FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Levack, MM Madariaga, ML Kaafarani, HMA AF Levack, Melissa M. Madariaga, Maria Lucia Kaafarani, Haytham M. A. TI Non-operative successful management of a perforated small bowel diverticulum SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Jejunal diverticula; Diverticulitis; Small bowel perforation; Antibiotics; Abscess AB Jejunoileal diverticula are rare and generally asymptomatic. In the few cases of patients who develop complications such as diverticulitis, perforation, obstruction, and/or hemorrhage, conventional treatment consists of surgical resection. We describe a case of perforated jejunoileal diverticulum with localized abscess and highlight the merits of surgical vs medical management. The patient is a 77-year-old male who presented with sharp, constant abdominal pain just inferior to the umbilicus. Administration of intravenous antibiotics results in complete and long-term resolution of the patient's symptoms. In this report, we establish a framework for safely treating perforated small bowel diverticulum without surgical exploration. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Levack, Melissa M.; Madariaga, Maria Lucia; Kaafarani, Haytham M. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Surg Crit Care,Div Trauma, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Surg Crit Care,Div Trauma, 165 Cambridge St Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu NR 6 TC 4 Z9 4 U1 0 U2 1 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC 28 PY 2014 VL 20 IS 48 BP 18477 EP 18479 DI 10.3748/wjg.v20.i48.18477 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AY3BY UT WOS:000347460700043 PM 25561819 ER PT J AU Ashley, JD Stefanick, JF Schroeder, VA Suckow, MA Alves, NJ Suzuki, R Kikuchi, S Hideshima, T Anderson, KC Kiziltepe, T Bilgicer, B AF Ashley, Jonathan D. Stefanick, Jared F. Schroeder, Valerie A. Suckow, Mark A. Alves, Nathan J. Suzuki, Rikio Kikuchi, Shohei Hideshima, Teru Anderson, Kenneth C. Kiziltepe, Tanyel Bilgicer, Basar TI Liposomal carfilzomib nanoparticles effectively target multiple myeloma cells and demonstrate enhanced efficacy in vivo SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Carfilzomib; Nanoparticle; Liposome; Multiple myeloma; Proteasome inhibitor ID MEDIATED DRUG-RESISTANCE; PEPTIDE-LINKER LENGTH; IRREVERSIBLE INHIBITOR; PROTEASOME INHIBITORS; MOLECULAR-MECHANISMS; THERAPEUTIC-EFFICACY; DELIVERY-SYSTEMS; CELLULAR UPTAKE; CANCER-THERAPY; BREAST-CANCER AB Carfilzomib, a recently FDA-approved proteasome inhibitor, has remarkable anti-myeloma (MM) activity. However, its effectiveness is limited by associated severe side-effects, short circulation half-life, and limited solubility. Here, we report the engineering of liposomal carfilzomib nanoparticles to overcome these problems and enhance the therapeutic efficacy of carfilzomib by increasing tumoral drug accumulation while decreasing systemic toxicity. In our design, carfilzomib was loaded into the bilayer of liposomes to yield stable and reproducible liposomal nanoparticles. Liposomal carfilzomib nanoparticles were efficiently taken up by MM cells, demonstrated proteasome inhibition, induced apoptosis, and exhibited enhanced cytotoxicity against MM cells. In vivo, liposomal carfilzomib demonstrated significant tumor growth inhibition and dramatically reduced overall systemic toxicity compared to free carfilzomib. Finally, liposomal carfilzomib demonstrated enhanced synergy in combination with doxorubicin. Taken together, this study establishes the successful synthesis of liposomal carfilzomib nanoparticles that demonstrates improved therapeutic index and the potential to improve patient outcome in MM. (C) 2014 Elsevier B.V. All rights reserved. C1 [Ashley, Jonathan D.; Stefanick, Jared F.; Alves, Nathan J.; Kiziltepe, Tanyel; Bilgicer, Basar] Univ Notre Dame, Dept Chem & Biomol Engn, Notre Dame, IN 46556 USA. [Schroeder, Valerie A.; Suckow, Mark A.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. [Schroeder, Valerie A.; Suckow, Mark A.] Univ Notre Dame, Freimann Life Sci Ctr, Notre Dame, IN 46556 USA. [Suzuki, Rikio; Kikuchi, Shohei; Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Kiziltepe, Tanyel; Bilgicer, Basar] Univ Notre Dame, Notre Dame, IN 46556 USA. [Kiziltepe, Tanyel; Bilgicer, Basar] Univ Notre Dame, Harper Canc Res Inst, Notre Dame, IN 46556 USA. RP Kiziltepe, T (reprint author), Univ Notre Dame, 171 Fitzpatrick Hall, Notre Dame, IN 46556 USA. EM bbilgicer@nd.edu; tkiziltepe@nd.edu RI Suckow, Mark/C-2696-2014; OI Suckow, Mark/0000-0001-7317-697X FU Leukemia Research Foundation FX We thank the Notre Dame Integrated Imaging Facility for confocal microscopy, the Center for Environmental Science and Technology for the use of DLS, and the Mass Spectrometry and Proteomics Facility for the use of MALDI-TOF-MS. We thank Deborah Donahue and the WM Keck Center for the irradiation of the mice. This work was supported by the Hollis Brownstein Research Program Grant from Leukemia Research Foundation. NR 38 TC 7 Z9 8 U1 4 U2 50 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD DEC 28 PY 2014 VL 196 BP 113 EP 121 DI 10.1016/j.jconrel.2014.10.005 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA AW2PZ UT WOS:000346132100013 PM 25312543 ER PT J AU Rasmussen, NR Debebe, Z Wright, TM Brooks, SA Sendor, AB Brannon, AR Hakimi, AA Hsieh, JJ Choueiri, TK Tamboli, P Maranchie, JK Hinds, P Wallen, EM Simpson, C Norris, JL Janzen, WP Rathmell, WK AF Rasmussen, Neal R. Debebe, Zufan Wright, Tricia M. Brooks, Samira A. Sendor, Adam B. Brannon, A. Rose Hakimi, A. Ari Hsieh, James J. Choueiri, Toni K. Tamboli, Pheroze Maranchie, Jodi K. Hinds, Peter Wallen, Eric M. Simpson, Catherine Norris, Jacqueline L. Janzen, William P. Rathmell, W. Kimryn TI Expression of Ror2 Mediates Invasive Phenotypes in Renal Cell Carcinoma SO PLOS