC1/3(738-750)) is necessary and sufficient to target a constitutively secreted protein to granules, and that L(745) anchors a hydrophobic patch that is critical for sorting. Also, we demonstrate that calcium binding by the second helix of PC1/3(711-753) promotes aggregation of the domain via the hydrophobic patch centered on L(745). These results provide a structure-function analysis of a DCSG-sorting domain, and reveal the importance of a hydrophobic patch and calcium binding in controlling the sorting of proteins containing alpha helices to DCSGs. C1 [Dikeakos, Jimmy D.; Lacombe, Marie-Josee; Reudelhuber, Timothy L.] Clin Res Inst Montreal, Lab Mol Biochem Hypertens, Montreal, PQ H2W 1R7, Canada. [Di Lello, Paola; Legault, Pascale; Omichinski, James G.] Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada. [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. RP Reudelhuber, TL (reprint author), Clin Res Inst Montreal, Lab Mol Biochem Hypertens, 110 Pine Ave W, Montreal, PQ H2W 1R7, Canada. EM reudelt@ircm.qc.ca; jg.omichinski@umontreal.ca RI Ghirlando, Rodolfo/A-8880-2009; di lello, paola/C-8605-2013 FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX The 800 MHz NMR experiments were recorded at the Quebec/Eastern Canada High Field NMR Facility, supported by grants from the Canada Foundation for Innovation and the Quebec Ministere de la Recherche en Science et Technologie. This work was supported by the Canadian Institutes of Health Research (CIHR) Grants MOP-135604 (to J.G.O.) and MOP-53177 ( to T. L. R.). J.D.D. is a recipient of a studentship from the Fonds de la Recherche en Sante du Quebec, and P. D. L. of a fellowship from the CIHR. P. L. is a Canadian Research Chair in Structural Biology of RNA. This work was also supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R. G.). NR 39 TC 21 Z9 21 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7408 EP 7413 DI 10.1073/pnas.0809576106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600028 PM 19376969 ER PT J AU Pedersen, MG Sherman, A AF Pedersen, Morten Gram Sherman, Arthur TI Newcomer insulin secretory granules as a highly calcium-sensitive pool SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta-cells; biphasic secretion; exocytosis; pancreatic islets; vesicles ID PANCREATIC BETA-CELLS; ADRENAL CHROMAFFIN CELLS; PROTEIN-KINASE-C; CA2+-SENSITIVE POOL; CA2+ SENSORS; MOLECULAR-MECHANISMS; TARGET MEMBRANE; FAST EXOCYTOSIS; VESICLE FUSION; INS-1 CELLS AB Insulin secretion is biphasic in response to a step in glucose stimulation. Recent experiments suggest that 2 different mechanisms operate during the 2 phases, with transient first-phase secretion due to exocytosis of docked granules but the second sustained phase due largely to newcomer granules. Another line of research has shown that there exist 2 pools of releasable granules with different Ca(2+) sensitivities. An immediately releasable pool (IRP) is located in the vicinity of Ca(2+) channels, whereas a highly Ca(2+)-sensitive pool (HCSP) resides mainly away from Ca(2+) channels. We extend a previous model of exocytosis and insulin release by adding an HCSP and show that the inclusion of this pool naturally leads to insulin secretion mainly from newcomer granules during the second phase of secretion. We show that the model is compatible with data from single cells on the HCSP and from stimulation of islets by glucose, including L- and R-type Ca(2+) channel knockouts, as well as from Syntaxin-1A-deficient cells. We also use the model to investigate the relative contribution of calcium signaling and pool depletion in controlling biphasic secretion. C1 [Pedersen, Morten Gram] Univ Padua, Dept Informat Engn, I-35131 Padua, Italy. [Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Pedersen, MG (reprint author), Univ Padua, Dept Informat Engn, Via Gradenigo 6-A, I-35131 Padua, Italy. EM pedersen@dei.unipd.it RI Pedersen, Morten/F-4134-2012 OI Pedersen, Morten/0000-0002-2639-2394 FU Intramural NIH HHS NR 61 TC 46 Z9 46 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7432 EP 7436 DI 10.1073/pnas.0901202106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600032 PM 19372374 ER PT J AU Paravastu, AK Qahwash, I Leapman, RD Meredith, SC Tycko, R AF Paravastu, Anant K. Qahwash, Isam Leapman, Richard D. Meredith, Stephen C. Tycko, Robert TI Seeded growth of beta-amyloid fibrils from Alzheimer's brain-derived fibrils produces a distinct fibril structure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer's disease; electron microscopy; solid-state nuclear magnetic resonance ID NUCLEAR-MAGNETIC-RESONANCE; SOLID-STATE NMR; EXPERIMENTAL CONSTRAINTS; DISTANCE MEASUREMENTS; DISEASE; PROTEIN; PEPTIDE; CONFORMATION; ORGANIZATION; POLYMORPHISM AB Studies by solid-state nuclear magnetic resonance (NMR) of amyloid fibrils prepared in vitro from synthetic 40-residue beta-amyloid (A beta(1-40)) peptides have shown that the molecular structure of A beta(1-40) fibrils is not uniquely determined by amino acid sequence. Instead, the fibril structure depends on the precise details of growth conditions. The molecular structures of beta-amyloid fibrils that develop in Alzheimer's disease (AD) are therefore uncertain. We demonstrate through thioflavin T fluorescence and electron microscopy that fibrils extracted from brain tissue of deceased AD patients can be used to seed the growth of synthetic A beta(1-40) fibrils, allowing preparation of fibrils with isotopic labeling and in sufficient quantities for solid-state NMR and other measurements. Because amyloid structures propagate themselves in seeded growth, as shown in previous studies, the molecular structures of brain-seeded synthetic A beta(1-40) fibrils most likely reflect structures that are present in AD brain. Solid-state (13)C NMR spectra of fibril samples seeded with brain material from two AD patients were found to be nearly identical, indicating the same molecular structures. Spectra of an unseeded control sample indicate greater structural heterogeneity. (13)C chemical shifts and other NMR data indicate that the predominant molecular structure in brain-seeded fibrils differs from the structures of purely synthetic A beta(1-40) fibrils that have been characterized in detail previously. These results demonstrate a new approach to detailed structural characterization of amyloid fibrils that develop in human tissue, and to investigations of possible correlations between fibril structure and the degree of cognitive impairment and neurodegeneration in AD. C1 [Paravastu, Anant K.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Qahwash, Isam; Meredith, Stephen C.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Qahwash, Isam; Meredith, Stephen C.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health [NS042852]; Alzheimer's Association [IIRG-06-27794] FX This work was supported by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases (to A. K. P. and R. T.); by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (to R. D. L.); and by the National Institutes of Health (grant NS042852, to S. C. M.); and by the Alzheimer's Association (grant IIRG-06-27794, to S. C. M.). NR 39 TC 156 Z9 156 U1 3 U2 49 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7443 EP 7448 DI 10.1073/pnas.0812033106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600034 PM 19376973 ER PT J AU Zheng, P Dean, J AF Zheng, Ping Dean, Jurrien TI Role of Filia, a maternal effect gene, in maintaining euploidy during cleavage-stage mouse embryogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aneuploidy; mitotic kinases; spindle assembly checkpoint ID EARLY EMBRYONIC-DEVELOPMENT; AURORA-A KINASE; LIM PROTEIN; RHO-GTPASES; HELA-CELLS; SPINDLE; OOCYTES; ACTIVATION; TRANSITION; CENTROSOME AB During oogenesis, mammalian eggs accumulate proteins required for early embryogenesis. Although limited data suggest a vital role of these maternal factors in chromatin reprogramming and embryonic genome activation, the full range of their functions in preimplantation development remains largely unknown. Here we report a role for maternal proteins in maintaining chromosome stability and euploidy in early-cleavage mouse embryogenesis. Filia, expressed in growing oocytes, encodes a protein that binds to MATER and participates in a subcortical maternal complex essential for cleavage-stage embryogenesis. The depletion of maternal stores of Filia impairs preimplantation embryo development with a high incidence of aneuploidy that results from abnormal spindle assembly, chromosome misalignment, and spindle assembly checkpoint (SAC) inactivation. In helping to ensure normal spindle morphogenesis, Filia regulates the proper allocation of the key spindle assembly regulators (i.e., AURKA, PLK1, and gamma-tubulin) to the microtubule-organizing center via the RhoA signaling pathway. Concurrently, Filia is required for the placement of MAD2, an essential component of the SAC, to kinetochores to enable SAC function. Thus, Filia is central to integrating the spatiotemporal localization of regulators that helps ensure euploidy and high-quality cell cycle progression in preimplantation mouse development. Defects in the well-conserved human homologue could play a similar role and account for recurrent human fetal wastage. C1 [Zheng, Ping; Dean, Jurrien] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM jurrien@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. We express our sincere appreciation to Drs. Chuxia Deng and Cuiling Li for establishing mutant mouse lines and to Dr. Boris Baibakov for his insightful assistance with confocal microscopy. NR 47 TC 66 Z9 68 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7473 EP 7478 DI 10.1073/pnas.0900519106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600039 PM 19376971 ER PT J AU Zhang, ML Yao, ZS Dubois, S Ju, W Muller, JR Waldmann, TA AF Zhang, Meili Yao, Zhengsheng Dubois, Sigrid Ju, Wei Mueller, Juergen R. Waldmann, Thomas A. TI Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE animal model; cancer immunotherapy; IL-15 receptor-alpha ID REGULATORY T-CELLS; DENDRITIC CELLS; NATURAL-KILLER; NK CELLS; LYMPHOID HOMEOSTASIS; GROWTH-FACTOR; BETA-CHAIN; IL-15; RECEPTOR; ANTITUMOR AB IL-15 has potential as an immunotherapeutic agent for cancer treatment because it is a critical factor for the proliferation and activation of natural killer (NK) and CD8(+) T cells. Administration of anti-CD40 antibodies has shown anti-tumor effects in vivo through a variety of mechanisms. Furthermore, activation of CD40 led to increased expression of IL-15 receptor-alpha by dendritic cells, an action that is critical for trans- presentation of IL-15 to NK and CD8(+) T cells. In this study, we investigated the therapeutic efficacy of the combination regimen of murine IL-15 (mIL-15) with an agonistic anti-CD40 antibody (FGK4.5) in murine lung metastasis models involving CT26 and MC38, which are murine colon cancer cell lines syngeneic to BALB/c and C57BL/6 mice, respectively. Treatment with mIL-15 or the anti-CD40 antibody alone significantly prolonged survival of both CT26 and MC38 tumor-bearing mice compared with the mice in the PBS solution control group (P < 0.01). Furthermore, combination therapy with both mIL-15 and the anti-CD40 antibody provided greater therapeutic efficacy as demonstrated by prolonged survival of the mice compared with either mIL-15 or the anti-CD40 antibody-alone groups (P < 0.001). We found that NK cells isolated from the mice that received the combination regimen expressed increased levels of intracellular granzyme B and showed stronger cytotoxic activity on the target cells. The findings from this study provide the scientific basis for clinical trials using the combination regimen of IL-15 with an anti-CD40 antibody for the treatment of patients with cancer. C1 [Zhang, Meili; Yao, Zhengsheng; Dubois, Sigrid; Ju, Wei; Mueller, Juergen R.; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhang, Meili] NCI, Lab Anim Sci Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov FU National Institutes of Health (NIH) [N01-CO-12400]; NCl, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), NCl, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the NCl, NIH, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 48 TC 64 Z9 65 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7513 EP 7518 DI 10.1073/pnas.0902637106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600046 PM 19383782 ER PT J AU Zhang, P Zhong, LL Struble, EB Watanabe, H Kachko, A Mihalik, K Virata-Theimer, ML Alter, HJ Feinstone, S Major, M AF Zhang, Pei Zhong, Lilin Struble, Evi Budo Watanabe, Hisayoshi Kachko, Alla Mihalik, Kathleen Virata-Theimer, Maria Luisa Alter, Harvey J. Feinstone, Stephen Major, Marian TI Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS-LIKE PARTICLES; CD81 BINDING; E2; GLYCOPROTEIN; INFECTION; IDENTIFICATION; REPLICATION; PROTEIN; PLASMA; AP33 AB Using human immune globulins made from antihepatitis C virus (HCV)-positive plasma, we recently identified two antibody epitopes in the E2 protein at residues 412-426 (epitope I) and 434-446 (epitope II). Whereas epitope I is highly conserved among genotypes, epitope II varies. We discovered that epitope I was implicated in HCV neutralization whereas the binding of non-neutralizing antibody to epitope II disrupted virus neutralization mediated by antibody binding at epitope I. These findings suggested that, if this interfering mechanism operates in vivo during HCV infection, a neutralizing antibody against epitope I can be restrained by an interfering antibody, which may account for the persistence of HCV even in the presence of an abundance of neutralizing antibodies. We tested this hypothesis by affinity depletion and peptide-blocking of epitope-II-specific antibodies in plasma of a chronically HCV-infected patient and recombinant E1E2 vaccinated chimpanzees. We demonstrate that, by removing the restraints imposed by the interfering antibodies to epitope-II, neutralizing activity can be revealed in plasma that previously failed to neutralize viral stock in cell culture. Further, cross-genotype neutralization could be generated from monospecific plasma. Our studies contribute to understanding the mechanisms of anti-body-mediated neutralization and interference and provide a practical approach to the development of more potent and broadly reactive hepatitis C immune globulins. C1 [Zhang, Pei; Zhong, Lilin; Struble, Evi Budo; Virata-Theimer, Maria Luisa] US FDA, Div Hematol, Bethesda, MD 20892 USA. [Watanabe, Hisayoshi; Kachko, Alla; Mihalik, Kathleen; Feinstone, Stephen; Major, Marian] US FDA, Div Viral Prod, Bethesda, MD 20892 USA. [Watanabe, Hisayoshi; Kachko, Alla; Mihalik, Kathleen; Feinstone, Stephen; Major, Marian] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Alter, Harvey J.] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), US FDA, Div Hematol, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov; halter@mail.nih.gov; marian.major@fda.hhs.gov NR 22 TC 86 Z9 88 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 5 PY 2009 VL 106 IS 18 BP 7537 EP 7541 DI 10.1073/pnas.0902749106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600050 PM 19380744 ER PT J AU Bernard, MA Blanchette, PL Brummel-Smith, K AF Bernard, Marie A. Blanchette, Patricia L. Brummel-Smith, Kenneth TI Strength and Influence of Geriatrics Departments in Academic Health Centers SO ACADEMIC MEDICINE LA English DT Article ID INTERNAL-MEDICINE; CARE; PHYSICIANS; STUDENTS AB The United States is establishing new medical schools and increasing class size by 30% in response to the predicted increased needs of the baby boom generation, which will retire soon and live longer than prior generations. Society in general and the medical profession in particular are ill equipped to care for the special needs of the elderly. Since the early 1980s, departments of geriatric medicine have been developed in the United States. However, the prevailing U.S. system for the training of physicians in geriatrics is through sections, divisions, or institutes. This article reviews the advantages and disadvantages of departments of geriatrics, using case examples from three (University of Oklahoma College of Medicine, Florida State University College of Medicine, and University of Hawaii at Manoa John A. Burns School of Medicine) of the extant 11 medical schools in the United States with departments of geriatrics. Commonalities among the three departments include a seat at the planning table in academic life, equal treatment and collaboration with other departments in academic and research program development, and direct access to key decision makers and opportunities for negotiation for funds. Each department has outreach to all undergraduate medical students through its training program. All three departments were launched through the investment of significant resources obtained both internally and externally. The challenge for the future will be to definitively demonstrate the efficacy of the department model versus the more prevalent section, division, and institute approach to training physicians to care for the elderly. C1 [Bernard, Marie A.] Univ Oklahoma, Coll Med, Reynolds Dept Geriatr, Oklahoma City, OK 73190 USA. [Blanchette, Patricia L.] Univ Hawaii Manoa, Dept Geriatr Med, John A Burns Sch Med, Honolulu, HI 96822 USA. [Brummel-Smith, Kenneth] Florida State Univ, Dept Geriatr, Coll Med, Tallahassee, FL 32306 USA. RP Bernard, MA (reprint author), NIA, NIH, Dept Hlth & Human Serv, Bldg 31,5C35,31 Ctr Dr MSC-2992, Bethesda, MD 20892 USA. EM mbernard@nia.nih.gov NR 21 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2009 VL 84 IS 5 BP 627 EP 632 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IR UT WOS:000267655300018 PM 19704196 ER PT J AU Lie, D Bereknyei, S Braddock, CH Encinas, J Ahearn, S Boker, JR AF Lie, Desiree Bereknyei, Sylvia Braddock, Clarence H., III Encinas, Jennifer Ahearn, Susan Boker, John R. TI Assessing Medical Students' Skills in Working With Interpreters During Patient Encounters: A Validation Study of the Interpreter Scale SO ACADEMIC MEDICINE LA English DT Article ID CLINICIAN COMMUNICATION-SKILLS; INFORMED DECISION-MAKING; HEALTH-CARE; EMERGENCY-DEPARTMENT; LANGUAGE CONCORDANCE; ENGLISH PROFICIENCY; OUTPATIENT PRACTICE; QUALITY; SERVICES; IMPACT AB Purpose Interpreted patient encounters require distinct communication skills. The absence of available reliable, valid, and practical measures hinders the assessment of these skills; therefore, the authors aimed to construct and validate the Interpreter Scale (IS). Method The authors constructed the IS based on expert consensus and prior studies. They administered the IS to two classes (n = 182) in an interpreted standardized patient (SP) case setting. Standardized interpreters in the examination room assessed, using the IS, students' communication skills. Concurrently, SIPS, using the validated Patient-Physician interaction scale (PPI) and the Interpreter Impact Rating Scale (IIRS), also assessed students' skills. Trained observers watched DVDs and used the Faculty Observer Rating Scale (FORS) to assess student performance. A prior study documented the qualities of the IIRS and FORS. The authors determined the internal consistency reliability and examined construct validity of IS scores through factor analysis and concordance with other measures' scores. Results IS reliability analysis yielded Cronbach alpha = 0.77. Factor analysis demonstrated two IS dimensions. Nine items, "managing the encounter," and four items, "setting the stage," explained 76% and 15% of score variance, respectively. IS and FORS scores significantly correlated (r = 0.385; P < .0001). IS factor 1 scores significantly correlated (all P < .0001) with FORS (r = 0.402), IIRS (r = 0.277), and PPI (r = 0.332) scores. Conclusions The IS has reasonable internal consistency reliability and construct validity to warrant use for formatively measuring student communication skills in interpreted SP encounters, and it needs testing in actual patient encounters. C1 [Lie, Desiree; Encinas, Jennifer] Univ Calif Irvine, Sch Med, Dept Family Med, Irvine, CA 92717 USA. [Ahearn, Susan] Univ Calif Irvine, Sch Med, Clin Skills Training Ctr, Irvine, CA 92717 USA. [Bereknyei, Sylvia; Braddock, Clarence H., III] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Bereknyei, Sylvia] NHLBI, NIH, Natl Consortium Multicultural Educ Hlth Profess, Stanford, CA USA. [Boker, John R.] Geisinger Hlth Syst, Danville, PA USA. RP Lie, D (reprint author), Dept Family Med, 101 City Dr S,Bldg 200,Rm 512, Orange, CA 92868 USA. EM dalie@uci.edu OI Bereknyei Merrell, Sylvia /0000-0002-5525-0379 FU National Institutes of Health (NIH); National Heart, Blood, and Lung Institute [K07 HL079256-01, K07 HL079330-04] FX This project was supported in part by a grant from the National Institutes of Health (NIH), National Heart, Blood, and Lung Institute, award #K07 HL079256-01, entitled "An Integrative, Evidence-Based Model of Cultural Competency Training in Latino Health Across the Continuum of Medical Education" (2004-2009), and award #K07 HL079330-04, entitled "Integrated Immersive Approaches to Cultural Competence." The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 42 TC 8 Z9 8 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2009 VL 84 IS 5 BP 643 EP 650 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IR UT WOS:000267655300020 PM 19704202 ER PT J AU Sherrill, JT Sommers, DI Nierenberg, AA Leon, AC Arndt, S Bandeen-Roche, K Greenhouse, J Guthrie, D Normand, SL Phillips, KA Shear, MK Woolson, R AF Sherrill, Joel T. Sommers, David I. Nierenberg, Andrew A. Leon, Andrew C. Arndt, Stephan Bandeen-Roche, Karen Greenhouse, Joel Guthrie, Donald Normand, Sharon-Lise Phillips, Katharine A. Shear, M. Katherine Woolson, Robert TI Integrating Statistical and Clinical Research Elements in Intervention-Related Grant Applications: Summary From an NIMH Workshop SO ACADEMIC PSYCHIATRY LA English DT Article ID MISSING DATA; TRIALS; POWER; CAUTION; ISSUES; SIZE AB Objective: The authors summarize points for consideration generated in a National Institute of Mental Health (NIMH) workshop convened to provide an opportunity for reviewers from different disciplines-specifically clinical researchers and statisticians-to discuss how their differing and complementary expertise can be well integrated in the review of intervention-related grant applications. Methods: A 1-day workshop was convened in October, 2004. The workshop featured panel presentations on key topics followed by interactive discussion. This article summarizes the workshop and subsequent discussions, which centered on topics including weighting the statistics/data analysis elements of an application in the assessment of the application's overall merit; the level of statistical sophistication appropriate to different stages of research and for different funding mechanisms; some key considerations in the design and analysis portions of applications; appropriate statistical methods for addressing essential questions posed by an application; and the role of the statistician in the application's development, study conduct, and interpretation and dissemination of results. Results: A number of key elements crucial to the construction and review of grant applications were identified. It was acknowledged that intervention-related studies unavoidably involve trade-offs. Reviewers are helped when applications acknowledge such trade-offs and provide good rationale for their choices. Clear linkage among the design, aims, hypotheses, and data analysis plan and avoidance of disconnections among these elements also strengthens applications. Conclusion: The authors identify multiple points to consider when constructing intervention-related grant applications. The points are presented here as questions and do not reflect institute policy or comprise a list of best practices, but rather represent points for consideration. C1 [Sommers, David I.] NIMH, Div Extramural Activ, Bethesda, MD 20892 USA. [Sherrill, Joel T.] NIMH, DSIR, Bethesda, MD 20892 USA. [Leon, Andrew C.] Cornell Univ, Dept Psychiat, Weill Med Coll, Ithaca, NY 14853 USA. [Arndt, Stephan] Univ Iowa Hosp & Clin, Iowa Consortium Subst Abuse Res, Iowa City, IA 52242 USA. [Greenhouse, Joel] Carnegie Mellon, Dept Stat, Pittsburgh, PA USA. [Guthrie, Donald] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Normand, Sharon-Lise] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Phillips, Katharine A.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Shear, M. Katherine] Columbia Univ, Sch Social Work, New York, NY 10027 USA. [Woolson, Robert] Med Univ S Carolina, Dept Psychiat Biostat, Charleston, SC USA. RP Sommers, DI (reprint author), NIMH, Div Extramural Activ, 6001 Execut Blvd,Room 6144, Bethesda, MD 20892 USA. EM dsommers@mail.nih.gov OI Arndt, Stephan/0000-0003-0783-8204 FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [K24 MH063975] NR 22 TC 6 Z9 6 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2009 VL 33 IS 3 BP 221 EP 228 PG 8 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 467CI UT WOS:000267713700009 PM 19574520 ER PT J AU Solomon, D Papillo, JL Davey, DD AF Solomon, Diane Papillo, Jacalyn L. Davey, Diane D. CA Consortium, CE&T TI Statement on HPV DNA Test Utilization SO ACTA CYTOLOGICA LA English DT Editorial Material DE cervical cancer; cervix neoplasms; human papillomavirus ID CANCER C1 [Solomon, Diane] NCI, Canc Prevent Div, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Fletcher Allen Hlth Care, Dept Anat Pathol, Burlington, VT USA. Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. RP Solomon, D (reprint author), NCI, Canc Prevent Div, Dept Hlth & Human Serv, NIH, Execut Plaza N,Room 2130,6130 Executive Blvd, Rockville, MD 20852 USA. EM ds87v@nih.gov NR 3 TC 5 Z9 5 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD MAY-JUN PY 2009 VL 53 IS 3 BP 247 EP 248 DI 10.1159/000325302 PG 2 WC Pathology SC Pathology GA 449NG UT WOS:000266336700002 PM 19534262 ER PT J AU Cox, JT Moriarty, AT Castle, PE AF Cox, J. Thomas Moriarty, Ann T. Castle, Philip E. TI Statement on HPV DNA Test Utilization Commentary SO ACTA CYTOLOGICA LA English DT Article DE cervical cancer; cervix neoplasms; human papillomavirus ID CANCER-SOCIETY GUIDELINE; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; SCREENING-TESTS; NEOPLASIA; COHORT; WOMEN; AMERICAN; RISK; METAANALYSIS AB Michaela had a Pap test at age 17, less than 3 months after her first intercourse. The Pap was interpreted as atypical squamous cells of undetermined significance (ASC-US), and the laboratory automatically "reflexed" this to human papillomavirus (HPV) testing. Michaela tested positive for high-risk, (carcinogenic) HPV, had colposcopy and biopsy, and cryotherapy for cervical intraepithelial neoplasia, grade 1 (CIN 1). Her 4-month postcrotherapy Pap was ASC-US HPV positive. C1 [Cox, J. Thomas] Univ Calif Santa Barbara, Gynecol & Colposcopy Clin, Student Hlth Serv, Santa Barbara, CA 93106 USA. [Moriarty, Ann T.] AmeriPath Indiana, Indianapolis, IN USA. [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Cox, JT (reprint author), Univ Calif Santa Barbara, Gynecol & Colposcopy Clin, Student Hlth Serv, Santa Barbara, CA 93106 USA. EM cox-t@sa.ucsb.edu NR 21 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD MAY-JUN PY 2009 VL 53 IS 3 BP 249 EP 252 PG 4 WC Pathology SC Pathology GA 449NG UT WOS:000266336700003 ER PT J AU Kurup, S Lew, J Byrnes, G Yeh, S Nussenblatt, R Levy-Clarke, G AF Kurup, Shree Lew, Julie Byrnes, Gordon Yeh, Steven Nussenblatt, Robert Levy-Clarke, Grace TI Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization SO ACTA OPHTHALMOLOGICA LA English DT Article DE anti-VEGF; bevacizumab; lupus retinopathy; neovascularization; proliferative retinopathy; sarcoidosis ID ENDOTHELIAL GROWTH-FACTOR; SARCOIDOSIS AB To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis-associated choroidal/retinal neovascularization. Two female patients (40 years, 15 years) with posterior uveitis, (one presumed ocular sarcoidosis, one lupus) were evaluated for neovascularization of the posterior segment. Both patients were given a single dose of 1.25 mg intravitreal bevacizumab. Significant anatomical and functional recovery was evident in both patients within a few weeks. In selected uveitic patients, bevacizumab may be an option for managing neovascularization. C1 [Kurup, Shree] Wake Forest Univ, Dept Ophthalmol, Ctr Eye, Winston Salem, NC 27101 USA. [Lew, Julie; Yeh, Steven; Nussenblatt, Robert; Levy-Clarke, Grace] NEI, NIH, Bethesda, MD 20892 USA. [Byrnes, Gordon] Retina Grp Washington, Chevy Chase, MD USA. RP Kurup, S (reprint author), Wake Forest Univ, Dept Ophthalmol, Ctr Eye, Winston Salem, NC 27101 USA. EM skurup@wfubmc.edu FU Intramural NIH HHS [ZIE EY000482-01] NR 7 TC 21 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD MAY PY 2009 VL 87 IS 3 BP 349 EP 352 DI 10.1111/j.1755-3768.2008.01208.x PG 4 WC Ophthalmology SC Ophthalmology GA 434BY UT WOS:000265251400021 PM 18513266 ER PT J AU Semba, RD Ferrucci, L Sun, K Patel, KV Guralnik, JM Fried, LP AF Semba, Richard D. Ferrucci, Luigi Sun, Kai Patel, Kushang V. Guralnik, Jack M. Fried, Linda P. TI Elevated serum advanced glycation end products and their circulating receptors are associated with anaemia in older community-dwelling women SO AGE AND AGEING LA English DT Article DE advanced glycation end products; anaemia; haemoglobin; women; elderly ID DIABETIC-NEPHROPATHY; SOLUBLE RECEPTOR; OXIDATIVE STRESS; GLYCOTOXINS; LINK; N-EPSILON-(CARBOXYMETHYL)LYSINE; ATHEROSCLEROSIS; ERYTHROCYTES; INFLAMMATION; ENDPRODUCTS AB Objective: to determine whether serum carboxymethyl-lysine, a dominant advanced glycation end product (AGE), and circulating total receptor for AGEs (sRAGE) and endogenous secretory receptor for AGEs (esRAGE) are associated with anaemia. Design: cross-sectional analysis. Setting: moderately severely disabled women, >= 65 years, living in the community in Baltimore, MD (the Women's Health and Aging Study I). Participants: 519 women with and without anaemia. Main outcome measure: haemoglobin and anaemia (haemoglobin < 12 g/dL). Results: of 519 women, 128 (24.7%) had anaemia. All odds ratios (OR) were expressed per one standard deviation. Serum CML was associated with anaemia [OR 1.47, 95% confidence interval (CI) 1.11-1.95, P = 0.008] in a multivariate logistic regression model adjusting for age, race, smoking, education and chronic diseases. Serum sRAGE (ng/mL) and esRAGE (ng/mL) were associated with anaemia (OR 1.52, 95% CI 1.21-1.92, P = 0.0004; OR 1.49, 95% CI 1.18-1.87, P = 0.0006, respectively) in separate multivariate logistic regression models, adjusting for the same covariates mentioned above. Serum CML (P = 0.004), sRAGE (P < 0.0001) and esRAGE (P < 0.0001) were inversely and independently associated with haemoglobin concentrations. Conclusion: AGEs and circulating RAGE are independently associated with haemoglobin and anaemia in older women. AGEs are amenable to interventions, as serum AGEs can be lowered by a change in dietary pattern and pharmacological treatment. C1 [Semba, Richard D.; Sun, Kai; Fried, Linda P.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. EM rdsemba@jhmi.edu FU National Institute on Aging [R01 AG029148, R01 AG027012, R37 AG19905]; Intramural Research Program; National Institute on Aging; NIH FX This work was supported by National Institute on Aging Grant R01 AG029148, R01 AG027012, R37 AG19905, and the Intramural Research Program, National Institute on Aging, NIH. NR 30 TC 5 Z9 6 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD MAY PY 2009 VL 38 IS 3 BP 283 EP 289 DI 10.1093/ageing/afp011 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 434HV UT WOS:000265266700009 PM 19252206 ER PT J AU Keyes, KM Geier, T Grant, BF Hasin, DS AF Keyes, Katherine M. Geier, Timothy Grant, Bridget F. Hasin, Deborah S. TI Influence of a Drinking Quantity and Frequency Measure on the Prevalence and Demographic Correlates of DSM-IV Alcohol Dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE At-Risk Drinking; Binge Drinking; Diagnostic and Statistical Manual of Mental and Behavior Disorders V; Alcohol Dependence; Epidemiology ID SUBSTANCE USE DISORDERS; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; ITEM RESPONSE THEORY; UNITED-STATES; DRUG-USE; METHODOLOGICAL ISSUES; SERVICE UTILIZATION; BREAST-CANCER AB Recent research suggests that adding a quantity/frequency alcohol consumption measure to diagnoses of alcohol use disorders may improve construct validity of the diagnoses for Diagnostic and Statistical Manual of Mental and Behavior Disorders (DSM-V). This study explores the epidemiological impact of including weekly at-risk drinking (WAD) in the DMS-IV diagnostic definition of alcohol dependence via 3 hypothetical reformulations of the current criteria. The sample was the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample with 43,093 adults aged > 18 in the U.S interviewed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule IV. The current (DSM-IV) definition of alcohol dependence was compared with 4 hypothetical alcohol dependence reformulations that included WAD: (1) WAD added as an eighth criteria; (2) WAD required for a diagnosis; (3) adding abuse and dependence criteria together, and including WAD with a 3 of 12 symptom threshold; (4) adding abuse and dependence criteria together, and including WAD with a 5 of 12 symptom threshold. The inclusion of at-risk drinking as an eighth criterion of alcohol dependence has a minimal impact on the sociodemographic correlates of alcohol dependence but substantially increases the prevalence of dependence (from 3.8% to 5.0%). At-risk drinking as a required criterion or as part of a diagnosis that combines abuse with dependence criteria with a higher threshold (5+ criteria) decreases prevalence and has a larger impact on sociodemographic correlates. Blacks, Hispanics, and women are less likely to be included in diagnostic reformulations that include WAD, whereas individuals with low-income and education are more likely to remain diagnosed. Including WAD as either a requirement of diagnosis or as an additional criterion would have a large impact on the prevalence of alcohol dependence in the general population. The inclusion of a quantity/frequency requirement may eliminate false positives from studies of alcohol disorder etiology and improve phenotype definition for genetic association studies by reducing heterogeneity in the diagnosis, but may also reduce eligibility for treatment services among women and racial/ethnic minorities compared. C1 [Keyes, Katherine M.; Geier, Timothy; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Keyes, Katherine M.; Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Dept Hlth & Human Serv,NIH, Bethesda, MD USA. [Hasin, Deborah S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Hasin, DS (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr 123, New York, NY 10032 USA. EM dsh2@columbia.edu FU National Institute on Alcoholism and Alcohol Abuse [K05 AA014223]; National Institute on Drug Abuse [RO1 DA018652]; National Institute of Mental Health [T32 MH013043-36] FX This research was supported in part by grants from the National Institute on Alcoholism and Alcohol Abuse (K05 AA014223, Hasin), the National Institute on Drug Abuse (RO1 DA018652, Hasin), a fellowship from the National Institute of Mental Health (T32 MH013043-36, Keyes), and support from New York State Psychiatric Institute. A version of this paper was presented at the 2008 meeting of the Research Society on Alcoholism in Washington, DC, where it received the Enoch Gordis prize for student psychosocial research. The authors wish to thank Sarah Braunstein and Ann Madsen for helpful comments on previous drafts of this manuscript. NR 84 TC 28 Z9 28 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2009 VL 33 IS 5 BP 761 EP 771 DI 10.1111/j.1530-0277.2009.00894.x PG 11 WC Substance Abuse SC Substance Abuse GA 432PG UT WOS:000265145600002 PM 19298332 ER PT J AU Hingson, RW Edwards, EM Heeren, T Rosenbloom, D AF Hingson, Ralph W. Edwards, Erika M. Heeren, Timothy Rosenbloom, David TI Age of Drinking Onset and Injuries, Motor Vehicle Crashes, and Physical Fights After Drinking and When Not Drinking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Drinking Onset; Injuries; Fights; Traffic Crashes; Alcohol Dependence ID DATING VIOLENCE VICTIMIZATION; IV ALCOHOL-ABUSE; HIGH-SCHOOL-STUDENTS; RISK BEHAVIORS; EPIDEMIOLOGIC SURVEY; COLLEGE DRINKING; DEPENDENCE; INVOLVEMENT; ASSOCIATION; ADOLESCENTS AB Earlier age of drinking onset has been associated with greater odds of involvement in motor vehicle crashes, unintentional injuries, and physical fights after drinking. This study explores whether early drinkers take more risks even when sober by comparing potential associations between age of drinking onset and these outcomes after drinking relative to when respondents have not been drinking. From a national sample, 4,021 ever-drinkers ages 18 to 39 were asked age of drinking onset, not counting tastes or sips. They were also asked if they were ever in motor vehicle crashes, unintentionally injured, or in physical fights after drinking and when not drinking. GEE logistic regression models for repeated measures dichotomous outcomes compared whether odds ratios between age of onset and these adverse outcomes significantly differed when they occurred after drinking versus when not drinking, controlling for respondents' demographic characteristics, cigarette and marijuana use, family history of alcoholism, ever experiencing alcohol dependence, and frequency of binge drinking. Compared with persons who started drinking at age 21+, those who started at ages < 14, 14 to 15, 16 to 17, and 18 to 20 had, after drinking, respectively greater odds: 6.3 (2.6, 15.3), 5.2 (2.2, 12.3), 3.3 (1.5, 7.3), and 2.2 (0.9, 5.1) of having been in a motor vehicle crash; 6.0 (3.4, 10.5), 4.9 (3.0, 8.6), 3.7 (2.4, 5.6), and 1.9 (1.2, 2.9) of ever being in a fight; and 4.6 (2.4, 8.7), 4.7 (2.6, 8.6), 3.2 (1.9, 5.6), and 2.3 (1.3, 4.0) of ever being accidentally injured. The odds of experiencing motor vehicle accidents or injuries when not drinking were not significantly elevated among early onset drinkers. The odds of earlier onset drinkers being in fights were also significantly greater when respondents had been drinking than not drinking. Starting to drink at an earlier age is associated with greater odds of experiencing motor vehicle crash involvement, unintentional injuries, and physical fights when respondents were drinking, but less so when respondents had not been drinking. These findings reinforce the need for programs and policies to delay drinking onset. C1 [Hingson, Ralph W.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. [Edwards, Erika M.; Heeren, Timothy; Rosenbloom, David] Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA USA. RP Hingson, RW (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane,Room 2077, Bethesda, MD 20892 USA. EM rhingson@mail.nih.gov OI Heeren, Timothy/0000-0001-5643-3559 FU National Institute on Alcohol Abuse and Alcoholism [P60-AA013759] FX This research was supported by grant P60-AA013759 from the National Institute on Alcohol Abuse and Alcoholism. NR 35 TC 73 Z9 74 U1 1 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2009 VL 33 IS 5 BP 783 EP 790 DI 10.1111/j.1530-0277.2009.00896.x PG 8 WC Substance Abuse SC Substance Abuse GA 432PG UT WOS:000265145600004 PM 19298330 ER PT J AU Harford, TC Yi, HY Faden, VB Chen, CM AF Harford, Thomas C. Yi, Hsiao-ye Faden, Vivian B. Chen, Chiung M. TI The Dimensionality of DSM-IV Alcohol Use Disorders Among Adolescent and Adult Drinkers and Symptom Patterns by Age, Gender, and Race/Ethnicity SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Adolescents; Adults; DSM-IV Alcohol Use Disorders; Item Response Theory; Symptom Patterns ID ITEM RESPONSE THEORY; NATIONAL EPIDEMIOLOGIC SURVEY; UNITED-STATES; 12-MONTH PREVALENCE; DEPENDENCE SYMPTOM; ABUSE; VALIDITY; CRITERIA; MODEL; CONSUMPTION AB There is limited information on the validity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorders (AUD) symptom criteria among adolescents in the general population. The purpose of this study is to assess the DSM-IV AUD symptom criteria as reported by adolescent and adult drinkers in a single representative sample of the U.S. population aged 12 years and older. This design avoids potential confounding due to differences in survey methodology when comparing adolescents and adults from different surveys. A total of 133,231 current drinkers (had at least 1 drink in the past year) aged 12 years and older were drawn from respondents to the 2002 to 2005 National Surveys on Drug Use and Health. DSM-IV AUD criteria were assessed by questions related to specific symptoms occurring during the past 12 months. Factor analytic and item response theory models were applied to the 11 AUD symptom criteria to assess the probabilities of symptom item endorsements across different values of the underlying trait. A 1-factor model provided an adequate and parsimonious interpretation for the 11 AUD criteria for the total sample and for each of the gender-age groups. The MIMIC model exhibited significant indication for item bias among some criteria by gender, age, and race/ethnicity. Symptom criteria for "tolerance,""time spent," and "hazardous use" had lower item thresholds (i.e., lower severity) and low item discrimination, and they were well separated from the other symptoms, especially in the 2 younger age groups (12 to 17 and 18 to 25). "Larger amounts,""cut down,""withdrawal," and "legal problems" had higher item thresholds but generally lower item discrimination, and they tend to exhibit greater dispersion at higher AUD severity, particularly in the youngest age group (12 to 17). Findings from the present study do not provide support for the 2 separate DSM-IV diagnoses of alcohol abuse and dependence among either adolescents or adults. Variations in criteria severity for both abuse and dependence offer support for a dimensional approach to diagnosis which should be considered in the ongoing development of DSM-V. C1 [Harford, Thomas C.; Yi, Hsiao-ye; Chen, Chiung M.] NIAAA, NIH, CSR Inc, Arlington, VA 22201 USA. [Faden, Vivian B.] NIAAA, NIH, Bethesda, MD USA. RP Yi, HY (reprint author), NIAAA, NIH, CSR Inc, 2107 Wilson Blvd,Suite 1000, Arlington, VA 22201 USA. EM hyi@csrincorporated.com FU Alcohol Epidemiologic Data System (AEDS) [N0AA32007]; Division of Epidemiology and Prevention Research; National Institute on Alcohol Abuse and Alcoholism FX This study was conducted for the Alcohol Epidemiologic Data System (AEDS) under Contract No. N0AA32007 for the Division of Epidemiology and Prevention Research, National Institute on Alcohol Abuse and Alcoholism. NR 33 TC 39 Z9 39 U1 6 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2009 VL 33 IS 5 BP 868 EP 878 DI 10.1111/j.1530-0277.2009.00910.x PG 11 WC Substance Abuse SC Substance Abuse GA 432PG UT WOS:000265145600014 PM 19320629 ER PT J AU Ramchandani, VA Plawecki, M Li, TK O'Connor, S AF Ramchandani, Vijay A. Plawecki, Martin Li, Ting-Kai O'Connor, Sean TI Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy Volunteers SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Clamp; Route of Administration; Physiologically-Based Pharmacokinetic Model; Pharmacokinetic Variability; Healthy Social Drinkers; Breath Alcohol Concentration ID FAMILY-HISTORY; RECENT DRINKING; MG-PERCENT; ELIMINATION; METABOLISM; GENDER; CLAMP; POLYMORPHISMS; RELIABILITY; RESPONSES AB Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (C(max)), times of peak BrAC (T(max)), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean C(max), T(max), and AUC did not differ by gender, indicating that calculation of oral doses based on total body water results in comparable BrAC-time courses, on average, for females and males. The IV infusion driven BrAC-time profiles demonstrated good fidelity to the BrAC-time curves resulting from oral alcohol: the mean %difference in C(max) and AUC were both 11%, while the mean %difference for T(max) was 27%. This degree of variability is less than half that seen across individuals following oral alcohol administration, which was substantial [coefficient of variation (%CV) ranging from 22 to 52%]. Despite the use of standardized doses and controlled experimental conditions, there was substantial between-subject variability in the BrAC time course following oral administration of alcohol. The PBPK-model-based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response. C1 [Ramchandani, Vijay A.] NIAAA, Unit Human Physiol & Pharmacokinet, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Plawecki, Martin; O'Connor, Sean] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [O'Connor, Sean] RL Roudeboush VA Med Ctr, Indianapolis, IN USA. RP Ramchandani, VA (reprint author), NIAAA, Unit Human Physiol & Pharmacokinet, Lab Clin & Translat Studies, 10 Ctr Dr,Bldg 10 CRC,Rm 2-2352,MSC 1540, Bethesda, MD 20892 USA. EM vijayr@mail.nih.gov FU PHS [P50 AA 07611, R37 AA 02342, M01 RR 750]; NIAAA Division of Intramural Clinical and Biological Research FX Supported by PHS Grants P50 AA 07611, R37 AA 02342, and M01 RR 750 and the NIAAA Division of Intramural Clinical and Biological Research. NR 27 TC 26 Z9 26 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2009 VL 33 IS 5 BP 938 EP 944 DI 10.1111/j.1530-0277.2009.00906.x PG 7 WC Substance Abuse SC Substance Abuse GA 432PG UT WOS:000265145600022 PM 19320632 ER PT J AU Carrillo, MC Sanders, CA Katz, RG AF Carrillo, Maria C. Sanders, Charles A. Katz, Russell G. TI Maximizing the Alzheimer's Disease Neuroimaging Initiative II SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Biomarkers; Neuroimaging; Early defection; Longitudinal study; Natural history study; Mild cognitive impairment ID PROGRESSION; MRI; AD AB The Alzheimer's Disease Neuroimaging Initiative is the largest public-private partnership on brain research underway at the National Institutes of Health. This 6-year Study tracks cognitive and brain changes in normal subjects, those with mild cognitive impairment, and individuals with Alzheimer's disease. It was designed to provide better tools for performing effective clinical trials, and is slated to run until 2010. While data are being generated and analyzed, researchers involved in the study are developing an extension, i.e., the Alzheimer's Disease Neuroimaging Initiative U. The Foundation for the National Institutes of Health and the Alzheimer's Association convened a meeting to review the progress, evaluate future directions, and obtain the United States Food and Drug Administration's perspective on how the Alzheimer's Disease Neuroimaging Initiative could affect the drug-approval process. (C) 2009 The Alzheimer's Association. All rights reserved. C1 [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Sanders, Charles A.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Katz, Russell G.] US FDA, Washington, DC 20204 USA. RP Carrillo, MC (reprint author), Alzheimers Assoc, Chicago, IL USA. EM Maria.Carrillo@alz.org NR 9 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2009 VL 5 IS 3 BP 271 EP 275 DI 10.1016/j.jalz.2009.02.005 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 445HW UT WOS:000266042900006 PM 19362888 ER PT J AU Duggan, PS Siegel, AW Blass, DM Bok, H Coyle, JT Faden, R Finkel, J Gearhart, JD Greely, HT Hillis, A Hoke, A Johnson, R Johnston, M Kahn, J Kerr, D King, P Kurtzberg, J Liao, SM McDonald, JW McKhann, G Nelson, KB Rao, M Regenberg, A Smith, K Solter, D Song, H Sugarman, J Traystman, RJ Vescovi, A Yanofski, J Young, W Mathews, DJH AF Duggan, P. S. Siegel, A. W. Blass, D. M. Bok, H. Coyle, J. T. Faden, R. Finkel, J. Gearhart, J. D. Greely, H. T. Hillis, A. Hoke, A. Johnson, R. Johnston, M. Kahn, J. Kerr, D. King, P. Kurtzberg, J. Liao, S. M. McDonald, J. W. McKhann, G. Nelson, K. B. Rao, M. Regenberg, A. Smith, K. Solter, D. Song, H. Sugarman, J. Traystman, R. J. Vescovi, A. Yanofski, J. Young, W. Mathews, D. J. H. TI Unintended Changes in Cognition, Mood, and Behavior Arising from Cell-Based Interventions for Neurological Conditions: Ethical Challenges SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE CNS; personal identity; risks; stem cells ID DEEP-BRAIN-STIMULATION; UMBILICAL-CORD BLOOD; STEM-CELLS; PARKINSONS-DISEASE; ELECTROCONVULSIVE-THERAPY; DISORDERS; TRANSPLANTATION; DEPRESSION; CHIMERAS; ISSUES AB The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment. C1 [Duggan, P. S.; Siegel, A. W.; Blass, D. M.; Bok, H.; Faden, R.; Finkel, J.; Gearhart, J. D.; Hillis, A.; Hoke, A.; Johnson, R.; Kerr, D.; McKhann, G.; Regenberg, A.; Smith, K.; Song, H.; Sugarman, J.; Mathews, D. J. H.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Blass, D. M.] Abarbanel Mental Hlth Ctr, Bat Yam, Israel. [Coyle, J. T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Greely, H. T.] Stanford Univ, Stanford, CA 94305 USA. [Kahn, J.] Univ Minnesota, Minneapolis, MN 55455 USA. [King, P.] Georgetown Univ, Washington, DC 20057 USA. [Kurtzberg, J.] Duke Univ, Durham, NC 27706 USA. [Liao, S. M.] Univ Oxford, Oxford OX1 2JD, England. [Nelson, K. B.] NIH, Bethesda, MD USA. [Rao, M.] Invitrogen Corp, Carlsbad, CA USA. [Solter, D.] Duke Natl Univ Singapore, Singapore, Singapore. [Traystman, R. J.] Univ Colorado, Boulder, CO 80309 USA. [Vescovi, A.] Univ Milano Bicocca, Milan, Italy. [Yanofski, J.] Univ Texas SW Med Ctr Dallas, Dallas, TX USA. [Young, W.] Rutgers State Univ, Piscataway, NJ 08855 USA. RP Mathews, DJH (reprint author), Johns Hopkins Univ, 624 N Broadway,Hampton House 352, Baltimore, MD 21205 USA. EM dmathews@jhmi.edu OI Hoke, Ahmet/0000-0003-1215-3373 NR 43 TC 14 Z9 14 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAY PY 2009 VL 9 IS 5 BP 31 EP 36 DI 10.1080/15265160902788645 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 446TU UT WOS:000266144900012 PM 19396681 ER PT J AU Gottlieb, SS Kop, WJ Ellis, SJ Binkley, P Howlett, J O'Connor, C Blumenthal, JA Fletcher, G Swank, AM Cooper, L AF Gottlieb, Stephen S. Kop, Willem J. Ellis, Stephen J. Binkley, Philip Howlett, Jonathan O'Connor, Christopher Blumenthal, James A. Fletcher, Gerald Swank, Ann M. Cooper, Lawton CA HF-ACTION Investigators TI Relation of Depression to Severity of Illness in Heart Failure (from Heart Failure And a Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; SYMPTOMS AB Depression is common in patients with heart failure (HF), prognostic for adverse outcomes and. purportedly related to disease severity. Psychological and physiologic factors relevant to HF were assessed in HF-ACTION, a large randomized study of aerobic exercise training in patients with systolic HF. The relation of objective and subjective parameters was compared with scores on the Beck Depression Inventory (BDI) to examine the hypothesis that depressive symptoms are better associated with perception of disease severity than with objective markers of HF severity. At baseline, 2,322 of 2,331 subjects entered into HF-ACTION completed questionnaires to assess depression (BDI) and quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]). Objective markers of HF severity included ejection fraction, B-type natriuretic peptide, and peak oxygen consumption (using cardiopulmonary exercise testing, with evaluation of duration and respiratory exchange ratio also performed). Measures more likely to be affected by perceived functional status included New York Heart Association (NYHA) classification and the 6-minute walk test. Objective assessments of disease severity were slightly related (peak oxygen consumption) or not related (B-type natriuretic peptide and ejection fraction) to BDI scores. Using multivariate analysis (KCCQ not included), only age, gender, cardiopulmonary exercise testing duration, NYHA class, 6-minute walk distance, and peak respiratory exchange ratio independently correlated with BDI scores. In conclusion, depression was minimally related to objective assessments of severity of disease in patients with HF, but was associated with patient (and clinician) perceptions of disease severity. Addressing depression might improve symptoms in patients with HF. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:1285-1289) C1 [Gottlieb, Stephen S.; Kop, Willem J.] Univ Maryland, Baltimore, MD 21201 USA. [Ellis, Stephen J.; O'Connor, Christopher; Blumenthal, James A.] Duke Univ, Med Ctr, Durham, NC USA. [Binkley, Philip] Ohio State Univ, Columbus, OH 43210 USA. [Howlett, Jonathan] Halifax Univ, Halifax, NS, Canada. [Fletcher, Gerald] Mayo Clin Florida, Jacksonville, FL USA. [Swank, Ann M.] Univ Louisville, Louisville, KY 40292 USA. [Cooper, Lawton] NHLBI, NIH, Bethesda, MD 20892 USA. RP Gottlieb, SS (reprint author), Univ Maryland, Baltimore, MD 21201 USA. EM sgottlie@medicine.umaryland.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [5 U01 HL063747-06] FX The HF-ACTION study was supported by Grant No. 5 U01 HL063747-06 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. NR 17 TC 52 Z9 55 U1 1 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2009 VL 103 IS 9 BP 1285 EP 1289 DI 10.1016/j.amjcard.2009.01.025 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 442TK UT WOS:000265863300018 PM 19406273 ER PT J AU Chen, LW Appel, LJ Loria, C Lin, PH Champagne, CM Elmer, PJ Ard, JD Mitchell, D Batch, BC Svetkey, LP Caballero, B AF Chen, Liwei Appel, Lawrence J. Loria, Catherine Lin, Pao-Hwa Champagne, Catherine M. Elmer, Patricia J. Ard, Jamy D. Mitchell, Diane Batch, Bryan C. Svetkey, Laura P. Caballero, Benjamin TI Reduction in consumption of sugar-sweetened beverages is associated with weight loss: the PREMIER trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID INSULIN-RESISTANCE SYNDROME; LIFE-STYLE MODIFICATION; BODY-MASS INDEX; BLOOD-PRESSURE; ENERGY-INTAKE; PHYSICAL-ACTIVITY; NUTRIENT INTAKE; DAIRY-PRODUCTS; CLINICAL-TRIAL; DIETARY-INTAKE AB Background: Consumption of liquid calories from beverages has increased in parallel with the obesity epidemic in the US population, but their causal relation remains unclear. Objective: The objective of this study was to examine how changes in beverage consumption affect weight change among adults. Design: This was a prospective study of 810 adults participating in the PREMIER trial, an 18-mo randomized, controlled, behavioral intervention trial. Measurements (weight, height, and 24-h dietary recall) were made at baseline, 6 mo, and 18 mo. Results: Baseline mean intake of liquid calories was 356 kcal/d (19% of total energy intake). After potential confounders and intervention assignment were controlled for, a reduction in liquid calorie intake of 100 kcal/d was associated with a weight loss of 0.25 kg (95% CI: 0.11, 0.39; P < 0.001) at 6 mo and of 0.24 kg (95% CI: 0.06, 0.41; P = 0.008) at 18 mo. A reduction in liquid calorie intake had a stronger effect than did a reduction in solid calorie intake on weight loss. Of the individual beverages, only intake of sugar-sweetened beverages (SSBs) was significantly associated with weight change. A reduction in SSB intake of 1 serving/d was associated with a weight loss of 0.49 kg (95% CI: 0.11, 0.82; P = 0.006) at 6 mo and of 0.65 kg (95% CI: 0.22, 1.09; P = 0.003) at 18 mo. Conclusions: These data support recommendations to limit liquid calorie intake among adults and to reduce SSB consumption as a means to accomplish weight loss or avoid excess weight gain. This trial was registered at clinicaltrials.gov as NCT00000616. Am J Clin Nutr 2009;89:1299-306. C1 [Chen, Liwei; Caballero, Benjamin] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD 21205 USA. [Appel, Lawrence J.] Johns Hopkins Sch Med, Dept Internal Med, Baltimore, MD USA. [Loria, Catherine] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Lin, Pao-Hwa] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Champagne, Catherine M.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Elmer, Patricia J.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Ard, Jamy D.] Univ Alabama, Div Clin Nutr & Dietet, Birmingham, AL USA. [Mitchell, Diane] Penn State Univ, Diet Assessment Ctr, University Pk, PA 16802 USA. [Batch, Bryan C.; Svetkey, Laura P.] Duke Univ, Duke Hypertens Ctr, Durham, NC USA. RP Caballero, B (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, 615 N Wolfe St,Room 2041, Baltimore, MD 21205 USA. EM caballero@jhu.edu FU National Heart, Lung, and Blood Institute; NIH [UO1 HL60570, UO1 HL60571, UO1 HL60573, UO1 HL60574, UO1 HL62828]; Center for Human Nutrition; Johns Hopkins Bloomberg School of Public Health; Eunice Kennedy Shriver National Institute of Child Health & Human Development FX Supported by the National Heart, Lung, and Blood Institute; NIH grants UO1 HL60570, UO1 HL60571, UO1 HL60573, UO1 HL60574, and UO1 HL62828; the Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health; and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. NR 46 TC 99 Z9 103 U1 0 U2 15 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY 1 PY 2009 VL 89 IS 5 BP 1299 EP 1306 DI 10.3945/ajcn.2008.27240 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 436EB UT WOS:000265394300005 PM 19339405 ER PT J AU Qi, L Cornelis, MC Zhang, CL van Dam, RM Hu, FB AF Qi, Lu Cornelis, Marilyn C. Zhang, Cuilin van Dam, Rob M. Hu, Frank B. TI Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GENOME-WIDE ASSOCIATION; PLASMA ADIPONECTIN CONCENTRATION; BODY IRON STORES; MEAT INTAKE; WOMEN; CONSUMPTION; INSULIN; DISEASE; VARIANT; LOCI AB Background: A widely held hypothesis is that interactions between genetic predisposition and Western-type lifestyle contribute to the epidemic of type 2 diabetes (T2D). No study has tested this hypothesis. Objective: The objective was to assess whether established genetic variants, mainly from genomewide association studies, modify dietary patterns in predicting diabetes risk. Design: We determined 10 polymorphisms in a prospective, nested, case-control study of 1196 diabetic and 1337 nondiabetic men. A genetic risk score (GRS) was generated by using an allele counting method. Baseline dietary intakes were collected by using a semi-quantitative food-frequency questionnaire. We used factor analysis to derive Western and "Prudent'' dietary patterns from 40 food groups. Results: A significant interaction (P = 0.02) was observed between the GRS and Western dietary pattern. The multivariable odds ratios (ORs) of T2D across increasing quartiles for the Western dietary pattern were 1.00, 1.23 (95% CI: 0.88, 1.73), 1.49 (1.06,2.09), and 2.06 (1.48, 2.88) among men with a high GRS (>= 12 risk alleles; P for trend 0.01). The Western dietary pattern was not associated with diabetes risk among those with a lower GRS. In addition, we found that intakes of processed meat, red meat, and heme iron, which characterized the Western dietary pattern, showed significant interactions with GRS in relation to diabetes risk (P for interaction 0.029, 0.02, and 0.0004, respectively). The diet-diabetes associations were more evident among men with a high GRS (>= 12) than in those with a low GRS. Conclusion: Genetic predisposition may synergistically interact with a Western dietary pattern in determining diabetes risk in men. Am J Clin Nutr 2009;89:1453-8. C1 [Qi, Lu; Cornelis, Marilyn C.; van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Qi, Lu; van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Qi, Lu; van Dam, Rob M.; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zhang, Cuilin] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU NIH [DK58845, CA87969, HL071981]; AHA Scientist Development [0730094N]; Boston Obesity Nutrition Research Center [DK46200] FX Supported by NIH grants DK58845 and CA87969. LQ was supported by NIH grant HL071981, AHA Scientist Development Grant award 0730094N, and the Boston Obesity Nutrition Research Center (DK46200). NR 27 TC 49 Z9 56 U1 1 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY 1 PY 2009 VL 89 IS 5 BP 1453 EP 1458 DI 10.3945/ajcn.2008.27249 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 436EB UT WOS:000265394300024 PM 19279076 ER PT J AU Jiao, L Silverman, DT Schairer, C Thiebaut, ACM Hollenbeck, AR Leitzmann, MF Schatzkin, A Stolzenberg-Solomon, RZ AF Jiao, Li Silverman, Debra T. Schairer, Catherine Thiebaut, Anne C. M. Hollenbeck, Albert R. Leitzmann, Michael F. Schatzkin, Arthur Stolzenberg-Solomon, Rachael Z. TI Alcohol Use and Risk of Pancreatic Cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 98th Annual Meeting of the American-Association-for-Cancer-Research CY APR 14-18, 2007 CL Los Angeles, CA SP Amer Assoc Canc Res DE alcohol drinking; cohort studies; pancreatic neoplasms; risk; smoking ID HEALTH-AMERICAN-ASSOCIATION; POPULATION-BASED COHORT; RETIRED-PERSONS DIET; UNITED-STATES; CIGARETTE-SMOKING; MEDICAL HISTORY; BEVERAGE CONSUMPTION; NATIONAL-INSTITUTES; COFFEE CONSUMPTION; DRINKING HABITS AB The epidemiologic evidence for the role of alcohol use in pancreatic cancer development is equivocal. The authors prospectively examined the relation between alcohol use and risk of pancreatic cancer among 470,681 participants who were aged 50-71 years in 1995-1996 in the US National Institutes of Health-AARP Diet and Health Study. The authors identified 1,149 eligible exocrine pancreatic cancer cases through December 2003. Multivariate Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals with the referent group being light drinkers (< 1 drink/day). The relative risks of developing pancreatic cancer were 1.45 (95% confidence interval (CI): 1.17, 1.80; P(trend) = 0.002) for heavy total alcohol use (>= 3 drinks/day, similar to 40 g of alcohol/day) and 1.62 (95% CI: 1.24, 2.10; P(trend) = 0.001) for heavy liquor use, compared with the respective referent group. The increased risk with heavy total alcohol use was seen in never smokers (relative risk = 1.35, 95% CI: 0.79, 2.30) and participants who quit smoking 10 or more years ago before baseline (relative risk = 1.41, 95% CI: 1.01, 2.00). These findings suggest a moderately increased pancreatic cancer risk with heavy alcohol use, particularly liquor; however, residual confounding by cigarette smoking cannot be completely excluded. C1 [Jiao, Li; Thiebaut, Anne C. M.; Leitzmann, Michael F.; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Schairer, Catherine] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Jiao, L (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 3032, Rockville, MD 20852 USA. EM jiaol@mail.nih.gov FU Intramural NIH HHS NR 63 TC 38 Z9 39 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2009 VL 169 IS 9 BP 1043 EP 1051 DI 10.1093/aje/kwp034 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 434HZ UT WOS:000265267100001 PM 19299403 ER PT J AU Chen, HL Mosley, TH Alonso, A Huang, XM AF Chen, Honglei Mosley, Thomas H. Alonso, Alvaro Huang, Xuemei TI Plasma Urate and Parkinson's Disease in the Atherosclerosis Risk in Communities (ARIC) Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; Parkinson disease; uric acid ID URIC-ACID LEVELS; OXIDATIVE STRESS; ASSOCIATION; COHORT; GOUT AB Higher plasma urate concentration has been linked to lower risk of Parkinson's disease in men, but data are lacking on women and African Americans. The authors examined plasma urate in relation to Parkinson's disease in the biracial, population-based Atherosclerosis Risk in Communities (ARIC) cohort. Between 1987 and 1989, 15,792 participants, aged 45-64 years, were recruited from 4 US communities and have since been followed with 3 triennial visits and annual surveillance. Plasma urate was measured at visits 1 and 2, and the concentrations were highly correlated. From visit 1 through 2004, 95 potential cases of Parkinson's disease were identified from multiple sources. Odds ratios and 95% confidence intervals were calculated from multivariate logistic regression models. Plasma urate concentration was inversely associated with Parkinson's disease occurrence. The odds ratios between extreme quartiles of plasma urate were 0.4 (95% confidence interval: 0.2, 0.8) in the overall analysis, 0.3 (95% confidence interval: 0.1, 0.7) for men, and 0.4 (95% confidence interval: 0.2, 1.0) for Caucasians. Such an association was also suggested among women and African Americans but was not statistically significant because of small sample sizes. These data support the previous finding that urate may be a protective factor against Parkinson's disease. C1 [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Div Geriatr Med, Jackson, MS 39216 USA. [Alonso, Alvaro] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol & Bioengn, Hershey, PA 17033 USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Hershey Brain Anal Res Lab Neurodegenerat Disorde, Hershey, PA 17033 USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Chen, Honglei/0000-0003-3446-7779 FU National Institutes of Health; National Institute of Environmental Health Sciences [Z01ES101986]; National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01HC- 55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (grant Z01ES101986). The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01HC- 55018, N01-HC-55019, N01-HC-55020, N01-HC55021, and N01-HC-55022. NR 26 TC 60 Z9 65 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2009 VL 169 IS 9 BP 1064 EP 1069 DI 10.1093/aje/kwp033 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 434HZ UT WOS:000265267100003 PM 19299404 ER PT J AU Whitehead, T Metayer, C Ward, MH Nishioka, MG Gunier, R Colt, JS Reynolds, P Selvin, S Buffler, P Rappaport, SM AF Whitehead, Todd Metayer, Catherine Ward, Mary H. Nishioka, Marcia G. Gunier, Robert Colt, Joanne S. Reynolds, Peggy Selvin, Steve Buffler, Patricia Rappaport, Stephen M. TI Is House-Dust Nicotine a Good Surrogate for Household Smoking? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE child; dust; environmental exposure; infant; leukemia; linear models; nicotine; smoking ID ENVIRONMENTAL TOBACCO-SMOKE; CHILDRENS-CANCER-GROUP; SELF-REPORTED SMOKING; PARENTAL SMOKING; CIGARETTE-SMOKING; CHILDHOOD-CANCER; ALCOHOL-CONSUMPTION; GENETIC POLYMORPHISMS; MYELOID-LEUKEMIA; URINARY COTININE AB The literature is inconsistent regarding associations between parental smoking and childhood leukemia, possibly because previous studies used self-reported smoking habits as surrogates for children's true exposures to cigarette smoke. Here, the authors investigated the use of nicotine concentrations in house dust as measures of children's exposure to cigarette smoke in 469 households from the Northern California Childhood Leukemia Study (1999-2007). House dust was collected by using high-volume surface samplers and household vacuum cleaners and was analyzed for nicotine via gas chromatography-mass spectrometry. Using multivariable linear regression, the authors evaluated the effects of self-reported parental smoking, parental demographics, house characteristics, and other covariates on house-dust nicotine concentrations. They observed that nicotine concentrations in house dust were associated with self-reported smoking for periods of months and years before dust collection. Furthermore, the authors found that the relation between nicotine dust levels and self-reported smoking varied by parental age and socioeconomic status. These findings suggest that house-dust nicotine concentrations reflect long-term exposures to cigarette smoke in the home and that they may be less biased surrogates for children's exposures to cigarette smoke than self-reported smoking habits. C1 [Whitehead, Todd; Metayer, Catherine; Selvin, Steve; Buffler, Patricia; Rappaport, Stephen M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Ward, Mary H.; Colt, Joanne S.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Nishioka, Marcia G.] Battelle Mem Inst, Columbus, OH 43201 USA. [Gunier, Robert; Reynolds, Peggy] No Calif Canc Ctr, Berkeley, CA USA. RP Whitehead, T (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 50 Univ Hall,MC 7360, Berkeley, CA 94720 USA. EM toddpwhitehead@berkeley.edu OI Gunier, Robert/0000-0001-5485-9919 FU National Institute of Environmental Health Sciences [R01ES009137, P-42-ES-04705-18]; National Cancer Institute, National Institute of Health [7590-S-04, 7590-S-01]; National Cancer Institute [N02-CP-11015] FX This work was supported by the National Institute of Environmental Health Sciences (grants R01ES009137, P-42-ES-04705-18), the Intramural Research Program of the National Cancer Institute, National Institute of Health (subcontracts 7590-S-04, 7590-S-01); and the National Cancer Institute (contract N02-CP-11015). NR 32 TC 27 Z9 27 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2009 VL 169 IS 9 BP 1113 EP 1123 DI 10.1093/aje/kwp021 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 434HZ UT WOS:000265267100009 PM 19299402 ER PT J AU Ferrucci, LM Sinha, R Graubard, BI Mayne, ST Ma, XM Schatzkin, A Schoenfeld, PS Cash, BD Flood, A Cross, AJ AF Ferrucci, Leah M. Sinha, Rashmi Graubard, Barry I. Mayne, Susan T. Ma, Xiaomei Schatzkin, Arthur Schoenfeld, Philip S. Cash, Brooks D. Flood, Andrew Cross, Amanda J. TI Dietary Meat Intake in Relation to Colorectal Adenoma in Asymptomatic Women SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HETEROCYCLIC AMINE CONTENT; N-NITROSO COMPOUNDS; BODY IRON STORES; NON-HEME IRON; RED MEAT; COLON-CANCER; ALCOHOL-CONSUMPTION; VARYING DEGREES; AVERAGE-RISK; COOKED FOOD AB OBJECTIVES: No previous study has concurrently assessed the associations between meat intake, meat-cooking methods and doneness levels, meat mutagens (heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons), heme iron, and nitrite from meat and colorectal adenoma in asymptomatic women undergoing colonoscopy. METHODS: Of the 807 eligible women in a cross-sectional multicenter colonoscopy screening study, 158 prevalent colorectal adenoma cases and 649 controls satisfactorily completed the validated food frequency and meat questionnaires. Using an established meat mutagen database and new heme iron and nitrite databases, we comprehensively investigated the components of meat that may be involved in carcinogenesis. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) within quartiles of meat-related variables. RESULTS: Red meat was associated positively with colorectal adenoma (OR fourth vs. first quartile = 2.02; 95% CI = 1.06-3.83; P trend = 0.38). Intake of pan-fried meat (OR = 1.72; 95% CI = 0.96-3.07; P trend = 0.01) and the HCA: 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx) (OR = 1.90; 95% CI = 1.05-3.42; P trend = 0.07) were also associated with an increased risk of colorectal adenoma. The new databases yielded lower estimates of heme iron and nitrite than previous assessment methods, although the two methods were highly correlated for both exposures. Although not statistically significant, there were positive associations between iron and heme iron from meat and colorectal adenoma. CONCLUSIONS: In asymptomatic women undergoing colonoscopy, colorectal adenomas were associated with high intake of red meat, pan-fried meat, and the HCA MeIQx. Other meat-related exposures require further investigation. C1 [Ferrucci, Leah M.; Sinha, Rashmi; Graubard, Barry I.; Schatzkin, Arthur; Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ferrucci, Leah M.; Mayne, Susan T.; Ma, Xiaomei] Yale Sch Publ Hlth, New Haven, CT USA. [Schoenfeld, Philip S.] Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI USA. [Schoenfeld, Philip S.] Vet Affairs Ctr Excellence Hlth Serv Res, Ann Arbor, MI USA. [Schoenfeld, Philip S.; Cash, Brooks D.] Uniformed Serv Univ Hlth Sci, Div Gastroenterol, Bethesda, MD 20814 USA. [Flood, Andrew] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Flood, Andrew] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. RP Ferrucci, LM (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. EM ferruccil@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU National Institutes of Health, National Cancer Institute; National Cancer Institute [TU2 CA105666] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and by Grant TU2 CA105666 from the National Cancer Institute. NR 58 TC 37 Z9 38 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2009 VL 104 IS 5 BP 1231 EP 1240 DI 10.1038/ajg.2009.102 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 447VB UT WOS:000266219000021 PM 19367270 ER PT J AU Furia, AC Lee, RE Strother, ML Huang, TTK AF Furia, Andrea C. Lee, Rebecca E. Strother, Myra L. Huang, Terry T-K TI College Students' Motivation to Achieve and Maintain a Healthy Weight SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE weight maintenance; obesity; overweight; motivation; college students ID PHYSICAL-ACTIVITY; UNITED-STATES; HIGH-SCHOOL; OBESITY; EXERCISE; OVERWEIGHT; PREDICTORS; BEHAVIORS; FRESHMAN; DISEASE AB Objectives: To develop and refine a scale of motivational factors related to healthy weight achievement and maintenance and to examine differences by gender and weight status. Methods: A cross-sectional survey of 300,university students aged 18-24 years. Results: Factor analysis yielded 6 factors - Intrinsic (Cronbach's alpha=0.73): affective motivation, self-efficacy/interest; Extrinsic (Cronbach's alpha=0.68): social reward, peer pressure, lack of choice, and authority influence. Males and normal-weight students showed higher affective motivation and overall intrinsic motivation compared to females and overweight students, (P<.001). Conclusion: Intrinsic motivational factors and gender differences should be considered in developing obesity prevention interventions in this age-group. C1 [Huang, Terry T-K] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Furia, Andrea C.] US FDA, Off Special Hlth Issues, Rockville, MD 20857 USA. [Lee, Rebecca E.] Univ Houston, Dept Hlth & Human Performance, Houston, TX USA. [Strother, Myra L.] Univ Kansas, Watkins Mem Hlth Ctr, Lawrence, KS 66045 USA. RP Huang, TTK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,4B11, Bethesda, MD 20892 USA. EM huangter@mail.nih.gov NR 26 TC 12 Z9 12 U1 4 U2 8 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAY-JUN PY 2009 VL 33 IS 3 BP 256 EP 263 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 439WE UT WOS:000265657400004 PM 19063647 ER PT J AU Kilfoy, BA Zheng, TZ Lan, Q Han, XS Qin, Q Rothman, N Holford, T Zhang, YW AF Kilfoy, Briseis A. Zheng, Tongzhang Lan, Qing Han, Xuesong Qin, Qin Rothman, Nathaniel Holford, Theodore Zhang, Yawei TI Genetic polymorphisms in glutathione S-transferases and cytochrome P450s, tobacco smoking, and risk of non-Hodgkin lymphoma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID B-CELL LYMPHOMA; CIGARETTE-SMOKING; POOLED ANALYSIS; UNITED-STATES; SUBTYPES; CANCER; WOMEN; P1-1; CONJUGATION; CONSORTIUM AB We investigated variation in glutathione S-transferases (GSTs) and cytochrome P450s (CYPs), and smoking in a population-based case-control study of NHL including 1,115 women. Although risk of NHL was not altered by variant polymorphisms in GSTs or CYPs, it was significantly changed for DLBCL when considered in conjunction with smoking behavior, though only in nonsmokers. An increased risk of DLBCL in nonsmokers was associated with the variant G allele for GSTP1 (OR = 1.6, 95% CI 1.0-2.3) and CYP1A1 (OR = 2.4; 95% CI 1.0-5.7), but a decreased risk for the variant G allele for CYP1B1 (OR = 0.6, 95% CI 0.4-1.0). Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL. Am. J. Hematol. 84:279-282, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Kilfoy, Briseis A.; Zheng, Tongzhang; Han, Xuesong; Holford, Theodore; Zhang, Yawei] Yale Univ, Sch Epidemiol & Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA. [Kilfoy, Briseis A.; Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA. [Qin, Qin] Univ So Maine, Ctr Toxicol & Environm Hlth, Portland, ME 04103 USA. RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St,LEPH 440,POB 208034, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Aschebrook-Kilfoy, Briseis/A-2537-2012 FU National Institutes of Health [CA62006, 1D43TW007864-01]; National Center for Research Resources [UL1 RR0241139]; NIH FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: CA62006, 1D43TW007864-01; Contract grant sponsor: National Center for Research Resources; Contract grant number: UL1 RR0241139; Contract grant sponsor: Intramural Research Program of the NIH. NR 31 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2009 VL 84 IS 5 BP 279 EP 282 DI 10.1002/ajh.21386 PG 4 WC Hematology SC Hematology GA 440ZR UT WOS:000265738900005 PM 19338043 ER PT J AU Soloway, LE Demerath, EW Ochs, N James, GD Little, MA Bindon, JR Garruto, RM AF Soloway, Laura E. Demerath, Ellen W. Ochs, Natalie James, Gary D. Little, Michael A. Bindon, James R. Garruto, Ralph M. TI Blood Pressure and Lifestyle on Saba, Netherlands Antilles SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; ENVIRONMENTAL CONTRIBUTIONS; HYPERTENSION; HERITABILITY; FAMILY; MODERNIZATION; MIGRATION; COMMUNITY; DISEASE; TRAITS AB During the 20th century, infectious disease morbidity and mortality generally waned whereas chronic degenerative diseases posed a growing burden at the global level. The population on Saba, Netherlands Antilles has recently experienced such an epidemiologic transition, and hypertension was reported to be extraordinarily high, although no prevalences have been reported and relationships with lifestyle factors associated with rapid modernization have not been explored. In this study, a medical and demographic questionnaires, as well as body composition and blood pressure measures were collected from 278 Saban men and women aged 18-91 years. When age and sex adjusted, 48% of the population was hypertensive. Age, BMI, and Afro-Caribbean descent were all associated with higher blood pressures. In a second phase, 124 individuals of the 278 were invited to receive a longer questionnaire on individual exposure to modernizing influences such as travel and education. Higher blood pressure was associated with having lived in fewer different places in the past; those who stayed only on Saba or Statia had higher blood pressures than those who had also lived in more modernized areas. However, this was no longer statistically significant after adjustment for age and BMI. Lifestyle incongruity was positively associated with higher blood pressure in that those with more discord between material wealth and income were more likely to be hypertensive, and this remained statistically significant after adjustment for age and adiposity. In summary, hypertension is highly prevalent on Saba and tended to be associated with greater age, adiposity, Afro-Caribbean ancestry, and lifestyle incongruity. Am. J. Hum. Biol. 21:319-325, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Soloway, Laura E.; Demerath, Ellen W.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ochs, Natalie] NIAID, NIH, Bethesda, MD 20892 USA. [James, Gary D.; Little, Michael A.; Garruto, Ralph M.] SUNY Binghamton, Dept Anthropol, Binghamton, NY USA. [James, Gary D.] SUNY Binghamton, Decker Sch Nursing, Binghamton, NY USA. [Bindon, James R.] Univ Alabama, Dept Anthropol, Tuscaloosa, AL USA. RP Soloway, LE (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55455 USA. EM solow002@umn.edu FU NHLBI NIH HHS [T32 HL007779-15, T32 HL007779] NR 32 TC 4 Z9 4 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD MAY-JUN PY 2009 VL 21 IS 3 BP 319 EP 325 DI 10.1002/ajhb.20862 PG 7 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 435IS UT WOS:000265338200006 PM 19189411 ER PT J AU Franceschini, N North, KE Arnett, D Pankow, JS Chung, JH Baird, L Leppert, MF Eckfeldt, JH Boerwinkle, E Gu, CC Lewis, CE Myers, RH Turner, ST Weder, A Kao, WHL Mosley, TH Chakravarti, A Kramer, H Zhang, J Hunt, SC AF Franceschini, Nora North, Kari E. Arnett, Donna Pankow, James S. Chung, Jay H. Baird, Lisa Leppert, Mark F. Eckfeldt, John H. Boerwinkle, Eric Gu, C. Charles Lewis, Cora E. Myers, Richard H. Turner, Stephen T. Weder, Alan Kao, W. H. Linda Mosley, Thomas H. Chakravarti, Aravinda Kramer, Holly Zhang, Jinghui Hunt, Steven C. TI The Association of Cell Cycle Checkpoint 2 Variants and Kidney Function: Findings of the Family Blood Pressure Program and the Atherosclerosis Risk in Communities Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID STAGE RENAL-DISEASE; URINARY ALBUMIN EXCRETION; GENOTYPE-PHENOTYPE ASSOCIATIONS; GLOMERULAR-FILTRATION-RATE; CARNOSINASE GENE CNDP1; DNA-DAMAGE CHECKPOINTS; LINKAGE ANALYSIS; ANGIOTENSIN-II; HYPERTENSIVE FAMILIES; DIABETIC-NEPHROPATHY AB BACKGROUND Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease. METHODS We used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. We performed replication analyses in the Genetic Epidemiology Network of Arteriopathy (GENOA) participants (1,746 African Americans and 1,418 whites), GenNet participants (706 whites), and Atherosclerosis Risk in Communities (ARIC) study participants (3,783 African Americans and 10,936 whites). All analyses were race-stratified and used additive genetic models with adjustments for covariates and for family structure, if needed. RESULTS One tag-SNP, rs5762764, was associated with eGFR in HyperGEN (P = 0.003) and GENOA white participants (P = 0.009), and it was significantly associated with eGFR in meta-analyses (P = 0.002). The associations were independent of type 2 diabetes. CONCLUSIONS These results suggest that CHEK2 variants may influence eGFR in the context of hypertension. C1 [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Arnett, Donna] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Chung, Jay H.] NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. [Baird, Lisa; Leppert, Mark F.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. [Baird, Lisa; Leppert, Mark F.] Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Gu, C. Charles] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Lewis, Cora E.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Turner, Stephen T.] Mayo Clin & Mayo Fdn, Div Nephrol & Hypertens, Dept Internal Med, Rochester, MN USA. [Weder, Alan] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA. [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kramer, Holly] Loyola Univ, Dept Prevent Med & Med, Maywood, IL 60153 USA. [Zhang, Jinghui] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD USA. [Hunt, Steven C.] Univ Utah, Sch Med, Div Cardiovasc Genet, Salt Lake City, UT USA. RP Franceschini, N (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. EM noraf@unc.edu RI Gu, Charles/A-7934-2010 OI Kramer, Holly/0000-0002-6374-837X; Myers, Richard/0000-0002-8365-2674; Gu, Charles/0000-0002-8527-8145 FU NHLBI NIH HHS [N01-HC-55019, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, U01 HL054509, U01 HL054509-10] NR 57 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2009 VL 22 IS 5 BP 552 EP 558 DI 10.1038/ajh.2009.41 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 435HP UT WOS:000265335100019 PM 19265784 ER PT J AU Bagrov, A Agalakova, NI Kashkin, VA Fedorova, OV AF Bagrov, AlexeiY Agalakova, Natalia I. Kashkin, Vladimir A. Fedorova, Olga V. TI Endogenous Cardiotonic Steroids and Differential Patterns of Sodium Pump Inhibition in NaCl-Loaded Salt-Sensitive and Normotensive Rats SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID DEPENDENT PROTEIN-KINASE; BLOOD-PRESSURE; HYPERTENSIVE-RATS; NA/K-ATPASE; MARINOBUFAGENIN; ANP; PHOSPHORYLATION; STIMULATION; DIGITALIS; ANTIBODY AB BACKGROUND Endogenous sodium pump inhibitors promote sodium excretion in normotensives and contribute to vasoconstriction in NaCl-sensitive hypertension. Marinobufagenin (MBG), an endogenous bufadienolide inhibitor of alpha-1 sodium pump, contributes to hypertension in Dahl salt-sensitive rats (DS). We hypothesized that in NaCl-loaded DS and normotensive Sprague-Dawley rats (S-D), MBG would elicit different patterns of sodium pump inhibition. METHODS We compared systolic blood pressure (SBP), renal sodium excretion, activity of the sodium pump in aorta and renal medulla, and levels of MBG, atrial natriuretic peptide (ANP), and cyclic guanosine monophosphate (cGMP) in salt-loaded DS and S-D (20% NaCl, 2.5 ml/kg, intraperitoneally). RESULTS NaCl loading produced sustained elevations in renal MBG excretion in both DS (2.41 +/- 0.24 vs. 0.79 +/- 0.08 pmol/h/kg, P < 0.01) and S-D (1.97 +/- 0.37 vs. 0.60 +/- 0.07 pmol/h/kg, P < 0.01) vs. that at baseline (n = 10 for each group). In NaCl-loaded DS, SBP rose by 18 mm Hg (P < 0.01) and aortic sodium pump was inhibited by 22% (P < 0.05 vs. control), while in S-D, SBP and activity of aortic sodium pump did not change. NaCl-loaded S-D excreted twice as much sodium as DS; in S-D, renal sodium pump was inhibited by 24% vs. 14% inhibition in DS (P < 0.05). NaCl loading elicited increases in plasma ANP and in renal cGMP excretion in S-D but not in DS. CONCLUSIONS Our present observations demonstrate that in NaCl-loaded S-D and DS, a comparable MBG response is associated with preferential inhibition of the sodium pump in the kidney and in vascular smooth muscle, respectively, resulting in an adaptive natriuresis in S-D but sodium retention and pressor response in DS. C1 [Bagrov, AlexeiY; Agalakova, Natalia I.; Kashkin, Vladimir A.; Fedorova, Olga V.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Fedorova, OV (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. EM FedorovO@mail.nih.gov OI Kashkin, Vladimir/0000-0002-7202-0233 FU National Institute on Aging, NIH FX This study has been supported by Intramural Research Program, National Institute on Aging, NIH. The authors gratefully acknowledge critical comments of Edward G. Lakatta, and David E. Anderson, and are grateful for excellent technical assistance by Danielle Joseph, Chad Boily, and Alexandra Newman (Namikas). NR 30 TC 12 Z9 12 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2009 VL 22 IS 5 BP 559 EP 563 DI 10.1038/ajh.2009.22 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 435HP UT WOS:000265335100020 PM 19229192 ER PT J AU Madero, M Sarnak, MJ Wang, XL Greene, T Beck, GJ Kusek, JW Collins, AJ Levey, AS Menon, V AF Madero, Magdalena Sarnak, Mark J. Wang, Xuelei Greene, Tom Beck, Gerald J. Kusek, John W. Collins, Allan J. Levey, Andrew S. Menon, Vandana TI Uric Acid and Long-term Outcomes in CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney disease; uric acid; outcomes; cardiovascular; mortality; kidney failure ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; KIDNEY-DISEASE; RENAL-DISEASE; FOLLOW-UP; ESSENTIAL-HYPERTENSION; IGA NEPHROPATHY; SCREENED COHORT; BLOOD-PRESSURE; RISK-FACTORS AB Background: Hyperuricemia is prevalent in patients with chronic kidney disease (CKD); however, data are limited about the relationship of uric acid levels with long-term outcomes in this patient population. Study Design: Cohort study. Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N = 840) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This analysis included 838 patients. Predictor: Uric acid level. Outcomes & Measurements: The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular disease (CVD) mortality, and kidney failure. Results: Mean age was 52 12 (SD) years, glomerular filtration rate was 33 +/- 12 mL/min/1.73 m(2), and uric acid level was 7.63 +/- 1.66 mg/dL. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) died of CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.07 to 2.32), a trend toward CVD mortality (HR, 1.47; 95% CI, 0.90 to 2.39), and no association with kidney failure (HR, 1.20; 95% CI, 0.95 to 1.51) compared with the lowest tertile. In continuous analyses, a 1-mg/dL greater uric acid level was associated with 17% increased risk of all-cause mortality (HR, 1.17; 95% CI, 1.05 to 1.30) and 16% increased risk of CVD mortality (HR, 1.16; 95% CI, 1.01 to 1.33), but was not associated with kidney failure (HR, 1.02; 95% CI, 0.97 to 1.07). Limitations: Primary analyses were based on a single measurement of uric acid. Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD. Conclusions: In patients with stages 3 to 4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality, but not kidney failure. Am J Kidney Dis 53:796-803. (C) 2009 by the National Kidney Foundation, Inc. All rights reserved. C1 [Sarnak, Mark J.; Levey, Andrew S.; Menon, Vandana] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA 02111 USA. [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez, Dept Med, Div Nephrol, Mexico City, DF, Mexico. [Wang, Xuelei; Beck, Gerald J.] Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. [Greene, Tom] Univ Utah, Div Clin Epidemiol, Salt Lake City, UT USA. [Kusek, John W.] NIH, Bethesda, MD 20892 USA. [Collins, Allan J.] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. RP Menon, V (reprint author), Tufts Med Ctr, Div Nephrol, Dept Med, Box 391,800 Washington St, Boston, MA 02111 USA. EM vmenon@tuftsmedicalcenter.org FU National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) [K23 DK067303, K23 DK02904, K24 DK078204, UO 1 DK35073]; TAP Pharmaceutical Products Inc FX This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) Grants K23 DK067303, K23 DK02904, K24 DK078204, and UO 1 DK35073, and TAP Pharmaceutical Products Inc. NR 32 TC 148 Z9 164 U1 3 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2009 VL 53 IS 5 BP 796 EP 803 DI 10.1053/j.ajkd.2008.12.021 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 443PY UT WOS:000265923500012 PM 19303683 ER PT J AU Greene, T Daugirdas, JT Depner, TA Gotch, F Kuhlman, M AF Greene, Tom Daugirdas, John T. Depner, Thomas A. Gotch, Frank Kuhlman, Martin CA Natl Inst Diabet & Digest & Kidney TI Solute Clearances and Fluid Removal in the Frequent Hemodialysis Network Trials SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Daily dialysis; nocturnal dialysis; kinetic modeling; clinical trials ID BLOOD-FLOW; UREA; DIALYSIS; HEMO; KT/V; BETA(2)-MICROGLOBULIN; MODEL AB Background: The Frequent Hemodialysis Network (FHN) is conducting 2 randomized clinical trials, a daytime in-center trial ("daily") comparing 6 versus 3 treatments/wk, and a home nocturnal trial comparing 6 nocturnal treatments versus 3 conventional treatments/wk. The goal of this study was to project separation between the treatment and control arms of these studies for measures of dialysis dose by using simulations based on 2-compartment variable-volume models. Setting & Participants: Data from the most recent hemodialysis treatment in 100 patients dialyzed 3 times/wk at facilities of the Renal Research Institute in New York and from 2 data sets (n = 154 and 115 patients) from the Hemodialysis (HEMO) trial. Design: Observational study. Predictor: Dialysis prescriptions for the treatment and control arms in the FHN trials. Dialysis Regimen Outcomes: Treatment time, ultrafiltration rate, standard Kt/V/wk for urea (stdKt/Vur.J, and continuous clearance estimates based on ratios of urea, creatinine, and normalized beta(2)-microglobulin generation rates (denoted by Gn) to time-averaged concentrations (TACs) of these solutes during 1 treatment week. Results: The expected differences between median values in the experimental and control groups were weekly treatment time: daily trial, 29%; nocturnal trial, 234%; ultrafiltration rate: daily, -20%; nocturnal, -69%; stdKt/V(urea): daily, 52%; nocturnal, 133%; Gn(urea)/TAC(urea): daily, 34%; nocturnal, 130%; Gn(cr)/TAC(cr): daily, 31%; nocturnal, 135%; and Gn(beta 2)/TAC(beta 2): daily, 8%; nocturnal, 67%. Limitations: Use of simulated data and assumption of equivalent volumes and ultrafiltration rates between treatment arms. Conclusions: The nocturnal 6-times-weekly regimen produces substantially greater separation between the treatment and control arms than the daytime 6-times-weekly regimen for a wide range of treatment parameters. However, the 6-times-weekly interventions in both FHN trials will produce substantially greater separation than in the HEMO trial, where separations in median weekly treatment time and stdKt/V(urea). between the 3-times-weekly high- and standard-dose groups were 18% and 17%, respectively. The FHN trials will test whether substantial increases in solute clearance and other effects of frequent hemodialysis materially influence selected intermediate outcome measures. Am J Kidney Dis 53:835-844. (C) 2009 by the National Kidney Foundation, Inc. C1 [Greene, Tom; Daugirdas, John T.; Depner, Thomas A.; Gotch, Frank; Kuhlman, Martin; Natl Inst Diabet & Digest & Kidney] NIDDK, NIH, Bethesda, MD USA. RP Greene, T (reprint author), Univ Utah, Div Epidemiol, 85 N Med Dr,E Rm 201, Salt Lake City, UT 84112 USA. EM tom.greene@hsc.utah.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health FX The HEMO Study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Baxter Healthcare and Fresenius Medical Care donated sonic of the dialyzers used by study patients. NR 26 TC 27 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2009 VL 53 IS 5 BP 835 EP 844 DI 10.1053/j.ajkd.2008.12.039 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 443PY UT WOS:000265923500016 PM 19339093 ER PT J AU Sperati, CJ Parekh, RS Berthier-Schaad, Y Jaar, BG Plantinga, L Fink, N Powe, NR Smith, MW Coresh, J Kao, WHL AF Sperati, C. John Parekh, Rulan S. Berthier-Schaad, Yvette Jaar, Bernard G. Plantinga, Laura Fink, Nancy Powe, Neil R. Smith, Michael W. Coresh, Josef Kao, W. H. Linda TI Association of Single-Nucleotide Polymorphisms in JAK3, STAT4, and STAT6 With New Cardiovascular Events in Incident Dialysis Patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Dialysis; cardiovascular diseases; inflammation; genes ID IN-VIVO; PSEUDOKINASE DOMAIN; COMPETING RISKS; DEFICIENT MICE; ATHEROSCLEROSIS; DISEASE; ACTIVATION; PATHWAY; INTERLEUKIN-10; ATHEROGENESIS AB Background: Increasing evidence supports a role for cell-mediated immunity in the pathogenesis of cardiovascular disease. Single-nucleotide polymorphisms (SNPs) in JAK3, STAT4, and STAT6 of the Janus kinase-signal transducer and activator of transcription (Jak-Stat) signal transduction pathway were examined for association with time to new cardiovascular events in incident dialysis patients from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. Study Design: Prospective cohort study. Setting & Participants: 764 white (n = 518) and black (n = 246) participants from 79 dialysis centers. Predictor: SNPs in JAK3, STAT4, and STAT6 selected using a pairwrise approach to identify a maximally informative set of tag SNPs for populations of European and African descent. Outcomes & Measurements: Cox proportional hazards models were used to estimate unadjusted and multivariable-adjusted hazard ratios (HRs) for incident cardiovascular disease events after dialysis therapy initiation associated with each race-specific SNP. Results: 2 European tag SNPs (rs3212780 and rs3213409) in JAK3 were associated with new cardiovascular disease events in white patients with unadjusted HRs of 1.92 (P < 0.001) and 1.82 (P = 0.07), respectively. One dual-tag SNP (rs3212752) in JAK3 was associated with new cardiovascular events in white patients with an unadjusted HR of 2.09 (P < 0.001) and in black patients with an HR of 2.07 (P = 0.007). SNP rs3213409 codes for a valine to isoleucine change at amino acid 722, a potentially functional mutation. SNPs in STAT4 and STAT6 were not associated with cardiovascular events after the initiation of dialysis therapy. Limitations: This study does not provide direct evidence for the mechanism of increased risk. Replication in independent cohorts is necessary. Conclusions: Genetic polymorphisms in the Jak-Stat signaling pathway are associated with an increased risk of new cardiovascular events in incident dialysis patients. Am J Kidney Dis 53:845-855. (C) 2009 by the National Kidney Foundation, Inc. C1 [Sperati, C. John; Parekh, Rulan S.; Jaar, Bernard G.] Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21205 USA. [Parekh, Rulan S.; Berthier-Schaad, Yvette; Jaar, Bernard G.; Fink, Nancy; Powe, Neil R.; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Parekh, Rulan S.; Jaar, Bernard G.; Plantinga, Laura; Powe, Neil R.; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Berthier-Schaad, Yvette; Smith, Michael W.] NCI, Lab Genom Div, Frederick, MD 21701 USA. [Fink, Nancy; Powe, Neil R.; Coresh, Josef] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Sperati, CJ (reprint author), Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, 1830 Monument St,Rm 416, Baltimore, MD 21205 USA. EM jsperati@jhmi.edu RI Jaar, Bernard/B-5026-2011; Smith, Michael/B-5341-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T32-DK-007732]; NIDDK [K24-DK-00264, RO1-DK-59616]; National Heart, Lung, and Blood Institute [RO1-HL62985] FX Dr Sperati was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) training grant T32-DK-007732, and Dr Powe was supported by NIDDK grant K24-DK-00264. CHOICE was supported by National Heart, Lung, and Blood Institute grant RO1-HL62985 and NIDDK grant RO1-DK-59616. NR 55 TC 12 Z9 12 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2009 VL 53 IS 5 BP 845 EP 855 DI 10.1053/j.ajkd.2008.12.025 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 443PY UT WOS:000265923500017 PM 19282076 ER PT J AU Solomon, BD Lacbawan, F Jain, M Domene, S Roessler, E Moore, C Dobyns, WB Muenke, M AF Solomon, Benjamin D. Lacbawan, Felicitas Jain, Mahim Domene, Sabina Roessler, Erich Moore, Cynthia Dobyns, William B. Muenke, Maximilian TI A Novel SIX3 Mutation Segregates With Holoprosencephaly in a Large Family SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE holoprosencephaly; HPE; SIX3 ID FOREBRAIN DEVELOPMENT; VENTRAL FOREBRAIN; LINKAGE ANALYSIS; EYE DEVELOPMENT; NEURAL PLATE; GENE; EXPRESSION; IDENTIFICATION; SPECIFICATION; POPULATION AB Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 1-5 years ago following the evaluation and subsequent genetic work-up of it female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now, report that a novel missense mutation in the SIX3 holoprosencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from phenotypically nomial adults (non-penetrance) to alobar holoprosencephaly incompatible with postnatal life. This particular family represents it seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation. Published 2009 Wiley-Liss, Inc. C1 [Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domene, Sabina; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Lacbawan, Felicitas] SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Moore, Cynthia] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Dobyns, William B.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Dobyns, William B.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Dobyns, William B.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov OI Dobyns, William/0000-0002-7681-2844 FU Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health FX The authors would like to thank Julia Fekecs for her help with illustrations and would like to extend deep gratitude to the family described here. This work was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health. NR 41 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2009 VL 149A IS 5 BP 919 EP 925 DI 10.1002/ajmg.a.32813 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 441YG UT WOS:000265805900015 PM 19353631 ER PT J AU Merideth, MA Vincent, LM Sparks, SE Hess, RA Manoli, I O'Brien, KJ Tsilou, E White, JG Huizing, M Gahl, WA AF Merideth, Melissa A. Vincent, Lisa M. Sparks, Susan E. Hess, Richard A. Manoli, Irini O'Brien, Kevin J. Tsilou, Ekaterina White, James G. Huizing, Marjan Gahl, William A. TI Hermansky-Pudlak Syndrome in Two African-American Brothers SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE albinism; Hermansky-Pudlak syndrome; platelet dense bodies; pulmonary fibrosis; splice-site mutation; silent mutation ID SUB-SAHARAN AFRICA; P-GENE-MUTATIONS; OCULOCUTANEOUS ALBINISM; LOCUS HETEROGENEITY; DENSE BODIES; SEROTONIN; PLATELETS; DELETION; DISEASE; PROTEIN AB Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding disorder, and, in some patients, granulomatous colitis and/or a fatal pulmonary fibrosis. There are eight different subtypes of HPS, each due to mutations in one of eight different genes,whose functions are thought to involve intracellular vesicle formation and trafficking. HPS has been identified in patients of nearly all ethnic groups, though it has primarily been associated with patients Of Puerto Rican, Northern European, Japanese and Israeli descent. We report oil the diagnosis of HPS type I in two African-American patients. Both brothers carried compound heterozygous Mutations in HPS1: previously reported p.M32.5WfsX6 (c.972deIC) and a novel silent mutation p.E169E (c.507G > A), which resulted in a splice defect. HPS may be under-diagnosed in African-American patients and other ethnic groups. A history of easy bruising or evidence of a bleeding disorder, combined with some degree of hypopigmentation, should prompt investigation into the diagnosis of HPS. Published 2009 Wiley-Liss, Inc. C1 [Merideth, Melissa A.; Vincent, Lisa M.; Hess, Richard A.; Manoli, Irini; O'Brien, Kevin J.; Huizing, Marjan; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Merideth, Melissa A.; O'Brien, Kevin J.; Gahl, William A.] NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. [Sparks, Susan E.] Childrens Natl Med Ctr, Div Genet & Metab, Washington, DC 20010 USA. [Tsilou, Ekaterina] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [White, James G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Merideth, MA (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Rm 10C-103, Bethesda, MD 20892 USA. EM mmeridet@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 FU National Human Genome Research Institute, National Institutes of Health, Bethesda, MD FX We thank the patients and their family for participating in the NI H protocol. We appreciate the nursing care provided by the NTH Clinical Center nurses. This Study was supported by the Intramural Research program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. NR 31 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2009 VL 149A IS 5 BP 987 EP 992 DI 10.1002/ajmg.a.32757 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 441YG UT WOS:000265805900025 PM 19334085 ER PT J AU Taylor, HA Akylbekova, EL Garrison, RJ Sarpong, D Joe, J Walker, E Wyatt, SB Steffes, MW AF Taylor, Herman A., Jr. Akylbekova, Ermeg L. Garrison, Robert J. Sarpong, Daniel Joe, Jennifer Walker, Evelyn Wyatt, Sharon B. Steffes, Michael W. TI Dyslipidemia and the Treatment of Lipid Disorders in African Americans SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE African Americans; Cardiovascular disease; Cholesterol; Dyslipidemia; Risk factors ID CORONARY-HEART-DISEASE; RISK-FACTORS; ATHEROSCLEROSIS RISK; NHANES-I; CARDIOVASCULAR HEALTH; MYOCARDIAL-INFARCTION; ETHNIC-DIFFERENCES; WHITE MEN; CHOLESTEROL; ADULTS AB BACKGROUND: Despite the high prevalence of cardiovascular disease documented among the African-American population, there has been little emphasis on the role of dyslipidemia as a prominent risk factor in this large subpopulation. Questions of medication efficacy also have been raised. Together, these factors may have affected awareness, diagnosis, and treatment rates. METHODS AND RESULTS: Dyslipidemia was defined as the presence of either hypercholesterolemia or hypertriglyceridemia using National Cholesterol Education Program III criteria and the fasting lipid measurements, self-reported treatment history, and medication survey available from 5302 Jackson Heart Study participants. Dyslipidemia was more common in men ( compared with women) aged less than 50 years and increased with age in both genders. Hypercholesterolemia prevalence rates approached 50% in women aged more than 65 years. The lifestyle-related attributes found to be related to prevalence were being overweight and less physically active, and all disease status variables exhibited significant (P < .05) associations. Awareness of hypercholesterolemia is approximately 55% or more in both men and women aged more than 35 years. Treatment rates lag far behind awareness, particularly in younger adult men, and less than 50% of women and men aged less than 65 years were treated for hypercholesterolemia. CONCLUSION: Higher rates of identification and effective treatment of dyslipidemia are clearly needed in this, and probably other African-American communities. Despite the less than optimal treatment, the identification and importance of the known cardiovascular disease states and risk factors in these analyses suggest the adoption of National Cholesterol Education Program III "high-risk strategy" algorithms in treatment recommendations and decisions by providers is occurring. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 454-463 C1 [Taylor, Herman A., Jr.; Garrison, Robert J.; Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Taylor, Herman A., Jr.; Akylbekova, Ermeg L.; Sarpong, Daniel] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Taylor, Herman A., Jr.] Tougaloo Coll, Jackson, MS USA. [Joe, Jennifer] Georgetown Univ Hosp, Div Internal Med, Washington, DC 20007 USA. [Walker, Evelyn] NHLBI, Jackson Heart Study, Jackson, MS USA. [Steffes, Michael W.] Univ Minnesota, Minneapolis, MN 55455 USA. RP Taylor, HA (reprint author), 350 W Woodrow Wilson,Suite 701, Jackson, MS 39213 USA. FU National Institutes of Health [N01-HC-95170, N01-HC-95171, N01-HC-95172] FX This research was supported by National Institutes of Health contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172, provided by the National Heart, Lung, and Blood Institute and the National Center for Minority Health and Health Disparities. NR 44 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2009 VL 122 IS 5 BP 454 EP 463 DI 10.1016/j.amjmed.2008.09.049 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 433XB UT WOS:000265238000013 PM 19375555 ER PT J AU Brubaker, L Chiang, SN Zyczynski, H Norton, P Kalinoski, L Stoddard, A Kusek, JW Steers, W AF Brubaker, Linda Chiang, Seine Zyczynski, Halina Norton, Peggy Kalinoski, Lynn Stoddard, Anne Kusek, John W. Steers, William CA Urinary Incontinence Treatment Net TI The impact of stress incontinence surgery on female sexual function SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Urogynecologic-Society CY SEP 04-06, 2008 CL Chicago, IL SP Amer Urogynecol Soc DE Burch; Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire; sexual function; sling; stress incontinence surgery ID PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; WOMEN; QUESTIONNAIRE; LIFE AB OBJECTIVE: We sought to describe change in sexual function 2 years after surgery to treat stress urinary incontinence. STUDY DESIGN: This analysis included 655 women randomized to Burch colposuspension or sling surgery. Sexual activity was assessed by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) among those sexually active at baseline and 2 years after surgery. RESULTS: Mean PISQ-12 total score improved from baseline 32.23 +/- 6.85 to 36.85 +/- 5.89. After surgery, fewer subjects reported incontinence (9% vs 53%; P < .0001), restriction of sexual activity as a result of fear of incontinence (10% vs 52%; P < .0001), avoidance of intercourse because of vaginal bulging (3% vs 24%; P < .0001), or negative emotional reactions during sex (9% vs 35%; P < .0001). Women with successful surgery had greater improvement PISQ-12 scores (5.77 vs 3.79; P < .006). Sexually active women were younger, thinner, and had lower Medical, Epidemiological, and Social Aspects of Aging scores ( total and urge subscale) than sexually inactive women. CONCLUSION: Sexual function improves after successful surgery and does not differ between Burch and sling. C1 [Brubaker, Linda] Loyola Univ Chicago, Dept Obstet & Gynecol, Maywood, IL USA. [Brubaker, Linda] Loyola Univ Chicago, Dept Urol, Maywood, IL USA. [Chiang, Seine] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Zyczynski, Halina] Univ Pittsburgh, Div Urogynecol & Pelv Reconstruct Surg, Pittsburgh, PA USA. [Norton, Peggy] Univ Utah, Dept Urol, Salt Lake City, UT USA. [Kalinoski, Lynn] Univ Calif San Diego, Div Urol, San Diego, CA 92103 USA. [Stoddard, Anne] New England Res Inst, Watertown, MA 02172 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Steers, William] Univ Virginia, Dept Urol, Charlottesville, VA USA. RP Brubaker, L (reprint author), Loyola Univ Chicago, Dept Obstet & Gynecol, Maywood, IL USA. FU NIDDK NIH HHS [U01 DK058231, U01 DK60401, U01 DK60395, U01 DK60380, U01 DK58229, U01 DK060397, U01 DK060379, U01 DK058234, U01 DK058225, U01 DK58234, U01 DK060379-01, U01 DK060393, U01 DK58225, U01 DK58231, U01 DK60379, U01 DK60397, U01 DK060401, U01 DK058229, U01 DK060380, U01 DK060395, U01 DK60393] NR 21 TC 4 Z9 5 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2009 VL 200 IS 5 AR 562.e1 DI 10.1016/j.ajog.2008.11.017 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 434CW UT WOS:000265253800036 PM 19286143 ER PT J AU Levens, ED Wesley, R Premkumar, A Blocker, W Nieman, LK AF Levens, Eric D. Wesley, Robert Premkumar, Ahalya Blocker, Wendy Nieman, Lynnette K. TI Magnetic resonance imaging and transvaginal ultrasound for determining fibroid burden: implications for research and clinical care SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE detection; imaging; magnetic resonance imaging; ultrasound; uterine fibroids ID HYSTEROSONOGRAPHIC EXAMINATION; UTERINE LEIOMYOMAS; REPRODUCIBILITY; MYOMAS; HYSTEROSCOPY; SONOGRAPHY; DIAGNOSIS; MRI; US AB OBJECTIVES: To compare magnetic resonance and ultrasound imaging for uterine fibroid measurement. STUDY DESIGN: Eighteen women undergoing hysterectomy for symptomatic fibroids underwent preoperative pelvic ultrasound and magnetic resonance imaging. Resected fibroids were correlated with the images. Weighted kappa agreement statistics and Spearman correlations for patient characteristics were calculated. RESULTS: Magnetic resonance imaging identified 121 of 151 pathologically confirmed fibroids, yielding 91% positive predictive value (95% confidence interval [CI], 85-95) and 80% sensitivity (95% CI, 73-86). Positive predictive value and sensitivity for ultrasound were 97% ( 95% CI, 89-100) and 40% (95% CI, 32-48), respectively. Mean diameter-equivalent discrepancies between imaging and pathologic measurements were 0.51 +/- 0.68 cm for magnetic resonance imaging and 0.76 +/- 0.88 cm for ultrasound. kappa statistics comparing imaging to pathology showed better agreement for magnetic resonance than ultrasound (kappa = 0.60 vs 0.36). The number of fibroids detected by magnetic resonance imaging predicted measurement errors (r = 0.76; P = .0002). CONCLUSION: Superior sensitivity and minimal measurement discrepancies suggest magnetic resonance imaging may be preferentially used for fibroid assessment in clinical research. C1 [Levens, Eric D.; Blocker, Wendy; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Wesley, Robert] NIH, Dept Biostat Serv, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Premkumar, Ahalya] NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHD, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@mail.nih.gov FU National Institutes of Health, Bethesda, MD FX This research was supported, in part, by the Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. NR 13 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2009 VL 200 IS 5 AR 537.e1 DI 10.1016/j.ajog.2008.12.037 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 434CW UT WOS:000265253800027 PM 19268886 ER PT J AU Scifres, CM Iams, JD Klebanoff, M Macones, GA AF Scifres, Christina M. Iams, Jay D. Klebanoff, Mark Macones, George A. TI Metaanalysis vs large clinical trials: which should guide our management? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE metaanalysis; randomized clinical trial ID LOW-DOSE ASPIRIN; INDIVIDUAL PATIENT DATA; RANDOMIZED-TRIAL; PREGNANT-WOMEN; CALCIUM INTAKE; PREVENT PREECLAMPSIA; HYPERTENSION; QUALITY; RISK; BIAS AB Large, randomized clinical trials have long been considered the gold standard to guide clinical care. Metaanalysis is a type of analysis in which results of a number of randomized clinical trials are combined and a summary measure of effect for a given treatment is ascertained. The clinician in practice often is faced with a dilemma regarding the type of evidence that should be used to guide clinical practice; for many clinical problems, there are both randomized controlled trials and metaanalyses available. The cases of calcium and aspirin therapy for the prevention of preeclampsia afford an opportunity to explore the benefits and limitations of each type of study to guide clinical practice. We conclude that, when available, large randomized clinical trials should be used to guide clinical practice. C1 [Scifres, Christina M.; Macones, George A.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Klebanoff, Mark] NICHHD, Div Epidemiol Stat & Prevent Res, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Scifres, CM (reprint author), Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. FU Intramural NIH HHS NR 25 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2009 VL 200 IS 5 AR 484.e1 DI 10.1016/j.ajog.2008.09.873 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 434CW UT WOS:000265253800004 PM 19027095 ER PT J AU Vink, J Incerti, M Toso, L Roberson, R Abebe, D Spong, CY AF Vink, Joy Incerti, Maddelena Toso, Laura Roberson, Robin Abebe, Daniel Spong, Catherine Y. TI Prenatal NAP plus SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-D-aspartic acid and gamma-aminobutyric acid receptors SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med DE Down syndrome; gamma-aminobutyric acid; learning; N-methyl-D-aspartic acid; NAPVSIPQ; SALLRSIPA; Ts65Dn ID FETAL ALCOHOL SYNDROME; VASOACTIVE-INTESTINAL-PEPTIDE; TS65DN MICE; LEARNING-DEFICITS; ABNORMALITIES; PROTEIN; GROWTH; MEMORY; NMDA AB OBJECTIVE: Down syndrome (DS) affects 1/800 infants. Prenatal NAPVSIPQ (NAP) and SALLRSIPA (SAL) (NAP + SAL) prevent developmental delay in Ts65Dn mice, a mouse model of DS. We investigated whether this finding involves N-methyl-D-aspartic acid and gamma-aminobutyric acid (GABA) receptor subunits. STUDY DESIGN: Pregnant Ts65Dn mice were treated with placebo or NAP + SAL on gestational days 8-12. After developmental delay prevention was shown, 4 trisomic (Ts), 4 control, and 3 Ts + NAP + SAL adult offspring brains (from 3 litters) were collected. Calibrator-normalized real-time polymerase chain reaction was performed using primers for N-methyl-D-aspartic acid subunits NR2A and NR2B, and for GABA subunits GABA(A)alpha 5 and GABA(A)beta 3 with glyceraldehyde-3-phosphate dehydrogenase stan-dardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. RESULTS: NR2A, NR2B, and GABA(A)beta 3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP + SAL increased NR2A, NR2B, and GABA(A)beta 3 to levels similar to control (all P < .05). A significant difference in GABA(A)alpha 5 levels was not found. CONCLUSION: Prenatal NAP + SAL increases NR2A, NR2B, and GABA(A)beta 3 expression in adult DS mice to levels similar to controls. This may explain how NAP + SAL improve developmental milestone achievement. C1 [Vink, Joy] Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. [Vink, Joy; Incerti, Maddelena; Roberson, Robin; Abebe, Daniel; Spong, Catherine Y.] NICHHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. [Toso, Laura] George Washington Univ, Dept Obstet & Gynecol, Washington, DC USA. RP Vink, J (reprint author), Georgetown Univ Hosp, Dept Obstet & Gynecol, 3800 Reservoir Rd,3 PHC, Washington, DC 20007 USA. EM joyvink@gmail.com FU Intramural NIH HHS NR 26 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2009 VL 200 IS 5 AR 524.e1 DI 10.1016/j.ajog.2009.01.052 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 434CW UT WOS:000265253800021 PM 19327737 ER PT J AU Chan, CC Sauer, TC AF Chan, Chi-Chao Sauer, Theodor C. TI Ocular Imaging in Primary Retinal Lymphoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID PRIMARY INTRAOCULAR LYMPHOMA; CENTRAL-NERVOUS-SYSTEM; DIAGNOSIS C1 [Chan, Chi-Chao; Sauer, Theodor C.] NEI, NIH, Immunopathol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, NIH, Immunopathol Sect, Immunol Lab, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 14 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2009 VL 147 IS 5 BP 764 EP 765 DI 10.1016/j.ajo.2008.12.029 PG 2 WC Ophthalmology SC Ophthalmology GA 441IQ UT WOS:000265762900002 PM 19376328 ER PT J AU Liu, Y Korn, EL Oh, HS Pearson, H Xu, TM Baumrind, S AF Liu, Yan Korn, Edward L. Oh, Hee Soo Pearson, Helmer Xu, Tian-Min Baumrind, Sheldon TI Comparison of Chinese and US orthodontists' averaged evaluations of "facial attractiveness'' from end-of-treatment facial photographs SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID DYNAMIC SMILE VISUALIZATION; SOFT-TISSUE PROFILE; PREFERENCES; QUANTIFICATION; POPULATION; AMERICANS; FACES; AGE AB Introduction: This study continues our assessment of agreement and disagreement among 25 Chinese and 20 US orthodontists in the ranking for facial attractiveness of end-of-treatment photographs of randomly sampled growing Chinese and white orthodontic patients. The main aims of this article were to (1) measure the overall pattern of agreement between the mean rankings of US and Chinese orthodontists, and (2) measure the strength of agreement between the rankings of the US and Chinese orthodontists for each patient. Methods: Each judge independently ranked standard clinical sets of profile, frontal, and frontal-smiling photographs of 43 US patients and 48 Chinese patients. For each patient, a separate mean rank was computed from the responses of each group of judges. Pearson correlations between the mean ranks of the 2 groups of judges were used to measure their overall agreement. Paired and unpaired t tests were used to measure the agreement between the judges of the 2 groups for each patient. Results: The overall agreement between the mean rankings of the US and Chinese judges was very high. For the US patients, the correlation between the Chinese and US judges means was r = 0.92, P <0.0001. For the Chinese patients, the analogous value was r = 0.86, P <0.0001. Agreement between the 2 groups of judges concerning each patient was also generally strong. For two thirds of the patients, the mean ranks of the US and Chinese judges differed by less than 1 unit in a scale of 12. However, for 6 patients considered individually (5 Chinese and 1 US), the assessment of the 2 groups of judges was statistically significantly different at P values ranging from 0.02 to less than 0.0001, even after the Bonferroni correction. Conclusions: These findings demonstrate that orthodontic clinicians can reliably identify and rank subtle differences between patients, and that differences between judges and between patients can be distinguished at a high level of statistical significance, given appropriate study designs. However, the reasons clinicians give for the differences in their judgments are more difficult to investigate and will require further study. (Am J Orthod Dentofacial Orthop 2009; 135: 621-34) C1 [Baumrind, Sheldon] Univ Pacific, Sch Dent, Craniofacial Res Instrumentat Lab, San Francisco, CA 94115 USA. [Oh, Hee Soo; Baumrind, Sheldon] Univ Pacific, Sch Dent, Dept Orthodont, San Francisco, CA 94115 USA. [Liu, Yan; Xu, Tian-Min] Peking Univ, Dept Orthodont, Sch Stomatol, Beijing 100871, Peoples R China. [Liu, Yan; Xu, Tian-Min] Peking Univ, Dept Orthodont, Hosp Stomatol, Beijing 100871, Peoples R China. [Korn, Edward L.] NCI, Biometr Res Branch, NIH, Rockville, MD USA. [Pearson, Helmer] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Orthodont, Newark, NJ 07103 USA. RP Baumrind, S (reprint author), Univ Pacific, Arthur A Dugoni Sch Dent, Craniofacial Res Instrumentat Lab, Room 617,2115 Webster St, San Francisco, CA 94115 USA. EM sbaumrind@pacific.edu FU NIH-NIDR [DE07332, DE08713]; American Association of Orthodontists Foundation FX Supported in part by NIH-NIDR grants DE07332 and DE08713, and the American Association of Orthodontists Foundation. NR 26 TC 6 Z9 8 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD MAY PY 2009 VL 135 IS 5 BP 621 EP 634 DI 10.1016/j.ajodo.2007.04.039 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 439UH UT WOS:000265652300024 PM 19409345 ER PT J AU Soulas, C Donahue, RE Dunbar, CE Persons, DA Alvarez, X Williams, KC AF Soulas, Caroline Donahue, Robert E. Dunbar, Cynthia E. Persons, Derek A. Alvarez, Xavier Williams, Kenneth C. TI Genetically Modified CD34(+) Hematopoietic Stem Cells Contribute to Turnover of Brain Perivascular Macrophages in Long-Term Repopulated Primates SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIMIAN IMMUNODEFICIENCY VIRUS; GREEN FLUORESCENT PROTEIN; MARROW-DERIVED ELEMENTS; LENTIVIRAL VECTOR; MOUSE-BRAIN; RAT-BRAIN; NONHUMAN-PRIMATES; BLOOD MONOCYTES; IN-SITU AB Studies in rodents have shown that brain perivascular macrophages are derived from bone marrow precursors. Less is known about the origin and turnover of perivascular cells in the human central nervous system. we took advantage of non-human primates reconstituted with autologous CD34+ hematopoietic stem cells that had been transduced with a lentiviral vector expressing the enhanced green fluorescent protein (EGFP) to study the ontogeny of brain macrophages of rhesus macaques. Flow cytometry and immunohistochemistry/fluorescence microscopy showed long-term reconstitution of monocytes/macrophages in the blood, lymphoid, and brain tissues 4 years post-transplant. In the brain, EGFP+ cells were detected in the choroid plexus, cerebellum, and cerebrum, where the percent engraftment between animals reflected the percentage of EGFP+ monocytes in the blood. Morphology and location of brain EGFP+ cells exclusively in the vicinity of blood vessels were consistent with perivascular macrophages. Up to 85% of brain EGFP+ cells expressed CD163, a marker of perivascular macrophages, and greater than 70% were CD68+ macrophages. These findings clearly demonstrate that a subpopulation of CD163+/CD68+ brain perivascular macrophages in rhesus macaques are renewed by CD34+ hematopoietic stem cell-derived precursors and exhibit a continuous long-lasting turnover. Because perivascular macrophages are significant targets of productive HIV/simian immunodeficiency virus infection in the brain, these observations point to hematopoietic stem cells as targets of both HIV/simian immunodeficiency virus infection and potential gene therapy. (Am J Pathol 2009, 174:1808-1817; DOI: 10.2353/ajpath.2009.081010) C1 [Soulas, Caroline; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, Rockville, MD USA. [Persons, Derek A.] St Jude Childrens Hosp, Dept Hematol, Memphis, TN 38105 USA. [Alvarez, Xavier] Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA USA. RP Williams, KC (reprint author), Boston Coll, Dept Biol, Higgins Hall 445B,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM williauy@bc.edu FU NIH; National Heart Lung and Blood Institute Program Project [P01HL05374921765]; Public Health Service [RR00164]; National Institute of Neurologic Disease and Stroke [NS040237, NS037654] FX Supported in part by the Intramural Research Program of the NIH (R.E.D. and C.E.D.), by National Heart Lung and Blood Institute Program Project P01HL05374921765 and American Lebanese Associated Charities (D.A.P.), by Public Health Service Grants RR00164 (X.A.H.) and by grants from the NIH, including the National Institute of Neurologic Disease and Stroke NS040237 and NS037654 (to K.C.W.), NR 41 TC 30 Z9 30 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2009 VL 174 IS 5 BP 1808 EP 1817 DI 10.2353/ajpath.2009.081010 PG 10 WC Pathology SC Pathology GA 438JK UT WOS:000265551500025 PM 19349370 ER PT J AU Iliff, JJ Wang, RK Zeldin, DC Alkayed, NJ AF Iliff, Jeffrey J. Wang, Ruikang Zeldin, Darryl C. Alkayed, Nabil J. TI Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cerebral blood flow regulation; cytochrome P-450 epoxygenase; epoxyeicosatrienoic acid; soluble epoxide hydrolase; perivascular nerves ID SOLUBLE EPOXIDE HYDROLASE; ARACHIDONIC-ACID EPOXYGENASE; ASTROCYTIC EPOXYEICOSATRIENOIC ACID; CORTICAL FUNCTIONAL HYPEREMIA; NITRIC-OXIDE; BLOOD-FLOW; PERIVASCULAR NERVES; ENDOTHELIAL-CELLS; RAT; STIMULATION AB Iliff JJ, Wang R, Zeldin DC, Alkayed NJ. Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels. Am J Physiol Heart Circ Physiol 296: H1352-H1363, 2009. First published March 20, 2009; doi:10.1152/ajpheart.00950.2008.-Epoxyeicosatrienoic acids (EETs) are potent vasodilators produced from arachidonic acid by cytochrome P-450 (CYP) epoxygenases and metabolized to vicinal diols by soluble epoxide hydrolase (sEH). In the brain, EETs are produced by astrocytes and the vascular endothelium and are involved in the control of cerebral blood flow (CBF). Recent evidence, however, suggests that epoxygenases and sEH are present in perivascular vasodilator nerve fibers innervating the cerebral surface vasculature. In the present study, we tested the hypothesis that EETs are nerve-derived relaxing factors in the cerebral circulation. We first traced these fibers by retrograde labeling in the rat to trigeminal ganglia (TG) and sphenopalatine ganglia (SPG). We then examined the expression of CYP epoxygenases and sEH in these ganglia. RT-PCR and Western blot analysis identified CYP2J3 and CYP2J4 epoxygenase isoforms and sEH in both TG and SPG, and immunofluorescence double labeling identified CYP2J and sEH immunoreactivity in neuronal cell bodies of both ganglia. To evaluate the functional role of EETs in neurogenic vasodilation, we elicited cortical hyperemia by electrically stimulating efferent cerebral perivascular nerve fibers and by chemically stimulating oral trigeminal fibers with capsaicin. Cortical blood flow responses were monitored by laser-Doppler flowmetry. Local administration to the cortical surface of the putative EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (30 mu mol/l) attenuated CBF responses to electrical and chemical stimulation. These results suggest that EETs are produced by perivascular nerves and play a role in neurogenic vasodilation of the cerebral vasculature. The findings have important implications to such clinical conditions as migraine, vasospasm after subarachnoid hemorrhage, and stroke. C1 [Iliff, Jeffrey J.; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Peri Operat Med, Portland, OR 97239 USA. [Iliff, Jeffrey J.; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Wang, Ruikang] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. [Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, Natl Inst Hlth, Res Triangle Pk, NC USA. RP Alkayed, NJ (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Peri Operat Med, 3181 SW Sam Jackson Pk Rd,UHS 2, Portland, OR 97239 USA. EM alkayedn@ohsu.edu FU Vertex Pharmaceuticals; National Institutes of Health (NIH) [F31-NS-060498, RO1-NS-044313, P01-NS-049210, 1-R01-HL-093140-01, Z01-ES-025034] FX This work was supported by an Oregon Health and Science University Graduate Student Fellowship for the Neurobiology of Disease funded by Vertex Pharmaceuticals; National Institutes of Health (NIH) Grants F31-NS-060498 (to J. J. Iliff), RO1-NS-044313 and P01-NS-049210 (to N. J. Alkayed), 1-R01-HL-093140-01 (to R. Wang), and Z01-ES-025034 (to D. C. Zeldin); and the Intramural Research Program of the NIH (to D. C. Zeldin). NR 36 TC 34 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2009 VL 296 IS 5 BP H1352 EP H1363 DI 10.1152/ajpheart.00950.2008 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 439WU UT WOS:000265659100023 PM 19304946 ER PT J AU Mukhopadhyay, P Rajesh, M Batkai, S Kashiwaya, Y Hasko, G Liaudet, L Szabo, C Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Batkai, Sandor Kashiwaya, Yoshihiro Hasko, Gyoergy Liaudet, Lucas Szabo, Csaba Pacher, Pal TI Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart failure; apoptosis; inducible nitric oxide synthase; hemodynamics ID INDUCED HEART-FAILURE; HEPATIC ISCHEMIA/REPERFUSION INJURY; LEFT-VENTRICULAR DYSFUNCTION; INDUCED CARDIAC DYSFUNCTION; INDUCED CARDIOMYOPATHY; INDUCED CARDIOTOXICITY; MATRIX METALLOPROTEINASE-2; ISCHEMIA-REPERFUSION; NITROSATIVE STRESS; HYDROGEN-PEROXIDE AB Mukhopadhyay P, Rajesh M, Batkai S, Yoshihiro K, Hasko G, Liaudet L, Szabo C, Pacher P. Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro. Am J Physiol Heart Circ Physiol 296: H1466-H1483, 2009. First published March 13, 2009; doi:10.1152/ajpheart.00795.2008.-Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited because of its cardiotoxicity. Cell death is a key component in DOX-induced cardiotoxicity, but its mechanisms are elusive. Here, we explore the role of superoxide, nitric oxide (NO), and peroxynitrite in DOX-induced cell death using both in vivo and in vitro models of cardiotoxicity. Western blot analysis, real-time PCR, immunohistochemistry, flow cytometry, fluorescent microscopy, and biochemical assays were used to determine the markers of apoptosis/necrosis and sources of NO and superoxide and their production. Left ventricular function was measured by a pressure-volume system. We demonstrated increases in myocardial apoptosis (caspase-3 cleavage/activity, cytochrome c release, and TUNEL), inducible NO synthase (iNOS) expression, mitochondrial superoxide generation, 3-nitrotyrosine (NT) formation, matrix metalloproteinase (MMP)-2/MMP-9 gene expression, poly(ADP-ribose) polymerase activation [without major changes in NAD(P) H oxidase isoform 1, NAD(P) H oxidase isoform 2, p22(phox), p40(phox), p47(phox), p67(phox), xanthine oxidase, endothelial NOS, and neuronal NOS expression] and decreases in myocardial contractility, catalase, and glutathione peroxidase activities 5 days after DOX treatment to mice. All these effects of DOX were markedly attenuated by peroxynitrite scavengers. Doxorubicin dose dependently increased mitochondrial superoxide and NT generation and apoptosis/necrosis in cardiac-derived H9c2 cells. DOX- or peroxynitrite-induced apoptosis/necrosis positively correlated with intracellular NT formation and could be abolished by peroxynitrite scavengers. DOX-induced cell death and NT formation were also attenuated by selective iNOS inhibitors or in iNOS knockout mice. Various NO donors when coadministered with DOX but not alone dramatically enhanced DOX-induced cell death with concomitant increased NT formation. DOX-induced cell death was also attenuated by cell-permeable SOD but not by cell-permeable catalase, the xanthine oxidase inhibitor allopurinol, or the NADPH oxidase inhibitors apocynine or diphenylene iodonium. Thus, peroxynitrite is a major trigger of DOX-induced cell death both in vivo and in vivo, and the modulation of the pathways leading to its generation or its effective neutralization can be of significant therapeutic benefit. C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Batkai, Sandor; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Kashiwaya, Yoshihiro] NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA. [Liaudet, Lucas] Univ Lausanne Hosp, Dept Intens Care Med, Lausanne, Switzerland. [Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health (NIH) [R01-GM-60915]; Swiss National Fund [PP00B-68882/1] FX This work was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health (NIH) (to P. Pacher), NIH Grant R01-GM-60915 (to C. Szabo), and Swiss National Fund PP00B-68882/1 (to L. Liaudet). NR 65 TC 144 Z9 151 U1 3 U2 26 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2009 VL 296 IS 5 BP H1466 EP H1483 DI 10.1152/ajpheart.00795.2008 PG 18 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 439WU UT WOS:000265659100036 PM 19286953 ER PT J AU Paolocci, N Wink, DA AF Paolocci, Nazareno Wink, David A. TI The shy Angeli and his elusive creature: the HNO route to vasodilation SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article ID CARDIAC SARCOPLASMIC-RETICULUM; NO-CENTER-DOT; NITRIC-OXIDE; IN-VIVO; NITROXYL HNO; S-NITROSOTHIOLS; L-CYSTEINE; MUSCLE; CHEMISTRY; SALT C1 [Paolocci, Nazareno] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Paolocci, Nazareno] Univ Perugia, Dept Clin Med, Sect Gen Pathol, I-06100 Perugia, Italy. [Wink, David A.] NCI, Radiat Biol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Paolocci, N (reprint author), Johns Hopkins Sch Med, Div Cardiol, Ross 858,720 Rutland Ave, Baltimore, MD 21205 USA. EM npaoloc1@jhmi.edu OI Paolocci, Nazareno/0000-0001-7011-997X FU NHLBI NIH HHS [R01 HL-075265] NR 44 TC 14 Z9 14 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2009 VL 296 IS 5 BP H1217 EP H1220 DI 10.1152/ajpheart.00243.2009 PG 4 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 439WU UT WOS:000265659100005 PM 19286958 ER PT J AU Sanchez-Lemus, E Benicky, J Pavel, J Larrayoz, IM Zhou, J Baliova, M Nishioku, T Saavedra, JM AF Sanchez-Lemus, Enrique Benicky, Julius Pavel, Jaroslav Larrayoz, Ignacio M. Zhou, Jin Baliova, Martina Nishioku, Tsuyoshi Saavedra, Juan M. TI Angiotensin II AT(1) blockade reduces the lipopolysaccharide-induced innate immune response in rat spleen SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE CD14; cyclooxygenase-2; NAPDH oxidase; inducible nitric oxide synthase; proinflammatory cytokines ID NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; SPONTANEOUSLY HYPERTENSIVE-RATS; TYPE-1 RECEPTOR ANTAGONIST; CYCLOOXYGENASE-2 EXPRESSION; ENDOTHELIAL DYSFUNCTION; VASCULAR INFLAMMATION; BRAIN MICROVESSELS; PASTE STANDARDS; INOS EXPRESSION AB Sanchez-Lemus E, Benicky J, Pavel J, Larrayoz IM, Zhou J, Baliova M, Nishioku T, Saavedra JM. Angiotensin II AT1 blockade reduces the lipopolysaccharide- induced innate immune response in rat spleen. Am J Physiol Regul Integr Comp Physiol 296: R1376-R1384, 2009. First published February 18, 2009; doi: 10.1152/ajpregu.90962.2008.