ONE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; RECEPTOR TYROSINE KINASE; BRACHYDACTYLY TYPE-B; TUMOR; METALLOPROTEINASE; OSTEOSARCOMA; PSEUDOKINASE; MELANOMA; DISEASE; CANCER AB Ror2 is a Wnt ligand receptor that is overexpressed in a variety of tumors including clear cell renal cell carcinoma (ccRCC). Here we demonstrate that expression of wild type Ror2 results in increased tumorigenic properties in in vitro cell culture and in vivo xenograft models. In addition, Ror2 expression produced positive changes in both cell migration and invasion, which were dependent on matrix metalloprotease 2 (MMP2) activity. Mutations in key regions of the kinase domain of Ror2 resulted in the abrogation of increased tumor growth, cell migration, and cell invasion observed with expression of wild-type Ror2. Finally, we examined Ror2 expression as a prognostic biomarker for ccRCC utilizing the TCGA ccRCC dataset. High expression of Ror2 showed a significant correlation with higher clinical stage, nuclear grade, and tumor stage. Furthermore, high expression of Ror2 in ccRCC patients correlated with significant lower overall survival, cancer specific survival, and recurrence free survival. Together, these findings suggest that Ror2 plays a central role in influencing the ccRCC phenotype, and can be considered as a negative prognostic biomarker and potential therapeutic target in this cancer. C1 [Rasmussen, Neal R.; Wright, Tricia M.; Brannon, A. Rose] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. [Rasmussen, Neal R.; Debebe, Zufan; Wright, Tricia M.; Brooks, Samira A.; Sendor, Adam B.; Brannon, A. Rose; Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Brooks, Samira A.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. [Brannon, A. Rose; Hakimi, A. Ari; Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Hakimi, A. Ari; Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02215 USA. [Tamboli, Pheroze] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Maranchie, Jodi K.; Hinds, Peter] Univ Pittsburgh, Med Ctr, Dept Urol Oncol, Pittsburgh, PA 15219 USA. [Wallen, Eric M.] Univ N Carolina, Dept Urol, Chapel Hill, NC 27599 USA. [Wallen, Eric M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Simpson, Catherine; Norris, Jacqueline L.; Janzen, William P.] Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC 27599 USA. [Rathmell, W. Kimryn] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Rathmell, W. Kimryn] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Rathmell, WK (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM Rathmell@med.unc.edu OI Sendor, Adam/0000-0003-4958-4660; Maranchie, Jodi/0000-0002-8534-9468 FU American Cancer Society Research Scholar [RSG-10-192-01]; National Heart, Lung, and Blood Institute [T32 HL069768-09]; National Cancer Institute [5T32CA160001] FX Funding provided by (www.cancer.org) American Cancer Society Research Scholar Grant RSG-10-192-01 (WKR), (www.nhlbi.nih.gov) National Heart, Lung, and Blood Institute T32 HL069768-09 (NR) and (www.cancer.gov) National Cancer Institute 5T32CA160001 (ARB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 4 Z9 5 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2014 VL 9 IS 12 AR e116101 DI 10.1371/journal.pone.0116101 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9RO UT WOS:000347239900141 PM 25542006 ER PT J AU Gandhi, RT Alkasab, TK Nardi, V Branda, JA AF Gandhi, Rajesh T. Alkasab, Tarik K. Nardi, Valentina Branda, John A. TI Case 40-2014: A 57-Year-Old Man with Inguinal Pain, Lymphadenopathy, and HIV Infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CAT-SCRATCH DISEASE; SYPHILITIC HEPATITIS; INFLAMMATORY PSEUDOTUMOR; BARTONELLA-HENSELAE; SECONDARY SYPHILIS; UNITED-STATES; CT; PREVALENCE; SARCOMA; CANCER C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alkasab, Tarik K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nardi, Valentina; Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Alkasab, Tarik K.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nardi, Valentina; Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU Gilead; Janssen; ViiV; Roche; DiaSorin; Alere; bioMerieux; Immunetics; AdvanDx FX Dr. Gandhi reports receiving grant support from Gilead, Janssen, ViiV, and Roche; and Dr. Branda, receiving grant support from DiaSorin, Alere, bioMerieux, and Immunetics and fees for serving on an advisory board from AdvanDx. No other potential conflict of interest relevant to this article was reported. NR 25 TC 1 Z9 1 U1 1 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2511 EP 2520 DI 10.1056/NEJMcpc1404518 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300012 PM 25539108 ER PT J AU Janesick, AS Shioda, T Blumberg, B AF Janesick, Amanda S. Shioda, Toshihiro Blumberg, Bruce TI Transgenerational inheritance of prenatal obesogen exposure SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Obesogen; Endocrine disrupting chemicals; Transgenerational; Obesity; Adipogenesis; Epigenetics ID ENDOCRINE-DISRUPTING CHEMICALS; ACTIVATED RECEPTOR-GAMMA; MESENCHYMAL STEM-CELLS; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; ENVIRONMENTAL CHEMICALS; ORGANOTIN COMPOUNDS; PERINATAL EXPOSURE; CHILDHOOD OBESITY; MICROBIAL ECOLOGY AB Obesity and metabolic syndrome diseases have exploded into an epidemic of global proportions. The generally accepted cause of obesity is overconsumption of calorie-dense food and diminished physical activity (the calories in-calories out model). However, emerging evidence demonstrates that environmental factors can predispose exposed individuals to gain weight, irrespective of diet and exercise. The environmental obesogen model proposes that chemical exposure during critical stages in development can influence subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage. Numerous obesogens have been identified in recent years and some of these have been shown to act through the peroxisome proliferator activated receptor gamma, the master regulator of adipogenesis. Others act through as yet unidentified pathways. Notably, some of these obesogens elicit transgenerational effects on a variety of health endpoints, including obesity in offspring after exposure of pregnant F0 females. Thus, prenatal exposure to xenobiotic compounds can have lasting, potentially permanent effects on the offspring of exposed animals. Transgenerational effects of chemical exposure raise the stakes in the debate about whether and how endocrine disrupting chemicals should be regulated. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Janesick, Amanda S.; Blumberg, Bruce] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. [Shioda, Toshihiro] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Blumberg, Bruce] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA. RP Blumberg, B (reprint author), Univ Calif Irvine, Dept Dev & Cell Biol, 2011 Biol Sci 3, Irvine, CA 92697 USA. EM blumberg@uci.edu OI Janesick, Amanda/0000-0001-7731-2756 FU NIH [1R01E5023316-01] FX This work was supported by a grant from NIH (B.B, T.S.) 1R01E5023316-01. NR 90 TC 12 Z9 12 U1 1 U2 30 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC 25 PY 2014 VL 398 IS 1-2 SI SI BP 31 EP 35 DI 10.1016/j.mce.2014.09.002 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AZ1RJ UT WOS:000348015300005 PM 25218215 ER PT J AU Lamas, D Rosenbaum, L AF Lamas, Daniela Rosenbaum, Lisa TI Very Complicated Math - Reconfiguring Organ Allocation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LIVER-TRANSPLANTATION C1 [Lamas, Daniela] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lamas, Daniela] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lamas, Daniela] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Lamas, D (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 5 TC 4 Z9 4 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2447 EP 2450 DI 10.1056/NEJMp1412764 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300002 PM 25539103 ER PT J AU Genovese, G Kahler, AK Handsaker, RE Lindberg, J Rose, SA Bakhoum, SF Chambert, K Mick, E Neale, BM Fromer, M Purcell, SM Svantesson, O Landen, M Hoglund, M Lehmann, S Gabriel, SB Moran, JL Lander, ES Sullivan, PF Sklar, P Gronberg, H Hultman, CM McCarroll, SA AF Genovese, Giulio Kaehler, Anna K. Handsaker, Robert E. Lindberg, Johan Rose, Samuel A. Bakhoum, Samuel F. Chambert, Kimberly Mick, Eran Neale, Benjamin M. Fromer, Menachem Purcell, Shaun M. Svantesson, Oscar Landen, Mikael Hoeglund, Martin Lehmann, Soeren Gabriel, Stacey B. Moran, Jennifer L. Lander, Eric S. Sullivan, Patrick F. Sklar, Pamela Groenberg, Henrik Hultman, Christina M. McCarroll, Steven A. TI Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; STEM-CELLS; MYELODYSPLASTIC SYNDROME; EPIGENETIC REGULATORS; PPM1D MUTATIONS; MOSAICISM; GENOME; AML; AGE; SCHIZOPHRENIA AB Background Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent. Methods We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling. Results Clonal hematopoiesis with somatic mutations was observed in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of age. Detectable clonal expansions most frequently involved somatic mutations in three genes (DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers. Clonal hematopoiesis was a strong risk factor for subsequent hematologic cancer (hazard ratio, 12.9; 95% confidence interval, 5.8 to 28.7). Approximately 42% of hematologic cancers in this cohort arose in persons who had clonality at the time of DNA sampling, more than 6 months before a first diagnosis of cancer. Analysis of bone marrow-biopsy specimens obtained from two patients at the time of diagnosis of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Conclusions Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently mutated in apparently healthy persons; these mutations may represent characteristic early events in the development of hematologic cancers. C1 [Genovese, Giulio; Handsaker, Robert E.; Rose, Samuel A.; Chambert, Kimberly; Neale, Benjamin M.; Moran, Jennifer L.; McCarroll, Steven A.] Stanley Ctr Psychiat Res, Cambridge, MA USA. [Genovese, Giulio; Handsaker, Robert E.; McCarroll, Steven A.] Program Med & Populat Genet, Cambridge, MA USA. [Gabriel, Stacey B.; Lander, Eric S.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Genovese, Giulio; Handsaker, Robert E.; McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Mick, Eran] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Kaehler, Anna K.; Lindberg, Johan; Svantesson, Oscar; Sullivan, Patrick F.; Groenberg, Henrik; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Lindberg, Johan] Karolinska Inst, Sci Life Lab, Stockholm, Sweden. [Lehmann, Soeren] Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden. [Lehmann, Soeren] Karolinska Univ Hosp, Ctr Hematol & Regenerat Med, Stockholm, Sweden. [Landen, Mikael] Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Gothenburg, Sweden. [Hoeglund, Martin] Univ Hosp, Dept Med Sci, Uppsala, Sweden. [Hoeglund, Martin] Univ Hosp, Div Hematol, Uppsala, Sweden. [Bakhoum, Samuel F.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Fromer, Menachem; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Fromer, Menachem; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP McCarroll, SA (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM giulio.genovese@gmail.com; mccarroll@genetics.med.harvard.edu OI McCarroll, Steven/0000-0002-6954-8184; Bakhoum, Samuel/0000-0002-4779-8422; Lindberg, Johan/0000-0003-3610-6774; Moran, Jennifer/0000-0002-5664-4716 FU National Human Genome Research Institute [U54 HG003067, R01 HG006855]; Stanley Center for Psychiatric Research; Alexander and Margaret Stewart Trust; National Institute of Mental Health [R01 MH077139, RC2 MH089905]; Sylvan C. Herman Foundation FX Supported by grants from the National Human Genome Research Institute (U54 HG003067 and R01 HG006855), the Stanley Center for Psychiatric Research, the Alexander and Margaret Stewart Trust, the National Institute of Mental Health (R01 MH077139 and RC2 MH089905), and the Sylvan C. Herman Foundation. NR 41 TC 314 Z9 322 U1 9 U2 41 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2477 EP 2487 DI 10.1056/NEJMoa1409405 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300007 PM 25426838 ER PT J AU Jaiswal, S Fontanillas, P Flannick, J Manning, A Grauman, PV Mar, BG Lindsley, RC Mermel, CH Burtt, N Chavez, A Higgins, JM Moltchanov, V Kuo, FC Kluk, MJ Henderson, B Kinnunen, L Koistinen, HA Ladenvall, C Getz, G Correa, A Banahan, BF Gabriel, S Kathiresan, S Stringham, HM McCarthy, MI Boehnke, M Tuomilehto, J Haiman, C Groop, L Atzmon, G Wilson, JG Neuberg, D Altshuler, D Ebert, BL AF Jaiswal, Siddhartha Fontanillas, Pierre Flannick, Jason Manning, Alisa Grauman, Peter V. Mar, Brenton G. Lindsley, R. Coleman Mermel, Craig H. Burtt, Noel Chavez, Alejandro Higgins, John M. Moltchanov, Vladislav Kuo, Frank C. Kluk, Michael J. Henderson, Brian Kinnunen, Leena Koistinen, Heikki A. Ladenvall, Claes Getz, Gad Correa, Adolfo Banahan, Benjamin F. Gabriel, Stacey Kathiresan, Sekar Stringham, Heather M. McCarthy, Mark I. Boehnke, Michael Tuomilehto, Jaakko Haiman, Christopher Groop, Leif Atzmon, Gil Wilson, James G. Neuberg, Donna Altshuler, David Ebert, Benjamin L. TI Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; B-CELL LYMPHOMA; MYELODYSPLASTIC SYNDROMES; DISTRIBUTION WIDTH; DNMT3A MUTATIONS; MYELOPROLIFERATIVE DISORDERS; POINT MUTATIONS; TET2 MUTATIONS; STEM-CELLS; CANCER AB Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. Methods We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. Results Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). Conclusions Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. C1 [Jaiswal, Siddhartha; Grauman, Peter V.; Mar, Brenton G.; Ebert, Benjamin L.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Lindsley, R. Coleman] Brigham & Womens Hosp, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Kuo, Frank C.; Kluk, Michael J.] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, Boston, MA 02115 USA. [Kuo, Frank C.; Kluk, Michael J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jaiswal, Siddhartha; Mermel, Craig H.; Chavez, Alejandro; Higgins, John M.; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Gabriel, Stacey; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Med, Div Endocrinol, Boston, MA 02114 USA. [Jaiswal, Siddhartha] Brigham & Womens Hosp, Boston Childrens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA. [Jaiswal, Siddhartha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mar, Brenton G.] Dept Pediat Oncol, Boston, MA USA. [Neuberg, Donna] Dept Biostat & Computat Biol, Boston, MA USA. [Higgins, John M.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. [Higgins, John M.] Dept Syst Biol, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Dept Med, Boston, MA USA. [Ebert, Benjamin L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ebert, Benjamin L.] Harvard Stem Cell Inst, Boston, MA USA. [Fontanillas, Pierre; Flannick, Jason; Manning, Alisa; Burtt, Noel; Gabriel, Stacey; Kathiresan, Sekar; Altshuler, David] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. [Moltchanov, Vladislav] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Moltchanov, Vladislav] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Koistinen, Heikki A.] Univ Helsinki, Cent Hosp, Minerva Fdn Inst Med Res, Helsinki, Finland. [Koistinen, Heikki A.] Univ Helsinki, Cent Hosp, Dept Med, Div Endocrinol, Helsinki, Finland. [Kinnunen, Leena; Koistinen, Heikki A.; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Henderson, Brian; Haiman, Christopher] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ladenvall, Claes; Groop, Leif] Lund Univ, Ctr Diabet, Dept Clin Sci, Clin Res Ctr,Skane Univ Hosp, Lund, Sweden. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Oxford, MS USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Oxford, MS USA. [Banahan, Benjamin F.] Univ Mississippi, Ctr Pharmaceut Mkt & Management, Oxford, MS USA. [Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford, England. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia. [Atzmon, Gil] Albert Einstein Coll Med, Dept Med & Genet, New York, NY USA. RP Ebert, BL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, 1 Blackfan Cir,Karp 5-210, Boston, MA 02115 USA. EM bebert@partners.org RI kinnunen, leena/B-7059-2012; OI kinnunen, leena/0000-0001-8739-4812; Lindsley, Coleman/0000-0001-9822-806X; Koistinen, Heikki/0000-0001-7870-070X; Mar, Brenton/0000-0002-3857-9324 FU National Institutes of Health (NIH) [R01HL082945]; Gabrielle's Angel Foundation; Leukemia and Lymphoma Society Scholar and Specialized Center of Research (SCOR); NIH [5T32HL066987, U01 DK085526, U01 DK085501, U01 DK085524, U01 DK085545, U01 DK085584, DK088389, P01AG021654, 1R01AG042188, P30AG038072]; Medical Research Council [G0601261]; Medical Research Council (High Throughput Genomics Hub) [G0900747 91070]; Wellcome Trust [090367, 090532, 098381, 083948, 085475]; Paul Glenn Foundation; National Heart, Lung, and Blood Institute [HSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; National Human Genome Research Institute (NHGRI) of the NIH [U54 HG003067] FX Supported by grants from the National Institutes of Health (NIH) (R01HL082945) and the Gabrielle's Angel Foundation, by Leukemia and Lymphoma Society Scholar and Specialized Center of Research (SCOR) Awards (to Dr. Ebert), and by an NIH Training Grant (5T32HL066987, to Dr. Jaiswal). The T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Multi-Ethnic Samples) consortium was supported by grants from the NIH (U01s DK085526, DK085501, DK085524, DK085545, and DK085584). The GoT2D (Genetics of Type 2 Diabetes) consortium is