- ANG II AT1 receptor blockade reduces inflammation in hypertension. To determine whether ANG II AT1 receptor blockers (ARBs) influence the innate immune inflammatory response in normotensive rats, we studied rat plasma and spleen after a 3-day subcutaneous pretreatment with the ARB candesartan followed by a single dose of the bacterial endotoxin LPS ( 50 mu g/kg ip). Peripheral administration of LPS to rodents produced a generalized inflammatory response with increased release of TNF-alpha, IL-1 beta, and IL-6 into the circulation. Candesartan pretreatment reduced the LPS-induced release of TNF-alpha, IL-1 beta, and IL-6 into the circulation. The red pulp of rat spleen expressed large numbers of AT1 receptors and the LPS receptors Toll-like receptor 4 and CD14. Candesartan administration significantly blocked AT1 receptors. The ARB reduced the LPS-induced upregulation of CD14 gene expression; expression of TNF-alpha and IL-6 mRNA and protein; expression of IL-1 beta and I kappa B-alpha mRNA; COX-2 mRNA and protein expression and PGE2 concentration; inducible nitric oxide synthase (iNOS) gene and protein expression and iNOS activity; and Nox2 gene expression and 8-isoprostane levels. In addition, candesartan reduced the CD14 protein expression in saline- and LPS-treated rats. Our results suggest that AT1 receptors are essential for the development of the full innate immune response to bacterial endotoxin. The ARB decreased the general peripheral inflammatory reaction to LPS and partially decreased the inflammatory response in the spleen. An unrestricted innate immune response to the bacterial endotoxin may have deleterious effects for the organism and may lead to development of chronic inflammatory disease. We postulate that ARBs may have therapeutic effects on inflammatory conditions. C1 [Sanchez-Lemus, Enrique; Benicky, Julius; Pavel, Jaroslav; Larrayoz, Ignacio M.; Zhou, Jin; Baliova, Martina; Nishioku, Tsuyoshi; Saavedra, Juan M.] NIMH, Pharmacol Sect, NIH, DHHS, Bethesda, MD 20892 USA. RP Sanchez-Lemus, E (reprint author), NIMH, Pharmacol Sect, NIH, DHHS, 10 Ctr Dr,Bldg 10,Rm 2D-57, Bethesda, MD 20892 USA. EM sancheze@mail.nih.gov RI Larrayoz, Ignacio/I-5613-2012 OI Larrayoz, Ignacio/0000-0003-1629-152X FU Division of Intramural Research Programs; National Institute of Mental Health FX This study was supported by the Division of Intramural Research Programs, National Institute of Mental Health. NR 63 TC 26 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAY PY 2009 VL 296 IS 5 BP R1376 EP R1384 DI 10.1152/ajpregu.90962.2008 PG 9 WC Physiology SC Physiology GA 448EW UT WOS:000266246900011 PM 19225144 ER PT J AU Elkareh, J Periyasamy, SM Shidyak, A Vetteth, S Schroeder, J Raju, V Hariri, IM El-Okdi, N Gupta, S Fedorova, L Liu, J Fedorova, OV Kahaleh, MB Xie, ZJ Malhotra, D Watson, DK Bagrov, AY Shapiro, JI AF Elkareh, Jihad Periyasamy, Sankaridrug M. Shidyak, Amjad Vetteth, Sandeep Schroeder, Jeremy Raju, Vanamala Hariri, Imad M. El-Okdi, Nasser Gupta, Shalini Fedorova, Larisa Liu, Jiang Fedorova, Olga V. Kahaleh, M. Bashar Xie, Zijian Malhotra, Deepak Watson, Dennis K. Bagrov, Alexei Y. Shapiro, Joseph I. TI Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol DE renal failure; cardiotonic steroids; fibrosis ID ETS ONCOGENE FAMILY; TRANSCRIPTION FACTOR; DERMAL FIBROBLASTS; GENE-EXPRESSION; COLLAGEN; RAT; ASSOCIATION; ACTIVATION; DISEASE AB Elkareh J, Periyasamy SM, Shidyak A, Vetteth S, Schroeder J, Raju V, Hariri IM, El-Okdi N, Gupta S, Fedorova L, Liu J, Fedorova OV, Kahaleh MB, Xie Z, Malhotra D, Watson DK, Bagrov AY, Shapiro JI. Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. Am J Physiol Renal Physiol 296: F1219-F1226, 2009. First published March 4, 2009; doi:10.1152/ajprenal.90710.2008.-The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear Fli-1 as well as increases in procollagen-1 expression in these cells. Transfection of a Fli-1 expression vector prevented increased procollagen-1 expression from MBG. MBG exposure induced a rapid translocation of the delta-isoform of protein kinase C (PKC delta) to the nucleus. This translocation was prevented by pharmacological inhibition of phospholipase C, and MBG-induced increases in procollagen-1 expression were prevented with a PKC delta-but not a PKC delta-specific inhibitor. Finally, immunoprecipitation studies strongly suggest that MBG induced phosphorylation of Fli-1. We feel these data support a causal relationship with MBG-induced translocation of PKC delta, which results in phosphorylation of as well as decreases in nuclear Fli-1 expression, which, in turn, leads to increases in collagen production. Should these findings be confirmed, we speculate that this pathway may represent a therapeutic target for uremic cardiomyopathy as well as other conditions associated with excessive fibrosis. C1 [Elkareh, Jihad; Periyasamy, Sankaridrug M.; Shidyak, Amjad; Vetteth, Sandeep; Schroeder, Jeremy; Raju, Vanamala; Hariri, Imad M.; El-Okdi, Nasser; Gupta, Shalini; Fedorova, Larisa; Liu, Jiang; Kahaleh, M. Bashar; Xie, Zijian; Malhotra, Deepak; Shapiro, Joseph I.] Univ Toledo, Coll Med, Dept Med, Toledo, OH 43614 USA. [Elkareh, Jihad; Periyasamy, Sankaridrug M.; Shidyak, Amjad; Vetteth, Sandeep; Schroeder, Jeremy; Raju, Vanamala; Hariri, Imad M.; El-Okdi, Nasser; Gupta, Shalini; Fedorova, Larisa; Liu, Jiang; Kahaleh, M. Bashar; Xie, Zijian; Malhotra, Deepak; Shapiro, Joseph I.] Univ Toledo, Coll Med, Dept Pharmacol, Toledo, OH 43614 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Watson, Dennis K.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Shapiro, JI (reprint author), Univ Toledo, Coll Med, Dept Med, Mail Stop 1186 Hlth Sci Campus,3000 Arlington Ave, Toledo, OH 43614 USA. EM joseph.shapiro@utoledo.edu FU Intramural NIH HHS [Z01 AG000609-17]; NCI NIH HHS [P01-CA-78582]; NHLBI NIH HHS [R01-HL-67963] NR 22 TC 34 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2009 VL 296 IS 5 BP F1219 EP F1226 DI 10.1152/ajprenal.90710.2008 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 438AZ UT WOS:000265529600032 PM 19261738 ER PT J AU Neubauer, B Machura, K Chen, M Weinstein, LS Oppermann, M Sequeira-Lopez, ML Gomez, RA Schnermann, J Castrop, H Kurtz, A Wagner, C AF Neubauer, Bjoern Machura, Katharina Chen, Min Weinstein, Lee S. Oppermann, Mona Sequeira-Lopez, Maria Luisa Gomez, R. Ariel Schnermann, Juergen Castrop, Hayo Kurtz, Armin Wagner, Charlotte TI Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE fetal kidney; transgenic mice ID CONTAINING CELLS; GENE-EXPRESSION; JUXTAGLOMERULAR APPARATUS; RESPONSIVE ELEMENT; FETAL DEVELOPMENT; STIMULATED RENIN; MESSENGER-RNA; RAT KIDNEYS; INHIBITION; MOUSE AB Neubauer B, Machura K, Chen M, Weinstein LS, Oppermann M, Sequeira-Lopez ML, Gomez RA, Schnermann J, Castrop H, Kurtz A, Wagner C. Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway. Am J Physiol Renal Physiol 296: F1006-F1012, 2009. First published March 4, 2009; doi:10.1152/ajprenal.90448.2008.-During metanephric kidney development, renin expression in the renal vasculature begins in larger vessels, shifting to smaller vessels and finally remaining restricted to the terminal portions of afferent arterioles at the entrance into the glomerular capillary network. The mechanisms determining the successive expression of renin along the vascular axis of the kidney are not well understood. Since the cAMP signaling cascade plays a central role in the regulation of both renin secretion and synthesis in the adult kidney, it seemed feasible that this pathway might also be critical for renin expression during kidney development. In the present study we determined the spatiotemporal development of renin expression and the development of the preglomerular arterial tree in mouse kidneys with renin cell-specific deletion of G(s alpha), a core element for receptor activation of adenylyl cyclases. We found that in the absence of the G(s alpha) protein, renin expression was largely absent in the kidneys at any developmental stage, accompanied by alterations in the development of the preglomerular arterial tree. These data indicate that the maintenance of renin expression following a specific spatiotemporal pattern along the preglomerular vasculature critically depends on the availability of G(s alpha). We infer from our data that the cAMP signaling pathway is not only critical for the regulation of renin synthesis and secretion in the mature kidney but that it also is critical for establishing the juxtaglomerular expression site of renin during development. C1 [Wagner, Charlotte] Univ Regensburg, Inst Physiol, Dept Physiol, D-93040 Regensburg, Germany. [Chen, Min; Weinstein, Lee S.; Schnermann, Juergen] NIH, Bethesda, MD 20892 USA. [Oppermann, Mona] Univ Regensburg, Fac Med, Dept Pediat, D-93040 Regensburg, Germany. [Sequeira-Lopez, Maria Luisa; Gomez, R. Ariel] Univ Virginia, Charlottesville, VA USA. RP Wagner, C (reprint author), Univ Regensburg, Inst Physiol, Dept Physiol, D-93040 Regensburg, Germany. EM charlotte.schmid@vkl.uni-regensburg.de OI Weinstein, Lee/0000-0002-1899-5152 FU Deutsche Forschungsgemeinschaft [SFB 699] FX The study was financially supported by Deutsche Forschungsgemeinschaft Grant SFB 699. NR 45 TC 26 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2009 VL 296 IS 5 BP F1006 EP F1012 DI 10.1152/ajprenal.90448.2008 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 438AZ UT WOS:000265529600008 PM 19261741 ER PT J AU Bowen, DJ Kreuter, M Spring, B Cofta-Woerpel, L Linnan, L Weiner, D Bakken, S Kaplan, CP Squiers, L Fabrizio, C Fernandez, M AF Bowen, Deborah J. Kreuter, Matthew Spring, Bonnie Cofta-Woerpel, Ludmila Linnan, Laura Weiner, Diane Bakken, Suzanne Kaplan, Cecilia Patrick Squiers, Linda Fabrizio, Cecilia Fernandez, Maria TI How We Design Feasibility Studies SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CANCER; ISSUES AB Public health is moving toward the goal of implementing evidence-based interventions. To accomplish this, there is a need to select, adapt, and evaluate intervention studies. Such selection relies, in part, on making judgments about the feasibility of possible interventions and determining whether comprehensive and multilevel evaluations are justified. There exist few published standards and guides to aid these judgments. This article describes the diverse types of feasibility studies conducted in the field of cancer prevention, using a group of recently funded grants from the National Cancer Institute. The grants were submitted in response to a request for applications proposing research to identify feasible interventions for increasing the utilization of the Cancer Information Service among underserved populations. (Am J Prev Med 2009;36(5):452-457) (c) 2009 Published by Elsevier Inc. oil behalf of American Journal of Preventive Medicine. C1 [Bowen, Deborah J.] Boston Univ, Dept Social & Behav Sci, Sch Publ Hlth, Boston, MA 02118 USA. [Kreuter, Matthew] St Louis Univ, Hlth Commun Res Lab, Sch Publ Hlth, St Louis, MO 63103 USA. [Spring, Bonnie] Northwestern Univ, Dept Behav Med, Chicago, IL 60611 USA. [Fernandez, Maria] Univ Texas Houston, Hlth Sci Ctr, Ctr Hlth Promot & Prevent Res, Houston, TX 77030 USA. [Cofta-Woerpel, Ludmila] Univ Texas Houston, MD Anderson Canc Ctr, NCI, Canc Informat Serv, Houston, TX 77030 USA. [Cofta-Woerpel, Ludmila] Univ Texas Houston, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. [Linnan, Laura] Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. [Weiner, Diane] Mashantucket Pcquot Tribal Nation, Mashantucket, CT USA. [Fabrizio, Cecilia] Yale Canc Ctr, NCI, Canc Informat Serv, New Haven, CT USA. [Bakken, Suzanne] Columbia Univ, Sch Nursing, New York, NY USA. [Kaplan, Cecilia Patrick] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Squiers, Linda] NCI, Canc Informat Serv, Bethesda, MD 20892 USA. RP Bowen, DJ (reprint author), Boston Univ, Dept Social & Behav Sci, Sch Publ Hlth, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM dbowen@bu.edu FU National Cancer Institute [1R21CA126325-01, 1R21CA126990-01, 1R21CA126326-01, 1R21CA126373-01, 1R21CA126450-01, 1R21CA126321-01] FX The projects described were supported by the following six grants from the National Cancer Institute: 1R21CA126325-01, 1R21CA126990-01, 1R21CA126326-01, 1R21CA126373-01, 1R21CA126450-01, and 1R21CA126321-01. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 13 TC 200 Z9 202 U1 7 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2009 VL 36 IS 5 BP 452 EP 457 DI 10.1016/j.amepre.2009.02.002 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 435AI UT WOS:000265315200013 PM 19362699 ER PT J AU Zheng, L Mack, WJ Dagerman, KS Hsiao, JK Lebowitz, BD Lyketsos, CG Stroup, TS Sultzer, DL Tariot, PN Vigen, C Schneider, LS AF Zheng, Ling Mack, Wendy J. Dagerman, Karen S. Hsiao, John K. Lebowitz, Barry D. Lyketsos, Constantine G. Stroup, T. Scott Sultzer, David L. Tariot, Pierre N. Vigen, Cheryl Schneider, Lon S. TI Metabolic Changes Associated With Second-Generation Antipsychotic Use in Alzheimer's Disease Patients: The CATIE-AD Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT International Conference on Alzheimers Disease CY JUL 26-31, 2008 CL Chicago, IL ID PLACEBO-CONTROLLED TRIALS; DOUBLE-BLIND; BEHAVIORAL DISTURBANCES; CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; DEMENTIA; PSYCHOSIS; RISPERIDONE; OLANZAPINE; SCHIZOPHRENIA AB Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects. Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models. Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., >= 7% of body weight) was seen among patients with antipsychotic use <= 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and >24 weeks (OR= 3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely. C1 Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Calif San Diego, Sch Med, Div Geriatr Psychiat, La Jolla, CA 92093 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Dept Psychiat, Baltimore, MD USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. VA Greater Angeles Healthcare Syst, Gero Neuropsychiat Div, Los Angeles, CA USA. Banner Alzheimers Inst, Phoenix, AZ USA. RP Schneider, LS (reprint author), 1510 San Pablo St, Los Angeles, CA 90033 USA. EM lschneid@usc.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH-9001, N01 MH90001] NR 29 TC 36 Z9 38 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2009 VL 166 IS 5 BP 583 EP 590 DI 10.1176/appi.ajp.2008.08081218 PG 8 WC Psychiatry SC Psychiatry GA 439YA UT WOS:000265662500013 PM 19369318 ER PT J AU Nowicki, S Izban, MG Pawelczyk, E Agboto, VK Pratap, S Olson, G Nowicki, B AF Nowicki, Stella Izban, Michael G. Pawelczyk, Edyta Agboto, Vincent K. Pratap, Siddarth Olson, Gayle Nowicki, Bogdan TI Preterm Labor: CD55 in Maternal Blood Leukocytes SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Infection; maternal circulatory immune response; preterm birth; preterm labor ID DECAY-ACCELERATING FACTOR; COMPLEMENT REGULATORY PROTEIN; FETAL MEMBRANE DISTENSION; ESCHERICHIA-COLI; FETOMATERNAL INTERFACE; HUMAN TROPHOBLAST; NITRIC-OXIDE; IN-VITRO; EXPRESSION; INFECTION AB Intrauterine inflammation is a frequent and significant factor associated with the pathogenesis of preterm labor/birth (PTL/PTB). However, it remains unclear whether the intrauterine inflammatory responses activate the maternal peripheral circulation. We explored the association between PTL/PTB and the 'activation' of the peripheral circulatory system by determining whether CD55 mRNA expression within peripheral WBCs differed between PTL and control patients not in labor. RNA was purified from white blood cells collected from pregnant women with preterm labor (n = 45), and from pregnant (n = 30) control women. CD55 gene expression was evaluated by quantitative PCR. The mean CD55 mRNA level within the PTL group (0.77 +/- 0.03) was 1.48-fold higher than that observed (0.52 +/- 0.02) within the control group (P < 0.0001); 71% of PTL patients and only 6.7% of control subjects expressed elevated CD55 mRNA. The receiver operating characteristics (with 95% CI) of CD55 as a marker for PTL were as follows: Sensitivity, 69% (53-82%); Specificity, 93% (78-99%); Positive Predictive Value, 94% (80-99%); and Negative Predictive Value, 67% (51-80%). In the patient population that delivered prematurely (before 37 weeks), 81% expressed elevated CD55 mRNA levels with a mean of 0.78 +/- 0.03 and 95% CI of 0.71-0.84. The receiver operating characteristics were as follows: Sensitivity, 73% (54-88%); Specificity, 86% (71-95%); Positive Predictive Value, 81.5% (62-94%); and Negative Predictive Value, 80% (64-91%). Here we report for the first time that CD55 mRNA expression was elevated in the peripheral WBCs of subjects with preterm labor compared with control gestationally-matched pregnant woman and that elevated leukocyte CD55 may be a useful predictor of subsequent PTB. C1 [Nowicki, Stella; Izban, Michael G.; Nowicki, Bogdan] Meharry Med Coll, Dept Microbial Pathogenesis, Nashville, TN 37208 USA. [Nowicki, Stella; Izban, Michael G.; Nowicki, Bogdan] Meharry Med Coll, Dept Immune Response, Nashville, TN 37208 USA. [Nowicki, Stella; Izban, Michael G.; Nowicki, Bogdan] Meharry Med Coll, Dept Obstr & Gynocol, Nashville, TN 37208 USA. [Agboto, Vincent K.] Meharry Med Coll, Clin Res Ctr, Nashville, TN 37208 USA. [Pawelczyk, Edyta] NIH, Ctr Clin, Expt Neuroimaging Sect, Bethesda, MD 20892 USA. [Pratap, Siddarth] Meharry Med Coll, Dept Microbial Pathogenesis & Immune Response, Nashville, TN 37208 USA. [Olson, Gayle] Univ Texas Med Branch, Dept Obster & Gynecol, Galveston, TX USA. RP Nowicki, S (reprint author), Meharry Med Coll, Dept Obstet & Gynecol, 1005 Dr DB Todd Jr Blvd, Nashville, TN 37208 USA. EM snowicki@mmc.edu OI Pratap, Siddharth/0000-0003-2200-0848 FU National Institute of Child Health and Human Development [HD41687]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK42029]; National Institutes of Health [P20RR011792]; RCMI [U54HD044315] FX This work was supported by Public Health Service grant HD41687 from the National Institute of Child Health and Human Development to S. Nowicki and B.J. Nowicki, and in part by grant DK42029 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to B.J. Nowicki. This research was supported in part by the Clinical Research Center of Meharry Medical College, grant #P20RR011792 from the National Institutes of Health and RCMI Clinical Research Infrastructure Initiative and U54HD044315 to B.J. Nowicki. We express our gratitude to Dr G. Anderson and Dr G. Hankins for assisting us with sample acquisition. NR 42 TC 8 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAY PY 2009 VL 61 IS 5 BP 360 EP 367 DI 10.1111/j.1600-0897.2009.00702.x PG 8 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 428BP UT WOS:000264823300006 PM 19341386 ER PT J AU Tomita, T Yamada, A Miyakoshi, M Kido, T Sheikh, F Srisodsai, A Miyajima, A Donnelly, RP Kimura, S AF Tomita, Takeshi Yamada, Atsushi Miyakoshi, Masaaki Kido, Taketomo Sheikh, Faruk Srisodsai, Achara Miyajima, Atsushi Donnelly, Raymond P. Kimura, Shioko TI Oncostatin M Regulates Secretoglobin 3A1 and 3A2 Expression in a Bidirectional Manner SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE oncostatin M; gene regulation; secretoglobin 3A1; secretoglobin 3A2; lung ID UTEROGLOBIN-RELATED PROTEIN-1; ALLERGIC AIRWAY INFLAMMATION; MUCIN GENE-EXPRESSION; IN-VITRO; EPITHELIAL-CELLS; MOUSE; HIN-1; MICE; FIBROBLASTS; LUNG AB Secretoglobin (SCGB) 3A1 and 3A2 are members of the small molecular weight secretoglobin gene superfamily. SCGB3A1 is a tumor suppressor gene, whereas SCGB3A2 has anti-inflammatory properties. Both genes are mainly expressed in the lung and trachea in mice. Whether the expression and/or function of these two genes are related is not known. Here we show that the expression of SCGB3A1 and SCGB3A2 are bidirectionally regulated by oncostatin M (OSM) when examined in a mouse transformed Clara cell line (mtCC); SCGB3A1 is up-regulated by OSM, while SCGB3A2 is downregulated in a time- and dose-dependent manner. OSM-activated STAT3/5, through binding to the STAT-binding element located at -201 to -209 by in the mouse Scgb3a1 gene promoter, and the extracellular signal-regulated kinase (ERK)- and p38-mitogen-activated protein kinase (MAPK) pathways are responsible for the OSM-induced up-regulation of SCGB3A1 expression. On the other hand, the -113 to -273 by region in the Scgb3a2 promoter appears to be responsible for the OSM induced down-regulation of the gene. No significant differences in the levels or patterns of specific DNA-binding proteins were found in the -113 to -273 by region as determined by electrophoretic mobility shift assays. Neither the ERK- nor p38-MAPK pathways were involved in the OSM-induced reduction of Scgb3a2 promoter activity. These results suggest that OSM-induced suppression of SCGB3A2 expression is an indirect effect of OSM. Expression of the Clara cell marker, CYP2F2, was markedly decreased upon OSM treatment in parallel with the decrease of SCGB3A2 expression in mtCC cells. The differential regulation of Scgb3a1 and Scgb3a2 gene expression by OSM may explain the unique functions of these genes in the lung. C1 [Tomita, Takeshi; Yamada, Atsushi; Miyakoshi, Masaaki; Kido, Taketomo; Srisodsai, Achara; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD USA. [Srisodsai, Achara] Khon Kaen Univ, Fac Pharmaceut Sci, Khon Kaen, Thailand. [Miyajima, Atsushi] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov FU National Cancer Institute FX This research was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. NR 47 TC 2 Z9 2 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2009 VL 40 IS 5 BP 620 EP 630 DI 10.1165/rcmb.2008-0062OC PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 439IH UT WOS:000265620300012 PM 18978304 ER PT J AU El-Khouli, R Macura, K Barker, P Jacobs, M Kamel, I Bluemke, D AF El-Khouli, R. Macura, K. Barker, P. Jacobs, M. Kamel, I Bluemke, D. TI Dynamic MRI of the Breast: Quantitative Method for Kinetic Curve Shape Assessment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [El-Khouli, R.; Bluemke, D.] NIH, Silver Spring, MD USA. [Macura, K.; Barker, P.; Jacobs, M.; Kamel, I] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. EM elkhoulir@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200132 ER PT J AU El-Khouli, R Jacobs, M Macura, K Barker, P Bluemke, D AF El-Khouli, R. Jacobs, M. Macura, K. Barker, P. Bluemke, D. TI Diffusion-Weighted Imaging and Apparent Diffusion Coefficients Mapping for Characterization of Focal Breast Lesions at 3T SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [El-Khouli, R.; Bluemke, D.] NIH, Bethesda, MD 20892 USA. [Jacobs, M.; Macura, K.; Barker, P.; Bluemke, D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. EM elkhoulir@cc.nih.gov RI Jacobs, Michael/G-2901-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200129 ER PT J AU Fayad, L Salibi, N Jacobs, M Ouwerker, R Okollie, B Eng, J Weber, K Barker, P Bluemke, D AF Fayad, L. Salibi, N. Jacobs, M. Ouwerker, R. Okollie, B. Eng, J. Weber, K. Barker, P. Bluemke, D. TI Quantitative Molecular Characterization of Musculoskeletal Lesions by Proton MR Spectroscopy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Fayad, L.; Jacobs, M.; Ouwerker, R.; Okollie, B.; Eng, J.; Weber, K.; Barker, P.; Bluemke, D.] Johns Hopkins Univ, Baltimore, MD USA. [Bluemke, D.] NIH, Bethesda, MD 20892 USA. EM lfayad1@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200199 ER PT J AU Rasiej, M Uldrick, T Joffe, R Austin, J Taub, R Ichise, M AF Rasiej, M. Uldrick, T. Joffe, R. Austin, J. Taub, R. Ichise, M. TI Malignant Peritoneal Mesothelioma: Characterization by CT, PET and PET-CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Rasiej, M.; Joffe, R.; Austin, J.; Taub, R.; Ichise, M.] Columbia Univ, NewYork Presbyterian Hosp, New York, NY USA. [Uldrick, T.] NCI, Bethesda, MD 20892 USA. EM rasiej@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200726 ER PT J AU Yao, L Gai, N AF Yao, L. Gai, N. TI Phase Sensitive Fat-Water Separation for Musculoskeletal Imaging: Core Concepts and Methodologies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Roentgen-Ray-Society CY APR 27-MAY 01, 2009 CL Boston, MA SP Amer Roentgen Ray Soc C1 [Yao, L.; Gai, N.] NIH, Bethesda, MD 20892 USA. EM lyao@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2009 VL 192 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 436BI UT WOS:000265387200633 ER PT J AU Moore, CC Jacob, ST Pinkerton, R Banura, P Meya, DB Reynolds, SJ Kenya-Mugisha, N Mayanja-Kizza, H Scheld, WM AF Moore, Christopher C. Jacob, Shevin T. Pinkerton, Relana Banura, Patrick Meya, David B. Reynolds, Steven J. Kenya-Mugisha, Nathan Mayanja-Kizza, Harriet Scheld, W. Michael CA PRISM U Study Grp TI Treatment of Severe Sepsis with Artemether-Lumefantrine Is Associated with Decreased Mortality in Ugandan Patients without Malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; SULFADOXINE-PYRIMETHAMINE; RANDOMIZED-TRIAL; SEPTIC SHOCK; CHILDREN; BACTEREMIA; MICROSCOPY; THERAPIES; AFRICA; ADULTS AB We enrolled 382 patients at two hospitals in Uganda ill a prospective observational Study of severe sepsis. Because artemisinins improve Survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan-Meier Curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank chi(2) = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores <= 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank chi(2) 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility. C1 [Moore, Christopher C.; Pinkerton, Relana; Scheld, W. Michael] Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Jacob, Shevin T.] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. [Banura, Patrick] Masaka Reg Referral Hosp, Dept Internal Med, Masaka, Uganda. [Meya, David B.; Mayanja-Kizza, Harriet] Makerere Univ, Fac Med, Infect Dis Inst, Kampala, Uganda. [Reynolds, Steven J.] NIAID, NIH, Washington, DC 20521 USA. [Kenya-Mugisha, Nathan] Minist Hlth, Kampala, Uganda. NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Moore, CC (reprint author), Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, 409 Land Rd,MR-4 Bldg,Room 2112, Charlottesville, VA 22908 USA. EM ccm5u@virginia.edu; sjacob@post.harvard.edu; rcp3w@virginia.edu; banura2003@yahoo.com; david.meya@gmail.com; sjr@jhmi.edu; nkmugisha@yahoo.com; hmk@mucwru.or.ug; wms@virginia.edu FU Pfizer Initiative in International Health at the University of Virginia; University Of Virginia; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Christopher C. Moore and Shevin T.Jacob received fellowships from the Pfizer Initiative in International Health at the University of Virginia to support this work. This Initiative was conceived 10 fund exchange programs of post-doctoral fellows and students between the University Of Virginia and several international partners to conduct research oil global health issues. The major purpose of this program is to foster and enhance bidirectional research training. An independent board at the University of Virginia determines which research proposals are funded. Pfizer provided funds to promote the Initiative, but has no role in the planning or execution of research protocols including the study described in our Manuscript. This work was also supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 27 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2009 VL 80 IS 5 BP 723 EP 728 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443GS UT WOS:000265898800008 PM 19407113 ER PT J AU Juliano, JJ Bacon, DJ Mu, JB Wang, XH Meshnick, SR AF Juliano, Jonathan J. Bacon, David J. Mu, Jianbing Wang, Xinhua Meshnick, Steven R. TI Novel dhps and pfcrt Polymorphisms in Plasmodium falciparum Detected by Heteroduplex Tracking Assay SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INFECTIONS; RESISTANCE; MALARIA AB Several single nucleotide polymorphisms (SNPs) have been linked to antimalarial drug resistance in Plasmodium falciparum. However, standard polymerase chain reaction (PCR) methods to detect these polymorphisms are unable to detect SNPs in variants representing <20% of the parasites in a mixed infection, nor can they detect polymorphisms at nearby loci. Here we use heteroduplex tracking assays (HTAs) to analyze dhps540 mutations in 96 samples from Peru and pfcrt76 mutations in 70 samples from China. All samples had been previously analyzed by standard PCR. We detected drug-resistant minority variants and two novel non-synonymous pfcrt mutations in China. In Peru, we found no drug-resistant minority variants and a synonymous mutation in dhps. Thus, even in regions of low malaria transmission, HTA assays are more informative than PCR with agarose gel electrophoresis. C1 [Juliano, Jonathan J.] Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC 27599 USA. [Bacon, David J.] UN Environm & Preventat Med Unit 2, Norfolk, VA 23511 USA. [Mu, Jianbing] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Wang, Xinhua] Guangzhou Univ Tradit Chinese Med, Guangzhou 510006, Guangdong, Peoples R China. [Meshnick, Steven R.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. US Naval Med Res Ctr Detachment, Lima, Peru. NIH, Lab Malaria & Vector Res, Rockville, MD USA. Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Juliano, JJ (reprint author), Univ N Carolina, Sch Med, Div Infect Dis, CB 7300, Chapel Hill, NC 27599 USA. EM jjuliano@med.unc.edu; david.bacon@med.navy.mil; jmu@niaid.nih.gov; xinhuaw@gzhtcm.edu.cn; meshnick@email.unc.edu FU NIH [1R21AI07-6785]; National Center for Research Resources [KL2RR025746]; Department of Defense-Global Emerging Infectious System (DoD-GEIS) [847705.82000.25GB.B0016] FX This project was funded in part by NIH 1R21AI07-6785 and the 2007 IDSA ERF/NFID Merle A. Sande/Pfizer Fellowship in International Infectious Diseases, KL2RR025746 from the National Center for Research Resources, and funds provided by the Department of Defense-Global Emerging Infectious System (DoD-GEIS) under Unit 847705.82000.25GB.B0016. These agencies had no involvement in the design, collection, analysis, or interpretation of data in this study or in writing this paper or submitting it for publication. NR 8 TC 2 Z9 3 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2009 VL 80 IS 5 BP 734 EP 736 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443GS UT WOS:000265898800010 PM 19407115 ER PT J AU Sapsford, KE Francis, J Sun, S Kostov, Y Rasooly, A AF Sapsford, Kim E. Francis, Jesse Sun, Steven Kostov, Yordan Rasooly, Avraham TI Miniaturized 96-well ELISA chips for staphylococcal enterotoxin B detection using portable colorimetric detector SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Electroluminescent (EL) illumination; CCD; Miniature ELISA; Staphylococcal enterotoxin B (SEB); Food; Colorimetric measurement; Biosensor ID ATOPIC-DERMATITIS; RHEUMATOID-ARTHRITIS; FOOD; IMMUNOASSAY; SEB; SUPERANTIGENS; CHROMATOGRAPHY; CONFIRMATION; PREVALENCE; ANTIBODIES AB A previously developed fluorescence sensing platform, combining spatial illumination using electroluminescence (EL) semiconductor strips with charge coupled device (CCD)-based detection (EL-CCD), was adapted to a new 96-well chip for colorimetric immunological assays, enhancing the capabilities of the EL-CCD platform. The modified system was demonstrated using a colorimetric-based enzyme linked immunosorbent assay (ELISA) for detection of staphylococcal enterotoxin B (SEB). Limits of detection (LODs) of 3.9 ng/mL (+/- 2.4 ng/mL) SEB were determined with the ELISA chip measured using the EL-CCD platform, following a standard 4-h ELISA protocol. The LODs were comparable to those obtained using standard 96-well ELISA plates measured using a standard laboratory 96-well plate reader. The miniature 96-well ELISA chip however required as little as 5-mu L samples, representing a tenfold reduction in sample volume compared to a standard 96-well ELISA plates. The ELISA chip also demonstrated detection of SEB spiked into various food matrices (milk, mushrooms, and mayonnaise) using limited-to-no sample preparation, with LODs ranging from 3.9 to 18.5 ng/mL depending on the matrix. The EL-CCD platform is versatile, capable of multi-mode detection (e. g., fluorescent and colorimetric along with solution and solid phase assays), and could readily be applied to other field portable or point-of-care applications. C1 [Rasooly, Avraham] NCI, NIH, Bethesda, MD 20892 USA. [Sapsford, Kim E.; Francis, Jesse; Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, CDRH, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. [Francis, Jesse; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21227 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Executive Blvd EPN,Room 6035A, Bethesda, MD 20892 USA. EM rasoolya@mail.nih.gov FU Office of Public Health emergency Preparedness (OPHEP) [IAG224-05-655, HHSF223200610765P]; CDRH/OSEL/Division of Biology funds FX This work was supported in part by the Office of Public Health emergency Preparedness (OPHEP) IAG224-05-655 (to A. Rasooly and by FDA contract) and HHSF223200610765P (to Dr. Yordan Kostov) and CDRH/OSEL/Division of Biology funds. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services NR 35 TC 26 Z9 27 U1 0 U2 17 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2009 VL 394 IS 2 BP 499 EP 505 DI 10.1007/s00216-009-2730-z PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 436BU UT WOS:000265388400013 PM 19290511 ER PT J AU Concheiro-Guisan, M Shakleya, DM Huestis, MA AF Concheiro-Guisan, Marta Shakleya, Diaa M. Huestis, Marilyn A. TI Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in human placenta by liquid chromatography mass spectrometry SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Placenta; Buprenorphine; LCMS; Ion trap ID N-DEALKYLATED METABOLITE; HUMAN-PLASMA; GAS-CHROMATOGRAPHY; HUMAN-URINE; ENZYME-IMMUNOASSAY; PREGNANT-WOMEN; HAIR SAMPLES; VALIDATION; ASSAY; METHADONE AB A LCMS method was developed and validated for the determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in placenta. Quantification was achieved by selected ion monitoring of m/z 468.4 (BUP), 414.3 (NBUP), 644.4 (BUP-Gluc), and 590 (NBUP-Gluc). BUP and NBUP were identified monitoring MS(2) fragments m/z 396, 414 and 426 for BUP, and 340, 364 and 382 for NBUP, and glucuronide conjugates monitoring MS(3) fragments m/z 396 and 414 for BUP-Gluc, and 340 and 382 for NBUP-Gluc. Linearity was 1-50 ng/g. Intra-day, inter-day and total assay imprecision (% RSD) were <13.4%, and analytical recoveries were 96.2-113.1%. Extraction efficiencies ranged from 40.7-68%, process efficiencies 38.8-70.5%, and matrix effect 1.3-15.4%. Limits of detection were 0.8 ng/g for all compounds. An authentic placenta from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. BUP was not detected but metabolite concentrations were NBUP-Gluc 46.6, NBUP 15.7 and BUP-Gluc 3.2 ng/g. C1 [Concheiro-Guisan, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, Natl Inst Hlth, BRC, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Natl Inst Hlth, BRC, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institutes of Health; Intramural Research Program; National Institute on Drug Abuse; Ministerio de Educacion y Ciencia of Spain [EX-2007-1194] FX This research was supported by the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse, and funding for Marta Concheiro, Ph. D. from the Ministerio de Educacion y Ciencia of Spain (Grant number EX-2007-1194). The authors would like to thank Drs. Fred Askin, Gerrun March, and Leigh Ruane from Johns Hopkins Bayview Medical Center (Baltimore, MD) for their help in providing placenta samples. NR 47 TC 13 Z9 13 U1 2 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2009 VL 394 IS 2 BP 513 EP 522 DI 10.1007/s00216-009-2706-z PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 436BU UT WOS:000265388400015 PM 19247639 ER PT J AU Zhu, AP Romero, R Petty, HR AF Zhu, Aiping Romero, Roberto Petty, Howard R. TI An enzymatic fluorimetric assay for glucose-6-phosphate: Application in an in vitro Warburg-like effect SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Leukocyte; Metabolism; Glucose-6-phosphate; Sugar phosphate; L-Phenylalanine ID 2-DEOXYGLUCOSE 6-PHOSPHATE; ELECTROSPRAY-IONIZATION; ESCHERICHIA-COLI; CHROMATOGRAPHY; AMPLIFICATION; METABOLITES; VALIDATION; CELLS AB Recently, there has been a resurgence of interest in the regulatory role of cell metabolism in tumor biology and immunology. To assess changes in metabolite levels in cell Populations and tissues, especially from small clinical samples, highly sensitive assays are required. Based on the reaction of glucose-6-phosphate (G6P) and the diaphorase-resazurin amplifying system, we have developed a fluorescence methodology to measure G6P concentrations in cell extracts. In this approach, G6P is oxidized by G6P dehydrogenase in the presence of NADP(+), and the stoichiometrically generated NADPH is then amplified by the diaphorase cycling system to produce a highly fluorescent molecule-resorufin. The limit of detection (LOD) of the assay is 10 pmol. The assay has a Z' factor of 0.81. Its usefulness is demonstrated by experiments in which the pyruvate kinase inhibitor, phenylalanine, is added to cells. After 2 h of incubation at 37 degrees C, G6P levels rose by 20%, thereby illustrating an in vitro Warburg-like effect on cell metabolism. (C) 2009 Elsevier Inc. All rights reserved. C1 [Zhu, Aiping; Petty, Howard R.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. [Romero, Roberto] Hutzel Hosp, Detroit, MI 48201 USA. [Petty, Howard R.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA. RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM hpetty@umich.edu FU National Institute of Child Health and Human Development; National Institutes of Health, U.S. Department of Health and Human Services FX This work was supported, in part, by the Intramural Program of the National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services. NR 20 TC 28 Z9 28 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 1 PY 2009 VL 388 IS 1 BP 97 EP 101 DI 10.1016/j.ab.2009.02.009 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 433TR UT WOS:000265229200013 PM 19454216 ER PT J AU Tan, HY AF Tan, Hao Yang TI Cognitive Dysfunction in Schizophrenia: A Perspective from the Clinic to Genetic Brain Mechanisms SO ANNALS ACADEMY OF MEDICINE SINGAPORE LA English DT Review DE Cognitive neuroscience; COMT; GRM3; Magnetic resonance imaging ID CATECHOL-O-METHYLTRANSFERASE; CORTICAL PYRAMIDAL NEURONS; WORKING-MEMORY; METABOTROPIC GLUTAMATE-RECEPTOR-3; PREFRONTAL CORTEX; FUNCTIONAL POLYMORPHISM; NEUROPSYCHOLOGICAL DYSFUNCTION; INTERMEDIATE PHENOTYPES; ANTIPSYCHOTIC-DRUGS; DOPAMINE MODULATION AB Schizophrenia is a brain disease with differing symptomatic presentations, outcomes, and complex genetic mechanisms. A selection of recent work integrating clinical observations, human brain imaging and genetics will be reviewed. While the mechanics of brain dysfunction in schizophrenia remains to be well understood, the emerging evidence suggests that a number of interacting genetic mechanisms in dopaminergic and glutamatergic systems affect fundamental disease-related cognitive brain processes and may do so early in disease neurodevelopment. The availability of new imaging and genetic technologies, and institutional support for research in the translational neurosciences, extends the hope that increased understanding of these brain processes could yield meaningful clinical applications. C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Tan, HY (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM tanh@mail.nih.gov NR 72 TC 3 Z9 3 U1 2 U2 4 PU ACAD MEDICINE SINGAPORE PI REPUBLIC SINGAPORE PA 142 NEIL RD, REPUBLIC SINGAPORE 088871, SINGAPORE SN 0304-4602 J9 ANN ACAD MED SINGAP JI Ann. Acad. Med. Singap. PD MAY PY 2009 VL 38 IS 5 BP 420 EP 424 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 460PH UT WOS:000267199100008 PM 19521642 ER PT J AU Taber, DR Stevens, J Murray, DM Elder, JP Webber, LS Jobe, JB Lytle, LA AF Taber, Daniel R. Stevens, June Murray, David M. Elder, John P. Webber, Larry S. Jobe, Jared B. Lytle, Lelie A. TI The Effect of a Physical Activity Intervention on Bias in Self-Reported Activity SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Bias (epidemiology); Intervention Studies; Adolescent; Exercise; Questionnaires; Social Desirability ID ADOLESCENT GIRLS TAAG; SOCIAL DESIRABILITY; OBESITY PREVENTION; CHILDREN; ACCELEROMETER; VALIDATION; TRIAL; QUESTIONNAIRES; CALIBRATION; INTENSITIES AB PURPOSE: A positive outcome in self-reported behavior could be detected erroneously if an intervention caused over-reporting of the targeted behavior. Data collected from a multi-site randomized trial were examined to determine if adolescent girls who received a physical activity intervention over-reported their activity more than girls who received no intervention. METHODS: Activity was measured using accelerometers and self-reports (3-Day Physical Activity Recall, 3DPAR) in cross-sectional samples preintervention (6th grade, n = 1,464) and post-intervention (8th grade, n = 3,114). Log-transformed accelerometer minutes were regressed on 3DPAR blocks, treatment group, and their interaction, while adjusting for race, body mass index, and timing of data collection. RESULTS: Preintervention, the association between measures did not differ between groups, but postintervention 3DPAR blocks were associated with fewer log-accelerometer minutes of moderate-vigorous physical activity (MVPA) in intervention girls than in control girls (p = 0.002). The group difference was primarily in the upper 15% of the 3DPAR distribution, where control girls had > 1.7 more accelerometer minutes of MVPA than intervention girls who reported identical activity levels. Group differences in this subsample were 8.5%-16.2% of the mean activity levels; the intervention was powered to detect a difference of 10%. CONCLUSION: Self-report measures should be interpreted with caution when used to evaluate a physical activity intervention. Ann Epidemiol 2009;19:316-322. (C) 2009 Elsevier Inc. All rights reserved. C1 [Taber, Daniel R.; Stevens, June] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Stevens, June] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Murray, David M.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Elder, John P.] San Diego State Univ, Div Hlth Promot & Behav Sci, San Diego, CA 92182 USA. [Webber, Larry S.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA USA. [Jobe, Jared B.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Lytle, Lelie A.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Taber, DR (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM dtaber@email.unc.edu RI Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 FU NHLBI [HL66845, HL66852, HL66853, HL66855, HL66856, HL66857, HL66858] FX This study was supported by funds from the NHLBI grant numbers HL66845, HL66852, HL66853, HL66855, HL66856, HL66857, and HL66858. NR 25 TC 20 Z9 22 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2009 VL 19 IS 5 BP 316 EP 322 DI 10.1016/j.annepidem.2009.01.001 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 435IL UT WOS:000265337500005 PM 19230711 ER PT J AU Hou, LF Shu, XO Gao, YT Ji, BT Weiss, JM Yang, G Li, HL Blair, A Zheng, W Chow, WH AF Hou, Lifang Shu, Xiao-Ou Gao, Yu-Tang Ji, Bu-Tian Weiss, Jocelyn M. Yang, Gong Li, Hong-Lan Blair, Aaron Zheng, Wei Chow, Wong-Ho TI Anthropometric Measurements, Physical Activity, and the Risk of Symptomatic Gallstone Disease in Chinese Women SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Body Mass Index; Gallstone Disease Risk; Physical Activity; Waist-to-Hip Ratio ID SHANGHAI BREAST-CANCER; GALLBLADDER-DISEASE; COLON-CANCER; FOLLOW-UP; OBESITY; HEALTH; EPIDEMIOLOGY; POPULATION; EXERCISE; FAT AB PURPOSE: Gallstone disease is more common among overweight individuals, particularly in women. We conducted a cross-sectional case-control study of Chinese women nested in the Shanghai Women's Health Study (SWHS) to evaluate the association of gallstone disease with body mass index (BMI), waist to hip ratio (WHR), and physical activity (PA). METHODS: The study included 8,485 women with self-reported, physician-diagnosed, prevalent gallstone disease and 16,970 frequency-matched controls by birth year and age at gallstone diagnosis (4-year intervals). Information on height, weight history, waist and hip circumferences, physical activities, and other exposures was obtained by in-person interview. RESULTS: : Usual BMI (p trend < 0.001) and WHR (p trend < 0.001) were both related to a high prevalence of gallstone disease, and a significant interaction between BMI and WHR on gallstone risk was found (odds ratio [OR] = 3.82, 95%CI [95% confidence interval] 2.47-5.23 for those with both highest BMI and WHR relative to those with lowest BMI and WHR, p interaction = 0.03). Gallstone risk was positively associated with cumulative occupational sitting time (P trend = 0.01) and inversely associated with occupational cumulative energy expenditure (p trend = 0.03) as well as with household PA (P trend = 0.02). CONCLUSIONS: Our findings further support that overall and central excessive adiposity is an independent risk factor for gallstones in women. In addition, regardless of adiposity level, being physically active may ameliorate the risk of this disease. Ann Epidemiol 2009; 19:344-350. (C) 2009 Elsevier Inc. All rights reserved. C1 [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Hou, Lifang; Ji, Bu-Tian; Weiss, Jocelyn M.; Blair, Aaron; Chow, Wong-Ho] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Ctr Hlth Serv Res, Nashville, TN USA. [Gao, Yu-Tang; Yang, Gong; Li, Hong-Lan] Shanghai Canc Inst, Shanghai, Peoples R China. RP Hou, LF (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM l-hou@northwestem.edu FU National Institute of Health (NIH) [R01 CA70867]; Intramural Research Program, Division of Cancer Epidemiology and Genetics FX This research was supported by National Institute of Health (NIH) research grant R01 CA70867 and by the Intramural Research Program, Division of Cancer Epidemiology and Genetics. The authors express their appreciation to Shanghai residents who participated in the study and thank the research staff of the Shanghai Women's Health Study for their dedication and contributions to the study. NR 47 TC 13 Z9 17 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2009 VL 19 IS 5 BP 344 EP 350 DI 10.1016/j.annepidem.2008.12.002 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 435IL UT WOS:000265337500009 PM 19362277 ER PT J AU Croswell, JM Kramer, BS Kreimer, AR Prorok, PC Xu, JL Baker, SG Fagerstrom, R Riley, TL Clapp, JD Berg, CD Gohagan, JK Andriole, GL Chia, D Church, TR Crawford, ED Fouad, MN Gelmann, EP Lamerato, L Reding, DJ Schoen, RE AF Croswell, Jennifer Miller Kramer, Barnett S. Kreimer, Aimee R. Prorok, Phil C. Xu, Jian-Lun Baker, Stuart G. Fagerstrom, Richard Riley, Thomas L. Clapp, Jonathan D. Berg, Christine D. Gohagan, John K. Andriole, Gerald L. Chia, David Church, Timothy R. Crawford, E. David Fouad, Mona N. Gelmann, Edward P. Lamerato, Lois Reding, Douglas J. Schoen, Robert E. TI Cumulative Incidence of False-Positive Results in Repeated, Multimodal Cancer Screening SO ANNALS OF FAMILY MEDICINE LA English DT Article DE Mass screening; neoplasms; false Positive reactions; randomized controlled trial ID BASE-LINE FINDINGS; COLORECTAL-CANCER; FLEXIBLE SIGMOIDOSCOPY; RANDOMIZED-TRIAL; BREAST-CANCER; COLON-CANCER; PROSTATE; LUNG; RISK; PROGRAM AB PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. After 14 tests, the cumulative risk of having at least I false-positive screening test is 60.4% (95% Cl, 59.8%-61.0%) for men, and 48.8% (95% CI, 48.1%-49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (Cl, 27.8%-29.3%) for men and 22.1% (95% Cl, 21.4%-22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening. Ann Fam Med 2009;7:212-222. DOI: 10.1370/afm.942. C1 [Croswell, Jennifer Miller; Kramer, Barnett S.] NIH, Off Director, Off Dis Prevent, Bethesda, MD 20892 USA. [Kreimer, Aimee R.; Xu, Jian-Lun; Baker, Stuart G.; Fagerstrom, Richard; Berg, Christine D.; Gohagan, John K.] NIH, Natl Canc Inst, Canc Prevent Div, Bethesda, MD 20892 USA. [Riley, Thomas L.; Clapp, Jonathan D.] IMS Inc, Washington, DC USA. [Andriole, Gerald L.] Washington Univ, Sch Med, St Louis, MO USA. [Chia, David] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Fouad, Mona N.] Univ Alabama, Birmingham, AL USA. [Gelmann, Edward P.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Lamerato, Lois] Henry Ford Hlth Syst, Detroit, MI USA. [Reding, Douglas J.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Schoen, Robert E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Croswell, JM (reprint author), NIH, Off Director, Off Dis Prevent, 6100 Execut Blvd,Suite 2B-03, Bethesda, MD 20892 USA. EM croswelllj@od.nih.gov RI Kreimer, Aimee/H-1687-2015; OI Church, Timothy R./0000-0003-3292-5035 FU US National Cancer Institute FX Funding for the overall Prostate, Lung, Colorectal, and Ovarian (PLOC) Cancer Screening Trial was provided by the US National Cancer Institute. No additional funding was provided for the design and conduct Of this study. NR 38 TC 58 Z9 59 U1 1 U2 14 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAY-JUN PY 2009 VL 7 IS 3 BP 212 EP 222 DI 10.1370/afm.942 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 448QI UT WOS:000266276700005 PM 19433838 ER PT J AU Shi, M Umbach, DM Weinberg, CR AF Shi, Min Umbach, David M. Weinberg, Clarice R. TI Using Case-parent Triads to Estimate Relative Risks Associated with a Candidate Haplotype SO ANNALS OF HUMAN GENETICS LA English DT Article DE Log-linear model; candidate haplotype; phase ambiguity; expectation maximization algorithm; Hardy-Weinberg equilibrium; maternal genetic effects; Yin-Yang haplotypes ID CASE/PSEUDOCONTROL ANALYSIS; LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENERAL PEDIGREES; NUCLEAR FAMILIES; LIKELIHOOD; DISEASE; RECONSTRUCTION; FREQUENCY; GENOTYPE AB Estimating haplotype relative risks in a family-based study is complicated by phase ambiguity and the many parameters needed to quantify relative risks for all possible diplotypes. This problem becomes manageable if a particular haplotype has been implicated previously as relevant to risk. We fit log-linear models to estimate the risks associated with a candidate haplotype relative to the aggregate of other haplotypes. Our approach uses existing haplotype-reconstruction algorithms but requires assumptions about the distribution of haplotypes among triads in the source population. We consider three levels of stringency for those assumptions: Hardy-Weinberg Equilibrium (HWE), random mating, and no assumptions at all. We assessed our method's performance through simulations encompassing a range of risk haplotype frequencies, missing data patterns, and relative risks for either offspring or maternal genetic effects. The unconstrained model provides robustness to bias from population structure but requires excessively large sample sizes unless there are few haplotypes. Assuming HWE accommodates many more haplotypes but sacrifices robustness. The model assuming random mating is intermediate, both in the number of haplotypes it can handle and in robustness. To illustrate, we reanalyze data from a study of orofacial clefts to investigate a 9-SNP candidate haplotype of the IRF6 gene. C1 [Shi, Min; Umbach, David M.; Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, NIH, DHHS, Mail Drop A3-03 101-A315, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences [Z01-ES04007-12] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES04007-12). We thank Drs. Jeffrey Murray and Theresa Zucchero for sharing the genotype data of their orofacial cleft study and Drs. Rolv Terje Lie and Dmitri Zaykin for helpful comments on the manuscript. NR 20 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 2009 VL 73 BP 346 EP 359 DI 10.1111/j.1469-1809.2009.00515.x PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 440NI UT WOS:000265706600009 PM 19344450 ER PT J AU Luo, Y Kuo, CC Shen, H Chou, J Greig, NH Hoffer, BJ Wang, Y AF Luo, Yu Kuo, Chi-Chung Shen, Hui Chou, Jenny Greig, Nigel H. Hoffer, Barry J. Wang, Yun TI Delayed Treatment with a p53 Inhibitor Enhances Recovery in Stroke Brain SO ANNALS OF NEUROLOGY LA English DT Article ID NEURAL STEM-CELLS; CEREBRAL-ISCHEMIA; ADULT BRAIN; NEUROGENESIS; DEATH; RAT; EXPRESSION; APOPTOSIS; PROTECTS; NEURONS AB Objective: Cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ). Most of these new cells die shortly after injury. The purpose of this study was to examine a novel strategy for treatment of stroke at 1 week after injury by enhancing the survival of ischemia-induced endogenous NPCs in SVZ. Methods: Adult rats were subjected to a 90-minutes middle cerebral artery occlusion. A p53 inhibitor pifithrin-alpha (PFT-alpha) was administered to stroke rats from days 6 to 9 after middle cerebral artery occlusion. Locomotor behavior was measured using an activity chamber. Proliferation, survival, migration, and differentiation of endogenous NPCs were examined using quantitative reverse transcription polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and immunohistochemistry. Results: PFT-alpha enhanced functional recover), as assessed by a significant increase in multiple behavioral measurements. Delayed PFT-alpha treatment had no effect on the cell death processes in the lesioned cortical region. However, it enhanced the survival of SVZ progenitor cells, and promoted their proliferation and migration. PFT-a inhibited the expression of a p53-dependent proapoptotic gene, termed PUMA (p53-upregulated modulator of apoptosis), within the SVZ of stroke animals. The enhancement of survival/proliferation of NPCs was further found in SVZ neurospheres in tissue culture. PFT-alpha dose-dependently increased the number and size of new neurosphere formation. Interpretation: Delayed treatment with a p53 inhibitor PFT-alpha is able to modify stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. C1 [Wang, Yun] NIDA, IRP, Neural Protect & Regenerat Sect, Baltimore, MD 21224 USA. [Greig, Nigel H.] NIA, NIH, Res Program, Baltimore, MD 21224 USA. RP Wang, Y (reprint author), NIDA, IRP, Neural Protect & Regenerat Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov RI luo, Yu (Agnes)/E-4446-2010 FU Intramural Research Programs; National Institute on Drug Abuse; National Institute of Aging FX This study was supported by the Intramural Research Programs at the NIH (National Institute on Drug Abuse; National Institute of Aging). NR 34 TC 53 Z9 54 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2009 VL 65 IS 5 BP 520 EP 530 DI 10.1002/ana.21592 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 453LJ UT WOS:000266611700008 PM 19475672 ER PT J AU Gschwendtner, A Bevan, S Cole, JW Plourde, A Matarin, M Ross-Adams, H Meitinger, T Wichmann, E Mitchell, BD Furie, K Slowik, A Rich, SS Syme, PD MacLeod, MJ Meschia, JF Rosand, J Kittner, SJ Markus, HS Muller-Myhsok, B Dichgans, M AF Gschwendtner, Andreas Bevan, Steve Cole, John W. Plourde, Anna Matarin, Mar Ross-Adams, Helen Meitinger, Thomas Wichmann, Erich Mitchell, Braxton D. Furie, Karen Slowik, Agnieszka Rich, Stephen S. Syme, Paul D. MacLeod, Mary J. Meschia, James F. Rosand, Jonathan Kittner, Steve J. Markus, Hugh S. Mueller-Myhsok, Bertram Dichgans, Martin CA Int Stroke Genetics Consortium TI Sequence Variants on Chromosome 9p21.3 Confer Risk for Atherosclerotic Stroke SO ANNALS OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; TRANSIENT ISCHEMIC ATTACK; SMOOTH-MUSCLE-CELLS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; PLAQUE VULNERABILITY; MEDIA THICKNESS; METAANALYSIS; REPLICATION AB Objective: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infiarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. Methods: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were Subsequently genotyped in 2,528 additional cases and 2,189 additional control Subjects from Europe and North America. Results: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary, artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% For atherosclerotic stroke. Interpretation: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease. C1 [Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. [Bevan, Steve; Markus, Hugh S.] Univ London, Ctr Clin Neurosci, London, England. [Cole, John W.; Mitchell, Braxton D.; Kittner, Steve J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Cole, John W.; Mitchell, Braxton D.; Kittner, Steve J.] Vet Affairs Med Ctr, Baltimore, MD USA. [Plourde, Anna; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Plourde, Anna; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Matarin, Mar] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Ross-Adams, Helen; MacLeod, Mary J.] Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. [Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Munich, Germany. [Wichmann, Erich] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany. [Wichmann, Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Syme, Paul D.] Univ Edinburgh, Dept Clin & Surg Sci, Edinburgh, Midlothian, Scotland. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Dichgans, M (reprint author), Marchioninistr 15, D-81377 Munich, Germany. EM martin.dichgans@med.uni-muenchen.de RI Muller-Myhsok, Bertram/A-3289-2013; Meitinger, Thomas/O-1318-2015; Matarin, Mar/F-1771-2016; OI Matarin, Mar/0000-0002-4717-5735; Bevan, Steve/0000-0003-0490-6830; Mitchell, Braxton/0000-0003-4920-4744; Macleod, Mary Joan/0000-0003-2115-8184 FU Chief Scientist Office [CZG/4/1/26]; NIDDK NIH HHS [P30 DK072488, P30 DK079637]; NINDS NIH HHS [K23 NS 042720, K23 NS042720-01, K23 NS042720-02, K23 NS042720-03, K23 NS042720-04, K23 NS042720-05, P50 NS 051343, P50 NS051343-01A2, R01 NS 42733, R01 NS042733, R01 NS042733-01, R01 NS042733-02, R01 NS042733-03, R01 NS042733-04, R01 NS042733-05, R01 NS045012, R01 NS045012-05] NR 38 TC 127 Z9 129 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2009 VL 65 IS 5 BP 531 EP 539 DI 10.1002/ana.21590 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 453LJ UT WOS:000266611700009 PM 19475673 ER PT J AU Qiu, CX Cotch, MF Sigurdsson, S Klein, R Jonasson, F Klein, BEK Garcia, M Jonsson, PV Harris, TB Eiriksdottir, G Kjartansson, O van Buchem, MA Gudnason, V Launer, LJ AF Qiu, Chengxuan Cotch, Mary Frances Sigurdsson, Sigurdur Klein, Ronald Jonasson, Fridbert Klein, Barbara E. K. Garcia, Melissa Jonsson, Palmi V. Harris, Tamara B. Eiriksdottir, Gudny Kjartansson, Olafur van Buchem, Mark A. Gudnason, Vilmundur Launer, Lenore J. TI Microvascular Lesions in the Brain and Retina: The Age, Gene/Environment Susceptibility-Reykjavik Study SO ANNALS OF NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; CEREBRAL MRI FINDINGS; ATHEROSCLEROSIS RISK; CARDIOVASCULAR HEALTH; CEREBROVASCULAR-DISEASE; VESSEL DIAMETERS; ROTTERDAM SCAN; BLOOD-PRESSURE; OLDER PERSONS; ABNORMALITIES AB Objective: To investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly. Methods: The study included 4,176 men and women (mean age, 76 years) who participated in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. Digital retinal images of both dilated eyes were taken and evaluated for the presence of retinal focal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) and retinopathy lesions (retinal blot hemorrhages and microaneurysms). Brain magnetic resonance imaging scans were acquired and evaluated for the presence and distribution of cerebral infarcts and WMHs. Logistic and multinomial logistic models were constructed to estimate the association of retinal microvascular signs to brain lesions. Results: Controlling for demographic and major cardiovascular risk factors, We found that retinal focal arteriolar signs, but not retinopathy lesions, were significantly associated with an increasing load of subcortical and periventricular WMHs. The strongest association was found between retinal arteriolar signs and a heavier WMH load, specifically in the subcortical frontal lobe, and periventricular frontal and parietal caps. There was a tendency toward bilateral retinal focal arteriolar narrowing being more strongly associated with the heavier load of subcortical WMHs. Arteriovenous nicking was significantly associated with subcortical infarcts. Interpretation: In older adults, retinal focal arteriolar signs, but not retinopathy lesions, are correlated with the load of diffuse WMHs, particularly those located in the subcortical frontal lobe, and the periventricular frontal and parietal caps of the brain. C1 [Qiu, Chengxuan; Garcia, Melissa; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Qiu, Chengxuan] Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol, Sch Med & Publ Hlth Madison, Madison, WI USA. [Jonasson, Fridbert; Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Jonasson, Fridbert] Natl Univ Hosp Reykjavik, Dept Ophthalmol, Reykjavik, Iceland. [Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland. [Kjartansson, Olafur] Landspitali Univ Hosp, Dept Radiol, Reykjavik, Iceland. [van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary Frances/0000-0002-2046-4350; Qiu, Chengxuan/0000-0003-1922-4912; Klein, Ronald/0000-0002-4428-6237 FU NIH [N01-AG-1-2100]; National Institute on Aging; National Eye Institute [Z01-EY00401]; Icelandic Heart Association; Icelandic Parliament; Swedish Council for Working Life and Social Research FX This research was supported by the NIH (Intramural Research Program of the National Institute on Aging and the National Eye Institute, Z01-EY00401 NIH contract number N01-AG-1-2100), the Icelandic Heart Association, the Icelandic Parliament, and the Swedish Council for Working Life and Social Research (C.C.Q) NR 38 TC 21 Z9 21 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2009 VL 65 IS 5 BP 569 EP 576 DI 10.1002/ana.21614 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 453LJ UT WOS:000266611700013 PM 19475677 ER PT J AU Scholz, SW Houlden, H Schulte, C Sharma, M Li, A Berg, D Melchers, A Paudel, R Gibbs, JR Simon-Sanchez, J Paisan-Ruiz, C Bras, J Ding, JH Chen, H Traynor, BJ Arepalli, S Zonozi, RR Revesz, T Holton, J Wood, N Lees, A Oertel, W Wullner, U Goldwurm, S Pellecchia, MT Illig, T Riess, O Fernandez, HH Rodriguez, RL Okun, MS Poewe, W Wenning, GK Hardy, JA Singleton, AB Gasser, T AF Scholz, Sonja W. Houlden, Henry Schulte, Claudia Sharma, Manu Li, Abi Berg, Daniela Melchers, Anna Paudel, Reema Gibbs, J. Raphael Simon-Sanchez, Javier Paisan-Ruiz, Coro Bras, Jose Ding, Jinhui Chen, Honglei Traynor, Bryan J. Arepalli, Sampath Zonozi, Ryan R. Revesz, Tamas Holton, Janice Wood, Nick Lees, Andrew Oertel, Wolfgang Wuellner, Ullrich Goldwurm, Stefano Pellecchia, Maria Teresa Illig, Thomas Riess, Olaf Fernandez, Hubert H. Rodriguez, Ramon L. Okun, Michael S. Poewe, Werner Wenning, Gregor K. Hardy, John A. Singleton, Andrew B. Gasser, Thomas TI SNCA Variants Are Associated with Increased Risk for Multiple System Atrophy SO ANNALS OF NEUROLOGY LA English DT Article ID ALPHA-SYNUCLEIN GENE; PARKINSONS-DISEASE; TRIPLICATION; DIAGNOSIS C1 [Scholz, Sonja W.; Gibbs, J. Raphael; Simon-Sanchez, Javier; Bras, Jose; Ding, Jinhui; Traynor, Bryan J.; Arepalli, Sampath; Zonozi, Ryan R.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Scholz, Sonja W.; Houlden, Henry; Li, Abi; Melchers, Anna; Paudel, Reema; Gibbs, J. Raphael; Paisan-Ruiz, Coro; Revesz, Tamas; Holton, Janice; Wood, Nick; Lees, Andrew; Hardy, John A.] UCL, Dept Mol Neurosci, London, England. [Scholz, Sonja W.; Houlden, Henry; Li, Abi; Melchers, Anna; Paudel, Reema; Gibbs, J. Raphael; Paisan-Ruiz, Coro; Revesz, Tamas; Holton, Janice; Wood, Nick; Lees, Andrew; Hardy, John A.] UCL, Inst Neurol, Reta Lila Weston Labs, London, England. [Schulte, Claudia; Sharma, Manu; Berg, Daniela; Gasser, Thomas] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Oertel, Wolfgang] Univ Marburg, Ctr Nervous Dis, Marburg, Germany. [Wuellner, Ullrich] Univ Hosp, Bonn Med Ctr, Dept Neurol, Bonn, Germany. [Goldwurm, Stefano] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy. [Pellecchia, Maria Teresa] Univ Naples Federico 2, Dept Neurol Sci, Naples, Italy. [Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Munich, Germany. [Riess, Olaf] Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany. [Fernandez, Hubert H.; Rodriguez, Ramon L.; Okun, Michael S.] Univ Florida, Dept Neurol & Neurosurg, Gainesville, FL USA. [Poewe, Werner; Wenning, Gregor K.] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria. RP Scholz, SW (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1014, Bethesda, MD 20892 USA. EM scholzs@mail.nih.gov RI Paisan-Ruiz, Coro/C-2912-2009; Hardy, John/C-2451-2009; Bras, Jose/D-3366-2009; Bras, Jose/A-1428-2011; Houlden, Henry/C-1532-2008; Wood, Nicholas/C-2505-2009; Goldwurm, Stefano/Q-8978-2016; Revesz, Tamas/A-8732-2010; Gibbs, J. Raphael/A-3984-2010; Singleton, Andrew/C-3010-2009; Holton, Janice/F-6831-2011; Lees, Andrew/A-6605-2009; Traynor, Bryan/G-5690-2010 OI Okun, Michael/0000-0002-6247-9358; Schulte, Claudia/0000-0003-4006-1265; Chen, Honglei/0000-0003-3446-7779; Scholz, Sonja/0000-0002-6623-0429; Houlden, Henry/0000-0002-2866-7777; Wood, Nicholas/0000-0002-9500-3348; Goldwurm, Stefano/0000-0002-1651-567X; Revesz, Tamas/0000-0003-2501-0259; Bras, Jose/0000-0001-8186-0333; Holton, Janice/0000-0002-3882-5249; FU Intramural NIH HHS [Z01 AG000957-06]; Medical Research Council [G0701075, G108/638]; NIA NIH HHS [Z01 AG000957, Z01-AG 000957-06]; NIEHS NIH HHS [Z01 ES101986, Z01-ES 101986]; Parkinson's UK [G-0907]; Telethon [GTB07001] NR 21 TC 131 Z9 138 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2009 VL 65 IS 5 BP 610 EP 614 DI 10.1002/ana.21685 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 453LJ UT WOS:000266611700018 PM 19475667 ER PT J AU Chen, HX AF Chen, H. X. TI MONOCLONAL ANTIBODIES (MABS) TARGETING THE TYPE I INSULIN-LIKE GROWTH FACTOR RECEPTOR (IGF-1R) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Chen, H. X.] NCI, Invest Drug Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100006 ER PT J AU Giaccone, G AF Giaccone, G. TI BCL-2 INHIBITION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Giaccone, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 19 EP 20 PG 2 WC Oncology SC Oncology GA 451VD UT WOS:000266498100015 ER PT J AU Kummar, S AF Kummar, S. TI STATUS OF POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS IN CLINICAL DEVELOPMENT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Kummar, S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 21 EP 21 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100023 ER PT J AU Pommier, Y Dexheimer, TS Marchand, C AF Pommier, Y. Dexheimer, T. S. Marchand, C. TI THE DNA REPAIR ENZYME, TYROSYL-DNA PHOSPHODIESTERASE (TDP1) AS A TARGET FOR ANTICANCER THERAPY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Pommier, Y.; Dexheimer, T. S.; Marchand, C.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 21 EP 22 PG 2 WC Oncology SC Oncology GA 451VD UT WOS:000266498100024 ER PT J AU Choyke, P Kurdziel, KA AF Choyke, P. Kurdziel, K. A. TI MOLECULAR IMAGING OF CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Choyke, P.; Kurdziel, K. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100025 ER PT J AU Setser, A Lacutoure, ME Anadkat, MJK Cotliar, JC Chen, A AF Setser, A. Lacutoure, M. E. Anadkat, M. J. K. Cotliar, J. C. Chen, A. TI NCI COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS UPDATED TO ENCOMPASS SKIN TOXICITIES FROM TARGETED THERAPIES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Setser, A.; Chen, A.] NCI, Rockville, MD USA. [Lacutoure, M. E.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Anadkat, M. J. K.] Washington Univ, Sch Med, Ctr Adv Med, St Louis, MO 63130 USA. [Cotliar, J. C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100030 ER PT J AU Aryankalayil, M Palayoor, S Cerna, D Coleman, CN AF Aryankalayil, M. Palayoor, S. Cerna, D. Coleman, C. N. TI GENE EXPRESSION PROFILING OF PROSTATE CANCER CELLS AFTER SINGLE AND FRACTIONATED DOSES OF RADIATION FOR MOLECULAR TARGETED THERAPY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Aryankalayil, M.] NCI, Bethesda, MD 20892 USA. [Palayoor, S.; Cerna, D.; Coleman, C. N.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100033 ER PT J AU Ivy, SP Chen, H AF Ivy, S. P. Chen, H. TI MULTI-TARGETED TYROSINE KINASE INHIBITORS PLUS CHEMOTHERAPY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Ivy, S. P.; Chen, H.] NCI IDB, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 25 EP 25 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100037 ER PT J AU Kummar, S Ji, J Zhang, Y Simmons, D Kinders, R Gutierrez, ME Allen, D Homeffer, Y Juwara, L Rubinstein, L Parchment, RE Murgo, AJ Chen, A Tomaszewski, JE Doroshow, JH AF Kummar, S. Ji, J. Zhang, Y. Simmons, D. Kinders, R. Gutierrez, M. E. Allen, D. Homeffer, Y. Juwara, L. Rubinstein, L. Parchment, R. E. Murgo, A. J. Chen, A. Tomaszewski, J. E. Doroshow, J. H. TI A PHASE I COMBINATION STUDY OF ABT-888 AND TOPOTECAN HYDROCHLORIDE IN ADULTS WITH REFRACTORY SOLID TUMORS AND LYMPHOMAS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Kummar, S.; Gutierrez, M. E.; Allen, D.; Homeffer, Y.; Doroshow, J. H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Rubinstein, L.; Murgo, A. J.; Chen, A.; Tomaszewski, J. E.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Ji, J.; Zhang, Y.; Simmons, D.; Kinders, R.; Juwara, L.; Parchment, R. E.] NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 42 EP 42 PG 1 WC Oncology SC Oncology GA 451VD UT WOS:000266498100092 ER PT J AU Rajan, A Gutierrez, M Kummar, S Yancey, M Ji, J Zhang, Y Simmons, D Parchment, R Tomaszewski, J Doroshow, JH Giaccone, G AF Rajan, A. Gutierrez, M. Kummar, S. Yancey, M. Ji, J. Zhang, Y. Simmons, D. Parchment, R. Tomaszewski, J. Doroshow, J. H. Giaccone, G. TI A PHASE I COMBINATION STUDY OF AZD2281 AND CISPLATIN PLUS GEMCITABINE IN ADULTS WITH SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 7th International Symposium on Targeted Anticancer Therapies CY MAR 23-25, 2009 CL Amsterdam, NETHERLANDS C1 [Rajan, A.; Gutierrez, M.; Kummar, S.; Yancey, M.; Ji, J.; Zhang, Y.; Simmons, D.; Parchment, R.; Tomaszewski, J.; Doroshow, J. H.; Giaccone, G.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2009 VL 20 BP 42 EP 43 PG 2 WC Oncology SC Oncology GA 451VD UT WOS:000266498100093 ER PT J AU Desai, D Goldbach-Mansky, R Milner, JD Rabin, RL Hull, K Pucino, F Colburn, N AF Desai, Ditina Goldbach-Mansky, Raphaela Milner, Joshua D. Rabin, Ronald L. Hull, Keith Pucino, Frank Colburn, Nona TI Anaphylactic Reaction to Anakinra in a Rheumatoid Arthritis Patient Intolerant to Multiple Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE adverse drug reactions; anakinra; anaphylactic reaction; antirheumatic drugs; biological therapy; rheumatoid arthritis ID NECROSIS-FACTOR-ALPHA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTI-TNF TREATMENT; CUTANEOUS VASCULITIS; LEUKOCYTOCLASTIC VASCULITIS; ETANERCEPT THERAPY; CROHNS-DISEASE; INFLIXIMAB; PHARMACOGENETICS; ADALIMUMAB AB OBJECTIVE: To report a case of probable anaphylaxis due to anakinra in a patient with rheumatoid arthritis and multiple drug allergies. CASE SUMMARY: A 46-year-old Indian female with rheumatoid arthritis demonstrated distinct adverse reactions to all commercially available anti-tumor necrosis factor therapies, sulfasalazine, and hydroxychloroquine. Over a 4-year period her disease remained active during therapy with methotrexate and prednisone. Biologics were added sequentially, with development of intolerable reactions, first to infliximab (urticarial rash, infusion reactions) after 3 doses, and then to etanercept (autoantibodies, worsening Raynaud's phenomenon, digital microinfarcts) after 1 year. Following 2 months of daily injections of anakinra, she experienced an immediate immunoglobulin E-mediated anaphylactic reaction within 20 minutes of an injection, as evidenced by positive testing to both anakinra and histamine with the skin prick method. The patient subsequently started adalimumab therapy, which was discontinued after the fourth dose due to the development of generalized hives. DISCUSSION: The Naranjo probability scale demonstrated a probable relationship between anaphylaxis and anakinra in this patient. Although cases of anakinra-related hypersensitivity have been reported in patients in which therapy was interrupted and then reintroduced, to our knowledge, this is the first report of anaphylaxis with continuous therapy. CONCLUSIONS: This unusual case of a patient with multiple drug allergies presents a difficult clinical scenario, which was unsuccessfully managed with multiple biologic therapies on a trial-and-error basis. In the future, pharmacogenetics may help to better identify individuals at risk for multiple drug reactions and preclude unnecessary exposure to potentially harmful therapeutic options in similar patients. C1 [Goldbach-Mansky, Raphaela; Colburn, Nona] NIAMSD, Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Milner, Joshua D.] NIAID, Immunol Lab, NIH, Bethesda, MD USA. [Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Pucino, Frank] NIH, Dept Pharm, Bethesda, MD USA. [Desai, Ditina] Warehouse Camden Yards, Baltimore, MD USA. RP Colburn, N (reprint author), NIAMSD, Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. EM colburnn@mail.nih.gov FU Intramural NIH HHS [ZIA AR041138-07] NR 45 TC 15 Z9 15 U1 1 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 2009 VL 43 IS 5 BP 967 EP 972 DI 10.1345/aph.1L573 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 445WR UT WOS:000266082700021 PM 19417117 ER PT J AU Cressey, TR Van Dyke, R Jourdain, G Puthanakit, T Roongpisuthipong, A Achalapong, J Yuthavisuthi, P Prommas, S Chotivanich, N Maupin, R Smith, E Shapiro, DE Mirochnick, M AF Cressey, Tim R. Van Dyke, Russell Jourdain, Gonzague Puthanakit, Thanyawee Roongpisuthipong, Anuvat Achalapong, Jullapong Yuthavisuthi, Prapap Prommas, Sinart Chotivanich, Nantasak Maupin, Robert Smith, Elizabeth Shapiro, David E. Mirochnick, Mark CA IMPAACT P1032 Team TI Early Postpartum Pharmacokinetics of Lopinavir Initiated Intrapartum in Thai Women SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NEVIRAPINE; ADULTS; DRUGS AB Lopinavir (LPV) exposure is reduced during the third trimester of pregnancy. We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor. In 16 human immunodeficiency virus-infected Thai women, the median (range) LPV area under the concentration-time curve and maximum and minimum concentrations in plasma were 99.7 (66.1 to 180.5) mu g.h/ml, 11.2 (8.0 to 17.5) mu g/ml, and 4.6 (1.7 to 12.5) mu g/ml, respectively, at 41 (12 to 74) h after delivery. All of the women attained adequate LPV levels through 30 days postpartum. No serious adverse events were reported. C1 [Cressey, Tim R.] Chiang Mai Univ, IRD174, Program HIV Prevent & Treatment, IRD,PHPT,Fac Associated Med Sci, Chiang Mai 50205, Thailand. [Van Dyke, Russell] Tulane Univ, New Orleans, LA 70118 USA. [Cressey, Tim R.; Jourdain, Gonzague; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Puthanakit, Thanyawee] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50205, Thailand. [Roongpisuthipong, Anuvat] Siriraj Hosp, Bangkok, Thailand. [Achalapong, Jullapong] Chiang Rai Prachanukoh Hosp, Chiang Rai, Thailand. [Yuthavisuthi, Prapap] Prapokklao Hosp, Chanthaburi, Thailand. [Prommas, Sinart] Bhumibol Adulyadej Hosp, Bangkok, Thailand. [Chotivanich, Nantasak] Chonburi Hosp, Chon Buri, Thailand. [Maupin, Robert] Louisiana State Univ, New Orleans, LA USA. [Smith, Elizabeth] NIAID, Pediat Med Branch, Div Aids, Bethesda, MD 20892 USA. [Mirochnick, Mark] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Cressey, TR (reprint author), Chiang Mai Univ, IRD174, Program HIV Prevent & Treatment, IRD,PHPT,Fac Associated Med Sci, 29-7-8 Samlan Rd,Soi 1 Prasing, Chiang Mai 50205, Thailand. EM tim@phpt.org FU NIAID NIH HHS [U01AI069512, U01 AI068632, U01 AI069399, U01 AI069512, U01AI069399] NR 7 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY 1 PY 2009 VL 53 IS 5 BP 2189 EP 2191 DI 10.1128/AAC.01091-08 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 438AQ UT WOS:000265528700070 PM 19237646 ER PT J AU Carta, D McGuigan, C Margolis, L Balzarini, J AF Carta, Davide McGuigan, Christopher Margolis, Leonid Balzarini, Jan TI Synthesis and Evaluation of Novel Acyclovir Phosphoramidates as Anti-HIV Agents SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 22nd International Conference on Antiviral Research CY MAY 03-07, 2009 CL Miami Beach, FL C1 [Carta, Davide; McGuigan, Christopher] Cardiff Univ, Welsh Sch Pharm, Cardiff, S Glam, Wales. [Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RI McGuigan, Chris/P-1580-2014 OI McGuigan, Chris/0000-0001-8409-710X NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2009 VL 82 IS 2 MA 127 BP A56 EP A56 DI 10.1016/j.antiviral.2009.02.132 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 437RM UT WOS:000265504600111 ER PT J AU Derudas, M McGuigan, C Brancale, A Margolis, L Balzarini, J AF Derudas, Marco McGuigan, Christopher Brancale, Andrea Margolis, Leonid Balzarini, Jan TI The Application of Phosphoramidate Protide Technology to Acyclovir confers Novel Anti-HIV Inhibition SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 22nd International Conference on Antiviral Research CY MAY 03-07, 2009 CL Miami Beach, FL C1 [Derudas, Marco; McGuigan, Christopher; Brancale, Andrea] Cardiff Univ, Welsh Sch Pharm, Cardiff, S Glam, Wales. [Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. RI Brancale, Andrea/N-9445-2014; McGuigan, Chris/P-1580-2014 OI Brancale, Andrea/0000-0002-9728-3419; McGuigan, Chris/0000-0001-8409-710X NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2009 VL 82 IS 2 MA 129 BP A57 EP A57 DI 10.1016/j.antiviral.2009.02.134 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 437RM UT WOS:000265504600113 ER PT J AU Selvam, P Maddali, K Pommier, Y AF Selvam, Periyasamy Maddali, Kasthuraiah Pommier, Yves TI Indole Derivatives Are Potent Inhibitors of HIV Integrase SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 22nd International Conference on Antiviral Research CY MAY 03-07, 2009 CL Miami Beach, FL C1 [Selvam, Periyasamy] Amrita Sch Pharm, Dept Med Chem, Kochi 26, India. [Maddali, Kasthuraiah; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2009 VL 82 IS 2 MA 84 BP A42 EP A42 DI 10.1016/j.antiviral.2009.02.089 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 437RM UT WOS:000265504600069 ER PT J AU Vercruysse, T Pavlakis, G Daelemans, D AF Vercruysse, Thomas Pavlakis, George Daelemans, Dirk TI High-throughput In Vitro HIV Rev-multimerization Assay SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 22nd International Conference on Antiviral Research CY MAY 03-07, 2009 CL Miami Beach, FL C1 [Vercruysse, Thomas; Daelemans, Dirk] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. [Pavlakis, George] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2009 VL 82 IS 2 MA 96 BP A46 EP A46 DI 10.1016/j.antiviral.2009.02.101 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 437RM UT WOS:000265504600080 ER PT J AU Lamb, ME Orbach, Y Sternberg, KJ Aldridge, J Pearson, S Stewart, HL Esplin, PW Bowler, L AF Lamb, Michael E. Orbach, Yael Sternberg, Kathleen J. Aldridge, Jan Pearson, Sally Stewart, Heather L. Esplin, Phillip W. Bowler, Lynn TI Use of a Structured Investigative Protocol Enhances the Quality of Investigative Interviews With Alleged Victims of Child Sexual Abuse in Britain SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID ANATOMICALLY DETAILED DOLLS; FORENSIC INTERVIEWS; PEDIATRIC EXAMINATION; EYEWITNESS TESTIMONY; PRESCHOOL-CHILDREN; AGE-DIFFERENCES; QUESTION TYPE; RESPONSES; WITNESSES; CONTRADICTIONS AB One hundred alleged victims of child sexual abuse (aged 4-13: M = 9.3 years) were interviewed by police investigators about their alleged experiences. Half of the children were interviewed using the National Institute of Child Health and Human Development (NICHD) structured interview Protocol, whereas the other children, matched with respect to their age, relationship with the alleged perpetrator, and seriousness of the alleged offenses, were interviewed by investigators following the Memorandum of Good Practice. Protocol-guided interviews elicited more information using freer: call invitations and less information using directive, option-posing and suggestive questions than did standard Memorandum interviews. There were no age differences in the proportion of total information provided in response to open-ended invitations in either condition, but there was a significant increase with age in the proportion of central information provided in response to open-ended invitations. Published in 2008 by John Wiley & Sons, Ltd. C1 [Lamb, Michael E.] Univ Cambridge, Dept Social & Dev Psychol, Fac Polit Psychol & Sociol, Cambridge CB2 3RQ, England. [Orbach, Yael; Sternberg, Kathleen J.] NICHHD, Bethesda, MD 20892 USA. [Aldridge, Jan; Pearson, Sally] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. [Stewart, Heather L.] Childrens Justice Ctr, Salt Lake City, UT USA. [Bowler, Lynn] Derbyshire Constabulary, Ripley, Derby, England. RP Lamb, ME (reprint author), Univ Cambridge, Dept Social & Dev Psychol, Fac Polit Psychol & Sociol, Free Sch Lane, Cambridge CB2 3RQ, England. EM mel37@cam.ac.uk NR 71 TC 26 Z9 26 U1 7 U2 18 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD MAY PY 2009 VL 23 IS 4 BP 449 EP 467 DI 10.1002/acp.1489 PG 19 WC Psychology, Experimental SC Psychology GA 429SV UT WOS:000264941300001 ER PT J AU Goldman, AL Pezawas, L Doz, P Mattay, VS Fischl, B Verchinski, BA Chen, Q Weinberger, DR Meyer-Lindenberg, A AF Goldman, Aaron L. Pezawas, Lukas Doz, Priv Mattay, Venkata S. Fischl, Bruce Verchinski, Beth A. Chen, Qiang Weinberger, Daniel R. Meyer-Lindenberg, Andreas TI Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HUMAN CEREBRAL-CORTEX; MONOZYGOTIC TWINS DISCORDANT; GENETICALLY COMPLEX TRAITS; 1ST EPISODE SCHIZOPHRENIA; MAGNETIC-RESONANCE IMAGES; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; GRAY-MATTER; UNAFFECTED SIBLINGS; HIPPOCAMPAL VOLUME AB Context: Schizophrenia is a brain disorder with predominantly genetic risk factors, and previous research has identified heritable cortical and subcortical reductions in local brain volume. To our knowledge, cortical thickness, a measure of particular interest in schizophrenia, has not previously been evaluated in terms of its heritability in relationship to risk for schizophrenia. Objective: To quantify the distribution and heritability of cortical thickness changes in schizophrenia. Design: We analyzed a large sample of normal controls, affected patients, and unaffected siblings using a surface-based approach. Cortical thickness was compared between diagnosis groups on a surfacewide node-by-node basis. Heritability related to disease risk was assessed in regions derived from an automated cortical parcellation algorithm by calculating the Risch lambda. Setting: Research hospital. Participants: One hundred ninety-six normal controls, 115 affected patients with schizophrenia, and 192 unaffected siblings. Main Outcome Measure: Regional cortical thickness. Results: Node-by-node mapping statistics revealed widespread thickness reductions in the patient group, most pronouncedly in the frontal lobe and temporal cortex. Unaffected siblings did not significantly differ from normal controls at the chosen conservative threshold. Risch lambda analysis revealed widespread evidence for heritability for cortical thickness reductions throughout the brain. Conclusions: To our knowledge, the present study provides the first evidence of broadly distributed and heritable reductions of cortical thickness alterations in schizophrenia. However, since only trend-level reductions of thickness were observed in siblings, cortical thickness per se (at least as measured by this approach) is not a strong intermediate phenotype for schizophrenia. Arch Gen Psychiatry. 2009; 66(5):467-477 C1 [Goldman, Aaron L.; Pezawas, Lukas; Mattay, Venkata S.; Verchinski, Beth A.; Chen, Qiang; Weinberger, Daniel R.; Meyer-Lindenberg, Andreas] NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr, Charlestown, MA USA. [Fischl, Bruce] MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RP Weinberger, DR (reprint author), NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH, 10 Ctr Dr,Bldg 10,Room 4S237B, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Meyer-Lindenberg, Andreas/H-1076-2011; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Pezawas, Lukas/0000-0002-1329-6352 FU National Center for Research Resources [P41RR14075, R01 RR16594-01A1]; NCRR BIRN Morphometric [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550]; National Institute for Neurological Disorders [R01 NS052585-01]; Mental Illness and Neuroscience Discovery Institute; NIH through the NIH Roadmap for Medical Research [U54 EB005149] FX This work was supported by the National Institute of Mental Health Intramural Research Program and used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (NIH) (http://biowulf.nih.gov). Support for this research was also provided in part by National Center for Research Resources grants P41RR14075, R01 RR16594-01A1, and NCRR BIRN Morphometric Project BIRN002, U24 RR021382; National Institute for Biomedical Imaging and Bioengineering grant R01 EB001550, and National Institute for Neurological Disorders and Stroke grant R01 NS052585-01 as well as the Mental Illness and Neuroscience Discovery Institute and is part of the National Alliance for Medical Image Computing, funded by NIH through the NIH Roadmap for Medical Research, grant U54 EB005149. NR 67 TC 140 Z9 144 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2009 VL 66 IS 5 BP 467 EP + PG 14 WC Psychiatry SC Psychiatry GA 441RV UT WOS:000265789100002 PM 19414706 ER PT J AU Kaye, J DeKosky, ST Williamson, JD Fitzpatrick, AL Kronmal, RA Ives, DG Saxton, JA Lopez, OL Burke, G Carlson, MC Fried, LP Kuller, LH Robbins, JA Tracy, RP Woolard, NF Dunn, L Snitz, BE Nahin, RL Furberg, CD AF Kaye, Jeffrey DeKosky, Steven T. Williamson, Jeff D. Fitzpatrick, Annette L. Kronmal, Richard A. Ives, Diane G. Saxton, Judith A. Lopez, Oscar L. Burke, Gregory Carlson, Michelle C. Fried, Linda P. Kuller, Lewis H. Robbins, John A. Tracy, Russell P. Woolard, Nancy F. Dunn, Leslie Snitz, Beth E. Nahin, Richard L. Furberg, Curt D. CA Ginkgo Evaluation Memory GEM Study TI Ginkgo biloba for Prevention of Dementia: A Randomized Controlled Trial SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID MILD COGNITIVE IMPAIRMENT; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; EFFICACY AB Context: Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G biloba on dementia incidence are lacking. Objective: To determine effectiveness of G biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixtynine community volunteers aged 75 years or older with normal cognition (n = 2587) or MCI (n = 482) at study entry were assessed every 6 months for incident dementia. Intervention: Twice-daily dose of 120-mg extract of G biloba (n = 1545) or placebo (n = 1524). Main Outcome Measures: Incident dementia and AD determined by expert panel consensus. Results: Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94-1.33; P = .21) and for AD, 1.16 (95% CI, 0.97-1.39; P = .11). G biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85-1.50; P = .39). Conclusions: In this study, G biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. C1 [Kaye, Jeffrey] Oregon Hlth & Sci Univ, NIA, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97239 USA. RP Kaye, J (reprint author), Oregon Hlth & Sci Univ, NIA, Layton Aging & Alzheimers Dis Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM kaye@ohsu.edu FU NIA NIH HHS [AG08017, AG024059, AG024978, AG10483] NR 20 TC 2 Z9 2 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2009 VL 66 IS 5 BP 652 EP 654 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 444PU UT WOS:000265993700014 PM 19433666 ER PT J AU Klein, AP Suktitipat, B Duggal, P Lee, KE Klein, R Bailey-Wilson, JE Klein, BEK AF Klein, Alison P. Suktitipat, Bhoom Duggal, Priya Lee, Kristine E. Klein, Ronald Bailey-Wilson, Joan E. Klein, Barbara E. K. TI Heritability Analysis of Spherical Equivalent, Axial Length, Corneal Curvature, and Anterior Chamber Depth in the Beaver Dam Eye Study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID HIGH MYOPIA MAPS; TANJONG-PAGAR SURVEY; HIGH-GRADE MYOPIA; GENOME-WIDE SCAN; OCULAR REFRACTION; VISUAL-ACUITY; CLINICAL RESEARCH; POPULATION; LINKAGE; LOCUS AB Objective: To examine genetic influences for quantitative refraction. Spherical equivalent and its related binary traits of myopia and hyperopia are highly correlated within families. Many linkage regions have been reported for myopia, high myopia, and quantitative refraction. However, the measured phenotype of spherical equivalent is in large part dictated by the relationship between the underlying optical components of axial length, corneal curvature, and anterior chamber depth. Methods: Using data from the fourth visit of the Beaver Dam Eye Study, we conducted familial correlation and heritability analysis of quantitative spherical equivalent, axial length, anterior chamber depth, and corneal curvature using data from 7.15 individuals in 189 pedigrees. Results: Overall, every trait was highly heritable. Heritability estimates were 0.58 (SE 0.13) for spherical equivalent after adjustment for age, education, and nuclear sclerosis; 0.95 (SE 0.11) for corneal curvature after adjustment for height; 0.67 (SE 0.14) for axial length after adjustment for height and education; and 0.78 (SE 0.14) for anterior chamber depth after adjustment for age, education, height, and nuclear sclerosis. Conclusion: Refraction and the underlying traits of axial length, corneal curvature, and anterior chamber depth are highly heritable. Genetic analysis of these traits may provide greater insight into the development of refractive errors. C1 [Klein, Alison P.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. [Klein, Alison P.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Klein, Alison P.; Suktitipat, Bhoom] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Duggal, Priya; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Suktitipat, Bhoom] Mahidol Univ, Dept Biochem, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Lee, Kristine E.; Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Klein, AP (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1550 Orleans St, Baltimore, MD 21231 USA. EM aklein1@jhmi.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920; Suktitipat, Bhoom/0000-0001-8034-7757 FU National Eye Institute [EY017237, EY06594, EY015286]; Research to Prevent Blindness; National Human Genome Research Institute; National Center for Research Resources [RR03655] FX This work was supported by grants EY017237 (Dr A. P. Klein), EY06594 (Drs R. Klein and B. E. K. Klein), and EY015286 (Dr B. E. K. Klein) from the National Eye Institute; grants from Research to Prevent Blindness (Drs R. Klein and B. E. K. Klein); and by the Intramural Research Program of the National Human Genome Research Institute. Some of the results of this article were obtained by using the program package S.A.G.E., which is supported by US Public Health Service Resource Grant RR03655 from the National Center for Research Resources. NR 49 TC 42 Z9 43 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2009 VL 127 IS 5 BP 649 EP 655 PG 7 WC Ophthalmology SC Ophthalmology GA 442NK UT WOS:000265847700010 PM 19433716 ER PT J AU Cao, DJ Igboeli, B Yuan, LJ Kapikian, AZ Ayers, JL Abinanti, FR Hoshino, Y AF Cao, Dianjun Igboeli, Blessing Yuan, Lijuan Kapikian, Albert Z. Ayers, Jess L. Abinanti, Francis R. Hoshino, Yasutaka TI A longitudinal cohort study in calves evaluated for rotavirus infections from 1 to 12 months of age by sequential serological assays SO ARCHIVES OF VIROLOGY LA English DT Article ID GROUP-A ROTAVIRUS; NEONATAL CALF DIARRHEA; SERUM NEUTRALIZING ANTIBODY; FED COLOSTRUM SUPPLEMENTS; BOVINE ROTAVIRUS; GNOTOBIOTIC CALVES; MOLECULAR CHARACTERIZATION; P-TYPE; MONOCLONAL-ANTIBODIES; PORCINE ROTAVIRUS AB Using an immunocytochemical staining assay involving six different recombinant baculoviruses with each expressing one of the major bovine rotavirus VP7 (G6, G8 and G10) and VP4 (P6[1], P7[5] and P8[11]) serotypes, we analyzed IgG antibody responses to individual proteins in archival serum samples collected from 31 calves monthly from 1 to 12 months of age during 1974-1975 in Higley, Arizona. Seroresponses to VP7 and VP4, as determined by a fourfold or greater antibody response, were not always elicited concurrently following infection: in some calves, (1) seroresponses to VP7 were detected earlier than to VP4 or vice versa; and (2) a subsequent second seroresponse was detected for VP7 or VP4 only. In addition, a second infection was more likely to be caused by different G and/or P types. Analyses of serum samples showed that the most frequent G-P combination was G8P6[1], followed by G8P7[5], G8P8[11] and G6P6[1]. C1 [Cao, Dianjun; Igboeli, Blessing; Kapikian, Albert Z.; Hoshino, Yasutaka] NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Yuan, Lijuan] Virginia Maryland Reg Coll Vet Med, Virol & Immunol Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. [Ayers, Jess L.; Abinanti, Francis R.] Univ Arizona, Dept Vet Sci, Tucson, AZ 85721 USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov RI Yuan, Lijuan/A-2468-2008 OI Yuan, Lijuan/0000-0003-0709-5228 FU Intramural Research Program of the National Institute of Allergy and Infectious Disease, National Institutes of Health, USA FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Disease, National Institutes of Health, USA. There is no conflict of interest to declare. NR 76 TC 4 Z9 5 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD MAY PY 2009 VL 154 IS 5 BP 755 EP 763 DI 10.1007/s00705-009-0331-y PG 9 WC Virology SC Virology GA 443MW UT WOS:000265915300003 PM 19343476 ER PT J AU Liu, YP Gutterman, DD AF Liu, Yanping Gutterman, David D. TI Vascular control in humans: focus on the coronary microcirculation SO BASIC RESEARCH IN CARDIOLOGY LA English DT Review DE coronary circulation; myogenic response; flow-mediated dilation; EDHF; reactive oxygen species; diabetes; K(+) channels ID SENSITIVE POTASSIUM CHANNELS; EPOXYGENASE-DERIVED EICOSANOIDS; CA2+-ACTIVATED K+ CHANNELS; MESENTERIC SMALL ARTERIES; FLOW-INDUCED DILATION; SMOOTH-MUSCLE-CELLS; ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION; LEFT-VENTRICULAR HYPERTROPHY; INTERNAL MAMMARY ARTERY; CAMP-MEDIATED DILATION AB Myocardial perfusion is regulated by a variety of factors that influence arteriolar vasomotor tone. An understanding of the physiological and pathophysiological factors that modulate coronary blood flow provides the basis for the judicious use of medications for the treatment of patients with coronary artery disease. Vasomotor properties of the coronary circulation vary among species. This review highlights the results of recent studies that examine the mechanisms by which the human coronary microcirculation is regulated in normal and disease states, focusing on diabetes. Multiple pathways responsible for myogenic constriction and flow-mediated dilation in human coronary arterioles are addressed. The important role of endothelium-derived hyperpolarizing factors, their interactions in mediating dilation, as well as speculation regarding the clinical significance are emphasized. Unique properties of coronary arterioles in human vs. other species are discussed. C1 [Gutterman, David D.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Liu, Yanping] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Gutterman, David D.] Med Coll Wisconsin, Dept Med & Cardiovasc Ctr, Vet Adm Med Ctr, Milwaukee, WI 53226 USA. RP Gutterman, DD (reprint author), Med Coll Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM dgutt@mcw.edu FU NIH-NHLBI [R01HL067968, R01HL080704]; American Heart Association Fellowship; VA Merit Review Program FX This review was supported by funding from NIH-NHLBI (R01HL067968 and R01HL080704), an American Heart Association Fellowship, and the VA Merit Review Program. NR 156 TC 42 Z9 44 U1 1 U2 7 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAY PY 2009 VL 104 IS 3 BP 211 EP 227 DI 10.1007/s00395-009-0775-y PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 431UB UT WOS:000265088400001 PM 19190954 ER PT J AU Chan, SSL Copeland, WC AF Chan, Sherine S. L. Copeland, William C. TI DNA polymerase gamma and mitochondrial disease: Understanding the consequence of POLG mutations SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article; Proceedings Paper CT International Symposium on Mitchondrial Physiology and Pathology CY JUN, 2008 CL Bari, ITALY DE Mitochondria; Mitochondrial disease; DNA polymerase gamma; Mitochondrial DNA replication; Oxidative stress ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; ALPERS-SYNDROME; CAG REPEAT; SACCHAROMYCES-CEREVISIAE; MALE-INFERTILITY; ACCESSORY SUBUNIT; W748S MUTATION; GENE POLG; POLYMORPHISM; DEFECTS AB DNA polymerase gamma is the only known DNA polymerase in human mitochondria and is essential for mitochondrial DNA replication and repair. It is well established that defects in mtDNA replication lead to mitochondrial dysfunction and disease. Over 160 coding variations in the gene encoding the catalytic subunit of DNA polymerase gamma (POLG) have been identified. Our group and others have characterized a number of the more common and interesting mutations, as well as those disease mutations in the DNA polymerase gamma accessory subunit. We review the results of these studies, which provide clues to the mechanisms leading to the disease state. Published by Elsevier B.V. C1 [Chan, Sherine S. L.; Copeland, William C.] Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Chan, SSL (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM sherine.s.l.chan@gmail.com; copelan1@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065078-14, Z01 ES065080-13]; NIEHS NIH HHS [1K99-ES015555-01, K99 ES015555, K99 ES015555-01, R00 ES015555] NR 52 TC 76 Z9 76 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD MAY PY 2009 VL 1787 IS 5 BP 312 EP 319 DI 10.1016/j.bbabio.2008.10.007 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 451MX UT WOS:000266475400005 PM 19010300 ER PT J AU Fung, KL Gottesman, MM AF Fung, King Leung Gottesman, Michael M. TI A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE ABCB1; MDR1; Polymorphism; Haplotype; Ribosome stalling ID HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE GENE; HEALTHY JAPANESE SUBJECTS; VIRUS EXPRESSION SYSTEM; CF-1 MICE DEFICIENT; HAMSTER OVARY CELLS; DRUG-RESISTANCE; CATALYTIC CYCLE; ATPASE ACTIVITY; SUBSTRATE-SPECIFICITY AB The MDR1 (ABCB1) gene encodes a membrane-bound transporter that actively effluxes a wide range of compounds from cells. The overexpression of MDR1 by multidrug-resistant cancer cells is a serious impediment to chemotherapy. MDR1 is expressed in various tissues to protect them from the adverse effect of toxins. The pharmacokinetics of drugs that are also MDR1 substrates also influence disease outcome and treatment efficacy. Although MDR1 is a well-conserved gene, there. is increasing evidence that its polymorphisms affect substrate specificity. Three single nucleotide polymorphisms (SNPs) occur frequently and have strong linkage, creating a common haplotype at positions 1236C>T (G412G), 2677G>T (A893S) and 3435C>T (111451). The frequency of the synonymous 3435C>T polymorphism has been shown to vary significantly according to ethnicity. Existing literature suggests that the haplotype plays a role in response to drugs and disease susceptibility. This review summarizes recent findings on the 3435C>T polymorphism of MDR1 and the haplotype to which it belongs. A possible molecular mechanism of action by ribosome stalling that can change protein structure and function by altering protein folding is discussed. Published by Elsevier B.V. C1 [Fung, King Leung; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov FU Intramural Research Program of the National Institutes of Health; National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. We thank Mr. George Leiman for editorial assistance. NR 136 TC 155 Z9 167 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAY PY 2009 VL 1794 IS 5 BP 860 EP 871 DI 10.1016/j.bbapap.2009.02.014 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 444CD UT WOS:000265956800015 PM 19285158 ER PT J AU Nayak, TK Brechbiel, MW AF Nayak, Tapan K. Brechbiel, Martin W. TI Radioimmunoimaging with Longer-Lived Positron-Emitting Radionuclides: Potentials and Challenges SO BIOCONJUGATE CHEMISTRY LA English DT Review ID RADIOLABELING MONOCLONAL-ANTIBODIES; BIFUNCTIONAL CHELATING AGENT; RECEPTOR-POSITIVE TUMORS; EMISSION-TOMOGRAPHY PET; IN-VIVO BIODISTRIBUTION; XENOGRAFT-BEARING MICE; NON-HODGKINS-LYMPHOMA; HUMAN GROWTH HORMONE; ANTI-CEA ANTIBODIES; CARRIER-FREE GA-66 AB Radioimmunoimaging and therapy has been an area of interest for several decades. Steady progress has been made toward clinical translation of radiolabeled monoclonal antibodies for diagnosis and treatment of diseases. Tremendous advances have been made in imaging technologies such as positron emission tomography (PET). However, these advances have so far eluded routine translation into clinical radioimmunoimaging applications due to the mismatch between the short half-lives of routinely used positron-emitting radionuclides such as (18)F versus the pharmacokinetics of most intact monoclonal antibodies of interest. The lack of suitable positron-emitting radionuclides that match the pharmacokinetics of intact antibodies has generated interest in exploring the use of longer-lived positron emitters that are more suitable for radioimmunoimaging and dosimetry applications with intact monoclonal antibodies. In this review, we examine the opportunities and challenges of radioimmunoimaging with select longer-lived positron-emitting radionuclides such as (124)I, (89)Zr, and (86)Y with respect to radionuclide production, ease of radiolabeling intact antibodies, imaging characteristics, radiation dosimetry, and clinical translation potential. C1 [Nayak, Tapan K.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room IB40, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov OI Nayak, Tapan/0000-0002-3706-6092 FU NIH; NCI; Center for Cancer Research; United States Department of Health and Human Services FX This report was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research, and the United States Department of Health and Human Services. Gratitude is expressed to Mike Slackenerny for constant encouragement and support. NR 182 TC 89 Z9 90 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY PY 2009 VL 20 IS 5 BP 825 EP 841 DI 10.1021/bc800299f PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 448WK UT WOS:000266292500001 PM 19125647 ER PT J AU Guo, YJ Ribeiro, JMC Anderson, JM Bour, S AF Guo, Yongjian Ribeiro, Jose M. C. Anderson, Jennifer M. Bour, Stephan TI dCAS: a desktop application for cDNA sequence annotation SO BIOINFORMATICS LA English DT Article ID SIALOME; INSIGHT; TOOL AB Motivation: Understanding gene regulation and expression is the key to the advancement of biology. EST sequence assembly and analysis provide unique benefits in this regard. We have developed a standalone application, dCAS (Desktop cDNA Annotation System), which performs automated EST cleaning, clustering, assembly and annotation on a desktop computer. Compared with other available tools, dCAS provides a more convenient and user-friendly solution to biologists for extracting biological meaning from sequence data. C1 [Guo, Yongjian; Bour, Stephan] Off Cyber Infrastruct & Computat Biol, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. [Ribeiro, Jose M. C.; Anderson, Jennifer M.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Guo, YJ (reprint author), Off Cyber Infrastruct & Computat Biol, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 11 TC 35 Z9 36 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2009 VL 25 IS 9 BP 1195 EP 1196 DI 10.1093/bioinformatics/btp129 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 437YR UT WOS:000265523300018 PM 19318425 ER PT J AU Wahlberg, K Ghatan, PH Modell, S Nygren, A Ingvar, M Asberg, M Heilig, M AF Wahlberg, Kristina Ghatan, Per Hamid Modell, Sieglinde Nygren, Ake Ingvar, Martin Asberg, Marie Heilig, Markus TI Suppressed Neuroendocrine Stress Response in Depressed Women on Job-Stress-Related Long-Term Sick Leave: A Stable Marker Potentially Suggestive of Preexisting Vulnerability SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ACTH; burnout; cortisol; depression; Dex-CRH-test; stress; vulnerability ID PITUITARY-ADRENAL AXIS; HIGH FAMILIAL RISK; AFFECTIVE-DISORDERS; BODILY DISORDERS; MOOD DISORDERS; ACTH RESPONSE; CRH TEST; DEXAMETHASONE; PATHOPHYSIOLOGY; STIMULATION AB Background: We recently reported marked hyporeactivity of the hypothalamo-pituitary-adrenal (HPA) axis in depressed women on job-stress-related long-term sick leave (LTSL). This unexpected finding prompted the question of whether HPA axis hypofunction in this group results from stress exposure or reflects preexisting vulnerability. Here, as a first step toward addressing this question, we assessed temporal stability of HPA axis reactivity in these subjects. Method: We used the combined dexamethasone/corticotropin-releasing hormone (DEX-CRH) test to retest HPA axis reactivity in 29 patients and 27 control subjects after 12 months of follow-up. Clinical status and cognitive performance was also retested. Results: Despite marked clinical improvement and normalization of initially observed impairments in attention and working memory, marked HPA axis hyporeactivity persisted in patients. A high test-retest correlation was found both at the level of corticotropin (R = .85, p < .001) and cortisol (R = .76, p < .001) responses. Conclusions: Hyporeactivity of the HPA was stable over 12 months in LTSL subjects, independent of clinical improvement and normalized cognitive function. The stability of this response over time suggests that decreased DEX-CRH responses in this group may be a trait rather than a state marker. This finding is compatible with a hypothesis that HPA axis hyporeactivity may reflect a preexisting vulnerability in these subjects. C1 [Wahlberg, Kristina; Ghatan, Per Hamid; Ingvar, Martin; Heilig, Markus] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Nygren, Ake; Asberg, Marie] Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Modell, Sieglinde] Bristol Myers Squibb Co, Munich, Germany. [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482; Ingvar, Martin/0000-0002-9041-5714 FU Swedish insurance company AFA FX The authors report no biomedical financial interests or Potential conflicts of interest. NR 33 TC 41 Z9 41 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2009 VL 65 IS 9 BP 742 EP 747 DI 10.1016/j.biopsych.2008.10.035 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 433XP UT WOS:000265239400004 PM 19058782 ER PT J AU Akimov, SA Hlaponin, EA Bashkirov, PV Boldyrev, IA Mikhalyov, II Telford, WG Molotkovskaya, IM AF Akimov, S. A. Hlaponin, E. A. Bashkirov, P. V. Boldyrev, I. A. Mikhalyov, I. I. Telford, W. G. Molotkovskaya, I. M. TI GANGLIOSIDE GM1 INCREASES LINE TENSION AT RAFT BOUNDARY IN MODEL MEMBRANES SO BIOLOGICHESKIE MEMBRANY LA English DT Article DE raft; ganglioside; apoptosis; line tension ID LIPID RAFTS; FLUORESCENCE MICROSCOPY; DOMAINS; MONOLAYERS; CERAMIDE; SEPARATION; CURVATURE; APOPTOSIS; VESICLES; PROBES AB Gangliosides are significant participants in suppression of immune system during tumor processes. It was shown that they can induce apoptosis of T-lymphocytes in a raft-dependent manner. Fluorescence confocal microscopy was used to study distribution and influence of ganglioside GM1 on raft properties in giant unilamellar vesicles. Both raft and non-raft phase markers were utilized. No visible phase separation was observed without GM1 unless lateral tension was applied to the membrane. At 2 mol % of GM1 large domains appeared indicating macroscopic phase separation. Increase of GM1 content to 5 mol % resulted in shape transformation of the domains consistent with growth of line tension at the domain boundary. At 10 mol % of GM1 almost all domains were pinched out from vesicles, forming their own homogeneous liposomes. Estimations showed that the change of the GM1 content from 2 to 5-10 mol % resulted in a several-fold increase of line tension. This finding provides a possible mechanism of apoptosis induction by GM1. Incorporation of GM1 into a membrane leads to an increase of the line tension. This results in a growth of the average size of rafts due to coalescence or merger of small domains. Thus, necessary proteins can find themselves in one common raft and start the corresponding cascade of reactions. C1 [Akimov, S. A.; Hlaponin, E. A.; Bashkirov, P. V.] Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Moscow 119991, Russia. [Boldyrev, I. A.; Mikhalyov, I. I.; Molotkovskaya, I. M.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Telford, W. G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Akimov, SA (reprint author), Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Leninsky Pr 3115, Moscow 119991, Russia. EM megakrot@mail.ru RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 FU ISTC [2654]; BTEP; Russian Academy of Sciences; Russian Foundation [07-04-01145, 06-04-48666]; National Institutes of Health; USA Department of Health and Human Services [R01 GM066837]; National Cancer Institute intramural research funds; Leading Scientific Schools of Russian Federation Program [4181.2008.4, 5946.2008.4] FX We are grateful to Yu.A. Chizmadzhev, Jul.G. Molotkovsky, D.G. Knyazev, and O.V. Batishchev for careful reading the manuscript and fruitful discussions. The work was supported by ISTC (no. 2654)/BTEP/(no. 57) program, the Program for Molecular and Cellular Biology of Presidium of Russian Academy of Sciences, Russian Foundation for Basic Research (nos. 07-04-01145 and 06-04-48666), National Institutes of Health, USA Department of Health and Human Services (R01 GM066837 and National Cancer Institute intramural research funds), President of Russian Federation for State Support of Leading Scientific Schools of Russian Federation Program (nos. 4181.2008.4 and 5946.2008.4). NR 31 TC 3 Z9 3 U1 0 U2 3 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD MAY-JUN PY 2009 VL 26 IS 3 BP 234 EP 239 PG 8 WC Cell Biology SC Cell Biology GA 454QN UT WOS:000266697500009 ER PT J AU Rossi, M Bang, JK Mazur, S Iera, JA Phillips, DC Zambetti, GP Appella, DH AF Rossi, Matteo Bang, Jeong-Kyu Mazur, Sharlyn Iera, Jaclyn A. Phillips, Darren C. Zambetti, Gerard P. Appella, Daniel H. TI Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L) SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Cancer; Apoptosis; Bcl-xL ID BCL-2 FAMILY-MEMBERS; PRIMA-1 INDUCES APOPTOSIS; THYMIDINE KINASE LOCUS; MUTANT P53; CELL-DEATH; WILD-TYPE; CYTOFLUOROMETRIC ANALYSIS; PROTEIN-INTERACTION; X-L; CANCER AB Cancer cells evade death by over-producing specific proteins that inhibit apoptosis. One such group of proteins is the Bcl-2 family, of which Bcl-x(L) is an important member. This protein binds and inhibits BAK, another protein that promotes apoptosis. While the development of chemical inhibitors that block Bcl-x(L)-BAK association have been the focus of intense research efforts, we demonstrate in this manuscript an alternative strategy to downregulate Bcl-x(L). We have identified a small molecule (Bang52) that induces apoptosis in a lymphoblast-derived cell line by lowering levels of Bcl-x(L). Since Bang52 bears no resemblance to any chemical binder of Bcl-x(L) we believe that degradation of the protein is stimulated by a new type of pathway. These findings highlight a novel approach to the development of small molecules that promote apoptosis. (c) 2009 Elsevier Ltd. All rights reserved. C1 [Iera, Jaclyn A.; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Rossi, Matteo; Bang, Jeong-Kyu; Mazur, Sharlyn] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Phillips, Darren C.; Zambetti, Gerard P.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov FU NIH [CA6320]; NIH/NCI Cancer Center [CA21765] FX The authors gratefully acknowledge financial support from the Intramural Research Program of NIH, CA6320 and NIH/NCI Cancer Center Support Grant CA21765. We are also grateful for the support of the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital. We also want to thank Tom Chittenden (Apoptosis Technology, Inc., Boston, MA) for providing the HeLa-xL cells, and Dr. Ana Robles (NCI) for providing the WTK1, NH32, and TK6 cells. NR 47 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 1 PY 2009 VL 19 IS 9 BP 2429 EP 2434 DI 10.1016/j.bmcl.2009.03.067 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 432MA UT WOS:000265137100011 PM 19349174 ER PT J AU Yuan, PX Salvadore, G Li, XX Zhang, L Du, J Chen, G Manji, HK AF Yuan, Peixiong Salvadore, Giacomo Li, Xiaoxia Zhang, Lei Du, Jing Chen, Guang Manji, Husseini K. TI Valproate activates the Notch3/c-FLIP signaling cascade: a strategy to attenuate white matter hyperintensities in bipolar disorder in late life? SO BIPOLAR DISORDERS LA English DT Article DE apoptosis; bipolar disorder; FLIP; hyperintensity; Notch3; VPA; VSMC ID SMOOTH-MUSCLE-CELLS; AUTOSOMAL-DOMINANT ARTERIOPATHY; FLICE-INHIBITORY PROTEIN; HISTONE DEACETYLASE; SUBCORTICAL INFARCTS; DOWN-REGULATION; C-FLIP; CHROMATIN CONDENSATION; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS AB Increased prevalence of deep white matter hyperintensities (DWMHs) has been consistently observed in patients with geriatric depression and bipolar disorder. DMWHs are associated with chronicity, disability, and poor quality of life. They are thought to be ischemic in their etiology and may be related to the underlying pathophysiology of mood disorders in the elderly. Notably, these lesions strikingly resemble radiological findings related to the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephelopathy (CADASIL) syndrome. CADASIL arises from mutations in Notch3, resulting in impaired signaling via cellular Fas-associated death domain-like interleukin-1-beta-converting enzyme-inhibitory protein (c-FLIP) through an extracellular signal-regulated kinase (ERK)-dependent pathway. These signaling abnormalities have been postulated to underlie the progressive degeneration of vascular smooth muscle cells (VSMC). This study investigates the possibility that the anticonvulsant valproate (VPA), which robustly activates the ERK mitogen-activated protein kinase (MAPK) cascade, may exert cytoprotective effects on VSMC through the Notch3/c-FLIP pathway. Human VSMC were treated with therapeutic concentrations of VPA subchronically. c-FLIP was knocked down via small interfering ribonucleic acid transfection. Cell survival, apoptosis, and protein levels were measured. VPA increased c-FLIP levels dose- and time-dependently and promoted VSMC survival in response to Fas ligand-induced apoptosis in VSMC. The anti-apoptotic effect of VPA was abolished by c-FLIP knockdown. VPA also produced similar in vivo effects in rat brain. These results raise the intriguing possibility that VPA may be a novel therapeutic agent for the treatment of CADASIL and related disorders. They also suggest that VPA might decrease the liability of patients with late-life mood disorders to develop DWMHs. C1 [Yuan, Peixiong; Salvadore, Giacomo; Du, Jing; Chen, Guang; Manji, Husseini K.] NIMH, NIH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Li, Xiaoxia; Zhang, Lei] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Manji, HK (reprint author), NIMH, NIH, Mol Pathophysiol Lab, 35 Convent Dr,Room 1C-912, Bethesda, MD 20892 USA. EM manji@nih.gov RI Du, Jing/A-9023-2012; Chen, Guang/A-2570-2017 FU Intramural NIH HHS [, NIH0010733956]; PHS HHS [NIH0010733956] NR 59 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2009 VL 11 IS 3 BP 256 EP 269 DI 10.1111/j.1399-5618.2009.00675.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 433DR UT WOS:000265185000002 PM 19419383 ER PT J AU Romero, R AF Romero, R. TI The Role of Infection and Inflammation in Preterm Labor and Fetal Injury SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Romero, R.] NICHHD, Perinatol Res Branch, Intramural Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 381 EP 381 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900010 ER PT J AU Gohlke, JM Stockton, P Sieber, S Foley, J Portier, CJ AF Gohlke, J. M. Stockton, P. Sieber, S. Foley, J. Portier, C. J. TI AhR-Mediated Gene Expression in the Developing Mouse Telencephalon SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Gohlke, J. M.; Portier, C. J.] NIEHS, Environm Syst Biol Grp, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Stockton, P.; Foley, J.] NIEHS, Lab Environm Pathol, Res Triangle Pk, NC 27709 USA. [Sieber, S.] NIEHS, Microarray Grp, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 405 EP 405 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900054 ER PT J AU Oz, OK Ford, J Umetami, M Hajibeigi, A Rodriguez, K Korach, K AF Oz, O. K. Ford, J. Umetami, M. Hajibeigi, A. Rodriguez, K. Korach, K. TI Estradiol regulates renal klotho through estrogen receptor alpha SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the International-Bone-and-Mineral-Society/Australian-New-Zealand-Bone-and-M ineral-Society CY MAR 21-25, 2009 CL Sydney, AUSTRALIA SP Int Bone & Mineral Soc, Australian & New Zealand Bone & Mineral Soc C1 [Oz, O. K.; Ford, J.; Umetami, M.; Hajibeigi, A.] Univ Texas SW Med Ctr Dallas, Dallas, TX, Australia. [Rodriguez, K.; Korach, K.] NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2009 VL 44 MA 476 BP S171 EP S171 DI 10.1016/j.bone.2009.01.364 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436SP UT WOS:000265436200380 ER PT J AU Yang, Y Mak, KK Guo, X Day, TF AF Yang, Y. Mak, K. K. Guo, X. Day, T. F. TI Wnt and Hh signaling in skeletal development and homeostasis SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the International-Bone-and-Mineral-Society/Australian-New-Zealand-Bone-and-M ineral-Society CY MAR 21-25, 2009 CL Sydney, AUSTRALIA SP Int Bone & Mineral Soc, Australian & New Zealand Bone & Mineral Soc C1 [Yang, Y.; Mak, K. K.; Guo, X.; Day, T. F.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2009 VL 44 MA 066 BP S41 EP S41 DI 10.1016/j.bone.2009.01.104 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436SP UT WOS:000265436200062 ER PT J AU Barazany, D Basser, PJ Assaf, Y AF Barazany, Daniel Basser, Peter J. Assaf, Yaniv TI In vivo measurement of axon diameter distribution in the corpus callosum of rat brain SO BRAIN LA English DT Article DE MRI; brain; corpus callosum; axon diameter distribution; diffusion ID MYELINATED NERVE-FIBERS; DIFFUSION-TENSOR; WHITE-MATTER; RESTRICTED DIFFUSION; CONDUCTION-VELOCITY; MRI; DEMYELINATION; SPECTROSCOPY; MORPHOLOGY; HUMANS AB Here, we present the first in vivo non-invasive measurement of the axon diameter distribution in the rat corpus callosum. Previously, this measurement was only possible using invasive histological methods. The axon diameter, along with other physical properties, such as the intra-axonal resistance, membrane resistance and capacitance etc. helps determine many important functional properties of nerves, such as their conduction velocity. In this work, we provide a novel magnetic resonance imaging method called AxCaliber, which can resolve the distinct signatures of trapped water molecules diffusing within axons as well as water molecules diffusing freely within the extra-axonal space. Using a series of diffusion weighted magnetic resonance imaging brain scans, we can reliably infer both the distribution of axon diameters and the volume fraction of these axons within each white matter voxel. We were able to verify the known microstructural variation along the corpus callosum of the rat from the anterior (genu) to posterior (splenium) regions. AxCaliber yields a narrow distribution centered 1 m in the genu and splenium and much broader distributions centered 3 m in the body of the corpus callosum. The axon diameter distribution found by AxCaliber is generally broader than those usually obtained by histology. One factor contributing to this difference is the significant tissue shrinkage that results from histological preparation. To that end, AxCaliber might provide a better estimate of the in vivo morphology of white matter. Being a magnetic resonance imaging based methodology, AxCaliber has the potential to be used in human scanners for morphological studies of white matter in normal and abnormal development, and white matter related diseases. C1 [Barazany, Daniel; Assaf, Yaniv] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. [Basser, Peter J.] NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Assaf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel. EM asafyan@zahav.net.il RI Basser, Peter/H-5477-2011 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; The Israel Science Foundation [994/08] FX Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (to P.J.B.); National Institutes of Health (to P.J.B.). The Israel Science Foundation grant no. 994/08 (to Y.A.). NR 40 TC 167 Z9 168 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2009 VL 132 BP 1210 EP 1220 DI 10.1093/brain/awp042 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 444AB UT WOS:000265950900010 PM 19403788 ER PT J AU Krasnova, IN Cadet, JL AF Krasnova, Irina N. Cadet, Jean Lud TI Methamphetamine toxicity and messengers of death SO BRAIN RESEARCH REVIEWS LA English DT Review DE Methamphetamine; Neurotoxicity; Dopamine; Oxidative stress; Serotonin; Cell death ID INDUCED DOPAMINERGIC NEUROTOXICITY; BLOOD-BRAIN-BARRIER; VESICULAR MONOAMINE TRANSPORTER-2; INDUCED NEURONAL APOPTOSIS; DISMUTASE TRANSGENIC MICE; NITRIC-OXIDE SYNTHASE; TYROSINE-HYDROXYLASE ACTIVITY; MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; NERVE-TERMINAL DEGENERATION AB Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. in the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, and endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity, Published by Elsevier B.V C1 [Krasnova, Irina N.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH DHHS, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse; NIH; DHHS FX This paper is Supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH, DHHS. The authors recognize and thank wholeheartedly two reviewers for their helpful comments on an original version of this review. NR 354 TC 227 Z9 233 U1 8 U2 46 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAY PY 2009 VL 60 IS 2 BP 379 EP 407 DI 10.1016/j.brainresrev.2009.03.002 PG 29 WC Neurosciences SC Neurosciences & Neurology GA 453YV UT WOS:000266649700008 PM 19328213 ER PT J AU Rebbeck, TR Antoniou, AC Llopis, TC Nevanlinna, H Aittomaki, K Simard, J Spurdle, AB Couch, FJ Pereira, LHM Greene, MH Andrulis, IL Pasche, B Kaklamani, V Hamann, U Szabo, C Peock, S Cook, M Harrington, PA Donaldson, A Male, AM Gardiner, CA Gregory, H Side, LE Robinson, AC Emmerson, L Ellis, I Peyrat, JP Fournier, J Vennin, P Adenis, C Muller, D Fricker, JP Longy, M Sinilnikova, OM Stoppa-Lyonnet, D Schmutzler, RK Versmold, B Engel, C Meindl, A Kast, K Schaefer, D Froster, UG Chenevix-Trench, G Easton, DF AF Rebbeck, Timothy R. Antoniou, Antonis C. Caldes Llopis, Trinidad Nevanlinna, Heli Aittomaki, Kristiina Simard, Jacques Spurdle, Amanda B. Couch, Fergus J. Pereira, Lutecia H. Mateus Greene, Mark H. Andrulis, Irene L. Pasche, Boris Kaklamani, Virginia Hamann, Ute Szabo, Csilla Peock, Susan Cook, Margaret Harrington, Patricia A. Donaldson, Alan Male, Allison M. Gardiner, Carol Anne Gregory, Helen Side, Lucy E. Robinson, Anne C. Emmerson, Louise Ellis, Ian Peyrat, Jean-Philippe Fournier, Joelle Vennin, Philippe Adenis, Claude Muller, Daniele Fricker, Jean-Pierre Longy, Michel Sinilnikova, Olga M. Stoppa-Lyonnet, Dominique Schmutzler, Rita K. Versmold, Beatrix Engel, Christoph Meindl, Alfons Kast, Karin Schaefer, Dieter Froster, Ursula G. Chenevix-Trench, Georgia Easton, Douglas F. CA KConFab Ontario Canc Genetics Network Breast Canc Family Registry EMBRACE GEMO TI No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BRCA2; Risk modifiers; Hereditary cancer ID TRANSFORMING-GROWTH-FACTOR-BETA-1 GENE; POLYMORPHISMS; BETA; SUSCEPTIBILITY; CONSORTIUM; TGF-BETA-1; VARIANT AB Background The transforming growth factor beta-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-beta, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. C1 Univ Pennsylvania Sch Med, Dept Biostatist & Epidemiol, Ctr Clin Epidemiol & Biostatist, Philadelphia, PA 19104 USA. Hosp Clinico San Carlos HCSC, Med Oncol Branch, Martin 28040, TN, Spain. Helsinki Univ Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland. Helsinki Univ Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Epidemiol & Biostat, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Antoniou, Antonis C.; Peock, Susan; Cook, Margaret; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge, England. [Caldes Llopis, Trinidad] HCSC, Med Oncol Branch, Madrid 28040, Spain. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canc Genom Lab, Oncol & Mol Endocrinol Res Ctr, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [KConFab] Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Couch, Fergus J.; Szabo, Csilla] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Pereira, Lutecia H. Mateus] NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Canc Care Ontario, Toronto, ON, Canada. [Ontario Canc Genetics Network] Ontario Canc Genet Network, Toronto, ON, Canada. [Pasche, Boris; Kaklamani, Virginia] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Breast Canc Family Registry] Breast Canc Family Registry, Toronto, ON, Canada. [Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Donaldson, Alan] St Michaels Hosp, S Western Reg Genet Serv, Cambridge, England. [Male, Allison M.] Inst Child Hlth, Clin & Mol Genet Unit, London, England. [Male, Allison M.] Great Ormond St Hosp Sick Children, London, England. [Gardiner, Carol Anne] Nottingham Univ Hosp NHS Trust, Nottingham Ctr Med Genet, Nottingham, England. [Gregory, Helen] NHS Grampian, N Scotland Reg Genet Serv, Aberdeen, Scotland. [Gregory, Helen] Univ Aberdeen, Aberdeen, Scotland. [Side, Lucy E.] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Robinson, Anne C.] Southend Univ Hosp NHS Fdn Trust, S Essex Canc Res Network, Southend On Sea, England. [Emmerson, Louise] Glan Clwyd Gen Hosp, All Wales Med Genet Serv, Rhyl, England. [Ellis, Ian] Alder Hey Childrens Hosp, Dept Clin Genet, Liverpool L12 2AP, Merseyside, England. [Peyrat, Jean-Philippe; Fournier, Joelle; Vennin, Philippe; Adenis, Claude] Ctr Oscar Lambret, F-59020 Lille, France. [Muller, Daniele; Fricker, Jean-Pierre] Ctr Paul Strauss, Strasbourg, France. [Longy, Michel] Inst Bergonie, Bordeaux, France. [Sinilnikova, Olga M.; GEMO] Univ Lyon 1, Unite Mixte Genet Constitut Canc Frequents, Hosp Civils Lyon, Ctr Leon Berard,CNRS,UMR5201, F-69365 Lyon, France. [Sinilnikova, Olga M.] Univ Lyon 1, Genet Mol Lab, CNRS, UMR5201, F-69365 Lyon, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, U509, Serv Genet Oncol, Paris, France. [Schmutzler, Rita K.; Versmold, Beatrix] Univ Cologne, Div Mol Gynecooncol, Dept Obstet & Gynecol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ, Dept Obstet & Gynaecol, Munich, Germany. [Kast, Karin] Tech Univ, Dept Obstet & Gynaecol, Dresden, Germany. [Schaefer, Dieter] Univ Frankfurt, Inst Human Genet, Frankfurt, Germany. [Froster, Ursula G.] Univ Leipzig, Inst Human Genet, Leipzig, Germany. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Epidemiol & Biostat, Ctr Clin Epidemiol & Biostat, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebbeck@mail.med.upenn.edu RI Spurdle, Amanda/A-4978-2011; Andrulis, Irene/E-7267-2013; OI Spurdle, Amanda/0000-0003-1337-7897; Eeles, Rosalind/0000-0002-3698-6241; Nevanlinna, Heli/0000-0002-0916-2976; Burn, John/0000-0002-9823-2322; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research - UK; [R01-CA102776]; [R01-CA112520] FX ACA, HAP and the CIMBA data management are funded by Cancer Research - UK. Douglas F. Easton is a Principal Research Fellow of Cancer Research - UK. Timothy R. Rebbeck is supported by R01-CA102776. Boris Pasche is supported by R01-CA112520. NR 28 TC 11 Z9 11 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2009 VL 115 IS 1 BP 185 EP 192 DI 10.1007/s10549-008-0064-8 PG 8 WC Oncology SC Oncology GA 436UA UT WOS:000265440400021 PM 18523885 ER PT J AU Basu, MK Poliakov, E Rogozin, IB AF Basu, Malay Kumar Poliakov, Eugenia Rogozin, Igor B. TI Domain mobility in proteins: functional and evolutionary implications SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE mobile domain; promiscuous domain; domain network; domain architecture; domain evolution ID MULTIDOMAIN PROTEINS; GENOME EVOLUTION; NETWORKS; GENES; DATABASE; CLASSIFICATION; FAMILY; ORGANIZATION; SEQUENCES; BEHAVIOR AB A substantial fraction of eukaryotic proteins contains multiple domains, some of which show a tendency to occur in diverse domain architectures and can be considered mobile (or promiscuous). These promiscuous domains are typically involved in proteinprotein interactions and play crucial roles in interaction networks, particularly those contributing to signal transduction. They also play a major role in creating diversity of protein domain architecture in the proteome. It is now apparent that promiscuity is a volatile and relatively fast-changing feature in evolution, and that only a few domains retain their promiscuity status throughout evolution. Many such domains attained their promiscuity status independently in different lineages. Only recently, we have begun to understand the diversity of protein domain architectures and the role the promiscuous domains play in evolution of this diversity. However, many of the biological mechanisms of protein domain mobility remain shrouded in mystery. In this review, we discuss our present understanding of protein domain promiscuity, its evolution and its role in cellular function. C1 [Poliakov, Eugenia] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Basu, MK (reprint author), J Craig Venter Inst, 9704 Med Ctr Dr, Rockville, MD 20850 USA. EM malaykbasu@gmail.com FU National Institutes of Health/DHHS FX We thank Kasturi Mitra, Dr Susan Gentleman and Charlie Shenitz for carefully reading and proof-reading the manuscript. This work was supported in part by the Intramural Research Program of the National Institutes of Health/DHHS. NR 60 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAY PY 2009 VL 10 IS 3 BP 205 EP 216 DI 10.1093/bib/bbn057 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 437YG UT WOS:000265522200001 PM 19151098 ER PT J AU Tuncbag, N Kar, G Keskin, O Gursoy, A Nussinov, R AF Tuncbag, Nurcan Kar, Gozde Keskin, Ozlem Gursoy, Attila Nussinov, Ruth TI A survey of available tools and web servers for analysis of protein-protein interactions and interfaces SO BRIEFINGS IN BIOINFORMATICS LA English DT Review DE protein-protein interactions; protein-protein interfaces; binding site prediction; docking; web servers; databases ID MOLECULAR INTERACTION DATABASE; BINDING SITE PREDICTION; HOT-SPOTS; SHAPE COMPLEMENTARITY; RECOGNITION SITES; QUATERNARY STRUCTURE; DOMAIN INTERACTIONS; CRYSTAL CONTACTS; PDB STRUCTURES; 3D STRUCTURE AB The unanimous agreement that cellular processes are (largely) governed by interactions between proteins has led to enormous community efforts culminating in overwhelming information relating to these proteins; to the regulation of their interactions, to the way in which they interact and to the function which is determined by these interactions. These data have been organized in databases and servers. However, to make these really useful, it is essential not only to be aware of these, but in particular to have a working knowledge of which tools to use for a given problem; what are the tool advantages and drawbacks; and no less important how to combine these for a particular goal since usually it is not one tool, but some combination of tool-modules that is needed. This is the goal of this review. C1 [Nussinov, Ruth] NCI, Ctr Canc Res, Nanobiol Program, SAIC, Frederick, MD 21702 USA. [Tuncbag, Nurcan] Koc Univ, Computat Sci & Engn Program, Istanbul, Turkey. [Kar, Gozde] Koc Univ, Chem & Biol Engn Program, Istanbul, Turkey. [Keskin, Ozlem] Koc Univ, Chem & Biol Engn Dept, Istanbul, Turkey. [Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey. [Gursoy, Attila] Koc Univ, Dept Comp Engn, Istanbul, Turkey. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet, Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Ctr Canc Res, Nanobiol Program, SAIC, Bldg 469,Rm 151, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov RI Tuncbag, Nurcan/D-3383-2011; Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 FU Turkish Academy of Sciences Distinguished Young Investigator Award; Scientific and Technological Research Council of Turkey; National Cancer Institute; National Institutes of Health [N01-CO-12400]; Center for Cancer Research (partial) FX Turkish Academy of Sciences Distinguished Young Investigator Award (to O.K.); the Scientific and Technological Research Council of Turkey Fellowship (to N.T.). Federal funds from the National Cancer Institute; National Institutes of Health; (under contract number N01-CO-12400). Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research (partial). NR 158 TC 88 Z9 89 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAY PY 2009 VL 10 IS 3 BP 217 EP 232 DI 10.1093/bib/bbp001 PG 16 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 437YG UT WOS:000265522200002 PM 19240123 ER PT J AU Kato, GJ Wang, ZN Machado, RF Blackwelder, WC Taylor, JG Hazen, SL AF Kato, Gregory J. Wang, Zeneng Machado, Roberto F. Blackwelder, William C. Taylor, James G. Hazen, Stanley L. TI Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE sickle cell disease; asymmetric dimethylarginine; symmetric dimethylarginine; arginine; pulmonary hypertension ID STAGE RENAL-DISEASE; ASYMMETRIC DIMETHYLARGININE; RISK-FACTOR; ENDOTHELIAL DYSFUNCTION; ARTERIAL-HYPERTENSION; ARGININE METABOLISM; MORTALITY; HEMOGLOBIN; ADMA; BIOAVAILABILITY AB Pulmonary hypertension (PH) in patients with sickle cell disease (SCD) is linked to intravascular haemolysis, impaired nitric oxide bioavailability, renal dysfunction, and early mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases (NOS), is associated with vascular disease in other populations. We determined the plasma concentrations for several key arginine metabolites and their relationships to clinical variables in 177 patients with SCD and 29 control subjects: ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl L-arginine (L-NMMA), N-omega-hydroxy-L-arginine (NOHA), arginine and citrulline. The median ADMA was significantly higher in SCD than controls (0.94 mu mol/l vs. 0.31 mu mol/l, P < 0.001). Patients with homozygous SCD had a remarkably lower ratio of arginine to ADMA (50 mu mol/l vs. 237, P < 0.001). ADMA correlated with markers of haemolysis, low oxygen saturation and soluble adhesion molecules. PH was associated with high levels of ADMA and related metabolites. Higher ADMA level was associated with early mortality, remaining significant in a multivariate analysis. Subjects with homozygous SCD have high systemic levels of ADMA, associated with PH and early death, implicating ADMA as a functional NOS inhibitor in these patients. These defects and others converge on the nitric oxide pathway in homozygous SCD with vasculopathy. C1 [Kato, Gregory J.; Machado, Roberto F.; Taylor, James G.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Kato, Gregory J.; Machado, Roberto F.; Blackwelder, William C.] NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Wang, Zeneng; Hazen, Stanley L.] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44106 USA. [Wang, Zeneng; Hazen, Stanley L.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Wang, Zeneng; Hazen, Stanley L.] Cleveland Clin, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44106 USA. RP Kato, GJ (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10 CRC,Room 5-5140, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU National Institutes of Health [P01HL087018, P01 HL076491, P01 HL077107] FX The authors gratefully acknowledge intellectual support from Mark Gladwin, protocol management support by Mary K. Hall, and research nursing support from Wynona Coles, James Nichols, and Lori Hunter. This research was supported by intramural research funds from the National Institutes of Health (G.J.K., R.F.M., W.C.B. and J.G.T.) and by National Institutes of Health grants P01HL087018, P01 HL076491 and P01 HL077107 (S.L.H.). NR 43 TC 44 Z9 45 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2009 VL 145 IS 4 BP 506 EP 513 DI 10.1111/j.1365-2141.2009.07658.x PG 8 WC Hematology SC Hematology GA 437IP UT WOS:000265480900007 PM 19344390 ER PT J AU Patel, KV Longo, DL Ershler, WB Yu, BB Semba, RD Ferrucci, L Guralnik, JM AF Patel, Kushang V. Longo, Dan L. Ershler, William B. Yu, Binbing Semba, Richard D. Ferrucci, Luigi Guralnik, Jack M. TI Haemoglobin concentration and the risk of death in older adults: differences by race/ethnicity in the NHANES III follow-up SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE anaemia; haemoglobin concentration; race; ethnicity; ageing; National Health and Nutrition Examination Survey ID IRON-DEFICIENCY; PHYSICAL PERFORMANCE; SERUM CREATININE; NATIONAL-HEALTH; UNITED-STATES; ANEMIA; MORTALITY; NUTRITION; BLACKS; WHITES AB Mildly low haemoglobin concentration is associated with increased mortality in older adults. However, this relationship has not been well characterized in racial/ethnic minorities. Therefore, this study determined the haemoglobin threshold below which risk of death is significantly increased in older non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Data on 4089 participants of the 1988-94 US National Health and Nutrition Examination Survey who were >= 65 years of age were analyzed with mortality follow-up through December 31, 2000. Mean haemoglobin in non-Hispanic whites (n = 2686) and Mexican Americans (n = 663) was 140 g/l, while in non-Hispanic blacks (n = 740) the mean was 10 g/l lower. A total of 1944 (47.5%) participants died. Among non-Hispanic whites and Mexican Americans, age- and sex-adjusted models showed that the haemoglobin thresholds below which mortality risk was significantly increased were 4 and 2 g/l respectively, above the World Health Organization (WHO) cut-off points for anaemia. In contrast, the threshold for non-Hispanic blacks was 7 g/l below the WHO criteria. Similar threshold effects were observed when analyzing haemoglobin in categories and adjusting for multiple confounders. In conclusion, the haemoglobin threshold below which mortality rises significantly is a full g/dl lower in non-Hispanic blacks than in non-Hispanic whites and Mexican Americans. C1 [Patel, Kushang V.; Yu, Binbing; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Longo, Dan L.; Ershler, William B.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Patel, KV (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM patelku@mail.nih.gov FU US National Institute on Aging; National Institutes of Health FX This study was supported by the Intramural Research Program of the US National Institute on Aging, National Institutes of Health. NR 40 TC 28 Z9 29 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2009 VL 145 IS 4 BP 514 EP 523 DI 10.1111/j.1365-2141.2009.07659.x PG 10 WC Hematology SC Hematology GA 437IP UT WOS:000265480900008 PM 19344387 ER PT J AU Ferrada, C Moreno, E Casado, V Bongers, G Cortes, A Mallol, J Canela, EI Leurs, R Ferre, S Lluis, C Franco, R AF Ferrada, Carla Moreno, Estefania Casado, Vicent Bongers, Gerold Cortes, Antoni Mallol, Josefa Canela, Enric I. Leurs, Rob Ferre, Sergi Lluis, Carme Franco, Rafael TI Marked changes in signal transduction upon heteromerization of dopamine D-1 and histamine H-3 receptors SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE dopaminergic transmission; histaminergic transmission; receptor heteromers; signal transduction; dopamine D-1 receptor; histamine H-3 receptor; MAPK pathway; bioluminescent resonance energy transfer ID MC NEUROBLASTOMA-CELLS; PROTEIN-COUPLED RECEPTORS; RAT STRIATAL SLICES; ADENOSINE RECEPTOR; OPIOID RECEPTORS; DRUG DISCOVERY; ACTIVATION; BRAIN; D1; HETERODIMERIZATION AB Functional interactions between the G protein-coupled dopamine D-1 and histamine H-3 receptors have been described in the brain. In the present study we investigated the existence of D-1-H-3 receptor heteromers and their biochemical characteristics. D-1-H-3 receptor heteromerization was studied in mammalian transfected cells with Bioluminescence Resonance Energy Transfer and binding assays. Furthermore, signalling through mitogen-activated protein kinase (MAPK) and adenylyl cyclase pathways was studied in co-transfected cells and compared with cells transfected with either D-1 or H-3 receptors. Bioluminescence Resonance Energy Transfer and binding assays confirmed that D-1 and H-3 receptors can heteromerize. Activation of histamine H-3 receptors did not lead to signalling towards the MAPK pathway unless dopamine D-1 receptors were co-expressed. Also, dopamine D-1 receptors, usually coupled to G(s) proteins and leading to increases in cAMP, did not couple to G(s) but to G(i) in co-transfected cells. Furthermore, signalling via each receptor was blocked not only by a selective antagonist but also by an antagonist of the partner receptor. D-1-H-3 receptor heteromers constitute unique devices that can direct dopaminergic and histaminergic signalling towards the MAPK pathway in a G(s)-independent and G(i)-dependent manner. An antagonist of one of the receptor units in the D-1-H-3 receptor heteromer can induce conformational changes in the other receptor unit and block specific signals originating in the heteromer. This gives rise to unsuspected therapeutic potentials for G protein-coupled receptor antagonists. C1 [Ferrada, Carla; Moreno, Estefania; Casado, Vicent; Cortes, Antoni; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Mol Neurobiol Unit, Dept Biochem & Mol Biol, Sch Biol,IDIBAPS,CIBERNED, Barcelona, Spain. [Bongers, Gerold; Leurs, Rob] Vrije Univ Amsterdam, VU Drug Discovery Ctr, Div Med Chem, Leiden Amsterdam Ctr Drug Res,Fac Sci, Amsterdam, Netherlands. [Franco, Rafael] Univ Navarra, Ctr Invest Med Aplicada, Pamplona 31008, Spain. [Ferre, Sergi] NIDA, IRP, NIH, DHHS, Baltimore, MD USA. RP Franco, R (reprint author), Univ Navarra, Ctr Invest Med Aplicada, Ave Pio 12 55, Pamplona 31008, Spain. EM rfranco@unav.es RI Bongers, Gerold/B-6503-2013; Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014 OI Bongers, Gerold/0000-0002-3187-120X; Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Moreno, Estefania/0000-0002-2491-5753; Casado, Vicent/0000-0002-1764-3825; Franco, Rafael/0000-0003-2549-4919; FU Spanish Ministerio de Ciencia y Tecnologia [SAF2005-00170, SAF2006-05481]; Fundacio La Marato de TV3 [060110]; National Institute on Drug Abuse FX This work was supported by Grants from Spanish Ministerio de Ciencia y Tecnologia (SAF2005-00170 to E.I.C. SAF2006-05481 to R.F), Grant 060110 from Fundacio La Marato de TV3 (RF) and by the intramural funds of the National Institute on Drug Abuse (SF). We acknowledge Dr Timothy A Esbenshade (Abbott Laboratories) for the kind gift of [3H]-A-349821. Sergi FerrE is employed by NIDA-NIH. No claim to US government work. NR 60 TC 60 Z9 61 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 2009 VL 157 IS 1 BP 64 EP 75 DI 10.1111/j.1476-5381.2009.00152.x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 430ZV UT WOS:000265032000008 PM 19413572 ER PT J AU De Angelis, R Tavilla, A Verdecchia, A Scoppa, S Hachey, M Feuer, EJ Mariotto, AB AF De Angelis, Roberta Tavilla, Andrea Verdecchia, Arduino Scoppa, Steve Hachey, Mark Feuer, Eric J. Mariotto, Angela B. TI Breast Cancer Survivors in the United States Geographic Variability and Time Trends, 2005-2015 SO CANCER LA English DT Article DE breast neoplasms; prevalence; registries; forecasting; regional health planning ID CHRONIC DISEASE MORBIDITY; REGISTRY DATA; PREVALENCE; MORTALITY AB BACKGROUND: Breast cancer continues to place a significant burden on the healthcare system. Regional prevalence measures are instrumental in the development of cancer control policies. Very few population-based cancer registries are able to provided local, long-term incidence and follow-up information that permits the direct calculation of prevalence. Model-based prevalence estimates are an alternative when this information is lacking or incomplete. The current work represents a comprehensive collection of female breast cancer prevalence from 2005 to 2015 in the United States and the District of Columbia (DC). METHODS: Breast cancer prevalence estimates were derived from state-specific cancer mortality and survival data using a statistical package called the Mortality-incidence Analysis Model or MIAMOD. Cancer survival models were derived from the Surveillance, Epidemiology, and End Results Program data and were adjusted to represent state-specific survival. Comparisons with reported incidence for 39 states and DC had validated estimates. RESULTS: By the year 2010, 2.9 million breast cancer survivors are predicted in the US, equaling 1.85% of the female population. Large variability in prevalent percentages was reported between states, ranging from 1.4% to 2.4% in 2010. Geographic variability was reduced when calculating age-standardized prevalence proportions or cancer survivors by disease duration, including 0 to 2 years and 2 to 5 years. The residual variability in age-adjusted prevalence was explained primarily by the state-specific, age-adjusted breast cancer incidence rates. State-specific breast cancer survivors are expected to increase from 16% to 51% in the decennium from 2005 to 2015 and by 31% at the national level. CONCLUSIONS: To the authors' knowledge, the current study is the first to provide systematic estimations of breast cancer prevalence in all US states through 2015. The estimated levels and time trends were consistent with the available population-based data on breast cancer incidence, prevalence, and population aging. Cancer 2009;115:1954-66. (C) 2009 American Cancer Society. C1 [De Angelis, Roberta; Tavilla, Andrea; Verdecchia, Arduino] Italian Natl Inst Hlth, Natl Ctr Epidemiol, Rome, Italy. [Scoppa, Steve; Hachey, Mark] Informat Management Serv Inc, Silver Spring, MD USA. [Feuer, Eric J.; Mariotto, Angela B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP De Angelis, R (reprint author), Ist Super Sanita, Ctr Nazl Epidemiol, Viale Regina Elena 299, I-00161 Rome, Italy. EM roberta.deangelis@iss.it FU National Institutes of Health [263-MQ-514300, 263-MQ-320101] FX Supported by grants 263-MQ-514300 (to A.T.) and 263-MQ-320101 (to A.T.) from the National Institutes of Health. NR 22 TC 31 Z9 33 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2009 VL 115 IS 9 BP 1954 EP 1966 DI 10.1002/cncr.24217 PG 13 WC Oncology SC Oncology GA 435OZ UT WOS:000265354500020 PM 19248047 ER PT J AU Newcomb, PA Chia, VM Hampton, JM Doria-Rose, VP Dietz, AT AF Newcomb, Polly A. Chia, Victoria M. Hampton, John M. Doria-Rose, V. Paul Dietz, Amy Trentham TI Hormone therapy in relation to survival from large bowel cancer SO CANCER CAUSES & CONTROL LA English DT Article DE Hormone therapy; Colorectal cancer; Mortality ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; COLORECTAL-CANCER; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; COLON-CANCER; BODY-MASS; RISK; DIAGNOSIS; MORTALITY AB Epidemiologic studies of hormone therapy (HT) and colorectal cancer incidence consistently show an inverse association; however, few studies have considered prediagnostic use of HT on mortality among colorectal cancer patients. We evaluated the relationship of HT and survival among a population-based cohort of women with large bowel cancer. Cases (n = 1,297) were newly diagnosed with invasive cancer of the colon or rectum, aged 40-74 years at diagnosis, who were identified by Wisconsin's statewide registry (1988-1991; 1997-2001) for two case-control studies. Information on HT use and other colorectal cancer risk factors was collected by standardized interview. There were 507 deaths (274 of these attributable to colorectal cancer) over 8.4 years of follow-up through December 2005. Hormone use was not associated with colorectal cancer mortality (adjusted hazard rate ratio = 1.09, confidence interval = 0.81-1.47). Colorectal cancer specific mortality was not associated with HT when considered separately by preparation type. Stage did not modify this relationship. Long-term HT was weakly positively associated with increased mortality after diagnosis of proximal colon, but not distal colon cancer. Because we detected no differences in survival among users of HT compared to non-users, the results suggest that HT use may affect only the incidence of some colorectal tumors. C1 [Newcomb, Polly A.; Chia, Victoria M.; Doria-Rose, V. Paul] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Newcomb, Polly A.; Hampton, John M.; Dietz, Amy Trentham] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. [Doria-Rose, V. Paul] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Newcomb, PA (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,Mailstop M4-B402, Seattle, WA 98109 USA. EM pnewcomb@fhcrc.org OI Doria-Rose, Vincent/0000-0002-8802-5143 FU Alcoholic Beverage Medical Research Foundation and National Institute of Health [CA47147] FX Financial support: This work was supported in part by the Alcoholic Beverage Medical Research Foundation and National Institute of Health grant CA47147. NR 28 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2009 VL 20 IS 4 BP 409 EP 416 DI 10.1007/s10552-008-9255-1 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 430VV UT WOS:000265018900001 PM 18998219 ER PT J AU Clegg, LX Reichman, ME Miller, BA Hankey, BF Singh, GK Lin, YD Goodman, MT Lynch, CF Schwartz, SM Chen, VW Bernstein, L Gomez, SL Graff, JJ Lin, CC Johnson, NJ Edwards, BK AF Clegg, Limin X. Reichman, Marsha E. Miller, Barry A. Hankey, Benjamin F. Singh, Gopal K. Lin, Yi Dan Goodman, Marc T. Lynch, Charles F. Schwartz, Stephen M. Chen, Vivien W. Bernstein, Leslie Gomez, Scarlett L. Graff, John J. Lin, Charles C. Johnson, Norman J. Edwards, Brenda K. TI Impact of socioeconomic status on cancer incidence and stage at diagnosis: selected findings from the surveillance, epidemiology, and end results: National Longitudinal Mortality Study SO CANCER CAUSES & CONTROL LA English DT Article DE SEER; NLMS; Cancer incidence; Stage; Education; Income; Poverty; Unemployment; SES; Race/ethnicity; Rural/urban; Health disparities; Record linkage ID BREAST-CANCER; UNITED-STATES; CERVICAL-CANCER; SOCIAL-CLASS; RACIAL-DIFFERENCES; COLORECTAL-CANCER; PROSTATE-CANCER; RESULTS PROGRAM; DEATH INDEX; US WOMEN AB Population-based cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute (NCI) are mainly based on medical records and administrative information. Individual-level socioeconomic data are not routinely reported by cancer registries in the United States because they are not available in patient hospital records. The U.S. representative National Longitudinal Mortality Study (NLMS) data provide self-reported, detailed demographic and socioeconomic data from the Social and Economic Supplement to the Census Bureau's Current Population Survey (CPS). In 1999, the NCI initiated the SEER-NLMS study, linking the population-based SEER cancer registry data to NLMS data. The SEER-NLMS data provide a new unique research resource that is valuable for health disparity research on cancer burden. We describe the design, methods, and limitations of this data set. We also present findings on cancer-related health disparities according to individual-level socioeconomic status (SES) and demographic characteristics for all cancers combined and for cancers of the lung, breast, prostate, cervix, and melanoma. Records of cancer patients diagnosed in 1973-2001 when residing 1 of 11 SEER registries were linked with 26 NLMS cohorts. The total number of SEER matched cancer patients that were also members of an NLMS cohort was 26,844. Of these 26,844 matched patients, 11,464 were included in the incidence analyses and 15,357 in the late-stage diagnosis analyses. Matched patients (used in the incidence analyses) and unmatched patients were compared by age group, sex, race, ethnicity, residence area, year of diagnosis, and cancer anatomic site. Cohort-based age-adjusted cancer incidence rates were computed. The impact of socioeconomic status on cancer incidence and stage of diagnosis was evaluated. Men and women with less than a high school education had elevated lung cancer rate ratios of 3.01 and 2.02, respectively, relative to their college educated counterparts. Those with family annual incomes less than $12,500 had incidence rates that were more than 1.7 times the lung cancer incidence rate of those with incomes $50,000 or higher. Lower income was also associated with a statistically significantly increased risk of distant-stage breast cancer among women and distant-stage prostate cancer among men. Socioeconomic patterns in incidence varied for specific cancers, while such patterns for stage were generally consistent across cancers, with late-stage diagnoses being associated with lower SES. These findings illustrate the potential for analyzing disparities in cancer outcomes according to a variety of individual-level socioeconomic, demographic, and health care characteristics, as well as by area measures available in the linked database. C1 [Clegg, Limin X.] US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC 20420 USA. [Reichman, Marsha E.; Miller, Barry A.; Edwards, Brenda K.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hankey, Benjamin F.] Informat Management Serv Inc, Silver Spring, MD USA. [Singh, Gopal K.] US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Lin, Yi Dan] Monash Univ, Sch Med, Melbourne, Vic 3004, Australia. [Goodman, Marc T.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Lynch, Charles F.] Univ Iowa, State Hlth Registry Iowa, Iowa City, IA USA. [Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Chen, Vivien W.] LSU Sch Publ Hlth, Louisiana Tumor Registry, New Orleans, LA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Gomez, Scarlett L.] No Calif Canc Ctr, Fremont, CA USA. [Graff, John J.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Lin, Charles C.; Johnson, Norman J.] US Bur Census, Suitland, MD USA. RP Clegg, LX (reprint author), US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, 54AA,810 Vermont Ave NW, Washington, DC 20420 USA. EM Lin.Clegg@va.gov FU National Cancer Institute FX We thank Marie-Josephe Horner, epidemiologist from the National Cancer Institute, for technical and editorial assistance in the preparation of this manuscript. NR 52 TC 238 Z9 239 U1 8 U2 55 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2009 VL 20 IS 4 BP 417 EP 435 DI 10.1007/s10552-008-9256-0 PG 19 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 430VV UT WOS:000265018900002 PM 19002764 ER PT J AU Berndt, SI Huang, WY Yeager, M Weissfeld, JL Chanock, SJ Hayes, RB AF Berndt, Sonja I. Huang, Wen-Yi Yeager, Meredith Weissfeld, Joel L. Chanock, Stephen J. Hayes, Richard B. TI Genetic variants in frizzled-related protein (FRZB) and the risk of colorectal neoplasia SO CANCER CAUSES & CONTROL LA English DT Article DE Colorectal adenoma; Colorectal cancer; Polymorphism; Wnt signaling pathway ID CANCER AB The Wnt/APC/beta-catenin signaling pathway, which includes frizzled-related protein (FRZB), plays a critical role in the development of colorectal cancer, and recent evidence suggests that the functional polymorphism, FRZB Arg324Gly, may be associated with risk for this disease. To determine if this finding could be replicated, we investigated the association between two FRZB polymorphisms (Arg324Gly and Arg200Trp) and the risk of colorectal adenoma and cancer in nested case-control studies. Participants consisted of 1,709 adenoma cases, 620 cancer cases, and 1,849 controls within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations with colorectal neoplasia. No association was observed for either polymorphism or any haplotypes with colorectal adenoma or colorectal cancer (p > 0.05 for all). Our study does not support the previously observed association between the FRZB 324Gly variant and colorectal cancer risk. However, further study of additional genetic variants within this pathway is still warranted, given the important role of the Wnt signaling pathway in colorectal carcinogenesis. C1 [Berndt, Sonja I.; Huang, Wen-Yi; Yeager, Meredith; Chanock, Stephen J.; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Weissfeld, Joel L.] Univ Pittsburgh, Pittsburgh, PA USA. [Yeager, Meredith] NCI, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8116,MSC 7240, Bethesda, MD 20892 USA. EM berndts@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health (NIH) FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, acknowledge the study participants for donating their time and making this study possible.National Institutes of Health (NIH). The authors thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, NCI, the screening center investigators and staff of the PLCO Cancer Screening Trial, Mr. Thomas Riley and staff at Information Management Services, Inc., and Ms. Barbara O'Brien and staff at Westat, Inc. for their contributions to the PLCO Cancer Screening Trial. Finally, we NR 9 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2009 VL 20 IS 4 BP 487 EP 490 DI 10.1007/s10552-008-9274-y PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 430VV UT WOS:000265018900007 PM 19067193 ER PT J AU Olson, SH Chen, C De Vivo, I Doherty, JA Hartmuller, V Horn-Ross, PL Lacey, JV Lynch, SM Sansbury, L Setiawan, VW Schouten, LJ Shu, XO AF Olson, Sara H. Chen, Chu De Vivo, Immaculata Doherty, Jennifer A. Hartmuller, Virginia Horn-Ross, Pamela L. Lacey, James V., Jr. Lynch, Shannon M. Sansbury, Leah Setiawan, V. Wendy Schouten, Leo J. Shu, Xiao Ou TI Maximizing resources to study an uncommon cancer: E2C2-Epidemiology of Endometrial Cancer Consortium SO CANCER CAUSES & CONTROL LA English DT Article DE Endometrial cancer; Epidemiology ID GENETIC POLYMORPHISMS; POSTMENOPAUSAL WOMEN; MULTIETHNIC COHORT; STEROID-HORMONES; RISK; CYP19A1; ASSOCIATION; CONSUMPTION; SOY AB Endometrial cancer affects more than 40,000 women a year in the U.S. While the association of this disease with high body mass index and sex steroid hormones is well known, there are many questions about etiology that have not been resolved. Little is known about the genetic basis for risk associated with hormones or obesity, other common genetic factors associated with risk, or gene-environment interactions. E2C2, the Epidemiology of Endometrial Cancer Consortium, was formed in 2006 to provide a collaborative environment for addressing these questions by pooling data from existing studies. This allows for investigations of uncommon risk factors, risk for rare histologic subtypes, and associations within strata that cannot be achieved in individual studies. This report describes the establishment of the consortium, ongoing projects that demonstrate the advantages of collaborative efforts, and challenges faced. Overall, the consortium promises to provide an important means of furthering our knowledge about this cancer. C1 [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Chen, Chu; Doherty, Jennifer A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. [Chen, Chu] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Sch Med, Seattle, WA 98195 USA. [De Vivo, Immaculata] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hartmuller, Virginia; Lynch, Shannon M.; Sansbury, Leah] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA. [Lacey, James V., Jr.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Setiawan, V. Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schouten, Leo J.] Maastricht Univ, Sch Oncol & Dev Biol, GROW, Dept Epidemiol, Maastricht, Netherlands. [Shu, Xiao Ou] Vanderbilt Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Shu, Xiao Ou] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Shu, Xiao Ou] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Olson, SH (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63 St, New York, NY 10065 USA. EM olsons@mskcc.org RI Schouten, Leo/G-3713-2012 FU NCI NIH HHS [R01 CA092585, K05 CA092002, K05 CA092002-04, N01 PC035137, P01 CA033619, P01 CA033619-209003, P01 CA077596, P01 CA077596-03, P01 CA087969, P01 CA087969-10, P30 CA016087, P30 CA016087-29S2, R01 CA047749, R01 CA047749-06, R01 CA049449, R01 CA049449-19, R01 CA058598, R01 CA058598-10, R01 CA063446, R01 CA063446-04, R01 CA063464, R01 CA063464-10, R01 CA070867, R01 CA070867-11, R01 CA074877-04, R01 CA075977, R01 CA075977-04, R01 CA077398, R01 CA083918, R01 CA083918-05, R01 CA087538, R01 CA087538-05, R01 CA092585-05, R01 CA098346, R01 CA098346-05, R01 CA098661, R01 CA098661-05, R01 CA105212, R01 CA105212-04, R03 CA080636, R03 CA080636-01, R35 CA039779, R35 CA039779-14, R37 CA054281, R37 CA054281-17]; NICHD NIH HHS [N01 HD923166]; NIEHS NIH HHS [P30 ES000260, P30 ES000260-46] NR 20 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2009 VL 20 IS 4 BP 491 EP 496 DI 10.1007/s10552-008-9290-y PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 430VV UT WOS:000265018900008 PM 19132539 ER PT J AU Sen, M Tosca, PJ Zwayer, C Ryan, MJ Johnson, JD Knostman, KAB Giclas, PC Peggins, JO Tomaszewski, JE McMurray, TP Li, CY Leibowitz, MS Ferris, RL Gooding, WE Thomas, SM Johnson, DE Grandis, JR AF Sen, Malabika Tosca, Patricia J. Zwayer, Christa Ryan, Michael J. Johnson, Jerry D. Knostman, Katherine A. B. Giclas, Patricia C. Peggins, James O. Tomaszewski, Joseph E. McMurray, Timothy P. Li, Changyou Leibowitz, Michael S. Ferris, Robert L. Gooding, William E. Thomas, Sufi M. Johnson, Daniel E. Grandis, Jennifer R. TI Lack of toxicity of a STAT3 decoy oligonucleotide SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE STAT3 decoy; Toxicity ID TRANSCRIPTION FACTOR DECOY; IN-VIVO; CANCER-THERAPY; NECK-CANCER; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCER; PROSTATE-CANCER; BREAST-CANCER; INHIBITION; APOPTOSIS AB Background STAT3 overexpression has been detected in several cancers including head and neck squamous cell carcinoma (HNSCC). Previous studies using intratumoral administration of a STAT3 decoy oligonucleotide that abrogates STAT3- mediated gene transcription in preclinical cancer models have demonstrated antitumor efficacy. This study was conducted to observe the toxicity and biologic effects of the STAT3 decoy in a non-human primate model, in anticipation of initiating a clinical trial in HNSCC patients. Methods Three study groups (two monkeys/sex/group) were administered a single intramuscular injection of low dose of STAT3 decoy (0.8 mg total dose/monkey), high dose of STAT3 decoy (3.2 mg total dose/monkey) or vehicle control (PBS alone) on day 1 and necropsies were performed on days 2 and 15 (one monkey/sex/group/day). Low and high doses of the decoy were administered in the muscle in a volume of 0.9 ml. Tissue and blood were harvested for toxicology and biologic analyses. Results Upon observation, the STAT3 decoy-treated animals exhibited behavior that was similar to the vehicle control group. Individual animal body weights remained within 1% of pretreatment weights throughout the study. Hematological parameters were not significantly different between the control and the treatment groups. Clinical chemistry fluctuations were considered within normal limits and were not attributed to the STAT3 decoy. Assessment of complement activation breakdown product (Bb) levels demonstrated no activation of the alternative pathway of complement in any animal at any dose level. At necropsy, there were no gross or microscopic findings attributed to STAT3 decoy in any organ examined. STAT3 target gene expression at the injection site revealed decreased Bcl-X-L and cyclin D1 expression levels in the animals treated with high dose of STAT3 decoy compared to the animals injected with low dose of STAT3 decoy or the vehicle as control. Conclusion Based on these findings, the no-observablead-verse-effect-level ( NOAEL) was greater than 3.2 mg/kg when administered as a single dose to male and female Cynomolgus monkeys. Plans are underway to test the safety and biologic effects of intratumoral administration of the STAT3 decoy in HNSCC patients. C1 [Grandis, Jennifer R.] Univ Pittsburgh, Inst Eye & Ear, Pittsburgh, PA 15213 USA. [Sen, Malabika; McMurray, Timothy P.; Leibowitz, Michael S.; Ferris, Robert L.; Thomas, Sufi M.; Grandis, Jennifer R.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Johnson, Daniel E.; Grandis, Jennifer R.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15213 USA. [Tosca, Patricia J.; Zwayer, Christa; Ryan, Michael J.; Johnson, Jerry D.; Knostman, Katherine A. B.] Battelle Toxicol, Columbus, OH 43201 USA. [Leibowitz, Michael S.; Ferris, Robert L.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA. [Gooding, William E.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. [Li, Changyou; Johnson, Daniel E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Giclas, Patricia C.] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. [Peggins, James O.; Tomaszewski, Joseph E.] NCI, Bethesda, MD 20892 USA. [Sen, Malabika; Tosca, Patricia J.; Zwayer, Christa; Ryan, Michael J.; Johnson, Jerry D.; Knostman, Katherine A. B.; Giclas, Patricia C.; Peggins, James O.; Tomaszewski, Joseph E.; McMurray, Timothy P.; Li, Changyou; Leibowitz, Michael S.; Ferris, Robert L.; Gooding, William E.; Thomas, Sufi M.; Johnson, Daniel E.; Grandis, Jennifer R.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Inst Eye & Ear, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu OI Thomas, Sufi/0000-0001-5370-0842 FU NCI RAID [P50 CA097190, R01 CA101840-01] FX This work was supported by the NCI RAID program, P50 CA097190, and R01 CA101840-01 (to JRG). NR 31 TC 28 Z9 28 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2009 VL 63 IS 6 BP 983 EP 995 DI 10.1007/s00280-008-0823-6 PG 13 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 434EF UT WOS:000265257300002 PM 18766340 ER PT J AU Lin, CC Calvo, E Papadopoulos, KP Patnaik, A Sarantopoulos, J Mita, AC Preston, GG Mita, MM Rodon, J Mays, T Yeh, IT O'Rourke, P Takimoto, CH Dancey, JE Chen, H Tolcher, AW AF Lin, Chia-Chi Calvo, Emiliano Papadopoulos, Kyriakos P. Patnaik, Amita Sarantopoulos, John Mita, Alain C. Preston, Glenn G. Mita, Monica M. Rodon, Jordi Mays, Theresa Yeh, I-Tien O'Rourke, Pat Takimoto, Chris H. Dancey, Janet E. Chen, Helen Tolcher, Anthony W. TI Phase I study of cetuximab, erlotinib, and bevacizumab in patients with advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 18th AACR/EORTC/NCI International Conference on Molecular Targets and Cancer Therapeutics CY NOV 07-10, 2006 CL Prague, CZECH REPUBLIC SP AACR, EORTC, NCI DE Epidermal growth factor receptor; Vascular endothelial growth factor; Renal cell carcinoma ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; GEFITINIB; COMBINATION; MUTATIONS; TRIAL; CARCINOMA AB Background Complex interrelationships exist between the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor pathways. EGFR activation elicits cell proliferation and increased VEGF expression. To maximally inhibit EGFR and then downstream VEGF activity, this phase I study was initiated to determine the maximum tolerated dose (MTD) of erlotinib with fixed-dose cetuximab, and then combine with bevacizumab in patients with advanced malignancies. Patients and methods Patients with advanced malignancies likely to express EGFR were treated with a full dose of cetuximab intravenous weekly, combined with various doses of oral erlotinib daily (Part 1). Once the MTD was determined in Part 1, escalating doses of bevacizumab were administered intravenously biweekly (Part 2). Results Forty patients were enrolled and received 155 courses over four dose levels. In Part 1, dose-limiting grade 3 rash occurred in two patients administered with erlotinib at 100 mg daily, and the MTD of erlotinib for this combination was 50 mg daily with standard-dose cetuximab (11 patients treated). Other adverse events included rash, diarrhea, fatigue, and hypomagnesemia. In Part 2, bevacizumab at 10 mg/kg intravenous every 2 weeks was safely added, with additional nondose-limiting headache, proteinuria, and hypertension. There was one partial response in a patient with renal cell carcinoma. Durable stable disease was observed in five patients for 6-11 months. Conclusions The MTD for Part 1 was 50 mg daily of erlotinib combined with standard cetuximab. Bevacizumab at 10 mg/kg biweekly can be safely administered with the MTD for erlotinib and cetuximab combination. C1 [Lin, Chia-Chi; Calvo, Emiliano; Papadopoulos, Kyriakos P.; Patnaik, Amita; Sarantopoulos, John; Mita, Alain C.; Mita, Monica M.; Rodon, Jordi; Mays, Theresa; O'Rourke, Pat; Takimoto, Chris H.; Tolcher, Anthony W.] Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. [Preston, Glenn G.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. [Yeh, I-Tien] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Dancey, Janet E.; Chen, Helen] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Tolcher, AW (reprint author), S Texas Accelerated Res Therapeut, 4319 Med Dr,Suite 205, San Antonio, TX 78229 USA. EM atolcher@start.stoh.com FU NCI NIH HHS [U01-CA069853] NR 36 TC 10 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2009 VL 63 IS 6 BP 1065 EP 1071 DI 10.1007/s00280-008-0811-x PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 434EF UT WOS:000265257300009 PM 18795291 ER PT J AU Schelman, WR Morgan-Meadows, S Marnocha, R Lee, F Eickhoff, J Huang, W Pomplun, M Jiang, ZS Alberti, D Kolesar, JM Ivy, P Wilding, G Traynor, AM AF Schelman, William R. Morgan-Meadows, Sherry Marnocha, Rebecca Lee, Fred Eickhoff, Jens Huang, Wei Pomplun, Marcia Jiang, Zhisheng Alberti, Dona Kolesar, Jill M. Ivy, Percy Wilding, George Traynor, Anne M. TI A phase I study of Triapine (R) in combination with doxorubicin in patients with advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Triapine (R); 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone Doxorubicin; Phase I; Ribonucleotide reductase ID RIBONUCLEOTIDE REDUCTASE-ACTIVITY; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; CELL LUNG-CANCER; HYDROXYUREA RESISTANCE; ANTITUMOR-ACTIVITY; INHIBITOR; POTENT; DRUG; CARDIOTOXICITY; GEMCITABINE AB Purpose To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine (R) administered in combination with doxorubicin. Study design Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine (R) IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine (R) 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Results Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine (R) 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine (R) 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine (R) were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Conclusions Pretreated patients with advanced malignancies can tolerate the combination of Triapine (R) and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine (R) 25 mg/m2 on days 1-4 of a 21-day cycle. C1 [Schelman, William R.; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M.; Wilding, George; Traynor, Anne M.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53792 USA. [Morgan-Meadows, Sherry] So Canc Ctr, Mobile, AL USA. [Ivy, Percy] NCI, Clin Trials Evaluat Program, Bethesda, MD 20892 USA. RP Traynor, AM (reprint author), Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, 600 Highland Ave,K6-568, Madison, WI 53792 USA. EM amt@medicine.wisc.edu FU Early Clinical Trials of Anti-Cancer Agents with PhaseI Emphasis, NCI [UO1 CA062491]; CTEP Translational Research Initiative [24XS090]; Clinical and Translational Science Award, National Center for ResearchResources, NIH [1UL1RR025011] FX The authors would like to thank the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC) Analytical Instrumentation Laboratory for Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics (3P Lab) for support in the acquisition of pharmacokinetic data for this research. The authors also would like to thank the patients who participated in this clinical trial, and the nurses and research specialist of the UWCCC phase I program for their efforts in conducting and managing this trial. UO1 CA062491, Early Clinical Trials of Anti-Cancer Agents with PhaseI Emphasis, NCI; CTEP Translational Research Initiative, Contract 24XS090; and 1UL1RR025011, Clinical and Translational Science Award, National Center for ResearchResources, NIH. NR 32 TC 14 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2009 VL 63 IS 6 BP 1147 EP 1156 DI 10.1007/s00280-008-0890-8 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 434EF UT WOS:000265257300019 PM 19082825 ER PT J AU Wentzensen, N Gravitt, PE Solomon, D Wheeler, CM Castle, PE AF Wentzensen, Nicolas Gravitt, Patti E. Solomon, Diane Wheeler, Cosette M. Castle, Philip E. TI A Study of Amplicor Human Papillomavirus DNA Detection in the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion Triage Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HYBRID CAPTURE 2; ABNORMAL PAP-SMEAR; CERVICAL-CANCER; RANDOMIZED-TRIAL; CYTOLOGY INTERPRETATIONS; HYBRID-CAPTURE-2 ASSAY; COST-EFFECTIVENESS; SCREENING-TESTS; ROCHE AMPLICOR; HPV GENOTYPES AB We analyzed the performance of Amplicor for detecting carcinogenic human papillomavirus (HPV) infections and cervical precancer in women with an atypical squamous cells of undetermined significance (ASCUS) Pap and compared the results with Hybrid Capture 2 (hc2) in the ASCUS and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS). Baseline specimens collected from women referred into ALTS based on an ASCUS Pap result were prospectively tested by hc2 and retrospectively tested by Amplicor (n = 3,277). Following receiver-operator-characteristics curve analysis, Amplicor performance was analyzed at three cutoffs (0.2, 1.0, and 1.5). Paired Amplicor and hc2 results were compared for the detection of 2-year cumulative cervical intraepithelial neoplasia (CIN) grade 3 and more severe disease outcomes (CIN3+) and for the detection of 13 targeted carcinogenic HPV types. Amplicor at the 0.2 cutoff had a higher sensitivity for the detection of CIN3+ (95.8% versus 92.6%, P = 0.01) but a much lower specificity (38.9% versus 50.6%, P < 0.001) than hc2. Amplicor at the 1.5 cutoff had an identical sensitivity for the detection of CIN3+ (92.6%) and a slightly lower specificity (47.5%; P < 0.001). The positive predictive value of hc2 was higher at all Amplicor cutoffs, whereas referral rates were significantly lower (53.2% for hc2 versus 64.1% at the 0.2 cutoff and 56.0% at the 1.5 cutoff, P < 0.001). Amplicor was more analytically specific for detecting targeted carcinogenic HPV types than hc2. Amplicor at the 1.5 cutoff had comparable performance with hc2. Whereas Amplicor missed more disease related to nontargeted types, hc2 was more likely to miss disease related to targeted types. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1341-9) C1 [Wentzensen, Nicolas; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20854 USA. [Solomon, Diane] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Rockville, MD 20854 USA. [Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Room 5012,6120 Execut Blvd, Rockville, MD 20854 USA. EM wentzenn@mail.nih.gov FU NIH; National Cancer Institute FX Grant support: Intramural Research Program of the NIH and the National Cancer Institute. NR 40 TC 16 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1341 EP 1349 DI 10.1158/1055-9965.EPI-08-1180 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500002 PM 19423515 ER PT J AU Han, XS Zheng, TZ Lan, Q Zhang, YQ Kilfoy, BA Qin, Q Rothman, N Zahm, SH Holford, TR Leaderer, B Zhang, YW AF Han, Xuesong Zheng, Tongzhang Lan, Qing Zhang, Yaqun Kilfoy, Briseis A. Qin, Qin Rothman, Nathaniel Zahm, Shelia H. Holford, Theodore R. Leaderer, Brian Zhang, Yawei TI Genetic Polymorphisms in Nitric Oxide Synthase Genes Modify the Relationship between Vegetable and Fruit Intake and Risk of Non-Hodgkin Lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ANTIOXIDANT-RELATED NUTRIENTS; OXIDATIVE STRESS GENES; DIETARY FACTORS; DNA-DAMAGE; NOS1 GENE; EXPRESSION; CANCER; CARCINOGENESIS; ASSOCIATION; CELLS AB Oxidative damage caused by reactive oxygen species and other free radicals is involved in carcinogenesis. it has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histologic subtypes in women from Connecticut, including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma and follicular lymphoma. Two single nucleotide polymorphisms in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma. When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruits were examined separately, strong interaction effects were narrowed to vegetable intake among patients with diffuse large B-cell lymphoma. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1429-38) C1 [Han, Xuesong; Zheng, Tongzhang; Kilfoy, Briseis A.; Holford, Theodore R.; Leaderer, Brian; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Lan, Qing; Rothman, Nathaniel; Zahm, Shelia H.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Zhang, Yaqun] Gansu Prov Design & Res Inst Environm, Lanzhou, Gansu, Peoples R China. [Qin, Qin] Univ So Maine, Ctr Toxicol & Environm Hlth, Portland, ME 04103 USA. RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St,LEPH 440,POB 208034, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Zahm, Shelia/B-5025-2015 FU NIH [CA62006, 1D43TW007864-01] FX Grant support: NIH grant CA62006, the Intramural Research Program of the NIH, National Cancer Institute, and the NIH Fogarty Training Grant 1D43TW007864-01. This publication was made possible by CTSA grant no. UL1 RR024139 from the National Center for Research Resources, a component of the NIH, and the NHL Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources. NR 68 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1429 EP 1438 DI 10.1158/1055-9965.EPI-09-0001 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500014 PM 19423521 ER PT J AU Rohrmann, S Sutcliffe, CG Bienstock, JL Monsegue, D Akereyeni, F Bradwin, G Rifai, N Pollak, MN Agurs-Collins, T Platz, EA AF Rohrmann, Sabine Sutcliffe, Catherine G. Bienstock, Jessica L. Monsegue, Deborah Akereyeni, Folasade Bradwin, Gary Rifai, Nader Pollak, Michael N. Agurs-Collins, Tanya Platz, Elizabeth A. TI Racial Variation in Sex Steroid Hormones and the Insulin-Like Growth Factor Axis in Umbilical Cord Blood of Male Neonates SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM TESTOSTERONE LEVELS; BONE-MINERAL DENSITY; PROSTATE-CANCER; WHITE MEN; BINDING GLOBULIN; AFRICAN-AMERICAN; FACTOR-I; BIRTH-WEIGHT; AMNIOTIC-FLUID; INCREASED RISK AB Background: To address whether umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis differ between African-American and White male neonates. Methods: In 2004 and 2005, venous cord blood samples were collected from 75 African-American and 38 White male full-term uncomplicated births along with birth weight, placental weight, mother's age and parity, and time of birth. Testosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) were measured by immunoassay, and IGF-I, IGF-2, and IGF binding protein (BP)-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed. Results: Androstanediol glucuronide, estradiol, and SHBG concentrations did not differ by race; however, the molar ratio of testosterone to SHBG was higher in African-American than White male babies after adjustment (P = 0.01). Both before and after adjustment, Whites had higher concentrations of IGF-I (adjusted; White, African-American, 93.1, 71.9 ng/mL), IGF-2 (537.3-474.8 ng/mL), and IGFBP-3 (1,673-1,482 ng/mL) than African-Americans (P < 0.05), although the molar ratio of IGF-I plus IGF-2 to IGFBP-3 did not differ by race. Conclusion: The higher cord blood testosterone to SHBG ratio in African-American compared with White male babies after taking into account maternal and birth factors is compatible with the hypothesis that differences in androgen levels in utero contribute to their higher prostate cancer risk, although we would have expected crude differences as well. Lower cord blood IGF-I and IGF-2 levels in African-American compared with White male babies are not consistent with the hypothesis that differences in growth factor levels contribute to their higher prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1484-91) C1 [Rohrmann, Sabine] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Sutcliffe, Catherine G.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Bienstock, Jessica L.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. [Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Monsegue, Deborah; Agurs-Collins, Tanya] Howard Univ, Ctr Canc, Washington, DC 20059 USA. [Akereyeni, Folasade] Howard Univ, Ctr Human Genome, Washington, DC 20059 USA. [Bradwin, Gary; Rifai, Nader] Harvard Univ, Sch Med, Dept Lab Med, Boston, MA USA. [Bradwin, Gary; Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ H3T 1E2, Canada. [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm E6132, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Perez , Claudio Alejandro/F-8310-2010; Pollak, Michael/G-9094-2011; Rohrmann, Sabine/D-2113-2012 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Pollak, Michael/0000-0003-3047-0604; FU National Cancer institute [U54 (Hopkins CA091409), U54 (Howard CA091431)] FX Grant support: National Cancer institute grant U54 (Hopkins CA091409) and U54 (Howard CA091431). NR 45 TC 20 Z9 21 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1484 EP 1491 DI 10.1158/1055-9965.EPI-08-0817 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500021 PM 19423525 ER PT J AU Moolchan, ET Parzynski, CS Jaszyna-Gasior, M Collins, CC Leff, MK Zimmerman, DL AF Moolchan, Eric T. Parzynski, Craig S. Jaszyna-Gasior, Maria Collins, Charles C. Leff, Michelle K. Zimmerman, Debra L. TI A Link between Adolescent Nicotine Metabolism and Smoking Topography SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID REPLACEMENT THERAPY; DEPENDENT SMOKERS; TOBACCO SMOKING; CYP2A6; ASSOCIATION; CIGARETTES; COTININE; SEX AB Adult slow nicotine metabolizers have lower smoke exposure, carbon monoxide levels, and plasma nicotine levels than normal and fast metabolizers. Emerging evidence suggests nicotine metabolism influences smoking topography. This study investigated the association of nicotine metabolism (the ratio of plasma 3-hydroxycotinine to cotinine; 3OHCOT/COT) with smoking topography in adolescent smokers (n = 85; 65% female, 68% European American; mean age, 15.3 +/- 1.2 years; mean cigarettes per day, 18.5 +/- 8.5; mean Fagerstrom Test for Nicotine Dependence, 7.0 +/- 1.2) presenting for a nicotine replacement therapy trial. Measures obtained included puff volume, interpuff interval, number of puffs, puff duration, and puff velocity. Linear regression analysis controlling for hormonal contraception use showed that 30HCOT/COT ratios predicted mean puff volume in the overall sample (t = 2.126; P = 0.037; adjusted R(2) = 0.067). After gender stratification, faster metabolism predicted higher mean puff volume (t = 2.81; P = 0.009; adjusted R(2) = 0.192) but fewer puffs (t = -3.160; P = 0.004; adjusted R(2) = 0.237) and lower mean puff duration (t = -2.06; P = 0.048; adjusted R(2) = 0.101) among boys only, suggesting that as nicotine metabolism increases, puff volume increases but puffing frequency decreases. No significant relationships were found between nicotine metabolism and total puff volume, mean puff duration, interpuff interval, or puff velocity. If confirmed in a broader sample of adolescent smokers, these findings suggest that as among dependent adult smokers, rate of metabolism among adolescent boys is linked to select parameters of puffing behavior that may affect cessation ability. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1578-83) C1 [Moolchan, Eric T.; Parzynski, Craig S.; Jaszyna-Gasior, Maria; Collins, Charles C.; Leff, Michelle K.; Zimmerman, Debra L.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD USA. RP Moolchan, ET (reprint author), Alkermes Inc, 88 Sidney St, Cambridge, MA 02139 USA. EM eric.moolchan@alkermes.com FU NIDA FX NIDA intramural research funds. NR 29 TC 10 Z9 10 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1578 EP 1583 DI 10.1158/1055-9965.EPI-08-0592 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500033 PM 19423535 ER PT J AU Gaudet, MM Milne, RL Cox, A Camp, NJ Goode, EL Humphreys, MK Dunning, AM Morrison, J Giles, GG Severi, G Baglietto, L English, DR Couch, FJ Olson, JE Wang, XS Chang-Claude, J Flesch-Janys, D Abbas, S Salazar, R Mannermaa, A Kataja, V Kosma, VM Lindblom, A Margolin, S Heikkinen, T Kampjarvi, K Aaltonen, K Nevanlinna, H Bogdanova, N Coinac, I Schurmann, P Dork, T Bartram, CR Schmutzler, RK Tchatchou, S Burwinkel, B Brauch, H Torres, D Hamann, U Justenhoven, C Ribas, G Arias, JI Benitez, J Bojesen, SE Nordestgaard, BG Flyger, HL Peto, J Fletcher, O Johnson, N Silva, ID Fasching, PA Beckmann, MW Strick, R Ekici, AB Broeks, A Schmidt, MK van Leeuwen, FE Van't Veer, LJ Southey, MC Hopper, JL Apicella, C Haiman, CA Henderson, BE Le Marchand, L Kolonel, LN Kristensen, V Alnae, GG Hunter, DJ Kraft, P Cox, DG Hankinson, SE Seynaeve, C Vreeswijk, MPG Tollenaar, RAEM Devilee, P Chanock, S Lissowska, J Brinton, L Peplonska, B Czene, K Hall, P Li, YQ Liu, JJ Balasubramanian, S Rafii, S Reed, MWR Pooley, KA Conroy, D Baynes, C Kang, D Yoo, KY Noh, DY Ahn, SH Shen, CY Wang, HC Yu, JC Wu, PE Anton-Culver, H Ziogoas, A Egan, K Newcomb, P Titus-Ernstoff, L Dietz, AT Sigurdson, AJ Alexander, BH Bhatti, P Allen-Brady, K Cannon-Albright, LA Wong, J Spurdle, AB Beesley, J Pharoah, PDP Easton, DF Garcia-Closas, M AF Gaudet, Mia M. Milne, Roger L. Cox, Angela Camp, Nicola J. Goode, Ellen L. Humphreys, Manjeet K. Dunning, Alison M. Morrison, Jonathan Giles, Graham G. Severi, Gianluca Baglietto, Laura English, Dallas R. Couch, Fergus J. Olson, Janet E. Wang, Xianshu Chang-Claude, Jenny Flesch-Janys, Dieter Abbas, Sascha Salazar, Ramona Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Lindblom, Annika Margolin, Sara Heikkinen, Tuomas Kampjarvi, Kati Aaltonen, Kirsimari Nevanlinna, Heli Bogdanova, Natalia Coinac, Irina Schuermann, Peter Doerk, Thilo Bartram, Claus R. Schmutzler, Rita K. Tchatchou, Sandrine Burwinkel, Barbara Brauch, Hiltrud Torres, Diana Hamann, Ute Justenhoven, Christina Ribas, Gloria Arias, Jose I. Benitez, Javier Bojesen, Stig E. Nordestgaard, Borge G. Flyger, Henrik L. Peto, Julian Fletcher, Olivia Johnson, Nichola Silva, Isabel dos Santos Fasching, Peter A. Beckmann, Matthias W. Strick, Reiner Ekici, Arif B. Broeks, Annegien Schmidt, Marjanka K. van Leeuwen, Flora E. Van't Veer, Laura J. Southey, Melissa C. Hopper, John L. Apicella, Carmel Haiman, Christopher A. Henderson, Brian E. Le Marchand, Loic Kolonel, Laurence N. Kristensen, Vessela Alnaes, Grethe Grenaker Hunter, David J. Kraft, Peter Cox, David G. Hankinson, Susan E. Seynaeve, Caroline Vreeswijk, Maaike P. G. Tollenaar, Rob A. E. M. Devilee, Peter Chanock, Stephen Lissowska, Jolanta Brinton, Louise Peplonska, Beata Czene, Kamila Hall, Per Li, Yuqing Liu, Jianjun Balasubramanian, Sabapathy Rafii, Saeed Reed, Malcolm W. R. Pooley, Karen A. Conroy, Don Baynes, Caroline Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Shen, Chen-Yang Wang, Hui-Chun Yu, Jyh-Cherng Wu, Pei-Ei Anton-Culver, Hoda Ziogoas, Argyrios Egan, Kathleen Newcomb, Polly Titus-Ernstoff, Linda Dietz, Amy Trentham Sigurdson, Alice J. Alexander, Bruce H. Bhatti, Parveen Allen-Brady, Kristina Cannon-Albright, Lisa A. Wong, Jathine Spurdle, Amanda B. Beesley, Jonathan Pharoah, Paul D. P. Easton, Doug F. Garcia-Closas, Montserrat CA Australian Ovarian Canc Study Grp Georgia Chenevix-Trench Breast Canc Assoc Consortium TI Five Polymorphisms and Breast Cancer Risk: Results from the Breast Cancer Association Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROGESTERONE-RECEPTOR GENE; TUMOR-NECROSIS-FACTOR; VARIANT; CASP8; APOPTOSIS; ERCC4 AB Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASPIO rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610-6) C1 [Gaudet, Mia M.] Mem Sloan Kettering Canc Ctr, Polish Breast Canc Study, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Chanock, Stephen; Brinton, Louise; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Chanock, Stephen; Brinton, Louise; Garcia-Closas, Montserrat] NCI, Core Genotyping Facil, Adv Technol Ctr, Gaithersburg, MD USA. [Peplonska, Beata] Ctr Canc, Warsaw, Poland. [Peplonska, Beata] M Sklodowska Curie Inst Oncol, Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Lodz, Poland. [Milne, Roger L.; Ribas, Gloria; Benitez, Javier] CNIO, Spanish Natl Canc Ctr Breast Canc Study BCS, Madrid, Spain. [Arias, Jose I.] Monte Naranco Hosp, Oviedo, Spain. [Cox, Angela; Balasubramanian, Sabapathy; Rafii, Saeed; Reed, Malcolm W. R.] Univ Sheffield, Sch Med, Sheffield Breast Canc Study, Sheffield, S Yorkshire, England. [Camp, Nicola J.; Allen-Brady, Kristina; Cannon-Albright, Lisa A.; Wong, Jathine] Univ Utah, Sch Med, Utah Breast Canc Study, Div Genet Epidemiol,Dept Biomed Informat, Salt Lake City, UT USA. [Goode, Ellen L.; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu] Mayo Clin, Coll Med, Mayo Clin Breast Canc Study, Rochester, MI USA. [Humphreys, Manjeet K.; Dunning, Alison M.; Morrison, Jonathan; Pooley, Karen A.; Conroy, Don; Baynes, Caroline; Pharoah, Paul D. P.; Easton, Doug F.] Univ Cambridge, Dept Oncol, Studies Epidemiol & Risk Factors Canc Hered, Cambridge, England. [Humphreys, Manjeet K.; Dunning, Alison M.; Morrison, Jonathan; Pooley, Karen A.; Conroy, Don; Baynes, Caroline; Pharoah, Paul D. P.; Easton, Doug F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; English, Dallas R.] German Canc Res Ctr, Melbourne Collaborat Cohort Study, Canc Epidemiol Ctr, D-6900 Heidelberg, Germany. [Chang-Claude, Jenny; Abbas, Sascha] German Canc Res Ctr, Mammary Carcinoma Risk Factor Invest MARIE, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Salazar, Ramona] Bioglobe GmbH, Hamburg, Germany. [Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Kuopio Breast Canc Project, Dept Pathol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti] Univ Kuopio, Inst Clin Med Pathol & Forens Med, FIN-70211 Kuopio, Finland. [Kataja, Vesa] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland. [Lindblom, Annika] Karolinska Inst, Karolinska Breast Canc Study, Dept Mol Med & Surg, Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Oncol, Stockholm, Sweden. [Heikkinen, Tuomas; Kampjarvi, Kati; Aaltonen, Kirsimari; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Helsinki Breast Canc Study, Dept Obstet & Gynecol, Helsinki, Finland. [Kampjarvi, Kati] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Bogdanova, Natalia; Coinac, Irina; Schuermann, Peter; Doerk, Thilo] Hannover Med Sch, Hannover Breast Canc Study, Clin Obstet & Gynecol, D-3000 Hannover, Germany. [Bogdanova, Natalia; Coinac, Irina; Schuermann, Peter; Doerk, Thilo] Hannover Med Sch, Hannover Breast Canc Study, Clin Radiat Oncol, D-3000 Hannover, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, German Consortium Hereditary Breast & Ovarian Can, Heidelberg, Germany. [Schmutzler, Rita K.] Univ Cologne, Ctr Clin, Div Mol Gynaecooncol, Dept Obstet & Gynaecol, Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Mol Med Cologne, Cologne, Germany. [Tchatchou, Sandrine; Burwinkel, Barbara] German Canc Res Ctr, Helmholtz Univ Grp Mol Epidemiol, D-6900 Heidelberg, Germany. [Brauch, Hiltrud; Justenhoven, Christina] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Brauch, Hiltrud; Justenhoven, Christina] Univ Tubingen, Tubingen, Germany. [Torres, Diana; Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Bojesen, Stig E.; Nordestgaard, Borge G.] Herlev Univ Hosp, Copenhagen Breast Canc Study, Copenhagen, Denmark. [Bojesen, Stig E.; Nordestgaard, Borge G.] Herlev Univ Hosp, Copenhagen City Heart Study, Dept Clin Biochem, Copenhagen, Denmark. [Bojesen, Stig E.; Flyger, Henrik L.] Herlev Univ Hosp, Dept Breast Surg, Copenhagen, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Peto, Julian; Fletcher, Olivia; Johnson, Nichola; Silva, Isabel dos Santos] Breakthrough Res Ctr, British Breast Canc Study, London, England. [Peto, Julian; Fletcher, Olivia; Johnson, Nichola; Silva, Isabel dos Santos] London Sch Hyg & Trop Med, London WC1, England. [Fasching, Peter A.; Beckmann, Matthias W.; Strick, Reiner] Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany. [Ekici, Arif B.] Univ Hosp Erlangen, Dept Human Genet, Erlangen, Germany. [Broeks, Annegien; Schmidt, Marjanka K.; van Leeuwen, Flora E.; Van't Veer, Laura J.] Netherlands Canc Inst, Amsterdam Breast Canc Study, Dept Expt Therapy, Amsterdam, Netherlands. [Broeks, Annegien; Schmidt, Marjanka K.; van Leeuwen, Flora E.; Van't Veer, Laura J.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Broeks, Annegien; Schmidt, Marjanka K.; van Leeuwen, Flora E.; Van't Veer, Laura J.] Netherlands Canc Inst, Dept Mol Pathol, Amsterdam, Netherlands. [Southey, Melissa C.; Hopper, John L.; Apicella, Carmel] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Australian Breast Canc Family Study, Melbourne, Vic, Australia. [Hopper, John L.; Apicella, Carmel] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. Univ Otago, Dept Prevent & Social Med, Dunedin, New Zealand. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Kristensen, Vessela; Alnaes, Grethe Grenaker] Norwegian Radium Hosp, Inst Canc Res, Dept Genet, Norwegian Breast Canc Study, Oslo, Norway. [Hunter, David J.; Kraft, Peter; Cox, David G.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol,Nurses Hlth Study, Boston, MA 02115 USA. [Hunter, David J.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Seynaeve, Caroline] Leiden Univ, Med Ctr Breast Canc Study ORIGO, Dept Med Oncol, Family Canc Clin,Erasmus MC Daniel den Hoed Canc, Rotterdam, Netherlands. [Vreeswijk, Maaike P. G.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Tollenaar, Rob A. E. M.] Leiden Univ, Dept Surg, Med Ctr, NL-2300 RA Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, NL-2300 RA Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Czene, Kamila; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Singapore & Swedish Breast Canc Study, Stockholm, Sweden. [Li, Yuqing; Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun] Seoul Natl Univ, Coll Med, Seoul Breast Canc Study, Seoul, South Korea. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun] Natl Canc Ctr, Seoul, South Korea. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Dept Surg, Ulsan 680749, South Korea. [Shen, Chen-Yang; Wang, Hui-Chun; Wu, Pei-Ei] Acad Sinica, Inst Biomed Sci, Taiwanese Breast Canc Study, Taipei, Taiwan. [Shen, Chen-Yang] China Med Univ, Grad Inst Environm Sci, Taichong, Taiwan. [Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan. [Anton-Culver, Hoda; Ziogoas, Argyrios; Garcia-Closas, Montserrat] Univ Calif Irvine, Sch Med, Dept Epidemiol, Univ Calif Irvine Breast Canc Study, Irvine, CA 92717 USA. [Egan, Kathleen] H Lee Moffitt Canc Ctr & Res Inst, US Three State Study, Tampa, FL USA. [Newcomb, Polly] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Grp, Seattle, WA 98104 USA. [Newcomb, Polly; Dietz, Amy Trentham] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. [Titus-Ernstoff, Linda] Dartmouth Med Ctr, Lebanon, NH USA. [Titus-Ernstoff, Linda] Norris Cotton Canc Ctr, Lebanon, NH USA. [Sigurdson, Alice J.; Bhatti, Parveen] NCI, US Radiol Technol Study, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. [Spurdle, Amanda B.; Beesley, Jonathan; Georgia Chenevix-Trench] Queensland Inst Med Res, Kathleen Cuningham Fdn Consortium Res Familial Br, Brisbane, Qld 4006, Australia. RP Gaudet, MM (reprint author), Mem Sloan Kettering Canc Ctr, Polish Breast Canc Study, Dept Epidemiol & Biostat, 3rd Floor,307 E 63rd St, New York, NY 10021 USA. EM gaudetm@mskcc.org RI Yoo, Keun-Young/J-5548-2012; Ekici, Arif/C-3971-2013; Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Dork, Thilo/J-8620-2012; Cox, David/A-2023-2009; Spurdle, Amanda/A-4978-2011; Wang, Hui-Chun/C-5680-2009; Noh, Dong-Young/G-5531-2011; Shen, CY/F-6271-2010; Kang, Dae Hee/E-8631-2012; Bowtell, David/H-1007-2016; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Cox, David/0000-0002-2152-9259; Spurdle, Amanda/0000-0003-1337-7897; Bowtell, David/0000-0001-9089-7525; Czene, Kamila/0000-0002-3233-5695; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; albright, lisa/0000-0003-2602-3668; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU Australian National Health and Medical Research Council [209057, 251533, 396414, 504711]; The Cancer Council Victoria; National Institutes of Health [CA98364]; U.S. medical research and materiel command breast cancer IDEA award [W81XWH-04-1-0588]; Eagles Cancer Research Fellow; Deutsche Krebshilfe e.V. [70-2892-Br 1]; Government Funding (EVO) of Kuopio University Hospital; Finnish Cancer Organisations; Cancer Fund of North Savo; Swedish Cancer Society; Gustav the V Jubilee Foundation; FoU Foundation; Bert von Kantzows Foundation; The Academy of Finland [110663]; Helsinki University Central Hospital; Sigrid Juselius Foundation; The Finnish Cancer Society; Hannover Medical School; Friends of Hannover Medical School; Deutsche Krebshilfe [107054]; Center of Molecular Medicine, Cologne; Helmholtz society; German Human Genome Project; Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Deutsches Krebsforschungszentrum, Heidelberg; Robert Bosch Foundation of Medical Research, Stuttgart, Germany; Genome Spain Foundation; Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Copenhagen County; CR-UK; Dutch Cancer Society [NKI 2001-2423, 2007-3839]; Dutch National Genomics Initiative; National Health and Medical Research Council (NHMRC) [145684, 288704, 454508, 199600]; Victorian Health Promotion Foundation; New South Wales Cancer Council; National Cancer Institute (USA) [CA-95-003]; National Cancer Institute (NCI) [CA63464, CA54281, CA2 R01, CA58860-14]; NCT [CA 0657245, CA098233]; Dutch Cancer Society; Agency for Science, Technology and Research of Singapore (A*STAR); Susan G. Komen Breast Cancer Foundation; Yorkshire Cancer Research; Breast Cancer Campaign; Cancer Research-UK (CR-UK); National Research and Development Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea [0620410-1]; Department of Health, Taiwan; Lon v smith Foundation (LVSF) [LVSF-41027, 3834, 42344]; American Registry of Radiologic Technologists; Susan G. Komen Foundation [BCTR0706911]; Utah Cancer Registry [N01-PC-35141]; Utah State Department of Health; University of Utah; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia. ACS/AOCS; U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729] FX The authors are grateful to Study Coordinators, Laboratory Specialst Kim Nguyen, and Computer Specialist Jathine Wong. We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704 and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. ACS/AOCS: The AOCS Management Group (D Bowtell, G Chenevix-Trench, A deFazio, D Gertig, A Green, P Webb) gratefully acknowledges the contribution of all the clinical and scientific collaborators (see http://www.aocstudy.org/), AOCS and the ACS Management Group (A Green, P Parsons, N Hayward, P Webb, D Whiteman) thank all of the project staff, collaborating institutions and Study participants. Financial support was provided by: U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study); The National Health and Medical Research Council of Australia (199600) (ACS study). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the CFRs Centers. The genotyping and analysis were supported by grants from the National Health and Medical Research Council (NHMRC). ABS was funded by an NHMRC Career Development Award, and GC-T and JLH are NHMRC Senior Principal Research Fellows. NR 20 TC 42 Z9 46 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1610 EP 1616 DI 10.1158/1055-9965.EPI-08-0745 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500037 PM 19423537 ER PT J AU Koshiol, J Hildesheim, A Gonzalez, P Bratti, MC Porras, C Schiffman, M Herrero, R Rodriguez, AC Wacholder, S Yeager, M Chanock, SJ Burk, RD Wang, SS AF Koshiol, Jill Hildesheim, Allan Gonzalez, Paula Bratti, M. Concepcion Porras, Carolina Schiffman, Mark Herrero, Rolando Rodriguez, Ana C. Wacholder, Sholom Yeager, Meredith Chanock, Stephen J. Burk, Robert D. Wang, Sophia S. TI Common Genetic Variation in TP53 and Risk of Human Papillomavirus Persistence and Progression to CIN3/Cancer Revisited SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID P53 CODON-72 POLYMORPHISM; INVASIVE CERVICAL-CANCER; COSTA-RICA; METAANALYSIS; NEOPLASIA; INFECTION; POPULATION; HAPLOTYPE; WOMEN; CARCINOGENESIS AB Driven by findings that human papillomavirus (HPV)induced degradation of p53 differs by a TP53 polymorphism at codon 72 (Pro72Arg), past studies of TP53 genetic variants and cervical cancer have focused on this nonsynonymous polymorphism, with mixed results. We analyzed common single nucleotide polymorphisms (SNP) across the TP53 locus in a population-based nested case-control study in Guanacaste, Costa Rica. We evaluated 11 SNPs, including Pro72Arg (rs1042522), among 1,281 women: 465 with cervical intraepithelial neoplasia grade 3/cancer (CIN3+), 380 with HPV persistence (median, 25 months), and 436 random population controls. We combined HPV persistence and CIN3+ into one case group because they did not differ in TP53 genotypic frequencies and calculated odds ratios and 95% confidence intervals (CI) for individual SNPs and inferred haplotypes. We observed that proline at codon 72 was associated with increased risk of CIN3+/persistence compared with population controls. Relative to GG (Arg), the CG (Pro/Arg) and CC (Pro) genotypes had a 1.3-fold (95% CI, 0.99-1.6) and 1.8-fold (95% CI, 1.2-2.7) increased risk, respectively (P(trend) < 0.01). rs12951053 and rs1642785 were also associated with CIN3+/persistence (P(trend), 0.05 and 0.04, respectively), as was a haplotype containing the codon 72 variant (rs1042522), rs12951053, rs1642785, and rs12947788 (odds ratio, 1.6; 95% CI, 1.1-2.3 versus the most common haplotype, which comprised the major alleles for all 11 SNPs). Although genetic variation in TP53 might affect the natural history of HPV and cervical cancer, further work is needed to elucidate the possible mechanism. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1631-7) C1 [Koshiol, Jill] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Koshiol, Jill] NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, NIH, Bethesda, MD 20892 USA. [Schiffman, Mark; Rodriguez, Ana C.; Wang, Sophia S.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Wacholder, Sholom] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. [Chanock, Stephen J.] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD USA. [Gonzalez, Paula; Bratti, M. Concepcion; Porras, Carolina; Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica. [Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Womens Hlth, Bronx, NY 10467 USA. RP Koshiol, J (reprint author), NIH, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7059, Rockville, MD 20852 USA. EM koshiolj@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU NIH; National Cancer Institute; Infections and Immunoepiderniology Branch FX Intramural Research Program of the NIH and the National Cancer Institute. R. Welch contributed as an author on this article until the time of his death in 2008. J. Koshiol is now a Research Fellow in the Infections and Immunoepiderniology Branch. NR 33 TC 19 Z9 19 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1631 EP 1637 DI 10.1158/1055-9965.EPI-08-0830 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500040 PM 19423538 ER PT J AU Rajaraman, P Brenner, AV Butler, MA Wang, SS Pfeiffer, RM Ruder, AM Linet, MS Yeager, M Wang, ZM Orr, N Fine, HA Kwon, D Thomas, G Rothman, N Inskip, PD Chanock, SJ AF Rajaraman, Preetha Brenner, Alina V. Butler, Mary Ann Wang, Sophia S. Pfeiffer, Ruth M. Ruder, Avima M. Linet, Martha S. Yeager, Meredith Wang, Zhaoming Orr, Nick Fine, Howard A. Kwon, Deukwoo Thomas, Gilles Rothman, Nathaniel Inskip, Peter D. Chanock, Stephen J. TI Common Variation in Genes Related to Innate Immunity and Risk of Adult Glioma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; BRAIN-TUMORS; SERUM IGE; POLYMORPHISMS; HISTORY; PRIVILEGE; ALLERGIES; SUSCEPTIBILITY; IDENTIFICATION; POPULATION AB Current evidence suggests that immune system alterations contribute to the etiology of adult glioma, the most common adult brain tumor. Although previous studies have focused on variation in candidate genes in the adaptive immune system, the innate immune system has emerged as a critical avenue for research given its known link with carcinogenesis. To identify genetic markers in pathways critical to innate immunity, we conducted an association study of 551 glioma cases and 865 matched controls of European ancestry to investigate "tag" single nucleotide polymorphisms (SNP) in 148 genetic regions. Two independent U.S. case-control studies included were as follows: a hospital-based study conducted by the National Cancer Institute (263 cases, 330 controls) and a community-based study conducted by the National Institute for Occupational Safety and Health (288 cases, 535 controls). Tag SNPs (1,397) chosen on the basis of an r(2) of >0.8 and minor allele frequency of >5% in Caucasians in HapMap1 were genotyped. Glioma risk was estimated by odds ratios. Nine SNPs distributed across eight genetic regions (ALOX5, IRAK3, ITGB2, NCF2, NFKB1, SELP, SOD1, and STAT1) were associated with risk of glioma with P value of <0.01. Although these associations were no longer statistically significant after controlling for multiple comparisons, the associations were notably consistent in both studies. Region-based tests were statistically significant (P < 0.05) for SELP, SOD, and ALOX5. Analyses restricted to glioblastoma (n = 254) yielded significant associations for the SELP, DEFB126/127, SERPINI1, and LY96 genetic regions. We have identified a promising set of innate immunity-related genetic regions for further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1651-8) C1 [Rajaraman, Preetha; Brenner, Alina V.; Wang, Sophia S.; Pfeiffer, Ruth M.; Linet, Martha S.; Kwon, Deukwoo; Rothman, Nathaniel; Inskip, Peter D.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Butler, Mary Ann; Ruder, Avima M.] NIOSH, Ctr Dis Control & Prevent, Dept Hlth & Human Serv, Cincinnati, OH 45226 USA. [Yeager, Meredith; Wang, Zhaoming; Orr, Nick; Thomas, Gilles; Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Rajaraman, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7058, Rockville, MD 20852 USA. EM rajarama@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 FU NCI, NIH, Department of Health and Human Services [N01-CO-12400] FX Intramural funds from the NCI, NIH, Department of Health and Human Services, and has been funded in whole or in part with federal funds from the NCI, NIH, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, or does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 43 TC 24 Z9 25 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2009 VL 18 IS 5 BP 1651 EP 1658 DI 10.1158/1055-9965.EPI-08-1041 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 445WF UT WOS:000266081500043 PM 19423540 ER PT J AU Symes, JC Siatskas, C Fowler, DH Medin, JA AF Symes, J. C. Siatskas, C. Fowler, D. H. Medin, J. A. TI Retrovirally transduced murine T lymphocytes expressing FasL mediate effective killing of prostate cancer cells SO CANCER GENE THERAPY LA English DT Article DE apoptosis; c-FLIP; docetaxel; Fas; gene transfer; mitoxantrone ID MHC CLASS-I; GENE-TRANSFER; CD95-MEDIATED APOPTOSIS; ANTITUMOR-ACTIVITY; CARCINOMA-CELLS; CD95 EXPRESSION; TUMOR-CELLS; LONG FORM; LIGAND; ACTIVATION AB Adoptively transferred T cells possess anticancer activities partially mediated by T-cell FasL engagement of Fas tumor targets. However, antigen-induced T-cell activation and clonal expansion, which stimulates FasL activity, is often inefficient in tumors. As a gene therapy approach to overcome this obstacle, we have created oncoretroviral vectors to overexpress FasL or non-cleavable FasL (ncFasL) on murine T cells of a diverse T-cell receptor repertoire. Expression of c-FLIP was also engineered to prevent apoptosis of transduced cells. Retroviral transduction of murine T lymphocytes has historically been problematic, and we describe optimized T-cell transduction protocols involving CD3/CD28 co-stimulation of T cells, transduction on ice using concentrated oncoretrovirus, and culture with IL-15. Genetically modified T cells home to established prostate cancer tumors in vivo. Co-stimulated T cells expressing FasL, ncFasL and ncFasL/c-FLIP each mediated cytotoxicity in vitro against RM-1 and LNCaP prostate cancer cells. To evaluate the compatibility of this approach with current prostate cancer therapies, we exposed RM-1, LNCaP, and TRAMP-C1 cells to radiation, mitoxantrone, or docetaxel. Fas and H-2(b) expression were upregulated by these methods. We have developed a novel FasL-based immuno-gene therapy for prostate cancer that warrants further investigation given the apparent constitutive and inducible Fas pathway expression in this malignancy. C1 [Medin, J. A.] Univ Toronto, Univ Hlth Network, Dept Med Biophys, Div Stem Cell & Differentiat, Toronto, ON, Canada. [Siatskas, C.; Medin, J. A.] Ontario Canc Inst, Div Stem Cell & Dev Biol, Toronto, ON M4X 1K9, Canada. [Fowler, D. H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Medin, J. A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. RP Medin, JA (reprint author), Univ Toronto, Univ Hlth Network, Dept Med Biophys, Div Stem Cell & Differentiat, 67 Coll St,CBS Bldg Room 406, Toronto, ON, Canada. EM jmedin@uhnres.utoronto.ca FU Prostate Cancer Research Foundation of Canada FX We thank Anton Neschadim and Dr Richard Miller for helpful discussions about transductions and T-cell biology. This work is supported by a grant from the Prostate Cancer Research Foundation of Canada. NR 59 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAY PY 2009 VL 16 IS 5 BP 439 EP 452 DI 10.1038/cgt.2008.96 PG 14 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 433ZR UT WOS:000265245500007 PM 19096446 ER PT J AU Zimonjic, DB Ullmannova-Benson, V Factor, VM Thorgeirsson, SS Popescu, NC AF Zimonjic, Drazen B. Ullmannova-Benson, Veronika Factor, Valentina M. Thorgeirsson, Snorri S. Popescu, Nicholas C. TI Recurrent and nonrandom DNA copy number and chromosome alterations in Myc transgenic mouse model for hepatocellular carcinogenesis: implications for human disease SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID GROWTH-FACTOR-ALPHA; CARCINOMA CELL-LINES; EXPRESSING C-MYC; FRAGILE SITES; II RECEPTOR; FHIT GENE; LIVER; CANCER; MICE; TUMORS AB Mouse models for hepatocellular carcinoma (HCC) provide an experimental ground for dissecting the genetic and biological complexities of human liver cancer and contribute to our ability to gain insights into the relevance of candidate cancer genes. We examined, using spectral karyotyping (SKY) and array-based CGH (aCGH), seven cell lines derived from HCC spontaneously developed in transgenic Myc mice (Myc), and four cell lines established from tumors induced in nude mice by inoculation with the original Myc cells (nuMyc). All the cell lines exhibited gain of material from chromosomes 5, 6, 8, 10, 11, 15, and 19 and DNA copy-number loss from chromosomes 2, 4, 7, 9, 12, 14, and X. In addition, several recurrent chromosome reorganizations were found, including del(3), t(3;8), del(4), t(4;11), t(6;5), del(7), del(8), del(9), t(10;14), del(11), and del(16). Chromosome breakpoints underlying rearrangements clustered in the regions previously identified as important for the early stages of Myc-induced hepatocarcinogenesis. The results strongly suggest the importance of recurrent breakage and loss of chromosomes 4, 9, and 14 and gain of chromosomes 15 and 19 in mouse liver neoplasia. Genomic changes observed in Myc HCC cell lines are also recurrent in HCC developed in other transgenic mouse models, in mouse spontaneous HCC and derivative cell lines, and in preneoplastic liver lesions induced with chemical carcinogens. Overall, the present results document selective, nonrandom genomic changes involving chromosomal regions homologous to those implicated in human HCC. (C) 2009 Elsevier Inc. All rights reserved. C1 [Zimonjic, Drazen B.; Ullmannova-Benson, Veronika; Factor, Valentina M.; Thorgeirsson, Snorri S.; Popescu, Nicholas C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr MSC 4262,Bldg 37,Room 4128B, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI Benson, Veronika/D-9942-2014 OI Benson, Veronika/0000-0003-4770-9909 FU Intramural Research Program of the National Cancer Institute; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 48 TC 6 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD MAY PY 2009 VL 191 IS 1 BP 17 EP 26 DI 10.1016/j.cancergencyto.2008.12.014 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 445BD UT WOS:000266023700003 PM 19389504 ER PT J AU Kelloff, GJ Sigman, CC Contag, CH AF Kelloff, Gary J. Sigman, Caroline C. Contag, Christopher H. TI Early Detection of Oral Neoplasia: Watching with New Eyes SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID NECK-CANCER; DRUG DEVELOPMENT; INTRAEPITHELIAL NEOPLASIA; CHEMOPREVENTION; HEAD; AUTOFLUORESCENCE; PREVENTION; PROGRESS; FIELD; RISK C1 [Kelloff, Gary J.] NCI, Div Canc Treatment & Diag, Canc Imaging Program, Rockville, MD 20852 USA. [Sigman, Caroline C.] CCS Associates, Mountain View, CA USA. [Contag, Christopher H.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Contag, Christopher H.] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. [Contag, Christopher H.] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Contag, Christopher H.] Stanford Univ, Mol Imaging Program, Sch Med, Stanford, CA 94305 USA. RP Kelloff, GJ (reprint author), NCI, Div Canc Treatment & Diag, Canc Imaging Program, 6130 Execut Blvd,Room 6058, Rockville, MD 20852 USA. EM kelloffg@dcpcepn.nci.nih.gov NR 40 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2009 VL 2 IS 5 BP 405 EP 408 DI 10.1158/1940-6207.CAPR-09-0064 PG 4 WC Oncology SC Oncology GA 441IU UT WOS:000265763300002 PM 19401527 ER PT J AU Vitale-Cross, L Czerninski, R Amornphimoltham, P Patel, V Molinolo, AA Gutkind, JS AF Vitale-Cross, Lynn Czerninski, Rakefet Amornphimoltham, Panomwat Patel, Vyomesh Molinolo, Alfredo A. Gutkind, J. Silvio TI Chemical Carcinogenesis Models for Evaluating Molecular-Targeted Prevention and Treatment of Oral Cancer SO CANCER PREVENTION RESEARCH LA English DT Review ID SQUAMOUS-CELL CARCINOMAS; UPPER AERODIGESTIVE TISSUE; 4-NITROQUINOLINE N-OXIDE; GROUP-A GENE; NECK-CANCER; ESOPHAGEAL CARCINOGENESIS; MUCOSAL CARCINOGENESIS; MOUSE TONGUE; K-RAS; MICE C1 [Vitale-Cross, Lynn; Czerninski, Rakefet; Amornphimoltham, Panomwat; Patel, Vyomesh; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU NIH; National Institute of Dental and Craniofacial Research FX Intramural Research Program of NIH, National Institute of Dental and Craniofacial Research. NR 41 TC 37 Z9 38 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2009 VL 2 IS 5 BP 419 EP 422 DI 10.1158/1940-6207.CAPR-09-0058 PG 4 WC Oncology SC Oncology GA 441IU UT WOS:000265763300004 PM 19401522 ER PT J AU Cekanova, M Lee, SH Donnell, RL Sukhthankar, M Eling, TE Fischer, SM Baek, SJ AF Cekanova, Maria Lee, Seong-Ho Donnell, Robert L. Sukhthankar, Mugdha Eling, Thomas E. Fischer, Susan M. Baek, Seung Joon TI Nonsteroidal Anti-inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis in Transgenic Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER CELLS; BETA SUPERFAMILY MEMBER; GROWTH-FACTOR-BETA; LUNG CARCINOGENESIS; CARCINOMA-CELLS; GAMMA LIGAND; NAG-1; PROTEIN; APOPTOSIS; MOUSE AB The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6 background). In the present study, we investigated whether the NAG-1 protein would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB background (NAG-1(Tg+/FVB)). NAG-1Tg+/FVB mice had both decreased number and size of urethane-induced tumors, compared with control littermates (NAG-1(Tg+/FVB) = 16 +/- 4 per mouse versus control = 20 +/- 7 per mouse, P < 0.05). Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control mice; however, only pulmonary adenomas were observed in NAG-1(Tg+/FVB) mice. Urethane-induced tumors from control littermates and NAG-1(Tg+/FVB) mice highly expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2, prostaglandin E synthase, and prostaglandin E(2) receptor) and highly activated several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation was decreased in NAG-1(Tg+/FVB) mice. Furthermore, significantly increased apoptosis in tumors of NAG-1(Tg+/FVB) mice compared with control mice was observed as assessed by caspase-3/7 activity. In addition, fewer inflammatory cells were observed in the lung tissue isolated from urethane-treated NAG-1(Tg+/FVB) mice compared with control mice. These results paralleled in vitro assays using human A549 pulmonary carcinoma cells. Less phosphorylated p38 MAPK was observed in cells overexpressing NAG-1 compared with control cells. Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer chemoprevention. C1 [Cekanova, Maria; Lee, Seong-Ho; Donnell, Robert L.; Sukhthankar, Mugdha; Baek, Seung Joon] Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. [Eling, Thomas E.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC USA. [Fischer, Susan M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Dept Carcinogenesis, Smithville, TX USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. EM sbaek2@utk.edu OI Cekanova, Maria/0000-0002-9651-1619; Donnell, Robert L./0000-0002-6778-954X FU American Cancer Society [CNE-111611]; NIH [RO1CA108975]; The University of Tennessee Center of Excellence in Livestock Diseases and Human Health; National Institute of Environmental Health Sciences/NIH FX American Cancer Society grant CNE-111611, NIH grant RO1CA108975, The University of Tennessee Center of Excellence in Livestock Diseases and Human Health (S.J. Baek), and National Institute of Environmental Health Sciences/NIH intramural research program (T. E. Eling). NR 35 TC 26 Z9 29 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2009 VL 2 IS 5 BP 450 EP 458 DI 10.1158/1940-6207.CAPR-09-0057 PG 9 WC Oncology SC Oncology GA 441IU UT WOS:000265763300008 PM 19401523 ER PT J AU Danforth, KN Gierach, GL Brinton, LA Hollenbeck, AR Katki, HA Leitzmann, MF Schatzkin, A Lacey, JV AF Danforth, Kim N. Gierach, Gretchen L. Brinton, Louise A. Hollenbeck, Albert R. Katki, Hormuzd A. Leitzmann, Michael F. Schatzkin, Arthur Lacey, James V., Jr. TI Nonsteroidal Anti-Inflammatory Drug Use and Endometrial Cancer Risk in the NIH-AARP Diet and Health Study SO CANCER PREVENTION RESEARCH LA English DT Article ID ADIPOSE-TISSUE; CYCLOOXYGENASE-2; INFLAMMATION; EXPRESSION; OBESITY AB Chronic inflammation may play an etiologic role in endometrial cancer. Nonsteroidal antiinflammatory drugs (NSAIDs) reduce inflammatory activity by inhibiting the proinflammatory cyclooxygenase enzymes and, therefore, may decrease cancer risk. However, few studies have examined the association between NSAID use and endometrial cancer. We conducted a prospective study among 72,524 women in the NIH-AARP Diet and Health Study. Women completed a questionnaire in 1996-1997 on lifestyle and health-related factors, including type and frequency of NSAID use within the past year, and were followed through 2003 by linkages to cancer registries and vital status databases. During 488,261 person-years of follow-up, there were 732 incident endometrial cancers. NSAID use, compared with non-use of NSAIDs, was not significantly associated with endometrial cancer risk [relative risk (RR), 0.90; 95% confidence interval (95% CI), 0.74-1.09]. Null associations were also observed by type of NSAID use [aspirin only: RR, 0.88; 95% CI, 0.70-1.11; nonaspirin NSAID (NA-NSAID) only: RR, 1.01; 95% CI, 0.79-1.29; both aspirin and NA-NSAIDs: RR, 0.85; 95% CI, 0.68-1.06]. Generally, results were not statistically significant by frequency of use for aspirin or NA-NSAIDs. Results did not change when women with a history of heart disease, hypertension, or diabetes were excluded to minimize the potential for confounding by indication. Overall, our data do not support an association between aspirin or NA-NSAID use and endometrial cancer risk. C1 [Danforth, Kim N.; Gierach, Gretchen L.; Brinton, Louise A.; Katki, Hormuzd A.; Leitzmann, Michael F.; Schatzkin, Arthur; Lacey, James V., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gierach, Gretchen L.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Leitzmann, Michael F.] Univ Hosp, Inst Epidemiol & Prevent Med, Regensburg, Germany. RP Danforth, KN (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 550,MSC 7234, Rockville, MD 20852 USA. EM danfortk@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU National Cancer Institute; NIH; Sallie Rosen Kaplan FX Intramural Research Program of the National Cancer Institute, NIH. K. Danforth was supported in part by the Sallie Rosen Kaplan Fellowship for Women Scientists in Cancer Research, National Cancer Institute, NIH. NR 17 TC 17 Z9 17 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2009 VL 2 IS 5 BP 466 EP 472 DI 10.1158/1940-6207.CAPR-08-0239 PG 7 WC Oncology SC Oncology GA 441IU UT WOS:000265763300010 PM 19401534 ER PT J AU Watters, JL Gail, MH Weinstein, SJ Virtamo, J Albanes, D AF Watters, Joanne L. Gail, Mitchell H. Weinstein, Stephanie J. Virtamo, Jarmo Albanes, Demetrius TI Associations between alpha-Tocopherol, beta-Carotene, and Retinol and Prostate Cancer Survival SO CANCER RESEARCH LA English DT Article ID DIETARY VITAMIN-E; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE; PHYSICIANS HEALTH; UNITED-STATES; FOLLOW-UP; RISK; SUPPLEMENTATION; SERUM; PREVENTION AB Previous studies suggest that carotenoids and tocopherols (vitamin E compounds) may be inversely associated with prostate cancer risk, yet little is known about how they affect prostate cancer progression and survival. We investigated whether serum alpha-tocopherol, P-carotene, and retinol concentrations, or the alpha-tocopherol and beta-carotene trial supplementation, affected survival of men diagnosed with prostate cancer during the alpha-Tocopherol, beta-Carotene Cancer Prevention Study, a randomized, double-blind, placebo-controlled primary prevention trial testing the effects of beta-carotene and alpha-tocopherol supplements on cancer incidence in adult male smokers in southwestern Finland (n = 29,133). Prostate cancer survival was examined using the Kaplan-Meier method with deaths from other causes treated as censoring, and using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CI) adjusted for family history of prostate cancer, age at randomization, benign prostatic hyperplasia, age and stage at diagnosis, height, body mass index, and serum cholesterol. As of April 2005, 1,891 men were diagnosed with prostate cancer and 395 died of their disease. Higher serum alpha-tocopherol at baseline was associated with improved prostate cancer survival (HR, 0.67; 95% CI, 0.45-1.00), especially among cases who had received the alpha-tocopherol intervention of the trial and who were in the highest quintile of alpha-tocopherol at baseline (HR, 0.51; 95% CI, 0.20-0.90) or at the 3-year follow-up measurement (HR, 0.26; 95% CI, 0.09-0.71). Serum beta-carotene, serum retinol, and supplemental beta-carotene had no apparent effects on survival. These findings suggest that higher alpha-tocopherol (and not beta-carotene or retinol) status increases overall prostate cancer survival. Further investigations, possibly including randomized studies, are needed to confirm this observation. [Cancer Res 2009;69(9):3833-41] C1 [Watters, Joanne L.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Watters, JL (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Suite 320, Bethesda, MD 20892 USA. EM wattersj@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU NIH; National Cancer Institute.; USPHS [N01-CN-45165, N01-RC-45035, N01-RC-37004]; Department of Health and Human Services. FX Intramural Research Program of the NIH and the National Cancer Institute. Additionally, this research was supported by USPHS contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer Institute, Department of Health and Human Services. NR 46 TC 25 Z9 26 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 IS 9 BP 3833 EP 3841 DI 10.1158/0008-5472.CAN-08-4640 PG 9 WC Oncology SC Oncology GA 441IG UT WOS:000265761900016 PM 19383902 ER PT J AU Hodge, DL Yang, J Buschman, MD Schaughency, PM Dang, H Bere, W Yang, YL Savan, R Subleski, JJ Yin, XM Loughran, TP Young, HA AF Hodge, Deborah L. Yang, Jun Buschman, Matthew D. Schaughency, Paul M. Dang, Hong Bere, William Yang, Yili Savan, Ram Subleski, Jeff J. Yin, Xiao-Ming Loughran, Thomas P., Jr. Young, Howard A. TI Interleukin-15 Enhances Proteasomal Degradation of Bid in Normal Lymphocytes: Implications for Large Granular Lymphocyte Leukemias SO CANCER RESEARCH LA English DT Article ID NATURAL-KILLER-CELLS; DNA-DAMAGE RESPONSE; LYMPHOPROLIFERATIVE DISEASE; APOPTOSIS INDUCTION; SIGNALING PATHWAYS; IL-2 RECEPTOR; BETA-CHAIN; MICE; SURVIVAL; PROLIFERATION AB Large granular lymphocyte (LGL) leukemia is a clonal proliferative disease of T and natural killer (NK) cells. Interleukin (IL)-15 is important for the development and progression of LGL leukemia and is a survival factor for normal NK and T memory cells. IL-15 alters expression of Bcl-2 family members, Bcl-2, Bcl-XL, Bim, Noxa, and Mcl-1; however, effects on Bid have not been shown. Using an adoptive transfer model, we show that NK cells from Bid-deficient mice survive longer than cells from wild-type control mice when transferred into IL-15-null mice. In normal human NK cells, IL-15 significantly reduces Bid accumulation. Decreases in Bid are not due to alterations in RNA accumulation but result from increased proteasomal degradation. IL-15 up-regulates the E3 ligase HDM2 and we find that HDM2 directly interacts with Bid. HDM2 suppression by short hairpin RNA increases Bid accumulation lending further support for HDM2 involvement in Bid degradation. In primary leukemic LGLs, Bid levels are low but are reversed with bortezomib treatment with subsequent increases in LGL apoptosis. Overall, these data provide a novel molecular mechanism for IL-15 control of Bid that potentially links this cytokine to leukemogenesis through targeted proteasome degradation of Bid and offers the possibility that proteasome inhibitors may aid in the treatment of LGL leukemia. [Cancer Res 2009;69(9):3986-94] C1 [Hodge, Deborah L.; Schaughency, Paul M.; Dang, Hong; Bere, William; Savan, Ram; Subleski, Jeff J.; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Hodge, Deborah L.; Schaughency, Paul M.; Dang, Hong; Bere, William; Savan, Ram; Subleski, Jeff J.; Young, Howard A.] SAIC Frederick, Frederick, MD 21702 USA. [Yang, Yili] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. [Buschman, Matthew D.] Burnham Inst Med Res, La Jolla, CA USA. [Yang, Jun; Loughran, Thomas P., Jr.] Penn State Univ, Penn State Canc Inst, Coll Med, Hershey, PA USA. [Yin, Xiao-Ming] Univ Pittsburgh, Sch Med, Dept Pathol, Div Mol Diagnost, Pittsburgh, PA USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM younghow@mail.nih.gov FU Intramural Research Program of die National Cancer Institute; NIH Center for Cancer Research; National Cancer Institute/NIH [N01CO-12400] FX Intramural Research Program of die National Cancer Institute/NIH Center for Cancer Research and National Cancer Institutc/NIH contract N01CO-12400. NR 47 TC 27 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 IS 9 BP 3986 EP 3994 DI 10.1158/0008-5472.CAN-08-3735 PG 9 WC Oncology SC Oncology GA 441IG UT WOS:000265761900034 PM 19366803 ER PT J AU Woo, HG Park, ES Lee, JS Lee, YH Ishikawa, T Kim, YJ Thorgeirsson, SS AF Woo, Hyun Goo Park, Eun Sung Lee, Ju-Seog Lee, Yun-Han Ishikawa, Tsuyoshi Kim, Yoon Jun Thorgeirsson, Snorri S. TI Identification of Potential Driver Genes in Human Liver Carcinoma by Genomewide Screening SO CANCER RESEARCH LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; MTOR PATHWAY; IN-VIVO; CANCER; EXPRESSION; CLASSIFICATION; METFORMIN; TUMORS; GROWTH; TRANSCRIPTION AB Genomic copy number aberrations and corresponding transcriptional deregulation in the cancer genome have been suggested to have regulatory roles in cancer development and progression. However, functional evaluation of individual genes from lengthy lists of candidate genes from genomic data sets presents a significant challenge. Here, we report effective gene selection strategies to identify potential driver genes based on systematic integration of genome scale data of DNA copy numbers and gene expression profiles. Using regional pattern recognition approaches, we discovered the most probable copy number-dependent regions and 50 potential driver genes. At each step of the gene selection process, the functional relevance of the selected genes was evaluated by estimating the prognostic significance of the selected genes. Further validation using small interference RNA-mediated knockdown experiments showed proof-of-principle evidence for the potential driver roles of the genes in hepatocellular carcinoma progression (i.e., NCSTN and SCRIB). In addition, systemic prediction of drug responses implicated the association of the 50 genes with specific signaling molecules (mTOR, AMPK, and EGFR). In conclusion, the application of an unbiased and integrative analysis of multidimensional genomic data sets can effectively screen for potential driver genes and provides novel mechanistic and clinical insights into the pathobiology of hepatocellular carcinoma. [Cancer Res 2009;69(9):4059-66] C1 [Thorgeirsson, Snorri S.] NCI, Ctr Excellence Integrat Canc Biol & Genom, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Park, Eun Sung; Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX 77030 USA. [Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea. RP Thorgeirsson, SS (reprint author), NCI, Ctr Excellence Integrat Canc Biol & Genom, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov RI Kim, Yoon Jun/J-2746-2012 FU Intramural NIH HHS [Z99 CA999999] NR 39 TC 60 Z9 64 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 IS 9 BP 4059 EP 4066 DI 10.1158/0008-5472.CAN-09-0164 PG 8 WC Oncology SC Oncology GA 441IG UT WOS:000265761900043 PM 19366792 ER PT J AU Abraham, I Jain, S Wu, CP Kuang, YH Lee, J Chen, X El Sayed, K Ambudkar, S Chen, ZS AF Abraham, Ioana Jain, Sandeep Wu, Chung-Pu Kuang, Yehong Lee, Jefferson Chen, Xiang El Sayed, Khalid Ambudkar, Suresh Chen, Zhe-Sheng TI Marine sponge-derived sipholane triterpenes reverse P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 St Johns Univ, Jamaica, NY 11439 USA. Univ Louisiana, Monroe, LA USA. NCI, Bethesda, MD 20892 USA. Cent S Univ, Xiang Ya Hosp, Changsha, Hunan, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 896 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802005 ER PT J AU Adiseshaiah, P Stern, S Dobrovolskaia, M Clogston, J Zeng, JW Hall, J Patri, A McNeil, S AF Adiseshaiah, Pavan Stern, Stephan Dobrovolskaia, Marina Clogston, Jeffrey Zeng, Jiwen Hall, Jennifer Patri, Anil McNeil, Scott TI Preclinical characterization of nanomaterial intended for cancer diagnosis and therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 ATP NCL, Frederick, MD USA. NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5362 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701085 ER PT J AU Adiseshaiah, P Stern, S Devalapally, H Ganta, S Dobrovolskaia, M Potter, T Mcleland, C Clogston, J Patri, A Amiji, M McNeil, S AF Adiseshaiah, Pavan Stern, Stephan Devalapally, Harikrishna Ganta, Srinivas Dobrovolskaia, Marina Potter, Timothy Mcleland, Christopher Clogston, Jeffrey Patri, Anil Amiji, Mansoor McNeil, Scott TI An evaluation of a novel nanoemulsion formulation of paclitaxel for cytotoxicity and apoptotic activity in human colon cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 ATP NCL, Frederick, MD USA. NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5374 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701096 ER PT J AU Ahn, J Schumacher, F Berndt, S Pfeiffer, R Kaaks, R Thun, M Hunter, D Hayes, R AF Ahn, Jiyoung Schumacher, Fredrick Berndt, Sonja Pfeiffer, Ruth Kaaks, Rudolf Thun, Michael Hunter, David Hayes, Richard CA Breast Prostate Canc Cohort TI Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3) SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCEG, Rockville, MD USA. Univ So Calif, Los Angeles, CA USA. German Canc Res Ctr, Heidelberg, Germany. Amer Canc Soc, Atlanta, GA 30329 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-239 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702706016 ER PT J AU Alessandro, R Fontana, S Barranca, M Corrado, C Giordano, M Zanella-Cleon, I Becchi, M Kohn, E De Leo, G AF Alessandro, Riccardo Fontana, Simona Barranca, Marilisa Corrado, Chiara Giordano, Margherita Zanella-Cleon, Isabel Becchi, Michel Kohn, Elise De Leo, Giacomo TI Molecular profiling of chronic myelogenous leukemia cell lines: identification of new molecular markers for the characterization of leukemia phenotype SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Palermo, Palermo, Italy. CNRS, Inst Biol & Chim Prot, Lyon, France. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4742 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701168 ER PT J AU Alley, M Plater, K Borgel, S Anver, M Hollingshead, M AF Alley, Michael Plater, Kevin Borgel, Suzanne Anver, Miriam Hollingshead, Melinda TI A method for obtaining improved growth of tumor xenografts from the surgical implantation of limited numbers of colonies derived from human colon cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Dev Therapeut Program, Frederick, MD 21701 USA. SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3170 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803462 ER PT J AU Anderson, K Mongin, S Sinha, R Gross, M Church, T AF Anderson, Kristin Mongin, Steven Sinha, Rashmi Gross, Myron Church, Timothy TI Pancreatic cancer risk: associations with meat-derived carcinogen intake SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Minnesota SPH, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-224 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703453 ER PT J AU Andreotti, G Hou, LF Freeman, LB Mahajan, R Koutros, S Coble, J Blair, A Hoppin, J Alavanja, M AF Andreotti, Gabriella Hou, Lifang Freeman, Laura Beane Mahajan, Rajeev Koutros, Stella Coble, Joseph Blair, Aaron Hoppin, Jane Alavanja, Michael TI Obesity, agricultural pesticide use and cancer incidence in the Agricultural Health Study Cohort SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2136 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704078 ER PT J AU Aprelikova, O Yu, X Palla, J John, S Yi, M Stephens, R Han, H Risinger, J Jazaeri, A Niederhuber, J AF Aprelikova, Olga Yu, Xiang Palla, John John, Simone Yi, Ming Stephens, Robert Han, Hui Risinger, John Jazaeri, Amir Niederhuber, John TI Differential expression of microRNAs in endometrial cancer microenvironment SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. SAIC, Frederick, MD USA. Mem Hlth Univ Med Ctr, Savannah, GA 31404 USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 591 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803131 ER PT J AU Arun, P Brown, M Ehsanian, R Chen, Z Van Waes, C AF Arun, Pattatheyil Brown, Matthew Ehsanian, Reza Chen, Zhong Van Waes, Carter TI Nuclear localized NF-kB Rel A is phosphorylated at Serine 276 by protein kinase A and contributes to the malignant phenotype of head and neck cancer. SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Arun, Pattatheyil; Brown, Matthew; Ehsanian, Reza; Chen, Zhong; Van Waes, Carter] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2758 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804131 ER PT J AU Bai, R Hamel, E AF Bai, Ruoli Hamel, Ernest TI Interaction of [H-3]halichondrin B with tubulin SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bai, Ruoli; Hamel, Ernest] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5570 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604329 ER PT J AU Baird, B Dickey, J Sedelnikova, O Redon, C Nakamura, A Bonner, W AF Baird, Brandon Dickey, Jennifer Sedelnikova, Olga Redon, Christophe Nakamura, Asako Bonner, William TI The bystander effect: a general cellular mechanism in response to various stresses including tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Baird, Brandon; Dickey, Jennifer; Sedelnikova, Olga; Redon, Christophe; Nakamura, Asako; Bonner, William] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1308 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801390 ER PT J AU Bandele, O Wang, XT Noureddine, M Resnick, M Bell, D AF Bandele, Oman Wang, Xuting Noureddine, Maher Resnick, Michael Bell, Douglas TI Single nucleotide polymorphisms alter sequence-specific p53-DNA binding to gene regulatory elements SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Bandele, Oman; Wang, Xuting; Noureddine, Maher; Resnick, Michael; Bell, Douglas] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4223 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802133 ER PT J AU Baranello, L Bertozzi, D Pommier, Y Capranico, G AF Baranello, Laura Bertozzi, Davide Pommier, Yves Capranico, Giovanni TI Induction of a novel long antisense RNA from the human HIF-1\#945; locus may contribute to HIF-1\#945; regulation and inhibition by camptothecins in cancer cells. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Bologna, Dept Biochem, I-40126 Bologna, Italy. NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3753 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604162 ER PT J AU Beck, G Camalier, C Young, M Yi, M Hood, B Perella, C Bobe, G Stephens, R Conrads, T Colburn, N AF Beck, George Camalier, Corinne Young, Matthew Yi, Ming Hood, Brian Perella, Christine Bobe, Gerd Stephens, Robert Conrads, Thomas Colburn, Nancy TI Inorganic phosphate is a mitogen that alters cell growth, transformation and tumorigenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA USA. NCI, Frederick, MD 21701 USA. SAIC NCI Frederick, Frederick, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 970 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801304 ER PT J AU Beckstead, W Wei, J Song, Y Chen, QR Khan, J AF Beckstead, Wesley Wei, Jun Song, Young Chen, Qing-Rong Khan, Javed TI Massively parallel sequencing of microRNAs in neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Beckstead, Wesley; Wei, Jun; Song, Young; Chen, Qing-Rong; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2595 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804115 ER PT J AU Behrsing, H Furniss, M Robillard, K Mesa, D Richards, R Hamre, J Tomaszewski, J Parchment, R AF Behrsing, Holger Furniss, Michael Robillard, Kristine Mesa, Danielle Richards, Ryan Hamre, John Tomaszewski, Joseph Parchment, Ralph TI In vitro detection of O4 benzylfolate modulated, BCNU toxicity in human bone marrow using CFU-GM and tumor cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI Frederick, SAIC Frederick, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4582 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705107 ER PT J AU Bekaii-Saab, T Phelps, M Li, XB Saji, M Kosuri, K Goff, L Kauh, J O'Neil, B South, C Thomas, J Balsom, S Chattah, N Balint, C Liersemann, R Vasko, V Marsh, W Doyle, LA Ellison, G Ringel, M Calero, MV AF Bekaii-Saab, Tanios Phelps, Mitch Li, Xiaobai Saji, Motoyasu Kosuri, Kavitha Goff, Laura Kauh, John O'Neil, Bert South, Christopher Thomas, James Balsom, Stephanie Chattah, Nicole Balint, Catherine Liersemann, Ryan Vasko, Vasily Marsh, William Doyle, L. Austin Ellison, Gilian Ringel, Matthew Calero, Miguel Villalona TI A Multi-institutional Study of AZD6244 (ARRY-142886) in Patients with Advanced Biliary Cancers. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Comp Canc Ctr, Columbus, OH 43210 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Emory Univ, Atlanta, GA 30322 USA. Univ N Carolina, Raleigh, NC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NCI, CTEP, Bethesda, MD 20892 USA. Astra Zeneca, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-129 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805307 ER PT J AU Bendiabdellah, Y Zinzalla, G Badarch, U Nahar, K Antonow, D Rahman, K Shoemaker, R Melillo, G Thurston, D AF Bendiabdellah, Yassine Zinzalla, Giovanna Badarch, Uranchimeg Nahar, Kazi Antonow, Dyeison Rahman, Khondaker Shoemaker, Robert Melillo, Giovanni Thurston, David TI Design, synthesis and biological evaluation of potential inhibitors of the HIF-1 \#945;:HIF-1\#946; protein-protein interaction SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ London, CR UK Prot Prot Interact Drug Discovery Res Grp, London, England. NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Dev Therapeut Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4646 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604187 ER PT J AU Berndt, S Huang, WY Yeager, M Schoen, R Chanock, S Hayes, R AF Berndt, Sonja Huang, Wen-Yi Yeager, Meredith Schoen, Robert Chanock, Stephen Hayes, Richard TI Large-scale investigation of candidate genes and risk of advanced colorectal adenoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 93 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704042 ER PT J AU Beumer, J Parise, R Eiseman, J Covey, J Egorin, M AF Beumer, Jan Parise, Robert Eiseman, Julie Covey, Joseph Egorin, Merrill TI Nonenzymatic formation of active products of benzaldehyde dimethane sulfonate (NSC 281612) and benzoic acid dimethane sulfonate: relevance for future trials SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4520 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704383 ER PT J AU Bi, K Wang, J Machleidt, T Hermanson, S Sakamuru, S Huang, RL Xia, MH AF Bi, Kun Wang, Jun Machleidt, Thomas Hermanson, Spencer Sakamuru, Srilatha Huang, Ruili Xia, Menghang TI Identification of small molecule inducers of endoplasmic reticulum stress response SO CANCER RESEARCH LA English DT Meeting Abstract C1 Invitrogen, Madison, WI USA. NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5246 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803322 ER PT J AU Black, A Sherman, M Duggan, M Carreon, J Berg, C Kessel, B Buys, S Ragard, L Johnson, K Dunn, B Lamerato, L Kreimer, A AF Black, Amanda Sherman, Mark Duggan, Maire Carreon, J. Berg, Christine Kessel, Bruce Buys, Saundra Ragard, Lawrence Johnson, Karen Dunn, Barbara Lamerato, Lois Kreimer, Aimee TI Pathologic findings following false positive CA-125 or transvaginal ultrasound screens for ovarian cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Calgary, Calgary, AB, Canada. Queens Med Ctr, Honolulu, HI USA. Univ Utah, Salt Lake City, UT USA. Westat Corp, Rockville, MD USA. Henry Ford Hlth Syst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4824 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801154 ER PT J AU Bobe, G Albert, P Lanza, E Schatzkin, A Colburn, N Cross, A AF Bobe, Gerd Albert, Paul Lanza, Elaine Schatzkin, Arthur Colburn, Nancy Cross, Amanda TI Interleukin-6 as a potential biomarker for dietary prevention of advanced colorectal adenoma recurrence in the polyp prevention trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CCR, Frederick, MD 21701 USA. NCI, DCTD, Rockville, MD USA. NCI, CCR, Rockville, MD USA. NCI, DCEG, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1915 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603174 ER PT J AU Boehm, A Higgins, J Franzusoff, A Schlom, J Hodge, J AF Boehm, Amanda Higgins, Jack Franzusoff, Alex Schlom, Jeffrey Hodge, James TI Vaccination with two distinct vaccine vector platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. GlobeImmune Inc, Louisville, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 347 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805243 ER PT J AU Bosquet, JG Yeager, M Kraft, P Jacobs, K Wacholder, S Hoover, R Thomas, G Hunter, D Chanock, S AF Bosquet, Jesus Gonzalez Yeager, Meredith Kraft, Peter Jacobs, Kevin Wacholder, Sholom Hoover, Robert Thomas, Gilles Hunter, David Chanock, Stephen TI Fine mapping breast cancer risk with haplotype association analysis SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CGEMS Initiat, DCEG, NIH,DHHS, Gaithersburg, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 101 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704051 ER PT J AU Bulut, G Chen, K Glasgow, E Hong, SH Lee, HS Toretsky, J Daar, I Khanna, C Uren, A AF Bulut, Gulay Chen, Kevin Glasgow, Eric Hong, Sung-Hyeok Lee, Hyun-Shik Toretsky, Jeffrey Daar, Ira Khanna, Chand Uren, Aykut TI Small molecule inhibitors of ezrin as anti-metastatic agents in osteosarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Lombardi Comp Canc Ctr, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4961 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603371 ER PT J AU Burgess, D Rodesch, M Bainbridge, M Nazareth, L Boland, J Munzy, D Kitzman, J D'Ascenzo, M Matthews, C Amundadottir, L Dannenberg, L Zhang, XM Richmond, T Jeddeloh, J Albert, T Channock, S Gibbs, R AF Burgess, Daniel Rodesch, Matthew Bainbridge, Matthew Nazareth, Lynne Boland, Joseph Munzy, Donna Kitzman, Jacob D'Ascenzo, Mark Matthews, Casey Amundadottir, Laufrey Dannenberg, Luke Zhang, Xinmin Richmond, Todd Jeddeloh, Jeffrey Albert, Thomas Channock, Stephen Gibbs, Richard TI Sequence capture approaches coupled to next generation sequencing to identify candidate somatic mutations in human tumors, and germ-line mutations predisposing human cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 Roche NimbleGen Inc, Madison, WI USA. Human Genome Sequencing Ctr, Houston, TX USA. NCI, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1399 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803465 ER PT J AU Burrell, A Porter-Gill, P Kohaar, I Arhancet, J Prokunina-Olsson, L AF Burrell, Allison Porter-Gill, Patricia Kohaar, Indu Arhancet, Juan Prokunina-Olsson, Ludmila TI Translational and genetic studies on JazF1 in prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Burrell, Allison; Porter-Gill, Patricia; Kohaar, Indu; Arhancet, Juan; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 91 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704040 ER PT J AU Calvert, R Maciag, A Gupta, M Anderson, L AF Calvert, Richard Maciag, Anna Gupta, Meghana Anderson, Lucy TI Mutant K-ras 4A protein expression shows a strong positive correlation with superoxide production in human lung adenocarcinoma cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, College Pk, MD USA. SAIC Frederick Inc, Frederick, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI Frederick, Comparat Carcinogenesis Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 437 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801314 ER PT J AU Camphausen, K AF Camphausen, Kevin TI Histone deacetylase inhibitors combined with radiation in the treatment of high grade gliomas SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Camphausen, Kevin] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY28-3 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702600112 ER PT J AU Camps, J Hummon, A Grade, M Emons, G Nguyen, Q Ghadimi, BM Difilippantonio, M Caplen, N Ried, T AF Camps, Jordi Hummon, Amanda Grade, Marian Emons, Georg Quang Nguyen Ghadimi, B. Michael Difilippantonio, Michael Caplen, Natasha Ried, Thomas TI Functional validation of deregulated genes on chromosome 13 identifies novel candidate oncogenes in colon cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Med Gottingen, Gottingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1444 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804016 ER PT J AU Carlson, M Chen, YY Annunziata, C Kohn, E Chiosis, G Robles, A Varticovski, L AF Carlson, Marisa Chen, Yun-Yun Annunziata, Christina Kohn, Elise Chiosis, Gabriela Robles, Ana Varticovski, Lyuba TI The novel HSP90 inhibitor, PU-H71, synergizes with cisplatin and blocks invasion and migration of ovarian cell lines. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Denver, Denver, CO USA. Univ Maryland, Bethesda, MD USA. NCI, CCR, Bethesda, MD 20892 USA. MSKCC, New York, NY USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1857 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802179 ER PT J AU Carol, H Lock, R Houghton, P Morton, C Maris, J Courtright, J Kolb, E Gorlick, R Friedman, H Keir, S Kang, M Reynolds, C Smith, M AF Carol, Hernan Lock, Richard Houghton, Peter Morton, Christopher Maris, John Courtright, Joshua Kolb, E. Gorlick, Richard Friedman, Henry Keir, Stephen Kang, Min Reynolds, C. Smith, Malcolm TI Pediatric preclinical testing program (PPTP) evaluation of the Akt inhibitor GSK690693 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Canc Inst, Sydney, NSW, Australia. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Alfred I DuPont Hosp Children, Wilmington, DE USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Duke Univ, Durham, NC USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3193 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803487 ER PT J AU Cerchietti, L Lopes, E Yang, SN Hatzi, K Shaknovich, R Robles, A Walling, J Bhalla, K Chiosis, G Melnick, A AF Cerchietti, Leandro Lopes, Eloisi Yang, Shao Ning Hatzi, Katerina Shaknovich, Rita Robles, Ana Walling, Jennifer Bhalla, Kapil Chiosis, Gabriela Melnick, Ari TI A purine scaffold heat shock protein 90 (Hsp90) inhibitor destabilizes BCL6 and has specific anti-tumor activity in BCL6 dependent lymphomas in vitro and in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. Sloan Kettering Inst, Dept Mol Pharmacol & Chem, New York, NY USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2937 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802118 ER PT J AU Chapman, C Perez-Galan, P Wiestner, A AF Chapman, Colby Perez-Galan, Patricia Wiestner, Adrian TI ON 01910.Na, a novel clinical grade PLK-1 inhibitor, selectively induces apoptosis in human B-cell chronic lymphocytic leukemia (B-CLL) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chapman, Colby; Perez-Galan, Patricia; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3654 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705185 ER PT J AU Chen, G Ghosh, P Longo, D AF Chen, Gang Ghosh, Paritosh Longo, Dan TI MEK1 activation results in sustained TGF-beta signaling and growth inhibition by stabilizing type II receptor expression in human B-cell lymphoma cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Chen, Gang; Ghosh, Paritosh; Longo, Dan] NIH NIA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4382 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804028 ER PT J AU Chen, QR Song, Y Yu, LR Wei, J Veenstra, T Khan, J AF Chen, Qing-Rong Song, Yong Yu, Li-Rong Wei, Jun Veenstra, Timothy Khan, Javed TI Genomic and proteomic analysis identifies biological pathways related to high-risk neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Gaithersburg, MD USA. SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2768 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802263 ER PT J AU Cheuk, A Taylor, J Tsang, P Chung, JY Song, Y Desai, K Yu, YL Chen, QR Shah, K Mendoza, A Wei, J Khanna, C Catchpoole, D Qualman, S Hewitt, S Merlino, G Chanock, S Khan, J AF Cheuk, Adam Taylor, James Tsang, Patricia Chung, Joon-Yong Song, Young Desai, Krupa Yu, Yanlin Chen, Qing-Rong Shah, Kushal Mendoza, Arnulfo Wei, Jun Khanna, Chand Catchpoole, Daniel Qualman, Stephen Hewitt, Stephen Merlino, Glenn Chanock, Stephen Khan, Javed TI Identification and characterization of activating mutations in the fibroblast growth factor receptor 4 in rhabdomyosarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. Childrens Hosp Westmead, Westmead, NSW, Australia. Nationwide Childrens Hosp, Columbus, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1883 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805008 ER PT J AU Chuang, SC Jenab, M Heck, J Olshan, A Bencko, V Schantz, S Curado, MP Mates, D McClean, M Daudt, A Franceschi, S Zaridze, D Koifman, S Lazarus, P Herrero, R Fabianova, E Luigino, DM Zhang, ZF Muscat, J Talamini, R Rudnai, P Fernandez, L Lissowska, J Menezes, A Levi, F Hayes, R Benhamou, S Eluf-Neto, J Boccia, S Matos, E AF Chuang, Shu-Chun Jenab, Mazda Heck, Julia Olshan, Andrew Bencko, Vladimir Schantz, Stimson Paula Curado, Maria Mates, Dana McClean, Michael Daudt, Alexander Franceschi, Silvia Zaridze, David Koifman, Sergio Lazarus, Philip Herrero, Rolando Fabianova, Eleonora Maso Luigino, Dal Zhang, Zuo-Feng Muscat, Joshua Talamini, Renato Rudnai, Peter Fernandez, Leticia Lissowska, Jola Menezes, Ana Levi, Fabio Hayes, Richard Benhamou, Simone Eluf-Neto, Jose Boccia, Stefania Matos, Elena TI Diet and the risk of head and neck cancer: A pooled analysis in the INHANCE consortium SO CANCER RESEARCH LA English DT Meeting Abstract C1 IARC, Lyon, France. UNC, Chapel Hill, NC USA. Charles Univ Prague, Prague, Czech Republic. MSKCC, New York, NY USA. Inst Publ Hlth, Bucharest, Romania. Boston Univ, Boston, MA 02215 USA. Hosp Clin Porto Allegre, Porto Alegre, RS, Brazil. Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. Escola Nacl Saude Publica, Rio De Janeiro, Brazil. Penn State Coll Med, Hershey, PA USA. Inst Invest Epidemiol, San Jose, Costa Rica. Specialized State Hlth Inst, Banska Bystrica, Slovakia. Aviano Canc Ctr, I-33081 Aviano, Italy. Univ Calif Los Angeles, Los Angeles, CA USA. Natl Inst Environm Hlth, Budapest, Hungary. Inst Oncol & Radiol, Havana, Cuba. Canc Ctr & Maria Sklodowska Curie, Warsaw, Poland. Univ Fed Pelotas, Pelotas, Brazil. Inst Univ Med Sociale & Prevent, CH-1005 Lausanne, Switzerland. NCI, Bethesda, MD 20892 USA. INSERM, Paris, France. Univ Sao Paulo, Sao Paulo, Brazil. Univ Cattolica Sacro Cuore, Rome, Italy. Univ Buenos Aires, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1978 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703105 ER PT J AU Costantino, C Witkiewicz, A Kuwano, Y Cozzitorto, J Yeo, C Gorospe, M Brody, J AF Costantino, Christina Witkiewicz, Agnieszka Kuwano, Yuki Cozzitorto, Joseph Yeo, Charles Gorospe, Myriam Brody, Jonathan TI Increased HuR expression in pancreatic cancer cells dramatically optimizes gemcitabine efficacy SO CANCER RESEARCH LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5539 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803239 ER PT J AU Coulouarn, C Factor, V Durkin, M Thorgeirsson, S AF Coulouarn, Cedric Factor, Valentina Durkin, Marian Thorgeirsson, Snorri TI Functional and clinical implications of miR-122 expression levels in human hepatocellular carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Coulouarn, Cedric; Factor, Valentina; Durkin, Marian; Thorgeirsson, Snorri] NIH, Bethesda, MD 20892 USA. RI Coulouarn, Cedric/E-5472-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2546 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803173 ER PT J AU Crende, O Sabatino, M Valcarcel, M Wang, E Marincola, F Vidal-Vanaclocha, F AF Crende, Olatz Sabatino, Marianna Valcarcel, Maria Wang, Ena Marincola, Francesco Vidal-Vanaclocha, Fernando TI Interleukin-18-dependent genes in highly metastatic VLA-4 integrin-expressing human melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Basque Country, Sch Med, Leioa 48940, Bizkaia, Spain. NCI, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA. Pharmakine SL, Derio, Spain. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4972 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603415 ER PT J AU Daffier, M Ford, M Jones, R Kovatich, A Hood, B Zhang, J Veenstra, T Conrads, T Krizman, D AF Daffier, Marlene Ford, Michael Jones, Richard Kovatich, Albert Hood, Brian Zhang, Jeff Veenstra, Timothy Conrads, Thomas Krizman, David TI Quantitation of Her2 protein expression in formalin fixed breast cancer tissue using a mass spectrometry based MRM assay SO CANCER RESEARCH LA English DT Meeting Abstract C1 Express Pathol Inc, Gaithersburg, MD USA. NextGen Sci, Ann Arbor, MI USA. MDR Global Syst LLC, Windber, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Merck & Co Inc, Rahway, NJ 07065 USA. NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2620 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805282 ER PT J AU Dai, CL Wang, YS Tiwari, A Wu, CP Su, XD Wang, SR Liu, DG Ashby, C Huang, Y Robey, R Liang, YJ Chen, LM Shi, CJ Ambudkar, S Chen, ZS Fu, LW AF Dai, Chun-ling Wang, Yan-sheng Tiwari, Amit Wu, Chung-pu Su, Xiao-dong Wang, Si-rong Liu, Dong-geng Ashby, Charles, Jr. Huang, Yan Robey, Robert Liang, Yong-ju Chen, Li-ming Shi, Cheng-jun Ambudkar, Suresh Chen, Zhe-sheng Fu, Liwu TI Lapatinib could reverse ABCB1 and ABCG2 mediated-multidrug resistance in Vitro, ex-vivo and in Vivo but increase exposure of chemotherapeutic agent SO CANCER RESEARCH LA English DT Meeting Abstract C1 Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, New York, NY USA. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 894 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802002 ER PT J AU Danforth, K Gierach, G Brinton, L Hollenbeck, A Katki, H Leitzmann, M Schatzkin, A Lacey, J AF Danforth, Kim Gierach, Gretchen Brinton, Louise Hollenbeck, Albert Katki, Hormuzd Leitzmann, Michael Schatzkin, Arthur Lacey, James, Jr. TI Nonsteroidal anti-inflammatory drug use and endometrial cancer risk in the NIH-AARP Diet and Health Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. AARP, Washington, DC USA. Univ Hosp, Inst Epidemiol & Prevent Med, Regensburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4862 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704145 ER PT J AU Nguyen, D Zajac-Kaye, M Voeller, D Rubinstein, L Tomaszewski, J Kummar, S Pommier, Y Doroshow, J Yang, S AF Dat Nguyen Zajac-Kaye, Maria Voeller, Donna Rubinstein, Larry Tomaszewski, Joseph Kummar, Shivaani Pommier, Yves Doroshow, James Yang, Sherry TI UCN-01 significantly enhances anti-cancer activity of poly(ADP-ribose) polymerase inhibition in combination with DNA damaging agent SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Dat Nguyen; Zajac-Kaye, Maria; Voeller, Donna; Rubinstein, Larry; Tomaszewski, Joseph; Kummar, Shivaani; Pommier, Yves; Doroshow, James; Yang, Sherry] NCI, Div Canc Treatment & Diag, Med Oncol Branch, Lab Mol Pharmacol,Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4701 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604311 ER PT J AU Daugherty, S Pfeiffer, R Hayes, R Leitzmann, M Sigurdson, A Silverman, D AF Daugherty, Sarah Pfeiffer, Ruth Hayes, Richard Leitzmann, Michael Sigurdson, Alice Silverman, Debra TI Non-steroidal anti-inflammatory drugs and bladder cancer: A pooled multi-cohort study. SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NYU, New York, NY USA. Univ Regensburg, D-93053 Regensburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-223 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703452 ER PT J AU De Luca, P Vazquez, E Moiola, C Gueron, G Zalazar, F Gardner, K De Siervi, A AF De Luca, Paola Vazquez, Elba Moiola, Cristian Gueron, Geraldine Zalazar, Florencia Gardner, Kevin De Siervi, Adriana TI BRCA1 orchestrates a novel molecular interplay at the BRCA1 and GADD153 promoters to regulate transcriptional responses to DNA damage SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Buenos Aires, Dept Biol Chem, Buenos Aires, Argentina. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1514 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804313 ER PT J AU DeCicco-Skinner, K Trovato, E Simmons, J Wiest, J AF DeCicco-Skinner, Kathleen Trovato, Erika Simmons, John Wiest, Jonathan TI Tpl2 knockout mice have a heightened inflammatory response to TPA: involvement of the NFkB signal transduction pathway SO CANCER RESEARCH LA English DT Meeting Abstract C1 Amer Univ, Washington, DC 20016 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3454 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803380 ER PT J AU Devor, C Hanson, J Bandle, R Emmert-Buck, M Pinto, P Levens, D Meltzer, P Killian, JK Rodriguez-Canales, J AF Devor, Christopher Hanson, Jeffrey Bandle, Russell Emmert-Buck, Michael Pinto, Peter Levens, David Meltzer, Paul Killian, J. Keith Rodriguez-Canales, Jaime TI Global histone modification and genome-wide methylation profiling reveals distinct epigenetic signatures in human prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Devor, Christopher; Hanson, Jeffrey; Bandle, Russell; Emmert-Buck, Michael; Pinto, Peter; Levens, David; Meltzer, Paul; Killian, J. Keith; Rodriguez-Canales, Jaime] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4744 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801457 ER PT J AU Diskin, S Cole, K Mosse, Y Sennett, R Lynch, J LaQuaglia, M Hou, CP Khan, J Asgharzadeh, S Seeger, R London, W Madhavan, S Gerhard, D Smith, M Attiyeh, E Maris, J AF Diskin, Sharon Cole, Kristina Mosse, Yael Sennett, Rachel Lynch, Jill LaQuaglia, Michael Hou, Cuiping Khan, Javed Asgharzadeh, Shahab Seeger, Robert London, Wendy Madhavan, Subha Gerhard, Daniela Smith, Malcolm Attiyeh, Edward Maris, John TI Identification of RAN as a neuroblastoma oncogene SO CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5679 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702209 ER PT J AU Diskin, S Cole, K Mosse, Y Sennett, R Lynch, J LaQuaglia, M Hou, CP Khan, J Asgharzadeh, S Seeger, R London, W Madhavan, S Gerhard, D Smith, M Attiyeh, E Maris, J AF Diskin, Sharon Cole, Kristina Mosse, Yael Sennett, Rachel Lynch, Jill LaQuaglia, Michael Hou, Cuiping Khan, Javed Asgharzadeh, Shahab Seeger, Robert London, Wendy Madhavan, Subha Gerhard, Daniela Smith, Malcolm Attiyeh, Edward Maris, John TI Identification of RAN as a neuroblastoma oncogene SO CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5679 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804368 ER PT J AU Diwan, B Waalkes, M AF Diwan, Bhalchandra Waalkes, Michael TI Induction of premalignant and malignant uterine lesions in mice exposed to "whole life" arsenic exposure: Overexpression of ER-alpha, COX-2, NF-kB and Cyclin D1. SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NIEHS, NCI, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1219 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800080 ER PT J AU Dong, LD Shu, XO Gao, YT Milne, G Ji, BT Yang, G Lai, HL Rothman, N Zheng, W Chow, WH Abnet, C AF Dong, Linda Shu, Xiao-Ou Gao, Yu-Tang Milne, Ginger Ji, Bu-Tian Yang, Gong Lai, Hong-Lan Rothman, Nathaniel Zheng, Wei Chow, Wong-Ho Abnet, Christian TI Urinary Prostaglandin E2 metabolite and Gastric Cancer Risk in the Shanghai Women\#8217;s Health Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCEG, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Shanghai Canc Inst, Shanghai, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1013 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801487 ER PT J AU Duell, E Lucenteforte, E La Vecchia, C Bracci, P Holly, E Li, DH Silverman, D Talamini, R Baghurst, P Bueno-de-Mesquita, HB Ghadirian, P Miller, A Zatonski, W Vrieling, A Fontham, E Su, J Gallinger, S Cotterchio, M Brennan, P Holcatova, I Ji, BT Olson, S Maisonneuve, P Lowenfels, AI Petersen, G Boffetta, P AF Duell, Eric Lucenteforte, Ersilia La Vecchia, Carlo Bracci, Paige Holly, Elizabeth Li, Donghui Silverman, Debra Talamini, Renato Baghurst, Peter Bueno-de-Mesquita, H. Bas Ghadirian, Parviz Miller, Anthony Zatonski, Witold Vrieling, Alina Fontham, Elizabeth Su, Joseph Gallinger, Steven Cotterchio, Michelle Brennan, Paul Holcatova, Ivana Ji, Bu-Tian Olson, Sara Maisonneuve, Patrick Lowenfels, A. I. Petersen, Gloria Boffetta, Paolo TI Pancreatitis and pancreatic cancer risk: A pooled analysis in the international pancreatic pancer case-control consortium (PanC4) SO CANCER RESEARCH LA English DT Meeting Abstract C1 IARC, Lyon, France. Ist Ric Farmacol Mario Negri, Milan, Italy. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Womens & Childrens Hosp, Adelaide, SA, Australia. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Hop Hotel Dieu, Ctr Rech CHUM, Montreal, PQ, Canada. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Warsaw, Poland. Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. Canc Care Ontario, Div Prevent Oncol, Toronto, ON, Canada. Inst Hyg & Epidemiol, CR-10042 Prague, Czech Republic. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. European Inst Oncol, Milan, Italy. New York Med Coll, Valhalla, NY 10595 USA. Mayo Clin, Coll Med, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2140 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702704083 ER PT J AU Eiseman, J Bai, LH Liggett, D Egorin, M Covey, J Beumer, J AF Eiseman, Julie Bai, Lihua Liggett, Dana Egorin, Merrill Covey, Joseph Beumer, Jan TI In vivo evaluation of combination treatment with gemcitabine (dFdC) and tetrahydrouridine (THU) in xenograft models of pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4524 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704387 ER PT J AU Eliassen, AH Ziegler, R Xu, X Veenstra, T Hankinson, S AF Eliassen, A. Heather Ziegler, Regina Xu, Xia Veenstra, Timothy Hankinson, Susan TI Reproducibility of fifteen urinary estrogens and estrogen metabolites (EM) in premenopausal women over 2 to 3 years SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3025 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703158 ER PT J AU ElMasri, W Kimm, D Devoogdt, N Virador, V Kohn, E AF ElMasri, Wafic Kimm, Daniel Devoogdt, Nick Virador, Victoria Kohn, Elise TI SLPI promotes EMT in HeyA8 and HaCaT cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [ElMasri, Wafic; Kimm, Daniel; Devoogdt, Nick; Virador, Victoria; Kohn, Elise] NCI, Bethesda, MD 20892 USA. RI Devoogdt, Nick/H-5156-2013 OI Devoogdt, Nick/0000-0001-9220-4833 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2211 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604082 ER PT J AU Elmore, E Jain, A Steele, V Redpath, J AF Elmore, Eugene Jain, Aarti Steele, Vernon Redpath, John TI Time dependent gene expression changes induced by NO-aspirin in a human colon polyp cell line SO CANCER RESEARCH LA English DT Meeting Abstract C1 UC Irvine, Irvine, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 956 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801289 ER PT J AU Engel, L Satagopan, J Orlow, I Sandler, D Sima, C Alavanja, M AF Engel, Lawrence Satagopan, Jaya Orlow, Irene Sandler, Dale Sima, Camelia Alavanja, Michael TI Sun exposure, vitamin D receptor polymorphisms, and breast cancer risk SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-225 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703454 ER PT J AU Erickson, H Rodriguez-Canales, J Albert, P Yan, WS Mukherjee, S Hu, N Goldstein, A Chuaqui, R Taylor, P Emmert-Buck, M AF Erickson, Heidi Rodriguez-Canales, Jaime Albert, Paul Yan, Wusheng Mukherjee, Sumana Hu, Nan Goldstein, Alisa Chuaqui, Rodrigo Taylor, Philip Emmert-Buck, Michael TI Expression Analysis of Transcripts on Chromosome Band 13q12 in Esophageal Squamous Cell Carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 UT MD Anderson, Houston, TX USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4329 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803252 ER PT J AU Feigelson, H Setiawan, V Ziegler, R Dossus, L Henderson, B AF Feigelson, Heather Setiawan, Veronica Ziegler, Regina Dossus, Laure Henderson, Brian TI Comprehensive analysis of genetic variation in 37 genes related to steroid hormone metabolism and risk of breast cancer in the Breast and Prostate Cancer Cohort Consortium (BPC3) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Kaiser Permanente, Denver, CO USA. Univ So Calif, Los Angeles, CA USA. NCI, Bethesda, MD 20892 USA. German Canc Res Ctr, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-240 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702706027 ER PT J AU Ferrucci, L Sinha, R Huang, WY Berndt, S Pinsky, P Schoen, R Hayes, R Cross, A AF Ferrucci, Leah Sinha, Rashmi Huang, Wen-Yi Berndt, Sonja Pinsky, Paul Schoen, Robert Hayes, Richard Cross, Amanda TI Meat and heme iron and risk of incident colorectal adenoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Canc Prevent Div, Rockville, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 61 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704390 ER PT J AU Finkelstein, D Edwards, C Kaplan-Singer, B Hozumi, K Koblinski, J AF Finkelstein, David Edwards, Chevaunne Kaplan-Singer, Benjamin Hozumi, Kenta Koblinski, Jennifer TI The laminin-\#945;1 chain peptide, AG73, binds to syndecan-1 and-4 on breast cancer cells, promotes up-regulation of oncogenes JUN and tenascin C, and increases bone and brain metastasis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Northwestern Univ, Chicago, IL 60611 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Tokyo Univ Pharm & Life Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2072 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804098 ER PT J AU Fiscus, R Johlfs, M Wong, J Bathina, M Goodman, O Vogelzang, N AF Fiscus, Ronald Johlfs, Mary Wong, Janica Bathina, Madhavi Goodman, Oscar Vogelzang, Nicholas TI Knockdown of the protein kinase G isoform PKG-I\#945; using siRNA and shRNA significantly decreases cell proliferation and increases apoptosis in mesothelioma and prostate cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Fiscus, Ronald; Johlfs, Mary; Wong, Janica; Bathina, Madhavi; Goodman, Oscar; Vogelzang, Nicholas] NCI, Las Vegas, NV USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2501 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802494 ER PT J AU Fiskus, W Wang, YC Rao, R Yang, YH Chen, JG Joshi, A Koul, S Upadhyay, S Balusu, R Fernandez, P Joshi, R Buckley, K Jillella, A Ustun, C Atadja, P Marquez, V Bhalla, K AF Fiskus, Warren Wang, Yongchao Rao, Rekha Yang, Yonghua Chen, Jianguang Joshi, Atul Koul, Sanjay Upadhyay, Sunil Balusu, Ramesh Fernandez, Pravina Joshi, Rajeshree Buckley, Kate Jillella, Anand Ustun, Celalettin Atadja, Peter Marquez, Victor Bhalla, Kapil TI Synergistic pre-clinical activity of combined epigenetic therapy with the EZH2 antagonist 3-Deazaneplanocinand HDAC inhibitor panobinostat against human AML and Mantle Cell Lymphoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Med Coll Georgia, Augusta, GA 30912 USA. Novartis Inst Biomed Res Inc, Cambridge, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4544 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704439 ER PT J AU Franco, A Malguarnera, R Kimura, S Pritchard, C Marais, R Ghossein, R Fagin, J AF Franco, Aime Malguarnera, Roberta Kimura, Shioko Pritchard, Catrin Marais, Richard Ghossein, Ronald Fagin, James TI Endogenous expression of oncogenic Braf cooperates with Pten loss to induce poorly differentiated thyroid cancers with complete penetrance and early lethality SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. Univ Leicester, Leicester, Leics, England. Inst Canc Res, London SW3 6JB, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2086 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804387 ER PT J AU Fukuda, T Sone, H Akanuma, H Toyoshiba, H Yamanaka, T Portier, C AF Fukuda, Tomokazu Sone, Hideko Akanuma, Hiromi Toyoshiba, Hiroyoshi Yamanaka, Takeharu Portier, Christopher TI Computational identification of oncogenic and tumor suppressor gene networks that related to the cell cycle regulation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Tohoku Univ, Sendai, Miyagi 980, Japan. Natl Inst Environm Studies Jpn, Hlth Effect Team, Tokyo, Japan. NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-302 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800385 ER PT J AU Fung, KL Effiong, U Gottesman, M AF Fung, King Leung Effiong, Uduak Gottesman, Michael TI Effect of human MDR1 (ABCB1) haplotype in resistance to chemotherapeutic drugs is substrate-dependent SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. Cell Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 901 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802010 ER PT J AU Gadalla, S Mueller, C Pfeiffer, R Moxley, R Kristinsson, S Bjorkolm, M Landgren, O Greene, M AF Gadalla, Shahinaz Mueller, Christine Pfeiffer, Ruth Moxley, Richard Kristinsson, Sigurdur Bjorkolm, Magnus Landgren, Ola Greene, Mark TI Cancer risk in patients with myotonic dystrophy (DM): A population-based study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Karolinska Univ Hosp Solna, Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2141 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704084 ER PT J AU Gaedcke, J Grade, M Sokilde, R Kaczkowski, B Difilippantonio, M Ghadimi, M Ried, T Litman, T AF Gaedcke, Jochen Grade, Marian Sokilde, Rolf Kaczkowski, Bogumil Difilippantonio, Michael Ghadimi, Michael Ried, Thomas Litman, Thomas TI miRNA profiles predictive for response to chemoradiotherapy in rectal cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Med Ctr, Gottingen, Germany. Exiqon, Vedbaek, Denmark. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 584 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803123 ER PT J AU Gail, M AF Gail, Mitchell TI The value for clinical and public health decisions of adding SNPs to a model to project breast cancer risk SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gail, Mitchell] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY26-3 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800014 ER PT J AU Gail, M AF Gail, Mitchell TI The value for clinical and public health decisions of adding SNPs to a model to project breast cancer risk d SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gail, Mitchell] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY26-3 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702602376 ER PT J AU Gao, Y Bjorkholm, M Krinstinsson, S Goldin, L Landgren, O AF Gao, Ying Bjorkholm, Magnus Krinstinsson, Sigurdur Goldin, Lynn Landgren, Ola TI Broad categories of infectious diseases in combination with genetic factors might play a role in the etiology of hodgkin lymphoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Rockville, MD USA. Karolinska Univ Hosp Solna, Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2147 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704091 ER PT J AU Garcia-Diaz, M Kunkel, T Chou, KM AF Garcia-Diaz, Miguel Kunkel, Thomas Chou, Kai-ming TI DNA polymerase lambda and therapeutic nucleoside analogs SO CANCER RESEARCH LA English DT Meeting Abstract C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. NIEHS, Res Triangle Pk, NC 27709 USA. IUPUI, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-53 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705065 ER PT J AU Garimella, S Murrow, L Caplen, N Lipkowitz, S AF Garimella, Sireesha Murrow, Lyndsay Caplen, Natasha Lipkowitz, Stan TI Identification of Weel as a molecular target in basal-type breast cancer by an siRNA screen of the human kinome SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2842 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802026 ER PT J AU Gaston, S Kishawi, I Guerra, A Cheng, YL Nadadur, R Kearney, M Meltzer, S Pinsky, P Sorbara, L Srivastava, S Gary, K AF Gaston, Sandra Kishawi, Iman Guerra, Andrew Cheng Yulan Nadadur, Rangarajan Kearney, Michael Meltzer, Stephen Pinsky, Paul Sorbara, Lynn Srivastava, Sudhir Gary, Kearney TI Expression of the metastatic prostate cancer biomarker miR-141 in prostate biopsy tissues SO CANCER RESEARCH LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Agilent Technol, Santa Clara, CA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Rockville, MD USA. New England Baptist Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3840 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805135 ER PT J AU Gaur, A Colburn, N Israel, M AF Gaur, Arti Colburn, Nancy Israel, Mark TI MicroRNA-21 is highly expressed in glioblastoma multiforme and may contribute to its malignant behavior through inhibition of Programmed Cell Death4 (Pdcd4) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2543 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803169 ER PT J AU Gillet, JP Rutledge, R Wu, CP Eliseeva, T Chen, K Fitzgerald, P Fales, H Xia, D Ambudkar, S Gottesman, M AF Gillet, Jean-Pierre Rutledge, Robert Wu, Chung-pu Eliseeva, Tatiana Chen, Kevin Fitzgerald, Peter Fales, Henry Xia, Di Ambudkar, Suresh Gottesman, Michael TI Characterization of ABCB5, a poorly studied ABC transporter highly expressed in melanomas ocr issue v22 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Gillet, Jean-Pierre; Rutledge, Robert; Wu, Chung-pu; Eliseeva, Tatiana; Chen, Kevin; Fitzgerald, Peter; Fales, Henry; Xia, Di; Ambudkar, Suresh; Gottesman, Michael] NCI CCR, Bethesda, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3881 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604369 ER PT J AU Giubellino, A Lee, MJ Shi, ZD Jenkins, L Appella, E Burke, T Trepel, J Bottaro, D AF Giubellino, Alessio Lee, Min-Jung Shi, Zhen-Dan Jenkins, Lisa Appella, Ettore Burke, Terrence Trepel, Jane Bottaro, Donald TI Extracellular localization of the adaptor protein Grb2 SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Giubellino, Alessio; Lee, Min-Jung; Shi, Zhen-Dan; Jenkins, Lisa; Appella, Ettore; Burke, Terrence; Trepel, Jane; Bottaro, Donald] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3513 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804279 ER PT J AU Glaze, E Harder, JB McCormick, D Johnson, W Detrisac, C Pommier, Y Tomaszewski, J AF Glaze, Elizabeth Harder, J. Brooks McCormick, David Johnson, William Detrisac, Carol Pommier, Yves Tomaszewski, Joseph TI Five-day intravenous toxicity study of indenoisoquinoline analogues in dogs SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. IIT Res Inst, Chicago, IL USA. Pathol Associates Inc, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2933 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802115 ER PT J AU Glick, A Perez-Lorenzo, R Mordasky-Markell, L Hogan, K Yuspa, S AF Glick, Adam Perez-Lorenzo, Rolando Mordasky-Markell, Laren Hogan, Kelly Yuspa, Stuart TI TGF\#946;1 dependent activation of PKC enhances tumor promotion in skin carcinogenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Penn State Univ, University Pk, PA 16802 USA. NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2374 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800177 ER PT J AU Glogowska, A Kehlen, A Hoang-Vu, C Cheng, SY Klonisch, T AF Glogowska, Aleksandra Kehlen, Astrid Cuong Hoang-Vu Cheng, Sheue-yann Klonisch, Thomas TI Expression and regulation of helix-loop-helix (HLH) inhibitory transcription factor Id2 in thyroid cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Manitoba, Winnipeg, MB, Canada. Probiodrug AG, Halle, Germany. Univ Halle Wittenberg, D-06108 Halle, Germany. NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 539 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802187 ER PT J AU Godiska, R Mead, D Usdin, K Perrault, J AF Godiska, Ronald Mead, David Usdin, Karen Perrault, Jacques TI Linear and circular vectors for cloning and mammalian expression of difficult DNAs. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Lucigen Corp, Middleton, WI USA. NIH, Bethesda, MD 20892 USA. San Diego State Univ, San Diego, CA 92182 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5219 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802276 ER PT J AU Grade, M Hummon, A Camps, J Emons, G Spitzner, M Gaedcke, J Difilippantonio, M Becker, H Beissbarth, T Ghadimi, M Caplen, N Ried, T AF Grade, Marian Hummon, Amanda Camps, Jordi Emons, Georg Spitzner, Melanie Gaedcke, Jochen Difilippantonio, Michael Becker, Heinz Beissbarth, Tim Ghadimi, Michael Caplen, Natasha Ried, Thomas TI Validation of novel colorectal cancer genes as potential therapeutic targets using functional genomics approaches SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Med Goettingen, Dept Gen & Visceral Surg, Gottingen, Germany. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1991 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604378 ER PT J AU Green, L Gillet, JP Calcagno, AM Samuel, M Hall, M Varma, S Shih, J Ambudkar, S Gottesman, M AF Green, Lisa Gillet, Jean Pierre Calcagno, Anna Maria Samuel, Michelle Hall, Matthew Varma, Sudhir Shih, Joannah Ambudkar, Suresh Gottesman, Michael TI Identification of a 3D model which best emulates clinical epithelial ovarian cancer multi-drug resistance profiles SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3214 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804324 ER PT J AU Griffin, L Grohar, P Pommier, Y Khanna, C Khan, J Heiman, L AF Griffin, Laurie Grohar, Patrick Pommier, Yves Khanna, Chand Khan, Javed Heiman, Lee TI ET-743 modulates EWS-FLi1 activity in Ewing\#8217;s sarcoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Griffin, Laurie; Grohar, Patrick; Pommier, Yves; Khanna, Chand; Khan, Javed; Heiman, Lee] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1501 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804303 ER PT J AU Gril, B Lockman, P Bohn, K Adkins, C Mittapali, R Taskar, K Radaruju, V Palmieri, D Smith, Q Steeg, P AF Gril, Brunilde Lockman, Paul Bohn, Kaci Adkins, Chris Mittapali, Rajendar Taskar, Kunal Radaruju, Vinay Palmieri, Diane Smith, Quentin Steeg, Patricia TI Vascular density in a brain metastasis of breast cancer mice model SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3171 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803463 ER PT J AU Grohar, P Woldemichael, G Griffin, L Yeung, C Chen, QR Khanna, C Khan, J McMahon, J Heiman, L AF Grohar, Patrick Woldemichael, Girma Griffin, Laurie Yeung, Choh Chen, Qingrong Khanna, Chand Khan, Javed McMahon, James Heiman, Lee TI Identification of transcription factor inhibitors: A method used to identify small molecules that block EWS-Fli1 transcription factor activity SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Ctr Canc Res, Mol Targets Dev Program, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3805 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800362 ER PT J AU Grubbs, C Kopelovich, L Boring, D Steele, V Juliana, MM Lubet, R AF Grubbs, Clinton Kopelovich, Levy Boring, Daniel Steele, Vernon Juliana, M. Margaret Lubet, Ronald TI Preventive effects of naproxen and NO-Naproxen in chemically induced models of urinary bladder and mammary cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2095 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801129 ER PT J AU Guenther, L Wan, XL Khanna, C Helman, L Kim, SY AF Guenther, Lillian Wan, Xiaolin Khanna, Chand Helman, Lee Kim, Su Young TI Investigation of MET modulation in osteosarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Guenther, Lillian; Wan, Xiaolin; Khanna, Chand; Helman, Lee; Kim, Su Young] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3398 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802472 ER PT J AU Guo, X Song, Y Chen, QR Khan, J AF Guo, Xiang Song, Young Chen, Qingrong Khan, Javed TI Alternative splicing profile for the prognosis of neuroblastoma patients SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI Frederick, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD USA. NCI, Oncogen Sect, Pediat Oncol Branch, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2599 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804160 ER PT J AU Hagelstrom, R Arora, S Gonzales, I Choudhary, A Khan, J Mousses, S Azorsa, D AF Hagelstrom, R. Arora, Shilpi Gonzales, Irma Choudhary, Ashish Khan, Javed Mousses, Spyro Azorsa, David TI Application of high-T\throughput RNAi for the identification of genes involved in proliferation and survival of Ewing\#8217;s sarcoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Translat Genom Res Inst, Scottsdale, AZ USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2188 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603038 ER PT J AU Han, S Lee, KM Park, SK Lee, JE Ahn, HS Shin, HY Kang, HJ Koo, HH Seo, JJ Choi, JE Ahn, YO Kang, D AF Han, Sohee Lee, Kyoung-Mu Park, Sue K. Lee, Jong Eun Ahn, Hyo Seop Shin, Hee Young Kang, Hyoung Jin Koo, Hong Hoe Seo, Jong Jin Choi, Ji Eun Ahn, Yoon-Ok Kang, Daehee TI A genome-wide association study for childhood acute lymphoblastic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. DNA Link Inc, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Pediat, Canc Res Inst, Seoul, South Korea. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul, South Korea. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pediat, Seoul, South Korea. Seoul Metropolitan Boramae Hosp, Dept Pediat, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Prevent Med, Canc Res Inst, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 97 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704047 ER PT J AU Han, YY Davis, D Weissfeld, J Dinse, G AF Han, Yueh-Ying Davis, Devra Weissfeld, Joel Dinse, Gregg TI Generational risks for cancers not related to tobacco, screening, or treatment in the United States SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 973 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703388 ER PT J AU Hance, K Rogers, C Zaharoff, D Schlom, J Greiner, J AF Hance, Kenneth Rogers, Connie Zaharoff, David Schlom, Jeffrey Greiner, John TI Gemcitabine preconditioning improves antigen-specific immune and antitumor responses to poxvirus vaccines SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hance, Kenneth; Rogers, Connie; Zaharoff, David; Schlom, Jeffrey; Greiner, John] NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-161 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805379 ER PT J AU Hance, K Rogers, C Zaharoff, D Schlom, J Greiner, J AF Hance, Kenneth Rogers, Connie Zaharoff, David Schlom, Jeffrey Greiner, John TI Gemcitabine preconditioning improves antigen-specific immune and antitumor responses to poxvirus vaccines. SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hance, Kenneth; Rogers, Connie; Zaharoff, David; Schlom, Jeffrey; Greiner, John] NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LE3-161 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702605341 ER PT J AU Harris, C Yanaihara, N Seike, M Wang, X Yokota, J Croce, C AF Harris, Curtis Yanaihara, Nozomu Seike, Masahiro Wang, Xin Yokota, Jun Croce, Carlo TI Inflammation and cancer: Microenvironment, cytokines, microRNA, and p53 SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Natl Canc Ctr, Tokyo, Japan. Ohio State Univ, Columbus, OH 43210 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY04-2 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701800269 ER PT J AU Heiskanen, M Klemm, J Messersmith, D Derr, L AF Heiskanen, Mervi Klemm, Juli Messersmith, Donna Derr, Leslie TI The cancer Biomedical Informatics Grid (R) (caBIG (R)): Resources to support translational research SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2446 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801041 ER PT J AU Henning, R Yu, MS Virador, V Kimm, D Perroy, A Kohn, E AF Henning, Ryan Yu, Minshu Virador, Victoria Kimm, Daniel Perroy, Alyssa Kohn, Elise TI A novel mechanism for L-asparaginase in solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Henning, Ryan; Yu, Minshu; Virador, Victoria; Kimm, Daniel; Perroy, Alyssa; Kohn, Elise] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4620 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705305 ER PT J AU Henson, B Bhattacharjee, S O'Dee, D Feingold, E Gollin, S AF Henson, Brian Bhattacharjee, Samsiddhi O'Dee, Dawn Feingold, Eleanor Gollin, Susanne TI The expression of miR-125b and miR-100 in OSCC and their contribution to malignancy SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2548 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803175 ER PT J AU Hollingshead, B Baker, A Hegamyer, G Colburn, N AF Hollingshead, Brett Baker, Alyson Hegamyer, Glenn Colburn, Nancy TI The identification of genes regulated by the AP-1 protein FRA-1 and required for its tumorigenic activity SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hollingshead, Brett; Baker, Alyson; Hegamyer, Glenn; Colburn, Nancy] NCI CCR, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4237 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802150 ER PT J AU Hosgood, HD Liu, CS Rothman, N Weinstein, S Bonner, M Shen, M Lim, U Virtamo, J Albanes, D Lan, Q AF Hosgood, H. Dean Liu, Chin-San Rothman, Nathaniel Weinstein, Stephanie Bonner, Matthew Shen, Min Lim, Unhee Virtamo, Jarmo Albanes, Demetrius Lan, Qing TI Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Changhua Christian Hosp, Changhua, Taiwan. Univ Buffalo State Univ New York, Buffalo, NY USA. Canc Res Ctr Hawaii, Honolulu, HI USA. Inst Publ Hlth, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 998 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801471 ER PT J AU Hsieh, SM Look, M Smith, R Lintell, N Sieuwerts, A Foekens, J Lyn, G Hunter, K AF Hsieh, Szu-Min Look, Maxine Smith, Robert Lintell, Nicholas Sieuwerts, Anieta Foekens, John Lyn, Griffiths Hunter, Kent TI Polymorphisms in the SIPA1 gene are associated with sporadic breast cancer susceptibility and hallmarks of poor prognosis in two independent studies SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CCR, Bethesda, MD 20892 USA. Erasmus MC, Rotterdam, Netherlands. Griffith Inst Hlth & Med Res, Gold Coast, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1911 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603169 ER PT J AU Hsing, A Yeboah, E Biritwum, R Tettey, Y DeMarzo, A Adjei, A Netto, G Yu, K Li, Y Chokkalingam, A Chia, D Jadallah, S Partin, A Thompson, I Quraishi, S Addo-Ayensu, G Niwa, S Tarone, R Hoover, R AF Hsing, Ann Yeboah, Edward Biritwum, Richard Tettey, Yao DeMarzo, Angelo Adjei, Andrew Netto, George Yu, Kai Li, Yan Chokkalingam, Anand Chia, David Jadallah, Sana Partin, Alan Thompson, Ian Quraishi, Sabah Addo-Ayensu, Gloria Niwa, Shelley Tarone, Robert Hoover, Robert TI High prevalence of screen detected prostate cancer in West Africans: Implications for racial disparity of prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCEG, Rockville, MD USA. Univ Ghana, Accra, Ghana. Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Fairfax Dept Hlth, Fairfax, VA USA. Westat Corp, Rockville, MD USA. Int Inst Epidemiol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1973 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703099 ER PT J AU Hudson, R Yi, M Volfovsky, N Tietcheu, S Liu, CG Stephens, R Calin, G Croce, C Ambs, S AF Hudson, Robert Yi, Ming Volfovsky, Natalia Tietcheu, Steves Liu, Chang-Gong Stephens, Robert Calin, George Croce, Carlo Ambs, Stefan TI Transcripts encoded by ultraconserved regions are altered in prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA. Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Canc Genet, Houston, TX 77030 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1968 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803143 ER PT J AU Huff, L Sackett, D Poruchynsky, M Fojo, T AF Huff, Lyn Sackett, Dan Poruchynsky, Marianne Fojo, Tito TI Tubulin homeostasis in neural cells but not in cancer cells leads to rapid proteasome-mediated tubulin degradation following drug-induced microtubule depolymerization SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3870 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604078 ER PT J AU Huh, JI Sato, M Calvo, A Green, J Tchou, J Herlyn, M AF Huh, Jung-Im Sato, Misako Calvo, Alfonso Green, Jeffrey Tchou, Julia Herlyn, Meenhard TI Amphiregulin regulates mammary epithelial cell motility and interaction between mammary epithelial cells and fibroblasts SO CANCER RESEARCH LA English DT Meeting Abstract C1 Korea Inst Toxicol, Daejeon, South Korea. NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. Univ Navarra, Div Oncol, CIMA, E-31080 Pamplona, Spain. Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. Univ Penn Hlth Syst, Dept Surg, Philadelphia, PA USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4301 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802302 ER PT J AU Hwang, C Fields, J Anderson, L Shiao, YH AF Hwang, Christopher Fields, Janet Anderson, Lucy Shiao, Yih-Horng TI Human lung adenocarcinoma cells have increases in precursor and mature rRNA and an antisense non-coding RNA species SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Hwang, Christopher; Fields, Janet; Anderson, Lucy; Shiao, Yih-Horng] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 589 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803129 ER PT J AU Janakiram, N Mohammed, A Qian, L Choi, CI Steele, V Rao, C AF Janakiram, Naveena Mohammed, Altaf Qian, Li Choi, Chang-In Steele, Vernon Rao, Chinthalapally TI Bexarotene, a selective RXR agonist, suppresses intestinal polyp formation and hyperlipidemia in Min mice SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Oklahoma, Inst Canc, OUHSC, Oklahoma City, OK USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 933 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801263 ER PT J AU Jeon, S Han, S Park, AK Lee, KM Park, SK Ahn, HS Shin, HY Kang, HJ Koo, HH Seo, JJ Ahn, JE Ahn, YO Kim, H Kang, D AF Jeon, Sujee Han, Sohee Park, Ae Kyung Lee, Kyoung-Mu Park, Sue K. Ahn, Hyo Seop Shin, Hee Young Kang, Hyoung Jin Koo, Hong Hoe Seo, Jong Jin Ahn, Ji Eun Ahn, Yoon-Ok Kim, Ho Kang, Daehee TI Association of SNPs in hematological malignancies and Leukemia in Korean children SO CANCER RESEARCH LA English DT Meeting Abstract C1 Seoul Natl Univ, Coll Med, Dept Canc Biol, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. Sch Publ Hlth, Div Epidemiol & Biostat, Seoul, South Korea. NIH, Div Canc Epidemiol & Genet, DHHS, Baltimore, MD USA. Dept Prevent Med, Seoul, South Korea. Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. Seoul Natl Univ, Dept Pediat, Seoul, South Korea. Seoul Natl Univ, Canc Res Inst, Seoul, South Korea. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul, South Korea. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pediat, Seoul, South Korea. Seoul Metropolitan Boramae Hosp, Dept Pediat, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3044 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703252 ER PT J AU Jiao, L Mitrou, P Reedy, J Graubard, B Hollenbeck, A Schatzkin, A Stoizenberg-Solomon, R AF Jiao, Li Mitrou, Panagiota Reedy, Jill Graubard, Barry Hollenbeck, Albert Schatzkin, Arthur Stoizenberg-Solomon, Rachael TI Is a combined healthy lifestyle score associated with pancreatic cancer risk? - a large cohort study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCEG, Rockville, MD USA. World Canc Res Fund Int, London, England. NCI, DCCPS, Rockville, MD USA. AARP, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4882 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704168 ER PT J AU Jin, CY Yang, YA Anver, M Morris, N Wang, XC Zhang, Y AF Jin, Chaoyang Yang, Yu-an Anver, Miriam Morris, Nicole Wang, Xiangchun Zhang, Ying TI Smurf2 promotes metastasis of breast cancer cells by enhancing migration and invasivenes SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CCR, Bethesda, MD 20892 USA. NCI Frederick, SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2212 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604084 ER PT J AU Johannessen, L Remsberg, J Tarasov, S Jiang, S Tarasova, N AF Johannessen, Liv Remsberg, Jarrett Tarasov, Sergey Jiang, Sheng Tarasova, Nadya TI Peptide structure stabilization by lipidation for development of potent inhibitors of protein-protein interactions: Application for generation of selective IGF1R antagonists SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NCI Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-79 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701031 ER PT J AU Johnson, W Glaze, E McCormick, D Detrisac, C Pommier, Y Tomaszewski, J AF Johnson, William Glaze, Elizabeth McCormick, David Detrisac, Carol Pommier, Yves Tomaszewski, Joseph TI Five-day intravenous toxicity study of indenoisoquinoline analogues in F344 rats SO CANCER RESEARCH LA English DT Meeting Abstract C1 IIT Res Inst, Chicago, IL USA. NCI, Bethesda, MD 20892 USA. Pathol Associates Inc, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2934 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802116 ER PT J AU Joo, KM Lee, J Kang, YJ Jin, J Kang, BG Kim, MH Lee, SJ Jo, MY Kim, H Nam, DH AF Joo, Kyeung Min Lee, Jeongwu Kang, Yun Jung Jin, Juyoun Kang, Bong Gu Kim, Mi Hyun Lee, Se Jeong Jo, Mi-Young Kim, Hyunggee Nam, Do-Hyun TI An essential role of c-Met/HGF signaling in glioblastoma initiating cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. NCI, Bethesda, MD 20892 USA. Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4895 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603240 ER PT J AU Juhasz, A Ge, Y Holbeck, S Shoemaker, R Roy, K Doroshow, J AF Juhasz, Agnes Ge, Yun Holbeck, Susan Shoemaker, Robert Roy, Krishnendu Doroshow, James TI Distinct pharmacologic mechanisms of action of the flavin dehydrogenase inhibitors diphenylene iodonium (DPI) and di-2-thienyliodonium (DTI) based on NCI60 tumor cell line panel profiling SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Juhasz, Agnes; Ge, Yun; Holbeck, Susan; Shoemaker, Robert; Roy, Krishnendu; Doroshow, James] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1549 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702700378 ER PT J AU Katayama, K Ambudkar, S AF Katayama, Kazuhiro Ambudkar, Suresh TI The mechanism of degradation of multidrug resistance-linked P-glycoprotein (ABCB1) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Katayama, Kazuhiro; Ambudkar, Suresh] NCI, LCB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 899 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802008 ER PT J AU Kauer, M Ban, J Jug, G Schwentner, R Walker, B Meltzer, P Kovar, H AF Kauer, Maximilian Ban, Jozef Jug, Gunhild Schwentner, Raphaela Walker, Bob Meltzer, Paul Kovar, Heinrich TI Motif analysis reveals a potential new link between EWS-FLI1 and cell cycle in Ewing Sarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 St Anna Children 92s Canc Res Inst, Vienna, Austria. NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2463 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801060 ER PT J AU Kaur, G Frary, S Holbeck, S Monks, A Hollingshead, M AF Kaur, Gurmeet Frary, Sadie Holbeck, Susan Monks, Anne Hollingshead, Melinda TI Evaluation of NSC83265: Histone H3, BubR1 and monoastral formation are potential pharmacodynamic biomarkers. SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. SAIC Frederick, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4616 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705300 ER PT J AU Kedei, N Czifra, G Telek, A Kraft, M Truong, A Li, W Sanchez, C Keck, G Blumberg, P AF Kedei, Noemi Czifra, Gabriella Telek, Andrea Kraft, Matthew Anh Truong Li, Wei Sanchez, Carina Keck, Gary Blumberg, Peter TI What distinguishes a PKC activator like phorbol ester from a PKC functional antagonist like bryostatin 1? Bryologues permit dissection of intermediate patterns of activity SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2667 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702700419 ER PT J AU Kenney, S Vistica, D Stockwin, L Burkett, S Hollingshead, M Borgel, S Schrump, D Shoemaker, R AF Kenney, Susan Vistica, David Stockwin, Luke Burkett, Sandra Hollingshead, Melinda Borgel, Suzanne Schrump, David Shoemaker, Robert TI Establishment and characterization of ASPS-1, a novel cell line derived from metastatic alveolar soft part sarcoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4044 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804081 ER PT J AU Killian, K Bilke, S Davis, S Walker, R Giaccone, G Smith, W Meltzer, P AF Killian, Keith Bilke, Sven Davis, Sean Walker, Robert Giaccone, Guiseppe Smith, William Meltzer, Paul TI Archival fine needle aspiration (FNA) smears: a novel resource for clinical molecular profiling SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Suburban Hosp, Dept Pathol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1649 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702009 ER PT J AU Kim, G Henning, R Yu, MS Davidson, B Kohn, E AF Kim, Geoffrey Henning, Ryan Yu, Minshu Davidson, Ben Kohn, Elise TI Proteomic array analysis of cell adhesion molecules of malignant ovarian cancer effusions SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Norwegian Radium Hosp, Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2265 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803174 ER PT J AU Kim, JM Kim, JK Shim, M Anna, C Chrysovergis, K Bradbury, J Kissling, GE Germolec, D Zeldin, DC Eling, TE AF Kim, Jeong-Min Kim, Jin Kook Shim, Minsub Anna, Colleen Chrysovergis, Kaliopi Bradbury, J. Kissling, Grace E. Germolec, Dori Zeldin, Darryl C. Eling, Thomas E. TI NAG-1 suppresses LPS-induced inflammation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kim, Jeong-Min; Kim, Jin Kook; Shim, Minsub; Anna, Colleen; Chrysovergis, Kaliopi; Bradbury, J.; Kissling, Grace E.; Germolec, Dori; Zeldin, Darryl C.; Eling, Thomas E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5337 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804489 ER PT J AU Kinsinger, C Mesri, M Hiltke, T Rodriguez, H AF Kinsinger, Chris Mesri, Mehdi Hiltke, Tara Rodriguez, Henry TI Building a robust and reliable proteomics biomarker pipeline: NCI\#8217;s CPTAC network SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kinsinger, Chris; Mesri, Mehdi; Hiltke, Tara; Rodriguez, Henry] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3556 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701125 ER PT J AU Klonisch, T Wark, L Hombach-Klonisch, S Cuong, HV Cheng, SY Mai, S AF Klonisch, Thomas Wark, Landon Hombach-Klonisch, Sabine Cuong Hoang-Vu Cheng, Sheue-yann Mai, Sabine TI Nuclear architecture in human thyroid carcinoma revealed by three-dimensional (3D) telomere imaging: New insight into genomic instability and potential diagnostic application SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Manitoba, Winnipeg, MB, Canada. Manitoba Inst Cell Biol, CancerCare Manitoba, Winnipeg, MB, Canada. Univ Halle Wittenberg, D-06108 Halle, Germany. NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 469 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801349 ER PT J AU Kobayashi, H Ogawa, M Kosaka, N Choyke, P Urano, Y AF Kobayashi, Hisataka Ogawa, Mikako Kosaka, Nobuyuki Choyke, Peter Urano, Yasuteru TI Simultaneous imaging of quantum dot-labeled cancer cell migration and lymphatic drainage using dendrimer-based optical agents SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CCR, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3991 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803201 ER PT J AU Koch, K Zhang, CO Guo, L Shahjee, H Kaczmarek, P Michejda, C Barchi, J Keay, S AF Koch, Kristopher Zhang, Chen-Ou Guo, Li Shahjee, Hanief Kaczmarek, Piotr Michejda, Christopher Barchi, Joseph Keay, Susan TI Inhibition of carcinoma and melanoma cell proliferation in vitro by a novel frizzled 8 protein-related anti proliferative factor (APF) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, VAMC, Baltimore, MD 21201 USA. NCI, Med Chem Lab, CCR, Frederick, MD 21701 USA. NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, CCR, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 851 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604404 ER PT J AU Kolb, E Gorlick, R Houghton, P Morton, C Maris, J Courtright, J Carol, H Lock, R Friedman, H Keir, S Kang, M Reynolds, C Smith, M AF Kolb, E. Gorlick, Richard Houghton, Peter Morton, Christopher Maris, John Courtright, Joshua Carol, Hernan Lock, Richard Friedman, Henry Keir, Stephen Kang, Min Reynolds, C. Smith, Malcolm TI Pediatric Preclinical Testing Program (PPTP) evaluation of the multi-targeted kinase inhibitor Sorafenib SO CANCER RESEARCH LA English DT Meeting Abstract C1 Alfred I DuPont Hosp Children, Wilmington, DE USA. Montefiore Med Ctr, Bronx, NY 10467 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Canc Inst, Sydney, NSW, Australia. Duke Univ, Durham, NC USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3196 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803490 ER PT J AU Komlodi-Pasztor, E Trostel, S Sackett, D Poruchynsky, M Fojo, T AF Komlodi-Pasztor, Edina Trostel, Shana Sackett, Dan Poruchynsky, Marianne Fojo, Tito TI Impaired p53 binding to importin: A novel mechanism of cytoplasmic sequestration identified in oxaliplatin-resistant cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 599 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804396 ER PT J AU Kong, HS Lee, S Jung, YJ Bchiri, J Trepel, J Neckers, L AF Kong, Hye-Sik Lee, Sunmin Jung, Yun-Jin Bchiri, Jamila Trepel, Jane Neckers, Leonard TI Nonsense-mediated mRNA decay regulates HIF-1\#945; expression in 786-O renal cell carcinoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Pusan Natl Univ, Busan, South Korea. INSERM, UMR S893, Team Microsatellite Instabil & Canc 13, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1530 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804330 ER PT J AU Kosak, K Saavedra, J Keefer, L Shami, P AF Kosak, Ken Saavedra, Joseph Keefer, Larry Shami, Paul TI A Pluronic (R) micelle formulation increases the stability of the novel anti-cancer nitric oxide prodrug JS-K. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. SAIC Frederick, Frederick, MD USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 643 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701020 ER PT J AU Koshiol, J Rotunno, M Consonni, D Pesatori, A Goldstein, A Chaturvedi, A Wacholder, S Landi, MT Lubin, J Caporaso, N AF Koshiol, Jill Rotunno, Melissa Consonni, Dario Pesatori, Angela Goldstein, Alisa Chaturvedi, Anil Wacholder, Sholom Landi, Maria Teresa Lubin, Jay Caporaso, Neil TI Previous lung diseases and altered risk of lung cancer in population-based case-control study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Milan, EPOCA Epidemiol Occupaz Clin & Ambientale, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2148 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704092 ER PT J AU Koutros, S Schumacher, F Ma, J Crawford, ED Huang, WY Hayes, R Berndt, S AF Koutros, Stella Schumacher, Fredrick Ma, Jing Crawford, E. David Huang, Wen-Yi Hayes, Richard Berndt, Sonja TI Pooled analysis of variants in the phosphatidylinositol 3-kinase (PI3K) pathway and risk of prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Colorado Hlth Sci, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 92 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704041 ER PT J AU Kummar, S Rubinstein, L Kinders, R Ji, JP Parchment, R Gutierrez, M Murgo, A Chen, A Khin, S Zhang, YP Simmons, D Yancey, MA Allen, D Horneffer, Y Juwara, L Chang, R Gordon, G Tomaszewski, J Doroshow, J AF Kummar, Shivaani Rubinstein, Larry Kinders, Robert Ji, Jiuping Parchment, Ralph Gutierrez, Martin Murgo, Anthony Chen, Alice Khin, Sonny Zhang, Yiping Simmons, Dwight Yancey, Mary Ann Allen, Deborah Horneffer, Yvonne Juwara, Lamin Chang, Richard Gordon, Gary Tomaszewski, Joseph Doroshow, James TI Correlation between inhibition of the activity of poly(ADP-ribose) polymerase (PARP) in human peripheral blood mononuclear cells (PBMCs) and tumor biopsies following treatment with ABT-888, an inhibitor of PARP SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI Frederick, SAIC Frederick Inc, Frederick, MD USA. Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5456 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701484 ER PT J AU Kwon, HC Oh, S Kil, W Burgan, W Carter, D Beam, K Tofilon, P Gardner, K Camphausen, K AF Kwon, Hyuk-Chan Oh, Sung Kil, Whoon Burgan, William Carter, Donna Beam, Katie Tofilon, Philip Gardner, Kevin Camphausen, Kevin TI Enhancement of radiosensitivity in DU145 human prostate carcinoma cells by a novel functional class of thalidomide analogs SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dong A Univ, Med Ctr, Busan, South Korea. NCI, NIH, Bethesda, MD 20892 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5594 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802128 ER PT J AU Kwon, MJ Kim, SS Choi, YL Marquez, V Shin, YK AF Kwon, Mi Jeong Kim, Sung-Su Choi, Yoon-La Marquez, Victor Shin, Young Kee TI Loss of repressive histone methylation is associated with CLDN3 overexpression and multiple histone modifications regulate CLDN3 expression in ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Seoul Natl Univ, Coll Pharm, Seoul, South Korea. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 488 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802049 ER PT J AU Lai, E Horak, K Machida, EO Havekes, B Huynh, TT Ohta, S Adams, K Albanese, C Baylin, S Pacak, K AF Lai, Edwin Horak, Kyle Machida, Emi Ota Havekes, Bas Thanh-Truc Huynh Ohta, Shoichiro Adams, Karen Albanese, Chris Baylin, Stephen Pacak, Karel TI High frequency of ASC/TMS1, Rassf1A, and p16INK4A promoter methylation in succinate dehydrogenase complex B pheochromocytomas SO CANCER RESEARCH LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Canc Comprehens Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5151 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801403 ER PT J AU Lai, JP Han, T Moser, C Aderca, I Lee, JS Thorgeirsson, S Roberts, L AF Lai, Jinping Han, Tao Moser, Catherine Aderca, Ileana Lee, Ju-Seog Thorgeirsson, Snorri Roberts, Lewis TI Sulfatase 2 (SULF2) functions as a novel oncogenic protein in hepatocellular carcinoma (HCC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5612 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802116 ER PT J AU Lam, E Ringel, M Kloos, R Collamore, M Arbogast, D Liang, J Hall, N Knopp, M Wright, J Shah, M AF Lam, Elaine Ringel, Matthew Kloos, Richard Collamore, Minden Arbogast, Dada Liang, Jiachao Hall, Nathan Knopp, Michael Wright, John Shah, Manisha TI A phase II study of sorafenib in patients with metastatic medullary thyroid carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, IDB, CTEP, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4513 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805363 ER PT J AU Landi, M Chatterjee, N Yu, K Jacobs, K Bergen, A Goldin, L Goldstein, A Wang, ZM Burdette, L Albanes, D Oken, M Thun, M Consonni, D Pesatori, A Amos, C Houlston, R Brennan, P Hung, R Gaborieau, V Spitz, M Wang, YF Krokan, H Vatten, L Benhamou, S Metsapalu, A Field, J Chen, C Goodman, G Bickeboller, H Risch, A Wichmann, HE Rafnar, T Stefansson, K Lathrop, M Bertazzi, PA Tucker, M Chanock, S Caporaso, N AF Landi, Maria Chatterjee, Nilanjan Yu, Kai Jacobs, Kevin Bergen, Andrew Goldin, Lynn Goldstein, Alisa Wang, Zhaoming Burdette, Laurie Albanes, Demetrius Oken, Martyn Thun, Michael Consonni, Dario Pesatori, Angela Amos, Christopher Houlston, Richard Brennan, Paul Hung, Rayjean Gaborieau, Valerie Spitz, Margaret Wang, Yufei Krokan, Hans Vatten, Lars Benhamou, Simone Metsapalu, Andres Field, John Chen, Chu Goodman, Gary Bickeboller, Heike Risch, Angela Wichmann, H-Erich Rafnar, Thorunn Stefansson, Kari Lathrop, Mark Bertazzi, Pier Alberto Tucker, Margaret Chanock, Stephen Caporaso, Neil CA Geneva STUDY TI A comprehensive genome-wide association study of lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Minnesota, Minneapolis, MN USA. Amer Canc Soc, Atlanta, GA 30329 USA. OMPMaRE, Milan, Italy. Univ Milan, Milan, Italy. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Inst Canc Res, Sutton, Surrey, England. Int Agcy Res Canc, F-69372 Lyon, France. Univ Toronto, Toronto, ON, Canada. Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. INSERM, Paris, France. Univ Tartu, EE-50090 Tartu, Estonia. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Gottingen, D-37073 Gottingen, Germany. German Canc Res Ctr, Heidelberg, Germany. Helmholtz Ctr, Munich, Germany. DeCODE Genet, Reykjavik, Iceland. CNG, Paris, France. Fdn Jean Dausset, CEPH, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-139 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805317 ER PT J AU Landi, MT Zhao, YD Rotunnno, M Koshiol, J Pesatori, A Burdette, L Linnoila, I Marincola, F Bertazzi, PA Caporaso, N McShane, L Wang, E AF Landi, Maria Teresa Zhao, Yingdong Rotunnno, Melissa Koshiol, Jill Pesatori, Angela Burdette, Laurie Linnoila, Ilona Marincola, Francesco Bertazzi, Pier Alberto Caporaso, Neil McShane, Lisa Wang, Ena TI MicroRNA expression, tobacco smoking, and genetic polymorphisms in lung cancer histology and survival SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Milan, Milan, Italy. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 585 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803124 ER PT J AU Lee, KM Baris, D Zhang, YW Hosgood, D Menashe, I Yeager, M Zahm, S Wang, S Purdue, M Chanock, S Zheng, TZ Rothman, N Lan, Q AF Lee, Kyoung-Mu Baris, Dalsu Zhang, Yawei Hosgood, Dean Menashe, Idan Yeager, Meredith Zahm, Shelia Wang, Sophia Purdue, Mark Chanock, Stephen Zheng, Tongzhang Rothman, Nathaniel Lan, Qing TI Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3049 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703257 ER PT J AU Lee, YH Song, HT Judge, A Andersen, J Ishikawa, T Avital, I Durkin, M Raggi, C Ton, A Conner, E MacLachlan, I Factor, V Thorgeirsson, S AF Lee, Yun-Han Song, Ho-Taek Judge, Adam Andersen, Jesper Ishikawa, Tsuyoshi Avital, Itzhak Durkin, Marian Raggi, Chiara Ton, Anita Conner, Elizabeth MacLachlan, Ian Factor, Valentina Thorgeirsson, Snorri TI Suppression of tumor growth in human hepatocellular carcinoma by systemic delivery of SNALP-formulated siRNA for downregulation of HDAC2 SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Yonsei Univ, Seoul 120749, South Korea. Protiva Biotherapeut Inc, Burnaby, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2857 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802180 ER PT J AU Li, GL Cai, QY Gao, YT Wen, WQ Shu, XO Yang, G Rothman, N Li, HL Chow, WH Zheng, W AF Li, Guoliang Cai, Qiuyin Gao, Yu-Tang Wen, Wanqing Shu, Xiao Ou Yang, Gong Rothman, Nathaniel Li, Hong-Lan Chow, Wong-Ho Zheng, Wei TI Copy number variation in the GSTM1 and GSTT1 genes and risk of breast, colorectal, and lung cancers: Results from the Shanghai Women\#8217;s Health Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN 37235 USA. Shanghai Canc Inst, Shanghai, Peoples R China. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3933 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703216 ER PT J AU Li, M Rayburn, E Wang, W Wang, F Covey, J Lee, M Zhang, RW AF Li, Mao Rayburn, Elizabeth Wang, Wei Wang, Feng Covey, Joseph Lee, Moses Zhang, Ruiwen TI Preclinical pharmacological evaluations of indolecarboxamine ML-970 (NSC 716970) SO CANCER RESEARCH LA English DT Meeting Abstract C1 UAB, Ctr Comprehens Canc, Birmingham, AL USA. NCI, Dev Therapeut Program, DCTD, Rockville, MD USA. Hope Coll, Dept Chem, Holland, MI 49423 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2930 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802112 ER PT J AU Li, SW Wang, JA Rajesh, S Moss, J Darling, T AF Li, Shaowei Wang, Ji-an Rajesh, Sangeetha Moss, Joel Darling, Thomas TI Rapamycin inhibits hyperactivation of mTORC1 signaling in a novel xenograft model of tuberous sclerosis complex skin tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1735 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705026 ER PT J AU Li, SL Park, H Trempus, C Gordon, D Cotsarelis, G Morris, R AF Li, Shulan Park, Heuijoon Trempus, Carol Gordon, Derek Cotsarelis, George Morris, Rebecca TI Evidence for polyfocal development of papillomas in the murine cutaneous epithelium SO CANCER RESEARCH LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. NIEHS, Res Triangle Pk, NC 27709 USA. Rutgers State Univ, Piscataway, NJ USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3144 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803434 ER PT J AU Li, Y Li, WP Jiao, ZX Yao, ZX Jessup, J Mishra, L AF Li, Ying Li, Wenping Jiao, Zhongxian Yao, Zhixing Jessup, John Mishra, Lopa TI CEA regulates CRC cells metastasis through multiple pathways SO CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3515 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804281 ER PT J AU Li, ZJ Tan, F Tong, JN McKee, A Thiele, C AF Li, Zhijie Tan, Fei Tong, Jenna McKee, Amy Thiele, Carol TI Perifosine, as a single agent, inhibits neuroblastoma tumor cell growth in in vitro and in vivo preclinical models. SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Li, Zhijie; Tan, Fei; Tong, Jenna; McKee, Amy; Thiele, Carol] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3205 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804002 ER PT J AU Lim, M Moore, H Compton, C AF Lim, Mark Moore, Helen Compton, Carolyn TI The "biospecimen research network": a resource from NCI'S office of biorepositories and biospecimen research SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lim, Mark; Moore, Helen; Compton, Carolyn] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1654 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702014 ER PT J AU Limgala, R Yee, C Terunuma, A Martin, P Kelly, K Vogel, J AF Limgala, Renuka Yee, Carole Terunuma, Atsushi Martin, Philip Kelly, Kathy Vogel, Jonathan TI Isolation of Prostate Cancer Stem Cells using Developmental Signaling Pathway Activities SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Limgala, Renuka; Yee, Carole; Terunuma, Atsushi; Martin, Philip; Kelly, Kathy; Vogel, Jonathan] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-71 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603190 ER PT J AU Lintel, N Walker, R Hunter, K AF Lintel, Nicholas Walker, Renard Hunter, Kent TI Ttc9c abrogates the metastasis promoter Sipa1, ablates lung metastasis and switches the Estrogen Receptor back on in a highly-metastatic, ER negative mouse mammary carcinoma cell-line SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lintel, Nicholas; Walker, Renard; Hunter, Kent] NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1181 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803152 ER PT J AU Liu, HF Fulmer-Smentek, S D'Andrade, P Lorenzi, P Weinstein, J Kohn, K Pommier, Y Reinhold, W AF Liu, Hongfang Fulmer-Smentek, Stephanie D'Andrade, Petula Lorenzi, Philip Weinstein, John Kohn, Kurt Pommier, Yves Reinhold, William TI Profiling and characterization of microRNA expression in the NCI-60 human cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Agilent Technol, Santa Clara, CA USA. NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 545 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803080 ER PT J AU Liu, W Zabirnyk, O Wang, HH Liu, YM Shiao, YH Anderson, LM Perantoni, AO Phang, JM AF Liu, Wei Zabirnyk, Olga Wang, Honghe Liu, Yongmin Shiao, Yih-Horng Anderson, Lucy M. Perantoni, Alan O. Phang, James M. TI Proline oxidase, a p53-induced cancer suppressor protein, is regulated by miR-23b*in renal cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Basic Res Program,SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Lab Canc & Dev Biol, Ctr Canc Res, Basic Res Program,SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2528 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803154 ER PT J AU Liu, W Zabirnyk, O Liu, YM Phang, JM AF Liu, Wei Zabirnyk, Olga Liu, Yongmin Phang, James M. TI Hypoxia induction of Proline oxidase is independent of HIF but dependent on the LKB1/AMPK signaling pathway SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Liu, Wei; Zabirnyk, Olga; Liu, Yongmin; Phang, James M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Basic Res Program,SAIC Frederick Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 271 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804079 ER PT J AU Liu, XF Bera, T Pastan, I AF Liu, Xiu Fen Bera, Tapan Pastan, Ira TI A primate-specific POTE-actin fusion protein has a role in genotoxic-agent induced apoptosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Liu, Xiu Fen; Bera, Tapan; Pastan, Ira] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5107 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801221 ER PT J AU Liu, YM Borchert, G Donald, S Diwan, B Phang, J AF Liu, Yongmin Borchert, Gregory Donald, Steve Diwan, Bhalchandra Phang, James TI Proline oxidase, a novel mitochondrial tumor suppressor in human cancers, reduces HIF signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4448 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802289 ER PT J AU Liu, YM Borchert, G Donald, S Diwan, B Phang, J AF Liu, Yongmin Borchert, Gregory Donald, Steve Diwan, Bhalchandra Phang, James TI Proline oxidase, a novel mitochondrial tumor suppressor in human cancers, reduces HIF signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4448 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804452 ER PT J AU Liu, ZF Xie, ZL Aimiuwu, J Ling, YH Covey, J Chan, K AF Liu, Zhongfa Xie, Zhiliang Aimiuwu, Josephine Ling, Yonghua Covey, Joseph Chan, Kenneth TI Cytotoxicity and hypomethylation activity of 5-Fluoro-2\#8217;-deoxycytidine and decitabine on human cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. NCI, Dev Therapeut Program, DCTD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3377 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802039 ER PT J AU Longmire, M Kosaka, N Ogawa, M Choyke, P Kobayashi, H AF Longmire, Michelle Kosaka, Nobuyuki Ogawa, Mikako Choyke, Peter Kobayashi, Hisataka TI Multi-color in vivo targeted imaging to guide real-time surgery of HER2-positive micro-metastases in a two-tumor coincident model of ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NCI CCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-290 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604017 ER PT J AU Lopes, E Cerchietti, L Ahn, J Robles, A Varticovski, L Melnick, A Chiosis, G AF Lopes, Eloisi Cerchietti, Leandro Ahn, James Robles, Ana Varticovski, Lyuba Melnick, Ari Chiosis, Gabriela TI Targeting triple-negative breast cancer via PU-H71, a purine-scaffold heat shock protein 90 (Hsp90) inhibitor SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Weill Cornell Med Oncol, New York, NY USA. NCI, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-7 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801232 ER PT J AU Lou, H Yeager, M Li, HC Bosquet, JG Hayes, R Orr, N Hutchinson, A Yu, K Jacobs, K Kraft, P Wacholder, S Chatterjee, N Feigelson, H Thun, M Diver, WR Albanes, D Willett, W Virtamo, J Weinstein, S Ma, J Gaziano, JM Stampfer, M Schumacher, F Giovannucci, E Cancel-Tassin, G Cussenot, O Valeri, A Andriole, G Crawford, ED Anderson, S Tucker, M Hoover, R Fraumeni, J Thomas, G Hunter, D Chanock, S Dean, M AF Lou, Hong Yeager, Meredith Li, Hongchuan Bosquet, Jesus Gonzalez Hayes, Richard Orr, Nick Hutchinson, Amy Yu, Kai Jacobs, Kevin Kraft, Peter Wacholder, Sholom Chatterjee, Nilanjan Feigelson, Heather Thun, Michael Diver, W. Ryan Albanes, Demetrius Willett, Walter Virtamo, Jarmo Weinstein, Stephanie Ma, Jing Gaziano, J. Michael Stampfer, Meir Schumacher, Fredrick Giovannucci, Edward Cancel-Tassin, Geraldine Cussenot, Olivier Valeri, Antoine Andriole, Gerald Crawford, E. David Anderson, Stephen Tucker, Margaret Hoover, Robert Fraumeni, Joseph Thomas, Gilles Hunter, David Chanock, Stephen Dean, Michael TI Functional analysis of the promoter of the beta-microseminoprotein gene MSMB demonstrates the importance of a single nucleotide polymorphism in prostate cancer susceptibility SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NCI, Bethesda, MD 20892 USA. Bioinformed Consulting Serv, Gaithersburg, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Natl Publ Hlth Inst, Helsinki, Finland. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Hop Tenon, Assistance Publ Hop Paris, Ctr Rech Pathol Prostat CeRePP, F-75970 Paris, France. Univ Colorado, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5613 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802117 ER PT J AU Lowy, D Day, P Kines, R Roberts, J Thompson, C Pang, S Buck, C Roden, R Schille, J AF Lowy, Douglas Day, Patricia Kines, Rhonda Roberts, Jeffrey Thompson, Cynthia Pang, Susana Buck, Christopher Roden, Richard Schille, John TI HPV vaccination: Current realities and future prospects SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY35-1 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702600016 ER PT J AU Lu, H Jaeschke, H Sterneck, E Klaassen, C AF Lu, Hong Jaeschke, Hartmut Sterneck, Esta Klaassen, Curtis TI C/EBP\#946; in hepatocytes promotes inflammation and disrupts whole-body metabolic homeostasis during endotoxemia SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3804 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800361 ER PT J AU Lubet, R Juliana, MM Bode, A Steele, V Grubbs, C AF Lubet, Ronald Juliana, M. Margaret Bode, Ann Steele, Vernon Grubbs, Clinton TI Preventive effects of Lapatinib, a combined EGFR1 and EGFR2 inhibitor on chemically-induced urinary bladder and estrogen receptor positive mammary cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 940 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801271 ER PT J AU Lung, M Chan, KC Yau, WL Lung, HL Sedlacek, R Miller, L Liu, E Lerman, M Zabarovsky, E Tsao, SW Chua, D AF Lung, Maria Chan, King Chi Yau, Wing Lau Lung, Hong Lok Sedlacek, Radek Miller, Lance Liu, Edison Lerman, Michael Zabarovsky, Eugene Tsao, Sai Wah Chua, Daniel TI Matrix metalloproteinase-19 involvement in nasopharyngeal carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 Hong Kong Univ Sci & Technol, Kowloon, Hong Kong, Peoples R China. Inst Biotechnol, Prague, Czech Republic. Genome Inst Singapore, Singapore, Singapore. NCI, Bethesda, MD 20892 USA. Karolinska Inst, Stockholm, Sweden. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3332 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801255 ER PT J AU Luo, JF Gao, YT Chow, WH Shu, XO Li, HL Yang, G Cai, QY Rothman, N Cai, H Shrubsole, M Franke, A Zheng, W Dai, Q AF Luo, Jianfeng Gao, Yu-Tang Chow, Wong-Ho Shu, Xiao-ou Li, Honglan Yang, Gong Cai, Qiuyin Rothman, Nathaniel Cai, Hui Shrubsole, Martha Franke, Adrian Zheng, Wei Dai, Qi TI Urinary polyphenols and breast cancer risk: results from the Shanghai Women Health Study (SWHS) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. US Dept HHS, Bethesda, MD USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2056 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801370 ER PT J AU Luo, JF Gao, YT Chow, WH Shu, XO Li, HL Yang, G Cai, QY Li, GL Rothman, N Cai, H Shrubsole, M Franke, A Zheng, W Dai, Q AF Luo, Jianfeng Gao, Yu-Tang Chow, Wong-Ho Shu, Xiao Ou Li, Honglan Yang, Gong Cai, Qiuyin Li, Guoliang Rothman, Nathaniel Cai, Hui Shrubsole, Martha Franke, Adrian Zheng, Wei Dai, Qi TI Interaction between urinary tea polyphenols and Glutathione S-transferase gene polymorphisms in relation to breast cancer risk: Results from the Shanghai Women's Health Study (SWHS) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37212 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-237 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704036 ER PT J AU Ly, D Savage, J Sowers, A Soule, B Saleh, A Mitchell, J Simone, N AF Ly, David Savage, Jason Sowers, Anastasia Soule, Benjamin Saleh, Anthony Mitchell, James Simone, Nicole TI Altered microRNA expression after irradiation may regulate the radiation induced toxicity of fibrosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, Radiat Biol Branch, Bethesda, MD 20892 USA. NIAID, NIH, Lab Host Def, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3967 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804029 ER PT J AU Maciag, A Cheng, YSR Romanowska, M Anderson, L AF Maciag, Anna Cheng, Y. S. Robert Romanowska, Malgorzata Anderson, Lucy TI Mutant K-rasV12 may upregulate COX-2 through Hmga1 and epiregulin, leading to reactive oxygen species generation. SO CANCER RESEARCH LA English DT Meeting Abstract C1 SAIC Frederick, Frederick, MD USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4354 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803439 ER PT J AU Maris, J Courtright, J Houghton, P Morton, C Kolb, E Gorlick, R Carol, H Lock, R Friedman, H Keir, S Kang, M Reynolds, C Smith, M AF Maris, John Courtright, Joshua Houghton, Peter Morton, Christopher Kolb, E. Gorlick, Richard Carol, Hernan Lock, Richard Friedman, Henry Keir, Stephen Kang, Min Reynolds, C. Smith, Malcolm TI Pediatric Preclinical Testing Program (PPTP) evaluation of the novel polyamine analogue PG11047 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Alfred I DuPont Hosp Children, Wilmington, DE USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Childrens Canc Inst, Sydney, NSW, Australia. Duke Univ, Durham, NC USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3194 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803488 ER PT J AU Marron, M Boffetta, P Benhamou, S Boccia, S Castellsague, X Chen, C Curado, MP Dal Maso, L Daudt, A Eluf-Neto, J Fabianova, E Fernandez, L Franceschi, S Hayes, R Herrero, R Kelsey, K Koifman, S La Vecchia, C Lazarus, P Levi, F Lissowska, J Mates, IN Purdue, M Rudnai, P Schwartz, S AF Marron, Manuela Boffetta, Paolo Benhamou, Simone Boccia, Stefania Castellsague, Xavier Chen, Chu Curado, Maria Paula Dal Maso, Luigino Daudt, Alexander Eluf-Neto, Jose Fabianova, Eleonora Fernandez, Leticia Franceschi, Silvia Hayes, Richard Herrero, Rolando Kelsey, Karl Koifman, Sergio La Vecchia, Carlo Lazarus, Philip Levi, Fabio Lissowska, Jolanta Mates, Ioan Nicolae Purdue, Mark Rudnai, Peter Schwartz, Stephen TI Alcohol drinking and the risk of head and neck cancer among younger, middle age and older populations SO CANCER RESEARCH LA English DT Meeting Abstract C1 Int Agcy Res Canc, F-69372 Lyon, France. INSERM, U794, Paris, France. Inst Gustave Roussy, Villejuif, France. Univ Cattolica Sacro Cuore, Rome, Italy. CIBER ESP, IDIBELL, ICO, Barcelona, Spain. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Hosp Araujo Jorge, Goiania, Go, Brazil. Aviano Canc Ctr, I-33081 Aviano, Italy. Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. Univ Sao Paulo, Sao Paulo, Brazil. Specialized State Hlth Inst, Bansk El Bystrica, Slovakia. Inst Oncol & Radiobiol, Havana, Cuba. NCI, Bethesda, MD 20892 USA. Inst Invest Epidemiol, San Jose, Costa Rica. Brown Univ, Boston, MA USA. Escola Nacl Saude Publica, Rio De Janeiro, Brazil. Ist Ric Farmacol Mario Negri, Milan, Italy. Univ Milan, Milan, Italy. Penn State Coll Med, Hershey, PA USA. Inst Univ Med Sociale & Prevent, Lausanne, Switzerland. M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. Univ Med & Pharm, Bucharest, Romania. Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina. Boston Univ, Boston, MA 02215 USA. Univ Fed Pelotas, Pelotas, Brazil. UNC Sch Publ Hlth, Chapel Hill, NC USA. Natl Inst Environm Hlth, Budapest, Hungary. RI Mates, Ioan Nicolae/E-9255-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2132 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702704074 ER PT J AU Marshall, JC Collins, J Ming, Z Veenstra, T Khanna, C Vidal-Vanaclocha, F Steeg, P AF Marshall, Jean-Claude Collins, Joshua Ming, Zhou Veenstra, Timothy Khanna, Chand Vidal-Vanaclocha, Fernando Steeg, Patricia TI An unbiased screen for Nm23-H1 interacting proteins identifies the cytoskeletal regulator Ezrin. SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Basque Country, Sch Med, Bizkaia, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4809 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803234 ER PT J AU Mckay, M Ritt, D Morrison, D AF Mckay, Melissa Ritt, Daniel Morrison, Deborah TI Signaling dynamics of the KSR1 scaffold complex SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Mckay, Melissa; Ritt, Daniel; Morrison, Deborah] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5233 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802409 ER PT J AU McNeely, S Conti, C Sheikh, T Pommier, Y Schwartz, G Tse, A AF McNeely, Samuel Conti, Chiara Sheikh, Tahir Pommier, Yves Schwartz, Gary Tse, Archie TI Chk1 inhibition after replicative stress causes a double strand break response mediated primarily by DNA-dependent protein kinase SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2488 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801163 ER PT J AU Menashe, I Anderson, W Jatoi, I Philip, R AF Menashe, Idan Anderson, William Jatoi, Ismail Philip, Rosenberg TI Underlying causes of the Black-White racial disparity in breast cancer mortality: A population-based analysis SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Natl Naval Med Ctr, Breast Care Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 972 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703387 ER PT J AU Menendez, D Yan, J Yang, XP Jetten, AM Resnick, M AF Menendez, Daniel Yan, Jun Yang, Xiao-Ping Jetten, Anton M. Resnick, Michael CA Ction LRB Chromosome Stability Grp LMG Cell BiologySe TI A regulatory loop composed of RAP80-HDM2-p53 provides RAP80 enhanced p53 degradation by HDM2 in response to DNA damage SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Menendez, Daniel; Yan, Jun; Yang, Xiao-Ping; Jetten, Anton M.; Resnick, Michael; Ction; LRB Chromosome Stability Grp LMG; Cell BiologySe] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 459 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801338 ER PT J AU Mirabello, L Garcia-Closas, M Cawthon, R Lissowska, J Peplonska, B Brinton, L Sherman, M Savage, S AF Mirabello, Lisa Garcia-Closas, Montserrat Cawthon, Richard Lissowska, Jolanta Peplonska, Beata Brinton, Louise Sherman, Mark Savage, Sharon TI Shorter germline telomere length is associated with increased ovarian cancer risk in the population-based Polish Ovarian Cancer Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCEG, NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT USA. M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3489 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804108 ER PT J AU Mishra, P Ha, LA Rieker, J Henrich, C Bennett, D Sviderskaya, E Merlino, G AF Mishra, Prasun Ha, Linan Rieker, Jennifer Henrich, Curtis Bennett, Dorothy Sviderskaya, Elena Merlino, Glenn TI The p53 and Ink4A independent tumor suppressor activity of ARF in melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. US FDA, Div Monoclonal Antibody, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. NCI, Mol Targets Dev Program, Frederick, MD 21701 USA. SAIC Fredrick Inc, Frederick, MD USA. Univ London, Div Basic Med Sci, St Georges, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5515 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803212 ER PT J AU Mohammed, A Qian, L Janakiram, N Choi, CI Zhang, YT Steele, V Rao, C AF Mohammed, Altaf Qian, Li Janakiram, Naveena Choi, Chang-In Zhang, Yuting Steele, Vernon Rao, Chinthalapally TI Chemoprevention of colon and small intestinal tumorigenesis in Apc(Min/+) mice by licofelone, a novel dual 5-LOX/COX inhibitor SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Oklahoma, Inst Canc, OUHSC, Oklahoma City, OK USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4781 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801170 ER PT J AU Mohebtash, M Madan, R Tsang, K Arlen, P Pazdur, M Jones, J Schlom, J Gulley, J AF Mohebtash, Mahsa Madan, Ravi Tsang, Kwong Arlen, Philip Pazdur, Mary Jones, Jacquin Schlom, Jeffrey Gulley, James TI Clinical outcomes following immunotherapy with a MUC1/CEA vaccine in patients with metastatic breast and ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Mohebtash, Mahsa; Madan, Ravi; Tsang, Kwong; Arlen, Philip; Pazdur, Mary; Jones, Jacquin; Schlom, Jeffrey; Gulley, James] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 718 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805217 ER PT J AU Monks, A Hose, C Zhang, JH Wu, XL Greenblum, S Hu, Y Clifford, R Collins, J Buetow, K Doroshow, J AF Monks, Anne Hose, Curtis Zhang, Jinghui Wu, Xiaolin Greenblum, Sharon Hu, Ying Clifford, Robert Collins, Jerry Buetow, Kenneth Doroshow, James TI Genomic taxonomy of anti-cancer drug activity: Profiling of doxorubicin-induced gene expression changes in the NCI-60 cancer cell line panel. SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI Frederick, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2426 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801020 ER PT J AU Moody, T Mantey, S Sancho, V Gonzalez, N Jensen, R AF Moody, Terry Mantey, Samuel Sancho, Veronica Gonzalez, Nieves Jensen, Robert TI Bobmesin Receptor Subtype-3 regulates EGF receptor transactivation in lung cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CCR, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 800 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702483 ER PT J AU Moore, L Brennan, P Nickerson, M Jaeger, E Rinsky, J Zaridze, D Janout, V Kollarova, H Bencko, V Holcatova, I Navratilova, M Szesznenia-Dabrowska, N Mates, D Schmidt, L Toro, J Linehan, M Merino, M Zbar, B Boffetta, P Chow, WH Waldman, F Rothman, N AF Moore, Lee Brennan, Paul Nickerson, Michael Jaeger, Erich Rinsky, Jessica Zaridze, David Janout, Vladimir Kollarova, Hellen Bencko, Vladimir Holcatova, Ivana Navratilova, Marie Szesznenia-Dabrowska, Neonilia Mates, Dana Schmidt, Laura Toro, Jorge Linehan, Marston Merino, Maria Zbar, Berton Boffetta, Paolo Chow, Wong-Ho Waldman, Frederick Rothman, Nathaniel TI VHL gene alteration and histopathologic risk factors in a large RCC case-control study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. IARC, Lyon Frace, Finland. NCI, Frederick, MD 21701 USA. UCSF, San Francisco, CA USA. CRC, Moscow, Russia. Placky Univ, Sch Med, Olomouc, Czech Republic. Charles Univ Prague, Sch Med, Prague, Czech Republic. Masaryk Mem Canc Inst, Brno, Czech Republic. Inst Occupat Med, Dept Epidemiol, Lodz, Poland. Inst Publ Hlth, Bucharest, Romania. SAIC Basic Res Program, Frederick, MD USA. UCSF Canc Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1018 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801493 ER PT J AU Mor, G Symanowski, J Visintin, I Birrer, M Ward, D AF Mor, Gil Symanowski, James Visintin, Irene Birrer, Michael Ward, David TI Six biomarker panel detects early stage ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. Nevada Canc Inst, Las Vegas, NV USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-244 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801214 ER PT J AU Morton, C Houghton, P Maris, J Courtright, J Kolb, E Gorlick, R Carol, H Lock, R Friedman, H Keir, S Kang, M Reynolds, C Smith, M AF Morton, Christopher Houghton, Peter Maris, John Courtright, Joshua Kolb, E. Gorlick, Richard Carol, Hernan Lock, Richard Friedman, Henry Keir, Stephen Kang, Min Reynolds, C. Smith, Malcolm TI Pediatric Preclinical Testing Program (PPTP) evaluation of PR-104 SO CANCER RESEARCH LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Alfred I DuPont Hosp Children, Wilmington, DE USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Childrens Canc Inst, Sydney, NSW, Australia. Duke Univ, Durham, NC USA. Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79409 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3195 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803489 ER PT J AU Moulick, K Ahn, J Beebe, K Ma, YL Zartoska, D Taldone, T Caldas-Lopez, E Gross, S Neckers, L Chiosis, G AF Moulick, Kamalika Ahn, James Beebe, Kristin Ma, Yuliang Zartoska, Danuta Taldone, Tony Caldas-Lopez, Eloise Gross, Steven Neckers, Len Chiosis, Gabriela TI Probing cancer-specific activating signaling pathways through a tumor-specific Hsp90 inhibitor SO CANCER RESEARCH LA English DT Meeting Abstract C1 MSKCC, New York, NY USA. NCI, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-86 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701170 ER PT J AU Mullighan, C Zhang, J Harvey, R Collins-Underwood, JR Tasian, S Schulman, B Phillips, L Loh, M Su, X Liu, W Devidas, M Atlas, S Chen, IM Clifford, R Gerhard, D Carroll, W Reaman, G Smith, M Downing, J Hunger, S Willman, C AF Mullighan, Charles Zhang, Jinghui Harvey, Richard Collins-Underwood, J. Racquel Tasian, Sarah Schulman, Brenda Phillips, Letha Loh, Mignon Su, Xiaoping Liu, Wei Devidas, Meenakshi Atlas, Susan Chen, I-Ming Clifford, Robert Gerhard, Daniela Carroll, William Reaman, Gergory Smith, Malcolm Downing, James Hunger, Stephen Willman, Cheryl CA Children's Oncology Grp TI Frequent JAK mutations in pediatric acute lymphoblastic leukemia with poor outcome: A new therapeutic target in resistant disease. SO CANCER RESEARCH LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NCI, Ctr Bioinformed Informat & Informat Technol, NIH, Rockville, MD USA. Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Florida, Coll Med, Gainesville, FL USA. Univ New Mexico, Phys & Astron, Albuquerque, NM 87131 USA. NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. NCI, Off Canc Gen, NIH, Bethesda, MD 20892 USA. NYU, Inst Canc, New York, NY USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. Univ Colorado Denver, Sch Med, Aurora, CO USA. Childrens Hosp, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-92 PG 2 WC Oncology SC Oncology GA V43TD UT WOS:000209702803304 ER PT J AU Murff, H Shu, XO Li, HL Chow, WH Dai, Q Kallianpur, A Yang, G Cai, H Wen, WG Gao, YT Zheng, W AF Murff, Harvey Shu, Xiao-ou Li, Honglan Chow, Wong-Ho Dai, Qi Kallianpur, Asha Yang, Gong Cai, Hui Wen, Wanging Gao, Yu-Tang Zheng, Wei TI Dietary polyunsaturated fatty acids, prostaglandin E-2 production and colorectal cancer risk in Chinese women SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Shanghai Canc Inst, Shanghai, Peoples R China. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1006 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703364 ER PT J AU Murff, H Shu, XO Li, HL Chow, WH Dai, Q Kallianpur, A Yang, G Cai, H Wen, WG Gao, YT Zheng, W AF Murff, Harvey Shu, Xiao-ou Li, Honglan Chow, Wong-Ho Dai, Qi Kallianpur, Asha Yang, Gong Cai, Hui Wen, Wanging Gao, Yu-Tang Zheng, Wei TI Dietary polyunsaturated fatty acids, prostaglandin E-2 production and colorectal cancer risk in Chinese women SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Shanghai Canc Inst, Shanghai, Peoples R China. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1006 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801480 ER PT J AU Murphy, G Pfeiffer, R Camargo, M Rabkin, C AF Murphy, Gwen Pfeiffer, Ruth Camargo, Maria Rabkin, Charles TI Sex difference in Epstein-Barr virus-positive gastric cancer: Results of a meta-analysis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Murphy, Gwen; Pfeiffer, Ruth; Camargo, Maria; Rabkin, Charles] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2155 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704098 ER PT J AU Nagata, S Ise, T Egland, K Onda, M Ho, M Pastan, I AF Nagata, Satoshi Ise, Tomoko Egland, Kristi Onda, Masanori Ho, Mitchell Pastan, Ira TI Monoclonal antibodies to non-ligand-binding sites on CD30 induce agonistic effects and growth inhibition of human lymphoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Sanford Res USD, Sioux Falls, SD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 860 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604413 ER PT J AU Nam, JS Kim, RJ Kim, SR Park, SB Roh, KJ Cho, EM Kang, KS Tang, BW Yang, YA Kohn, E Wakefield, L AF Nam, Jeong-Seok Kim, Ran-Ju Kim, Soo-Rim Park, Sang-Bum Roh, Kyung-Jin Cho, Eun-Mi Kang, Kyung-Sun Tang, Binwu Yang, Yu-An Kohn, Ethan Wakefield, Lalage TI Ras activation contributes the maintenance and expansion of putative cancer stem cells in breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Res Inst, Lab Tumor Suppressor, Inchon, South Korea. Seoul Natl Univ, Coll Vet Med, Dept Vet Publ Hlth, Lab Stem Cell & Tumor Biol, Seoul, South Korea. NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3072 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603144 ER PT J AU Newman, D AF Newman, David TI Microbial natural products, derivatives, and mimics as antitumor agents SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Newman, David] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY30-1 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800024 ER PT J AU Newman, D AF Newman, David TI Microbial natural products, derivatives, and mimics as antitumor agents SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Newman, David] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY30-1 PG 2 WC Oncology SC Oncology GA V43TD UT WOS:000209702806015 ER PT J AU Nick, A Spannuth, W Landen, C Kim, HS Kamat, A Lin, Y Merritt, W Stone, R Mangala, L Armaiz-Pena, G Deavers, M Lopez-Berestein, G Birrer, M Coleman, R Sood, A AF Nick, Alpa Spannuth, Whitney Landen, Charles Kim, Hye Sun Kamat, Aparna Lin, Yvonne Merritt, William Stone, Rebecca Mangala, Lingegowda Armaiz-Pena, Guillermo Deavers, Michael Lopez-Berestein, Gabriel Birrer, Michael Coleman, Robert Sood, Anil TI Targeting p130cas in ovarian carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 UT MD Anderson Canc Ctr, Houston, TX USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4657 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604200 ER PT J AU Ogawa, M Kosaka, N Choyke, P Kobayashi, H AF Ogawa, Mikako Kosaka, Nobuyuki Choyke, Peter Kobayashi, Hisataka TI Target-specific activatable molecular imaging probes using conjugates of clinically approved monoclonal antibodies and indocyanine green, a near infrared dye SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4468 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701079 ER PT J AU Ohnuma, S Sauna, Z Nandigama, K Ambudkar, S AF Ohnuma, Shinobu Sauna, Zuben Nandigama, Krishnamachary Ambudkar, Suresh TI The development of an ATP analog, 5-fluorosulfonylbenzonyl 5-adenosine (FSBA) as a potent modulator of the multidrug resistance-linked P-glycoprotein (ABCB1) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ohnuma, Shinobu; Sauna, Zuben; Nandigama, Krishnamachary; Ambudkar, Suresh] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 898 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802007 ER PT J AU Olivero, O Gorgifard, S Yu, M Poirier, M AF Olivero, Ofelia Gorgifard, Sayeh Yu, Mia Poirier, Miriam TI A novel mechanism of genotoxicity induced by antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs) in erythrocebus patas bone marrow SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Olivero, Ofelia; Gorgifard, Sayeh; Yu, Mia; Poirier, Miriam] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1869 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800146 ER PT J AU Olivo-Marston, S Yang, P Mechanic, L Bowman, E Pine, S Loffredo, C Alberg, A Caporaso, N Shields, P Chanock, S Wu, YH Jiang, RX Cunningham, J Jen, J Harris, C AF Olivo-Marston, Susan Yang, Ping Mechanic, Leah Bowman, Elise Pine, Sharon Loffredo, Christopher Alberg, Anthony Caporaso, Neil Shields, Peter Chanock, Stephen Wu, Yanhong Jiang, Ruoxiang Cunningham, Julie Jen, Jin Harris, Curtis TI Childhood exposure to secondhand smoke and alterations in innate immunity increase adult lung cancer risk among never smokers SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Westat Corp, Rockville, MD USA. Georgetown Univ, Washington, DC USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1976 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703103 ER PT J AU Onnis, B Uranchimeg, B Rapisarda, A Shoemaker, R Melillo, G AF Onnis, Barbara Uranchimeg, Badarch Rapisarda, Annamaria Shoemaker, Robert Melillo, Giovanni TI Response of colon cancer cells to the hypoxic microenvironment: characterization of pathways involved in survival and tumorigenicity SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Onnis, Barbara; Uranchimeg, Badarch; Rapisarda, Annamaria; Shoemaker, Robert; Melillo, Giovanni] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 250 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604009 ER PT J AU Ota, T Bell, D Gonzalez-Bosquet, J Shridhar, V Hartmann, L Fan, JB Chien, J AF Ota, Takayo Bell, Debra Gonzalez-Bosquet, Jesus Shridhar, Vijayalakshmi Hartmann, Lynn Fan, Jian-Bing Chien, Jeremy TI Molecular features and therapeutic targets in stage 1 epithelial ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, Gaithersburg, MD USA. Illumina Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5206 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802262 ER PT J AU Palmieri, D Hua, E Qian, YZ Herring, J Liewehr, D Steinberg, S Laquerre, S Dar, M Steeg, P AF Palmieri, Diane Hua, Emily Qian, Yongzhen Herring, Jeanne Liewehr, David Steinberg, Seth Laquerre, Sylvie Dar, Mohammed Steeg, Patricia TI Preclinical studies investigating the efficacy of GSK461364A, an inhibitor of Polo-like kinase-1, for the prevention of breast cancer brain metastases SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD USA. GlaxoSmithKline, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4767 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604230 ER PT J AU Paoloni, M Mazcko, C Currier, D Yu, YK Cao, L Khanna, C AF Paoloni, Melissa Mazcko, Christina Currier, Duane Yu, Yunkai Cao, Liang Khanna, Chand TI Comparative oncology modeling of rapalog development SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Paoloni, Melissa; Mazcko, Christina; Currier, Duane; Yu, Yunkai; Cao, Liang; Khanna, Chand] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2345 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804283 ER PT J AU Pastorino, F Loi, M Marchio, S Di Paolo, D Becherini, P Curnis, F Longhi, R Nico, B Bussollno, F Ribatti, D Cilli, M Arap, W Pasqualini, R Corti, A Allen, T Ponzoni, M AF Pastorino, Fabio Loi, Monica Marchio, Serena Di Paolo, Daniela Becherini, Pamela Curnis, Fiavio Longhi, Renato Nico, Beatrice Bussollno, Fedrico Ribatti, Domenico Cilli, Michele Arap, Wadih Pasqualini, Renata Corti, Angelo Allen, Theresa Ponzoni, Mirco TI Combination of peptides-targeted liposomal chemotherapy against neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 G Gaslini Childrens Hosp, Genoa, Italy. Univ Turin, Dept Oncol Sci, Candiolo, TO, Italy. San Raffaele, Dept Mol Oncol, Milan, Italy. CNR, Ist Chim Riconoscimento Mol, I-20133 Milan, Italy. Univ Bari, Dept Human Anat & Histol, Bari, Italy. Natl Canc Inst, Anim Res Facil, Genoa, Italy. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada. RI Di Paolo, Daniela/J-7681-2016 OI Di Paolo, Daniela/0000-0001-7264-6888 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3677 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705269 ER PT J AU Pastorino, F Loi, M Cilli, M Zhao, H Sapra, P Greenberger, L Ribatti, D Ponzoni, M AF Pastorino, Fabio Loi, Monica Cilli, Michele Zhao, Hong Sapra, Puja Greenberger, Lee Ribatti, Domenico Ponzoni, Mirco TI EZN-2208, a novel pegylated SN-38 drug conjugate, markedly inhibits tumor growth and metastatic spreading of human neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 G Gaslini Childrens Hosp, Lab Oncol, Genoa, Italy. Natl Canc Inst, Anim Res Facil, Genoa, Italy. Enzon Pharmaceut, Piscataway, NJ USA. Univ Bari, Dept Human Anat, Bari, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1699 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704427 ER PT J AU Perez-Galan, P Mora-Jensen, H Weniger, M Chapman, C Wiestner, A AF Perez-Galan, Patricia Mora-Jensen, Helena Weniger, Marc Chapman, Colby Wiestner, Adrian TI Resistance to bortezomib in mantle cell lymphoma is associated with differentiation towards a plasma cell phenotype SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Perez-Galan, Patricia; Mora-Jensen, Helena; Weniger, Marc; Chapman, Colby; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4540 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704405 ER PT J AU Pichiorri, F Sung-Suk, S Taccioli, C Hofmeister, C Benson, D Kuehl, M Munker, R Huebner, K Ageilan, RI Croce, CM AF Pichiorri, Flavia Sung-Suk, Suh Taccioli, Cristian Hofmeister, Craig Benson, Don Kuehl, Michael Munker, Reinhold Huebner, Kay Ageilan, Rami I. Croce, Carlo M. TI Regulation of expression of multiple miRNAs defines the cellular response to non genotoxic p53 activation in multiple myeloma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. Louisiana State Univ, Shreveport, LA 71105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2637 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804063 ER PT J AU Pittman, G Perera, F Herbstman, J Edwards, S Tang, DL Wang, XT Jedrychowski, W Bell, D AF Pittman, Gary Perera, Frederica Herbstman, Julie Edwards, Susan Tang, Deliang Wang, Xuting Jedrychowski, Wieslaw Bell, Douglas TI In utero PAH exposure alters CpG methylation status in neonates SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Jagiellonian Univ, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3015 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703148 ER PT J AU Ptaszynska, M Pendrak, M Roberts, D AF Ptaszynska, Malgorzata Pendrak, Michael Roberts, David TI VEGF and ATX cross-talk presents a new aspect of tumor-endothelial cell interaction in the tumor microenviorment SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3502 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804267 ER PT J AU Quinlan, S Anderson, L Pfieffer, R Morton, L Landgren, O Berndt, S Warren, J Engels, E AF Quinlan, Scott Anderson, Lesley Pfieffer, Ruth Morton, Lindsay Landgren, Ola Berndt, Sonja Warren, Joan Engels, Eric TI Spectrum of hematologic malignancies associated with solid organ transplantation: results of a US population-based case-control study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI DCEG, Rockville, MD USA. NCI DCCPS, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2145 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704088 ER PT J AU Raggi, C Marquardt, J Andersen, J Avital, I Factor, V Thorgeirsson, S AF Raggi, Chiara Marquardt, Jens Andersen, Jesper Avital, Itzhak Factor, Valentina Thorgeirsson, Snorri TI Epigenetic modulation of liver cancer cell lines reduces heterogeneity of cancer stem cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Raggi, Chiara; Marquardt, Jens; Andersen, Jesper; Avital, Itzhak; Factor, Valentina; Thorgeirsson, Snorri] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3138 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803427 ER PT J AU Ramaswamy, B Bhalla, K Cohen, B Pellegrino, C Hershman, D Chuang, E Somlo, G Goetz, M Swaby, R Stearns, V Nonemaker, J Hopkins, U Christos, P Espinoza-Delgado, I Sparano, J AF Ramaswamy, B. Bhalla, K. Cohen, B. Pellegrino, C. Hershman, D. Chuang, E. Somlo, G. Goetz, M. Swaby, R. Stearns, V. Nonemaker, J. Hopkins, U. Christos, P. Espinoza-Delgado, I. Sparano, J. TI Phase I-II study of the histone deacetylase inhibitor vorinostat plus paclitaxel and bevacizumab in patients with metastatic breast cancer: New York Cancer Consortium trial P7703 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. Med Coll Georgia, Augusta, GA 30912 USA. Montefiore Einstein Canc Ctr, Bronx, NY USA. New York Presbyterian Hosp, New York, NY USA. Weill Cornell Univ, New York, NY USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Mayo Clin, Rochester, MN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Kimmel Canc Ctr, Baltimore, MD USA. NCI, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3571 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805324 ER PT J AU Rao, C Mohammed, A Qian, L Janakiram, N Choi, CI Zhang, YT Lightfoot, S Steele, V AF Rao, Chinthalapally Mohammed, Altaf Qian, Li Janakiram, Naveena Choi, Chang-In Zhang, Yuting Lightfoot, Stan Steele, Vernon TI Delayed progression of pancreatic carcinoma in a conditional K-ras(G12D) mice by nitric oxide (NO)-releasing aspirin SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Oklahoma, Inst Canc, OUHSC, Oklahoma City, OK USA. Univ Oklahoma, Coll Med, Dept Pathol, Oklahoma City, OK 73190 USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2062 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801377 ER PT J AU Rapisarda, A Uranchimeg, B Scudiero, D Ngo, A Bee, NS Everett, M Cardellina, J Shoemaker, R Melillo, G AF Rapisarda, Annamaria Uranchimeg, Badarch Scudiero, Dominic Ngo, Anna Bee, Ng Siew Everett, Martin Cardellina, John Shoemaker, Robert Melillo, Giovanni TI Identification and characterization of a novel HIF-1 inhibitor that selectively induces DNA damage under hypoxic conditions SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. MerLion Pharmaceut, Singapore, Singapore. NCI, DTP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 256 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804065 ER PT J AU Reid, J McGovern, R Buhrow, S Jia, L Ames, M AF Reid, Joel McGovern, Renee Buhrow, Sarah Jia, Lee Ames, Matthew TI LC/MS/MS assay and mouse pharmacokinetics of the eukaryotic elongation factor-2 kinase inhibitor NSC 745343 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2932 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802114 ER PT J AU Reinhold, W Pfister, T Liu, HF Gingeras, T Kaldjian, E Selzer, R Ryan, M Parchment, R Tomaszewski, J Kinders, R Weinstein, J Pommier, Y AF Reinhold, William Pfister, Thomas Liu, Hongfang Gingeras, Thomas Kaldjian, Eric Selzer, Rebecca Ryan, Michael Parchment, Ralph Tomaszewski, Joseph Kinders, Robert Weinstein, John Pommier, Yves TI Transcript expression analysis of TOP1 at the exon level reveals potential intragenic regulation, association with DNA copy number, and is associated with genomic stability, and response to the indenoisoquinolines in the NCI-60 SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. SIAC, Frederick, MD USA. Affymetrix Inc, Santa Clara, CA USA. Transgenomic Inc, Omaha, NE USA. Roche NimbleGen Inc, Madison, WI USA. TigerTeam Consulting, Fairfax, VA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1705 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704433 ER PT J AU Rime, BJ Arur, S Thaker, P Golden, A Schedl, T Goodfellow, P AF Rime, B. J. Arur, Swathi Thaker, Premal Golden, Andy Schedl, Tim Goodfellow, Paul TI DICER1 is a target of ERK1/2 in mammalian cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Washington Univ, Siteman Canc Ctr, St Louis, MO USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4381 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805476 ER PT J AU Roccaro, A Sacco, A Chen, CZ Leleu, X Runnels, J Azab, AK Azab, F Jia, XY Ngo, H Melhem, M Varticovski, L Novina, C Rollins, B Anderson, K Ghobrial, I AF Roccaro, Aldo Sacco, Antonio Chen, Changzhong Leleu, Xavier Runnels, Judith Azab, Abdel Kareem Azab, Feda Jia, Xiaoying Ngo, Hai Melhem, Molly Varticovski, Lyuba Novina, Carl Rollins, Barrett Anderson, Kenneth Ghobrial, Irene TI MicroRNA in the biology, prognosis and therapy of Waldenstrom macroglobulinemia SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1393 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803205 ER PT J AU Rodriguez, V Carlson, B Noma, A Elkahloun, A Green, J Suzuki, T Chandrasekharappa, S AF Rodriguez, Virginia Carlson, Bradley Noma, Akiko Elkahloun, Abdel Green, Jeffrey Suzuki, Tsutomu Chandrasekharappa, Settara TI TRMT12 overexpression in cancer cells affects the cell cycle and the nonsense mediated decay pathways by regulating the SMG-1 kinase, a member of the PIKK family of kinases SO CANCER RESEARCH LA English DT Meeting Abstract C1 NHGRI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2486 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801161 ER PT J AU Rosenberg, S AF Rosenberg, Steven TI Effective cell transfer therapy for patients with metastatic melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Rosenberg, Steven] NCI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA SY35-3 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701800044 ER PT J AU Rotunno, M Yu, K Lubin, J Consonni, D Pesatori, A Goldstein, A Goldin, L Wacholder, S Welch, R Burdette, L Chanock, S Caporaso, N Bertazzi, PA Tucker, M Chatterjee, N Bergen, A Landi, MT AF Rotunno, Melissa Yu, Kai Lubin, Jay Consonni, Dario Pesatori, Angela Goldstein, Alisa Goldin, Lynn Wacholder, Sholom Welch, Robert Burdette, Laurie Chanock, Stephen Caporaso, Neil Bertazzi, Pier Alberto Tucker, Margaret Chatterjee, Nilanjan Bergen, Andrew Landi, Maria Teresa TI Phase I metalbolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Rockville, MD USA. Dept Occupat & Environm Hlth, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 106 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704056 ER PT J AU Ryscavage, A Suh, K Shukla, A Malik, M Crutchley, J Nolan, L Dumont, R Cheng, C Fernandez-Salas, E Yuspa, S AF Ryscavage, Andrew Suh, Kwang Shukla, Anjali Malik, Mariam Crutchley, John Nolan, Lisa Dumont, Rebecca Cheng, Christina Fernandez-Salas, Ester Yuspa, Stuart TI CLIC4 is a tumor suppressor for cutaneous squamous cell cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Ryscavage, Andrew; Suh, Kwang; Shukla, Anjali; Malik, Mariam; Crutchley, John; Nolan, Lisa; Dumont, Rebecca; Cheng, Christina; Fernandez-Salas, Ester; Yuspa, Stuart] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5346 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804499 ER PT J AU Saleh, A Ly, D Soule, B DeGraff, W Savage, J Mitchell, J Gius, D Simone, N AF Saleh, Anthony Ly, David Soule, Benjamin DeGraff, William Savage, Jason Mitchell, James Gius, David Simone, Nicole TI The response of the microRNA let-7b to ionizing radiation may involve p53 SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3976 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804036 ER PT J AU Samimi, G Mok, S Birrer, M AF Samimi, Goli Mok, Sam Birrer, Michael TI Expression of CTGF in ovarian tumor stroma and its role ovarian tumor progression SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 270 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804078 ER PT J AU Samuels, Y Palavalli, L Prickett, T Wunderlich, J Wei, XM Burrell, A Porter-Gill, P Lin, J Molinolo, A Weeraratna, A Brody, L Rosenberg, S Davis, S Wang, CW Cronin, J Agrawal, N Westbroek, W Hoogstraten-Miller, S Fetsch, P Filie, A O'Connell, M Buckhaults, P Banister, C Howard, J AF Samuels, Yardena Palavalli, Lavanya Prickett, Todd Wunderlich, John Wei, Xiaomu Burrell, Allison Porter-gill, Patricia Lin, Jimmy Molinolo, Alfredo Weeraratna, Ashani Brody, Lawrrence Rosenberg, Steven Davis, Sean Wang, Chenwei Cronin, Julie Agrawal, Neena Westbroek, Wendy Hoogstraten-Miller, Shelly Fetsch, Patricia Filie, Armando O'Connell, Michael Buckhaults, Phillip Banister, Carolyn Howard, Jason TI Analysis of the Matrix Metalloproteinase Family Reveals MMP-8 is often mutated in Melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. JHU, Baltimore, MD USA. Univ S Carolina, Sch Med, Columbia, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-100 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802122 ER PT J AU Samuni, Y Ishii, H Krishna, M Mitchell, J AF Samuni, Yuval Ishii, Hisanari Krishna, Murali Mitchell, James TI Superoxide-dependent hepatotoxicity of the Hsp90 inhibiting anticancer drugs geldanamycin and its two derivatives SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Samuni, Yuval; Ishii, Hisanari; Krishna, Murali; Mitchell, James] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1854 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802177 ER PT J AU Santhanam, A Baker, A Hegamyer, G Kirschmann, D Colburn, N AF Santhanam, Arti Baker, Alyson Hegamyer, Glenn Kirschmann, Dawn Colburn, Nancy TI Pdcd4 inhibition of lysyl oxidase contributes to hypoxia-induced breast cancer invasion SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. Northwestern Univ, Childrens Mem Res Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3099 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803154 ER PT J AU Sato, M Kadota, M Robert, C Zhang, HE Lee, M Wakefield, L AF Sato, Misako Kadota, Mitsutaka Robert, Clifford Zhang, Hongen Lee, Maxwell Wakefield, Lalage TI Identification of direct Smad3 target genes mediating the TGF-beta-dependent \#8220;metastatic switch\#8221; SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Sato, Misako; Kadota, Mitsutaka; Robert, Clifford; Zhang, Hongen; Lee, Maxwell; Wakefield, Lalage] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2589 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804049 ER PT J AU Schetter, A Nguyen, G Bowman, E Matte, E Yuen, S Croce, C Leung, S Harris, C AF Schetter, Aaron Giang Nguyen Bowman, Elise Matte, Ewy Yuen, Siu Croce, Carlo Leung, Suet Harris, Curtis TI Prediction of survival in early stage colon adenocarcinoma using the expression of inflammatory genes and a microRNA SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1612 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805150 ER PT J AU Schmid, T Blees, J Baker, A Henrich, C Young, M Brune, B McMahon, J Colburn, N AF Schmid, Tobias Blees, Johanna Baker, Alyson Henrich, Curtis Young, Matthew Bruene, Bernhard McMahon, James Colburn, Nancy TI Targeting translation to inhibit tumorigenesis - development of a high-throughput screen to discover compounds stabilizing tumor suppressor Pdcd4 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Goethe Univ Frankfurt, D-60054 Frankfurt, Germany. NCI, Frederick, MD 21701 USA. NCI, MTDP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1558 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702700387 ER PT J AU Shan, ZH Simmons, J Shakoori, A Jen, J Wiest, J AF Shan, Zhihong Simmons, John Shakoori, Abbas Jen, Jin Wiest, Jonathan TI TUSC1, a putative tumor suppressor gene in human lung cancer potentially functions in autophagy SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. CCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 386 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800400 ER PT J AU Sharma, S Wang, XJ Gao, P Steele, V AF Sharma, Sheela Wang, Xiaojuan Gao, Pu Steele, Vernon TI Alternative approach to aerosolized chemopreventive agent delivery to respiratory tract epithelium SO CANCER RESEARCH LA English DT Meeting Abstract C1 Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2093 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702801127 ER PT J AU Shatz, M Menendez, D Resnick, M AF Shatz, Maria Menendez, Daniel Resnick, Michael TI The p53 tumor suppressor as a regulator of innate immunity genes SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Shatz, Maria; Menendez, Daniel; Resnick, Michael] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4253 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802222 ER PT J AU Shebl, F Engels, E Goedert, J Chaturvedi, A AF Shebl, Fatma Engels, Eric Goedert, James Chaturvedi, Anil TI Pulmonary infactions and risk of lung cancer among people with AIDS SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Shebl, Fatma; Engels, Eric; Goedert, James; Chaturvedi, Anil] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2149 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704093 ER PT J AU Simmons, J DeCicco-Skinner, K Pandey, J Shan, ZH Reddi, T Wiest, J AF Simmons, John DeCicco-Skinner, Kathleen Pandey, Jyotsna Shan, Zhihong Reddi, Tejaswini Wiest, Jonathan TI Loss of Tpl2 enhances tumorigenesis and affects tumor phenotype during promotion SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Amer Univ, Washington, DC 20016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 450 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801328 ER PT J AU Slager, S Goldin, L Strom, S Lanasa, M Spector, L Rassenti, L Leis, J Camp, N Kay, N Vachon, C Weinberg, J Rabe, K Achenbach, S Hanson, C Marti, G Call, T Caporaso, N Cerhan, J AF Slager, Susan Goldin, Lynn Strom, Sara Lanasa, Mark Spector, Logan Rassenti, Laura Leis, Jose Camp, Nicola Kay, Neil Vachon, Celine Weinberg, J. Rabe, Kari Achenbach, Sara Hanson, Curtis Marti, Gerald Call, Timothy Caporaso, Neil Cerhan, James TI Confirmation of a set of genetic susceptibility variants for chronic lymphocytic leukemia (CLL) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, DCEG, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Minnesota, Minneapolis, MN USA. UCSD, Moores Canc Ctr, La Jolla, CA USA. Mayo Clin, Scottsdale, AZ USA. Univ Utah, Sch Med, Salt Lake City, UT USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 96 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704045 ER PT J AU Smith, S Salcido, C Carlson, M Hursting, S Varticovski, L AF Smith, Sarah Salcido, Crystal Carlson, Marisa Hursting, Stephen Varticovski, Lyuba TI Wnt-1 mammary tumors are enriched in CD44+/CD24-cells with cancer stem cell characteristics. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas Austin, Austin, TX 78712 USA. NCI, CCR, Bethesda, MD 20892 USA. Univ Denver, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3087 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603161 ER PT J AU Smits, M Mir, S Niers, J Marquez, V Tannous, B Cloos, J Noske, D Wurdinger, T AF Smits, Michiel Mir, Shahryar Niers, Johanna Marquez, Victor Tannous, Bakhos Cloos, Jacqueline Noske, David Wurdinger, Tom TI MicroRNA-101 targets EZH2 and controls angiogenesis in glioblastoma multiforme SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4761 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804254 ER PT J AU Sohn, J Yfantis, H Khan, M Bowman, E Trivers, G Hussain, S Zanetti, K Harris, C AF Sohn, Jane Yfantis, Harris Khan, Mohammed Bowman, Elise Trivers, Glennwood Hussain, S. Zanetti, Krista Harris, Curtis TI Inflammation is associated with aging and DNA damage response in inflammatory bowel disease SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3493 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804112 ER PT J AU Sorbara, L Kishawi, I Pinsky, P Meltzer, S Franklin, W Bemis, L Gaston, S Rom, W Srivastava, S AF Sorbara, Lynn Kishawi, Iman Pinsky, Paul Meltzer, Stephen Franklin, Wilbur Bemis, Lynne Gaston, Sandra Rom, William Srivastava, Sudhir TI MicroRNA microarrays for biomarker discovery: Joint EDRN-Agilent project SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Agilent Technol, Santa Clara, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Colorado, Denver, CO 80202 USA. Harvard, Beth Israel Deaconess Med Ctr, Boston, MA USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5383 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803344 ER PT J AU Sosa, MS Yang, CF Lopez-Haber, C Klein-Szanto, A Lemmon, M Gutkind, JS Kazanietz, M AF Sosa, Maria Soledad Yang, Chengfeng Lopez-Haber, Cynthia Klein-Szanto, Andres Lemmon, Mark Gutkind, J. Silvio Kazanietz, Marcelo TI The Rac-GEF P-Rex1is an essential mediator of Rac activation and motility downstream of ErbB receptors in breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Michigan State Univ, E Lansing, MI 48824 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2497 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802489 ER PT J AU Sparano, J Moulder, S Kazi, A Coppola, D Negassa, A Vandat, L Li, TH Christine, P Fineberg, S Munster, P Malafa, M David, L Hoschander, S Hopkins, U Hershman, D Wright, J Kleer, C Merjver, S Sebti, S AF Sparano, Joseph Moulder, Stacy Kazi, Aslamuzzaman Coppola, Domenico Negassa, Abdissa Vandat, Linda Li, Tianhong Christine, Pellegrino Fineberg, Susan Munster, Pam Malafa, Mokenge David, Lee Hoschander, Shira Hopkins, Una Hershman, Dawn Wright, John Kleer, Celina Merjver, Sofia Sebti, Said TI Phase II trial of the farnesyl transferase inhibitor tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Montefiore Einstein Canc Ctr, Bronx, NY USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Weill Cornell Med Ctr, New York, NY USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NCI, CTEP, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5624 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805372 ER PT J AU Stark, K Shelton, P Gorski, D Ethier, S Chen, A Nguyen, B Burger, A AF Stark, Karri Shelton, Phillip Gorski, David Ethier, Stephen Chen, Alice Binh Nguyen Burger, Angelika TI Vorinostat can sensitize triple negative breast cancer cell lines to Aminoflavone Prodrug SO CANCER RESEARCH LA English DT Meeting Abstract C1 Wayne State Univ, Detroit, MI USA. Univ Maryland, Baltimore, MD 21201 USA. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA. Tigris Pharmaceut, Bonita Springs, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2905 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802085 ER PT J AU Stepp, MA Jurjus, R Pal-Ghosh, S Tadvalkar, G Cataisson, C Ryscavage, A Yuspa, S AF Stepp, Mary Ann Jurjus, Rosalyn Pal-Ghosh, Sonali Tadvalkar, Gauri Cataisson, Christophe Ryscavage, Andrew Yuspa, Stuart TI Syndecan-1 is required for formation of cutaneous squamous cell carcinomas after chemical carcinogenesis. SO CANCER RESEARCH LA English DT Meeting Abstract C1 George Washington Univ, Sch Med, Washington, DC USA. NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2222 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604093 ER PT J AU Stepp, MA Jurjus, R Pal-Ghosh, S Tadvalkar, G Cataisson, C Ryscavage, A Yuspa, S AF Stepp, Mary Ann Jurjus, Rosalyn Pal-Ghosh, Sonali Tadvalkar, Gauri Cataisson, Christophe Ryscavage, Andrew Yuspa, Stuart TI Syndecan-1 is required for formation of cutaneous squamous cell carcinomas after chemical carcinogenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 George Washington Univ, Sch Med, Washington, DC USA. NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2222 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803101 ER PT J AU Stone, R Nick, A Spannuth, W Bonome, T Lutgendorf, S De Geest, K Merritt, W Lin, Y Gershenson, D Coleman, R Birrer, M Sood, A AF Stone, Rebecca Nick, Alpa Spannuth, Whitney Bonome, Tomas Lutgendorf, Susan De Geest, Koen Merritt, William Lin, Yvonne Gershenson, David Coleman, Robert Birrer, Michael Sood, Anil TI The clinical and biological significance of focal adhesion kinase activation in ovarian carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 UT MD Anderson Canc Ctr, Houston, TX USA. NIH, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3636 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705166 ER PT J AU Stuelten, C Busch, J Tang, BW Oshima, A Sutton, E Karpova, T Roberts, A Wakefield, L Niederhuber, J AF Stuelten, Christina Busch, Johanna Tang, Binwu Oshima, Akira Sutton, Emily Karpova, Tatiana Roberts, Anita Wakefield, Lalage Niederhuber, John TI Transient tumor-fibroblast interactions durably increase tumor cell malignancy by a TGF-beta mediated mechanism SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Stuelten, Christina; Busch, Johanna; Tang, Binwu; Oshima, Akira; Sutton, Emily; Karpova, Tatiana; Roberts, Anita; Wakefield, Lalage; Niederhuber, John] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3504 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804269 ER PT J AU Sudarshan, S Sourbier, C Kong, HS Block, K Romero, V Yang, YF Galindo, C Mollapour, M Scroggins, B Goode, N Lee, MJ Gourlay, C Trepel, J Linehan, WM Neckers, L AF Sudarshan, Sunil Sourbier, Carole Kong, Hye-Sik Block, Karen Romero, Vladimir Yang, Youfeng Galindo, Cynthia Mollapour, Mehdi Scroggins, Bradley Goode, Norman Lee, Min-Jung Gourlay, Campbell Trepel, Jane Linehan, W. Marston Neckers, Len TI Fumarate hydratase deficiency induces glycolytic addiction and a HIF1-\#945; amplification loop stabilized by glucose dependent generation of reactive oxygen species SO CANCER RESEARCH LA English DT Meeting Abstract C1 UT Hlth Sci Ctr, San Antonio, TX USA. NCI, Bethesda, MD 20892 USA. Univ Kent, Canterbury CT2 7NZ, Kent, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5302 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802198 ER PT J AU Takikita, M Hu, N Giffen, C Taylor, P Hewitt, S AF Takikita, Mikiko Hu, Nan Giffen, Carol Taylor, Philip Hewitt, Stephen TI Cytokeratin 14 and fascin are associated with histological differentiation in esophageal squamous cell carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1010 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801484 ER PT J AU Tanaka, H Yamamoto, M Miyakoshi, M Tamakawa, S Tokusashi, Y Yaginuma, Y Ogawa, K AF Tanaka, Hiroki Yamamoto, Masahiro Miyakoshi, Masaaki Tamakawa, Susumu Tokusashi, Yoshihiko Yaginuma, Yuji Ogawa, Katsuhiro TI Rapamycin induces necrosis in mouse hepatocellular carcinomas by antiangiogenic activity, but also activates cap-independent translation of HIF-1\#945; in hepatocellular carcinoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 LSU Hlth Sci Ctr, Shreveport, LA USA. Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 125 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702602471 ER PT J AU Tasevska, N Cross, A Dodd, K Ziegler, R Caporaso, N Sinha, R AF Tasevska, Natasa Cross, Amanda Dodd, Kevin Ziegler, Regina Caporaso, Neil Sinha, Rashmi TI The effect of meat consumption, meat cooking preferences, meat mutagens and heme iron on lung cancer risk in the Prostate, Lung, Colorectral, and Ovarian Cancer Screening Trial (PLCO) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tasevska, Natasa; Cross, Amanda; Dodd, Kevin; Ziegler, Regina; Caporaso, Neil; Sinha, Rashmi] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 62 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704401 ER PT J AU Terzuoli, E Uranchimeg, B Rapisarda, A Burger, A Ziche, M Melillo, G AF Terzuoli, Erika Uranchimeg, Badarch Rapisarda, Annamaria Burger, Angelika Ziche, Marina Melillo, Giovanni TI Modulation of HIF-1\#945; mRNA processing by Aminoflavone: a novel mechanism of HIF-1\#945; inhibition in breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Siena, Dept Mol Biol, I-53100 Siena, Italy. NCI, Frederick, MD 21701 USA. Barbara Ann Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 266 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804074 ER PT J AU Truong, T Sauter, W McKay, J Hosgood, D Boffetta, P Brennan, P Hung, R AF Therese Truong Sauter, Wiebke McKay, James Hosgood, Dean Boffetta, Paolo Brennan, Paul Hung, Rayjean CA Int Lung Canc Consort TI Coordinated association study of 10 potential lung cancer susceptibility variants by the International Lung Cancer Consortium (ILCCO) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Int Agcy Res Canc, F-69372 Lyon, France. Helmholtz Zentrum Munich, German Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany. NCI, DCEG, Bethesda, MD 20892 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1914 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603173 ER PT J AU Tian, S Bank, A Huang, JQ Yoshimura, T Zeng, X AF Tian, Song Bank, Alexander Huang, Jiaqiang Yoshimura, Teizo Zeng, Xiao TI siRNA array study identified the NFkB pathway as an important controller for high CCL2 expression in glioma cell line U105MG SO CANCER RESEARCH LA English DT Meeting Abstract C1 SABiosciences Corp, Frederick, MD USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1545 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804346 ER PT J AU Tosca, P Merrill, J Ryan, M Knostman, K Johnson, J Peggins, J Tomaszewski, J AF Tosca, Patricia Merrill, John Ryan, Michael Knostman, Katherine Johnson, Jerry Peggins, James Tomaszewski, Joseph TI A comparative neurotoxicity study of Breflate and six Brefeldin-A prodrugs administered IV to male Fischer 344 rats SO CANCER RESEARCH LA English DT Meeting Abstract C1 Battelle Mem Inst, Columbus, OH USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5102 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801216 ER PT J AU Trempus, C Wei, SJ Humble, M Dang, H Bortner, C Williams, J Morris, R Tennant, R AF Trempus, Carol Wei, Sung-Jen Humble, Margaret Dang, Hong Bortner, Carl Williams, Jason Morris, Rebecca Tennant, Raymond TI Overexpression of the T-box transcription factor, Tbx1, abrogates cellular transformation in culture and delays tumor growth in mice SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Alpha Gamma Technol Inc, Raleigh, NC USA. Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2375 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701800178 ER PT J AU Tripathi, V Zimonjic, D Popescu, N AF Tripathi, Veenu Zimonjic, Drazen Popescu, Nicholas TI DLC1 associates with cell-cell adhesion complex and induces expression of E-cadherin in GAP dependent manner SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tripathi, Veenu; Zimonjic, Drazen; Popescu, Nicholas] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 619 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804418 ER PT J AU Tsai, HT Caporaso, N Kyle, R Katzmann, J Dispenzieri, A Hayes, R Marti, G Albitar, M Ghia, P Rajkumar, V Landgren, O AF Tsai, Huei-Ting Caporaso, Neil Kyle, Robert Katzmann, Jerry Dispenzieri, Angela Hayes, Richard Marti, Gerald Albitar, Maher Ghia, Paolo Rajkumar, Vincent Landgren, Ola TI Evidence of immune disruption up to 9.8 years prior to diagnosis of chronic lymphocytic leukemia: A prospective study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Mayo Clin, Div Hematol & Internal Med, Rochester, MN USA. Mayo Clin, Div Clin Biochem & Immunol, Rochester, MN USA. Mayo Clin, Lab Med & Pathol, Rochester, MN USA. NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. Quest Diagnost, Nichols Inst, San Juan Capistrano, CA USA. Univ Vita Salute San Raffaele, Dept Oncol, Unit & Lab Lymphoid Malignancies, Milan, Italy. Ist Sci San Raffaele, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1680 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702330 ER PT J AU Tsang, P Cheuk, A Chen, QR Khan, J AF Tsang, Patricia Cheuk, Adam Chen, Qing-Rong Khan, Javed TI High throughput siRNA screening identifies NF-kB as a target for combination therapy in neuroblastoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tsang, Patricia; Cheuk, Adam; Chen, Qing-Rong; Khan, Javed] NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5677 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804366 ER PT J AU Uzturk, G Chatterjee, C Ginsburg, E Rheey, J Vonderhaar, B Berg, P AF Uzturk, Gizem Chatterjee, Cynthia Ginsburg, Erika Rheey, Jinguen Vonderhaar, Barbara Berg, Patricia TI Prolactin stimulates pBP1, a homeotic protein frequently activated in breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 George Washington Univ, Washington, DC USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3349 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801274 ER PT J AU van der Watt, P Maske, C Hendricks, D Parker, I Denny, L Govender, D Birrer, M Leaner, V AF van der Watt, Pauline Maske, Christopher Hendricks, Denver Parker, Iqbal Denny, Lynette Govender, Dhirendra Birrer, Michael Leaner, Virna TI The Karyopherin proteins, Crm1 and Karyopherin \#946;1, are overexpressed in cervical cancer and critical for cancer cell survival and proliferation. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Cape Town, ZA-7925 Cape Town, South Africa. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 535 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802184 ER PT J AU Varticovski, L Pine, S Salcido, C Robles, A Ryan, B LaRochelle, A Harris, C AF Varticovski, Lyuba Pine, Sharon Salcido, Crystal Robles, Ana Ryan, Brid LaRochelle, Andre Harris, Curtis TI Identification of cancer stem cells in small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 LHC CCR NCI NIH, Bethesda, MD USA. NCI CCR, Bethesda, MD USA. NHBLI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 176 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603206 ER PT J AU Vora, M Calcagno, A Ambudkar, S Gottesman, M Gillet, JP AF Vora, Meena Calcagno, Anna Ambudkar, Suresh Gottesman, Michael Gillet, Jean-Pierre TI Characterization of multidrug resistance-linked gene signatures from TaqMan low density arrays, microarray gene expression and cellular assays for the NCI-60 panel using an integrative data analysis system, SIMUSITE (TM) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Biophase Syst, Fremont, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2466 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801063 ER PT J AU Wali, A Cavallo-Medved, D Lonardo, F Lei, J Wang, Y Rishi, A Carbone, M Sloane, B Ruckdeschel, J Pass, H AF Wali, Anil Cavallo-Medved, Dora Lonardo, Fulvio Lei, Jing Wang, Ying Rishi, Arun Carbone, Michele Sloane, Bonnie Ruckdeschel, John Pass, Harvey TI Gene expression pattern and clinical significance of cathepsin B in malignant pleural mesothelioma. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Wayne State Univ, Dept Surg, John D Dingell VA Med Ctr, Detroit, MI USA. Wayne State Univ, Dept Pathol, John D Dingell VA Med Ctr, Detroit, MI 48202 USA. Wayne State Univ, Dept Pharmacol, John D Dingell VA Med Ctr, Detroit, MI 48201 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Canc Res Ctr Hawaii, Thorac Oncol Program, Honolulu, HI USA. NYU, Sch Med, Dept Cardiothorac Surg, New York, NY USA. NCI, Ctr Canc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2602 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804193 ER PT J AU Walker, A Kotz, H Minasian, L Venkatasen, A Turkbey, B Houston, N Kohn, E Annunziata, C AF Walker, Amanda Kotz, Herbert Minasian, Lori Venkatasen, Aradhana Turkbey, Baris Houston, Nicole Kohn, Elise Annunziata, Christina TI Phase II study of clinical activity and proteomic profiling of the VEGFR2 inhibitor vandetanib in women with relapsed or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Walker, Amanda; Kotz, Herbert; Minasian, Lori; Venkatasen, Aradhana; Turkbey, Baris; Houston, Nicole; Kohn, Elise; Annunziata, Christina] NCI, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3581 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805335 ER PT J AU Wang, F Yang, XP Burnett, J Friedman, J Lu, H Cohen, J Chen, Z Van Waes, C AF Wang, Frederick Yang, Xinping Burnett, Jeffrey Friedman, Jay Lu, Hai Cohen, Jonah Chen, Zhong Van Waes, Carter TI TGF-\#946; receptor Ill is downregulated by \#916;Np63 and methylation and contributes to altered TGF-\#946; and NF -\#954;B signaling and the malignant phenotype in head and neck squamous cell cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, HHMI, Res Scholars Program, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-13 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801239 ER PT J AU Wang, SQ Tsutsumi, S Xu, WP Neckers, L AF Wang, Suiquan Tsutsumi, Shinji Xu, Wanping Neckers, Len TI Cancer cells harboring MET gene amplification are sensitive to Hsp90 inhibitor 17-AAG SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wang, Suiquan; Tsutsumi, Shinji; Xu, Wanping; Neckers, Len] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1853 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802176 ER PT J AU Wang, XY Lu, JC Penalva, L Okano, H Linnoila, R Glazer, R AF Wang, Xiao-Yang Lu, Jiachun Penalva, Liuz Okano, Hideyuki Linnoila, R. Glazer, Robert TI Musashi1 regulates breast cancer stem cell self-renewal and is a predictor of human breast cancer survival SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Guangzhou Med Univ, Guangzhou, Guangdong, Peoples R China. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Keio Univ, Sch Med, Tokyo, Japan. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3059 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702603131 ER PT J AU Wang, Y Ozawa, A Agarwal, S Marx, S AF Wang, Yan Ozawa, Atsushi Agarwal, Sunita Marx, Stephen TI Menin regulates the AKT signaling pathway through its interaction with AKT SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wang, Yan; Ozawa, Atsushi; Agarwal, Sunita; Marx, Stephen] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3832 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804431 ER PT J AU Warren, K Gururangan, S Balis, F Berg, S Blaney, S Wallace, D Boyett, J Kun, L AF Warren, Katherine Gururangan, Sri Balis, Frank Berg, Stacey Blaney, Susan Wallace, Dana Boyett, James Kun, Larry TI Phase II Trial of 06-Benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas (BSG): A Pediatric Brain Tumor Consortium (PBTC) Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. Texas Childrens Canc Ctr, Houston, TX USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4056 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702198 ER PT J AU Warren, K Gururangan, S Balis, F Berg, S Blaney, S Wallace, D Boyett, J Kun, L AF Warren, Katherine Gururangan, Sri Balis, Frank Berg, Stacey Blaney, Susan Wallace, Dana Boyett, James Kun, Larry TI Phase II Trial of O6-Benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas (BSG): A Pediatric Brain Tumor Consortium (PBTC) Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. Texas Childrens Canc Ctr, Houston, TX USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4056 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804058 ER PT J AU Watters, J Park, Y Hollenbeck, A Schatzkin, A Albanes, D AF Watters, Joanne Park, Yikyung Hollenbeck, Albert Schatzkin, Arthur Albanes, Demetrius TI Cigerette smoking and prostate cancer in a prospective US cohort study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. AARP, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2130 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704072 ER PT J AU Wei, BR Hoover, S Spehalski, E Zhou, WD Edwards, J Tessitore, A Ross, M Risinger, J Goldsmith, P Alvord, W Quinones, O Woolard, K Liotta, L Petricoin, E Simpson, RM AF Wei, Bih-Rong Hoover, Shelley Spehalski, Elizabeth Zhou, Weidong Edwards, Jennifer Tessitore, Alessandra Ross, Mark Risinger, John Goldsmith, Paul Alvord, W. Quinones, Octavio Woolard, Kevin Liotta, Lance Petricoin, Emanuel Simpson, R. Mark TI Mass spectrometry driven discovery proteomics of serum from mice with human ovarian cancer resulted in identification of a potential cancer-origin biomarker that correlates with peritoneal tumor burden SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Mol Pathol Unit, LCBG, Bethesda, MD 20892 USA. NCI, Antibody & Prot Purificat Unit, CCR, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. Mem Hlth Univ Med Ctr Inc, Anderson Canc Inst, Savannah, GA USA. NCI, Data Management Serv Inc, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4480 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701142 ER PT J AU Wei, J Johansson, P Chen, QR Song, Y Durinck, S Wen, XY Cheuk, A Ludwig, A Shohet, J Smith, M Houghton, P Morton, C Badgett, T Khan, J AF Wei, Jun Johansson, Peter Chen, Qingrong Song, Young Durinck, Steffen Wen, Xinyu Cheuk, Adam Ludwig, Andrew Shohet, Jason Smith, Malcolm Houghton, Peter Morton, Christopher Badgett, Thomas Khan, Javed TI microRNA profiling identifies cancer specific and prognostic signatures in pediatric malignancies SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2594 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804104 ER PT J AU Wen, XY Chen, QR Wei, J Song, Y Guo, X Khan, J AF Wen, Xinyu Chen, Qing-Rong Wei, Jun Song, Young Guo, Xiang Khan, Javed TI The Oncogenomics Data Center: an integrated, multi-platform, multifunctional database system SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wen, Xinyu; Chen, Qing-Rong; Wei, Jun; Song, Young; Guo, Xiang; Khan, Javed] NCI, NIH, SAIC Frederick, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2471 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801069 ER PT J AU White, R Lu, SL Bornstein, S Salter, K Olson, S Anderson, P Reh, D Malkoski, S Deng, CX Wang, XJ AF White, Ruth Lu, Shi-Long Bornstein, Sophia Salter, Kelli Olson, Susan Anderson, Peter Reh, Douglas Malkoski, Steven Deng, Chuxia Wang, Xiao-Jing TI Smad4 deletion leads to spontaneous head and neck cancer formation associated with genomic instability SO CANCER RESEARCH LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2084 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804385 ER PT J AU Wilkinson, S Fernandez, D Chan, W Gascoyne, R Campo, E Jaffe, E Staudt, L Delabie, J Rosenwald, A Rimsza, L AF Wilkinson, Sarah Fernandez, Diane Chan, Wing Gascoyne, Randy Campo, Elias Jaffe, Elaine Staudt, Louis Delabie, Jan Rosenwald, Andreas Rimsza, Lisa TI MHC class II loss in diffuse large B-cell lymphoma is inversely correlated with MUM1/IRF4 expression SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Arizona, Tucson, AZ USA. Univ Nebraska Med Ctr, Omaha, NE USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. Norwegian Radium Hosp, Oslo, Norway. Univ Wurzburg, D-97070 Wurzburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2712 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702112 ER PT J AU Williams, J Ji, P Zhou, H Rigas, B Kopelovich, L AF Williams, Jennie Ji, Ping Zhou, Hui Rigas, Basil Kopelovich, Levy TI Nitric oxide-donating aspirin S-nitrosylates signaling proteins in human cancer cells: implications for its mechanism of action SO CANCER RESEARCH LA English DT Meeting Abstract C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 20 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801004 ER EF