supported by grants from the Medical Research Council (G0601261 and High Throughput Genomics Hub grant G0900747 91070), the Wellcome Trust (090367, 090532, 098381, 083948, 085475), and the NIH (DK088389). The Longevity Genes Project is supported by grants from the NIH (P01AG021654, 1R01AG042188, P30AG038072), and by a Paul Glenn Foundation Grant. The Jackson Heart Study is supported by contracts (HSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C) from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Dr. McCarthy is a Wellcome Trust Senior Investigator and an NIH Research Senior Investigator. Exome sequencing in the Jackson Heart Study was funded by an award from the National Human Genome Research Institute (NHGRI) of the NIH (U54 HG003067, to Dr. Gabriel). NR 45 TC 351 Z9 362 U1 6 U2 34 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2488 EP 2498 DI 10.1056/NEJMoa1408617 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300008 PM 25426837 ER PT J AU Rustgi, AK El-Serag, HB AF Rustgi, Anil K. El-Serag, Hashem B. TI Esophageal Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SQUAMOUS-CELL CARCINOMA; GENOME-WIDE ASSOCIATION; HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL-REFLUX DISEASE; NUTRITION INTERVENTION TRIALS; HIGH-RISK POPULATION; BARRETTS-ESOPHAGUS; SUSCEPTIBILITY LOCI; GASTRIC CARDIA; ORAL BISPHOSPHONATES C1 [Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Abramson Canc Ctr,Perelman Sch Med, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Genet, Philadelphia, PA 19104 USA. [El-Serag, Hashem B.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.edu NR 97 TC 115 Z9 128 U1 7 U2 27 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2499 EP 2509 DI 10.1056/NEJMra1314530 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300009 PM 25539106 ER PT J AU Schwamm, LH AF Schwamm, Lee H. TI Progesterone for Traumatic Brain Injury - Resisting the Sirens' Song SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED-TRIAL; CLINICAL-TRIAL C1 [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,TeleStroke & Acute Stroke Serv, Boston, MA 02163 USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Heart Vasc & Stroke Care, Boston, MA USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Schwamm, LH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,TeleStroke & Acute Stroke Serv, Boston, MA 02163 USA. NR 8 TC 15 Z9 16 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 25 PY 2014 VL 371 IS 26 BP 2522 EP 2523 DI 10.1056/NEJMe1412951 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AX4RZ UT WOS:000346920300013 PM 25493975 ER PT J AU Vaina, LM Rana, KD Cotos, I Chen, LY Huang, MA Podea, D AF Vaina, Lucia M. Rana, Kunjan D. Cotos, Ionela Chen Li-Yang Huang, Melissa A. Podea, Delia TI When does Subliminal Affective Image Priming Influence the Ability of Schizophrenic Patients to Perceive Face Emotions? SO MEDICAL SCIENCE MONITOR LA English DT Article DE Affective Symptoms; Schizophrenia; Subliminal Stimulation ID FACIAL-AFFECT RECOGNITION; AFFECTIVE-DISORDERS; RATING-SCALE; IDENTIFICATION; PERCEPTION; DISCRIMINATION; AWARENESS; TOOLBOX AB Background: Deficits in face emotion perception are among the most pervasive aspects of schizophrenia impairments which strongly affects interpersonal communication and social skills. Material/Methods: Schizophrenic patients (PSZ) and healthy control subjects (HCS) performed 2 psychophysical tasks. One, the SAFFIMAP test, was designed to determine the impact of subliminally presented affective or neutral images on the accuracy of face-expression (angry or neutral) perception. In the second test, FEP, subjects saw pictures of face-expression and were asked to rate them as angry, happy, or neutral. The following clinical scales were used to determine the acute symptoms in PSZ: Positive and Negative Syndrome (PANSS), Young Mania Rating (YMRS), Hamilton Depression (HAM-D), and Hamilton Anxiety (HAM-A). Results: On the SAFFIMAP test, different from the HCS group, the PSZ group tended to categorize the neutral expression of test faces as angry and their response to the test-face expression was not influenced by the affective content of the primes. In PSZ, the PANSS-positive score was significantly correlated with correct perception of angry faces for aggressive or pleasant primes. YMRS scores were strongly correlated with PSZ's tendency to recognize angry face expressions when the prime was a pleasant or a neutral image. The HAM-D score was positively correlated with categorizing the test-faces as neutral, regardless of the affective content of the prime or of the test-face expression (angry or neutral). Conclusions: Despite its exploratory nature, this study provides the first evidence that conscious perception and categorization of facial emotions (neutral or angry) in PSZ is directly affected by their positive or negative symptoms of the disease as defined by their individual scores on the clinical diagnostic scales. C1 [Vaina, Lucia M.; Rana, Kunjan D.; Chen Li-Yang; Huang, Melissa A.] Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, Boston, MA 02215 USA. [Vaina, Lucia M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Vaina, Lucia M.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Vaina, Lucia M.] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA. [Cotos, Ionela; Podea, Delia] Cty Emergency Clin Hosp, Dept Psychiat, Arad, Romania. RP Vaina, LM (reprint author), Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, Boston, MA 02215 USA. EM vaina@bu.edu FU Brain and Vision research fund FX This work was supported, in part, by the Brain and Vision research fund to LMV NR 35 TC 0 Z9 0 U1 2 U2 11 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1643-3750 J9 MED SCI MONITOR JI Med. Sci. Monitor PD DEC 24 PY 2014 VL 20 BP 2788 EP 2798 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CC3ZM UT WOS:000350290000001 PM 25537115 ER PT J AU van Heesch, S Simonis, M van Roosmalen, MJ Pillalamarri, V Brand, H Kuijk, EW de Luca, KL Lansu, N Braat, AK Menelaou, A Hao, WS Korving, J Snijder, S van der Veken, LT Hochstenbach, R Knegt, AC Duran, K Renkens, I Alekozai, N Jager, M Vergult, S Menten, B de Bruijn, E Boymans, S Ippel, E van Binsbergen, E Talkowski, ME Lichtenbelt, K Cuppen, E Kloosterman, WP AF van Heesch, Sebastiaan Simonis, Marieke van Roosmalen, Markus J. Pillalamarri, Vamsee Brand, Harrison Kuijk, Ewart W. de Luca, Kim L. Lansu, Nico Braat, A. Koen Menelaou, Androniki Hao, Wensi Korving, Jeroen Snijder, Simone van der Veken, Lars T. Hochstenbach, Ron Knegt, Alida C. Duran, Karen Renkens, Ivo Alekozai, Najla Jager, Myrthe Vergult, Sarah Menten, Bjoern de Bruijn, Ewart Boymans, Sander Ippel, Elly van Binsbergen, Ellen Talkowski, Michael E. Lichtenbelt, Klaske Cuppen, Edwin Kloosterman, Wigard P. TI Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements SO CELL REPORTS LA English DT Article ID AUTISM SPECTRUM DISORDERS; COPY NUMBER VARIATION; PROSTATE-CANCER; DE-NOVO; STRUCTURAL VARIATION; GENE FUSIONS; REPAIR; ETV1; IDENTIFICATION; ABNORMALITIES AB Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted. C1 [van Heesch, Sebastiaan; Simonis, Marieke; Kuijk, Ewart W.; de Luca, Kim L.; Lansu, Nico; Hao, Wensi; Korving, Jeroen; de Bruijn, Ewart; Boymans, Sander; Cuppen, Edwin] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands. [van Heesch, Sebastiaan; Simonis, Marieke; Kuijk, Ewart W.; de Luca, Kim L.; Lansu, Nico; Hao, Wensi; Korving, Jeroen; de Bruijn, Ewart; Boymans, Sander; Cuppen, Edwin] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [van Roosmalen, Markus J.; Menelaou, Androniki; van der Veken, Lars T.; Hochstenbach, Ron; Duran, Karen; Renkens, Ivo; Alekozai, Najla; Jager, Myrthe; Ippel, Elly; van Binsbergen, Ellen; Lichtenbelt, Klaske; Cuppen, Edwin; Kloosterman, Wigard P.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, NL-3584 CG Utrecht, Netherlands. [Pillalamarri, Vamsee; Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Braat, A. Koen] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. [Snijder, Simone; Knegt, Alida C.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Vergult, Sarah; Menten, Bjoern] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. RP Cuppen, E (reprint author), Hubrecht Inst KNAW, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. EM e.cuppen@hubrecht.eu; w.kloosterman@umcutrecht.nl RI Cuppen, Edwin/H-2389-2016 OI Cuppen, Edwin/0000-0002-0400-9542 FU Cancer Genomics Center and Netherlands Center for Systems Biology programs of the Netherlands Genomics Initiative; Child Health Priority Program of the University Medical Center Utrecht, an NWO Vici grant [865.13.004]; Wilhelmina Children's Hospital; NIH [GM061354, HD065286, MH095867] FX We would like to thank A. de Graaff and the Hubrecht Imaging Center for supporting the imaging, M. van Dooren, L. van Zutven, and A. Baas for providing access to patient data, and A. Marcozzi for help with artwork. This work was supported by the Cancer Genomics Center and Netherlands Center for Systems Biology programs of the Netherlands Genomics Initiative, the Child Health Priority Program of the University Medical Center Utrecht, an NWO Vici grant (865.13.004) to E.C., a research grant from the Wilhelmina Children's Hospital to W.P.K., and the NIH (GM061354, HD065286, and MH095867 to M.E.T.). NR 44 TC 5 Z9 5 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 24 PY 2014 VL 9 IS 6 BP 2001 EP 2010 DI 10.1016/j.celrep.2014.11.022 PG 10 WC Cell Biology SC Cell Biology GA AX3PX UT WOS:000346852400003 PM 25497101 ER PT J AU Vaduganathan, M Prasad, V AF Vaduganathan, Muthiah Prasad, Vinay TI Modern Drug Development Which Patients Should Come First? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID METASTATIC BREAST-CANCER; HEART-FAILURE; TRASTUZUMAB; PERTUZUMAB; ENALAPRIL; TRIAL C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Prasad, Vinay] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Prasad, V (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, 615 N Wolfe St,Room W1015, Baltimore, MD 21205 USA. EM vprasad4@jhu.edu OI Prasad, Vinay/0000-0002-6110-8221 NR 7 TC 3 Z9 3 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 24 PY 2014 VL 312 IS 24 BP 2619 EP 2620 DI 10.1001/jama.2014.15221 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AX5KW UT WOS:000346966100010 PM 25420013 ER PT J AU Trinh, NHT Nadler, DL Shie, V Fregni, F Gilman, SE Ryan, CM Schneider, JC AF Trinh, Nhi-Ha T. Nadler, Deborah L. Shie, Vivian Fregni, Felipe Gilman, Stephen E. Ryan, Colleen M. Schneider, Jeffrey C. TI Psychological Sequelae of the Station Nightclub Fire: Comparing Survivors with and without Physical Injuries Using a Mixed-Methods Analysis SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; BECK DEPRESSION INVENTORY; PSYCHOMETRIC PROPERTIES; MEDICAL ILLNESS; BURN INJURIES; HEALTH SCALE; PREVALENCE; DISASTERS AB Background: Surveying survivors from a large fire provides an opportunity to explore the impact of emotional trauma on psychological outcomes. Methods: This is a cross-sectional survey of survivors of The Station Fire. Primary outcomes were post-traumatic stress (Impact of Event Scale - Revised) and depressive (Beck Depression Inventory) symptoms. Linear regression was used to examine differences in symptom profiles between those with and without physical injuries. The free-response section of the survey was analyzed qualitatively to compare psychological sequelae of survivors with and without physical injuries. Results: 104 participants completed the study survey; 47% experienced a burn injury. There was a 42% to 72% response rate range. The mean age of respondents was 32 years, 62% were male, and 47% experienced a physical injury. No significant relationships were found between physical injury and depressive or post-traumatic stress symptom profiles. In the qualitative analysis, the emotional trauma that survivors experienced was a major, common theme regardless of physical injury. Survivors without physical injuries were more likely to experience survivor guilt, helplessness, self-blame, and bitterness. Despite the post-fire challenges described, most survivors wrote about themes of recovery and renewal. Conclusions: All survivors of this large fire experienced significant psychological sequelae. These findings reinforce the importance of mental health care for all survivors and suggest a need to understand factors influencing positive outcomes. C1 [Trinh, Nhi-Ha T.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Nadler, Deborah L.; Shie, Vivian; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Nadler, Deborah L.; Shie, Vivian; Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Ctr Neuromodulat, Boston, MA USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sumner Redstone Burn Ctr,Surg Serv, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children Boston, Boston, MA USA. RP Trinh, NHT (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. EM ntrinh@partners.org RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU International Association of Fire Fighters; Department of Education; National Institute on Disability and Rehabilitation Research [H133A120034] FX This project was supported in part by a pilot grant from the International Association of Fire Fighters and under a grant from the Department of Education, National Institute on Disability and Rehabilitation Research grant number H133A120034. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 1 Z9 1 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2014 VL 9 IS 12 AR e115013 DI 10.1371/journal.pone.0115013 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ9UY UT WOS:000348563300027 PM 25536085 ER PT J AU Troisi, R Ganmaa, D Silva, ID Davaalkham, D Rosenberg, PS Rich-Edwards, J Frasier, L Houghton, L Janes, C Stanczyk, F Hoover, RN AF Troisi, Rebecca Ganmaa, Daavasambuu Silva, Isabel dos Santos Davaalkham, Dambadarjaa Rosenberg, Philip S. Rich-Edwards, Janet Frasier, Lindsay Houghton, Lauren Janes, Craig Stanczyk, Frank Hoover, Robert N. TI The Role of Hormones in the Differences in the Incidence of Breast Cancer between Mongolia and the United Kingdom SO PLOS ONE LA English DT Article ID RISK; WOMEN; SUSCEPTIBILITY AB Background: There are striking differences in breast cancer incidence between Asian and western women. Rates vary substantially within Asia also, with Mongolia's even lower than China's. These profound differences have been speculated to be due in part to diet, mediated by circulating hormone concentrations. Methods: Sex steroid hormone concentrations were measured in women living in Ulaanbaatar, Mongolia and the United Kingdom (U.K.). Diet was obtained by interview and national survey data. Mean hormone differences were compared by country, and systematic variation by number of days since last menstrual period was modeled and adjusted for age and parity; difference in overall area under the curves was assessed. Findings: The diet in Mongolia was higher in meat and dairy than in the U.K. Mean testosterone concentrations were 18.5% lower (p<0.0001) while estradiol concentrations were 19.1% higher (p=0.02) in Mongolian than British women, adjusted for age and parity. Progesterone was almost 50% higher in Mongolian women (p=0.04), particularly during the follicular phase and early luteal surge. Hormone concentrations generally were similar in Mongolian women born in Ulaanbaatar compared with those born in rural areas, although there was a decreasing progesterone trend by degree of westernization (rural Mongolia; urban Mongolia; U.K.). Mean hormone differences were similar when restricted to parous women, and with further adjustment for body mass index, height, and smoking status. Interpretation: These data augment accumulating evidence that circulating estrogens are unlikely to explain reduced breast cancer rates in Asia compared with the west, and suggest casting a wider net with respect to biomarkers. Lower testosterone and higher progesterone in Mongolian women raise the possibility that these hormones may be important to consider. In addition, the almost exclusive dietary reliance of Mongolians on meat and dairy argues against beneficial effects of a low-fat diet on circulating hormones explaining international breast cancer differences. C1 [Troisi, Rebecca; Rosenberg, Philip S.; Houghton, Lauren; Hoover, Robert N.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20850 USA. [Ganmaa, Daavasambuu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ganmaa, Daavasambuu] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ganmaa, Daavasambuu; Davaalkham, Dambadarjaa] Hlth Sci Univ Mongolia, Ulaanbaatar, Mongol Peo Rep. [Silva, Isabel dos Santos] Univ London London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England. [Rich-Edwards, Janet] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Rich-Edwards, Janet] Harvard Univ, Brigham & Womens Hosp, Sch Med, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Frasier, Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Janes, Craig] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Stanczyk, Frank] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Stanczyk, Frank] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Troisi, R (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20850 USA. EM troisir@mail.nih.gov FU U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX All funding for this study was provided by the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Drs. Troisi and Hoover represented the NCI and had a role in the study design, data collection and analysis, decision to publish and preparation of the ms. NR 18 TC 4 Z9 4 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2014 VL 9 IS 12 AR e114455 DI 10.1371/journal.pone.0114455 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AZ9UY UT WOS:000348563300012 PM 25536229 ER PT J AU Dodge, HH Katsumata, Y Zhu, J Mattek, N Bowman, M Gregor, M Wild, K Kaye, JA AF Dodge, Hiroko H. Katsumata, Yuriko Zhu, Jian Mattek, Nora Bowman, Molly Gregor, Mattie Wild, Katherine Kaye, Jeffrey A. TI Characteristics associated with willingness to participate in a randomized controlled behavioral clinical trial using home-based personal computers and a webcam SO TRIALS LA English DT Article DE Sample recruitment selection bias; Volunteer bias; Behavioral randomized controlled trial; PC; Internet; Webcam; Conversation-based social interaction; Cognitive function; Mild cognitive impairment ID OLDER-ADULTS; RECRUITMENT; DEMENTIA; RETENTION; SELECTION; ANXIETY AB Background: Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Methods: Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Results: Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Conclusion: Increasing potential participants' familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. C1 [Dodge, Hiroko H.; Mattek, Nora; Bowman, Molly; Gregor, Mattie; Wild, Katherine; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Dodge, Hiroko H.] Univ Michigan, Dept Neurol, Michigan Alzheimers Dis Ctr, Ann Arbor, MI USA. [Dodge, Hiroko H.; Mattek, Nora; Bowman, Molly; Wild, Katherine; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Katsumata, Yuriko] Univ Kentucky, Coll Publ Hlth, Lexington, KY USA. [Zhu, Jian] Univ Michigan, Grad Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. EM dodgeh@ohsu.edu FU National Institute on Aging [R01AG033581, P30AG008017, P30AG024978, R01AG024059]; National Institutes of Health; US Department of Health and Human Services FX Funding sources: R01AG033581, P30AG008017, P30AG024978, and R01AG024059 from National Institute on Aging, National Institutes of Health, US Department of Health and Human Services. NR 18 TC 3 Z9 3 U1 4 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD DEC 23 PY 2014 VL 15 AR 508 DI 10.1186/1745-6215-15-508 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY9FA UT WOS:000347853900002 PM 25539637 ER PT J AU Isselbacher, EM AF Isselbacher, Eric M. TI Trends in Thoracic Aortic Aneurysms and Dissection Out of the Shadows and Into the Light SO CIRCULATION LA English DT Editorial Material DE Editorials; aneurysm; aortic diseases; dissection; thoracic diseases ID ATHEROSCLEROSIS; REPAIR C1 [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02144 USA. [Isselbacher, Eric M.] Harvard Univ, Sch Med, Boston, MA USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 5800, Boston, MA 02144 USA. EM eisselbacher@partners.org NR 14 TC 2 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 23 PY 2014 VL 130 IS 25 BP 2267 EP 2268 DI 10.1161/CIRCULATIONAHA.114.013603 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AX1PQ UT WOS:000346719100008 PM 25394734 ER PT J AU Chatterjee, NA Steiner, J Lewis, GD AF Chatterjee, Neal A. Steiner, Johannes Lewis, Gregory D. TI It Is Time to Look at Heart Failure With Preserved Ejection Fraction From the Right Side SO CIRCULATION LA English DT Editorial Material DE Editorials; heart failure; heart ventricles; pulmonary; circulation; ventricular dysfunction, right ID PULMONARY ARTERIAL-HYPERTENSION; RIGHT-VENTRICULAR FUNCTION; PHOSPHODIESTERASE-5 INHIBITION; ECHOCARDIOGRAPHIC-ASSESSMENT; EXERCISE CAPACITY; SYSTOLIC FUNCTION; EUROPEAN-SOCIETY; VENOUS-PRESSURE; DOUBLE-BLIND; TRIAL C1 [Chatterjee, Neal A.; Steiner, Johannes; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org FU NHLBI NIH HHS [5U10HL110337, R01 HL119154, U10 HL110337] NR 35 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 23 PY 2014 VL 130 IS 25 BP 2272 EP 2277 DI 10.1161/CIRCULATIONAHA.114.013536 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AX1PQ UT WOS:000346719100010 PM 25391521 ER PT J AU Waldo, SW Secemsky, EA O'Brien, C Kennedy, KF Pomerantsev, E Sundt, TM McNulty, EJ Scirica, BM Yeh, RW AF Waldo, Stephen W. Secemsky, Eric A. O'Brien, Cashel Kennedy, Kevin F. Pomerantsev, Eugene Sundt, Thoralf M., III McNulty, Edward J. Scirica, Benjamin M. Yeh, Robert W. TI Surgical Ineligibility and Mortality Among Patients With Unprotected Left Main or Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention SO CIRCULATION LA English DT Article DE eligibility determination; percutaneous coronary intervention; risk adjustment; surgery ID CARDIOVASCULAR DATA REGISTRY; DRUG-ELUTING STENTS; BYPASS-GRAFTING SURGERY; RISK PREDICTION; REVASCULARIZATION; SOCIETY; ANGIOPLASTY; IMPROVEMENT; STRATEGIES; OUTCOMES AB Background-Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. Methods and Results-All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16-18.15; P<0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88-4.72, P<0.001) after percutaneous coronary intervention. Conclusions-Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization. C1 [Waldo, Stephen W.; Secemsky, Eric A.; O'Brien, Cashel; Pomerantsev, Eugene; Yeh, Robert W.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Kennedy, Kevin F.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [McNulty, Edward J.] Kaiser Permanente Med Ctr, Div Cardiol, San Francisco, CA USA. [Scirica, Benjamin M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 8-843, Boston, MA 02114 USA. EM ryeh@partners.org FU National Heart, Lung, and Blood Institute; Hassenfeld Scholars Program FX Dr Yeh is supported by a career development award from the National Heart, Lung, and Blood Institute. The study was supported in part by the Hassenfeld Scholars Program. NR 25 TC 23 Z9 23 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 23 PY 2014 VL 130 IS 25 BP 2295 EP 2301 DI 10.1161/CIRCULATIONAHA.114.011541 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AX1PQ UT WOS:000346719100013 PM 25391519 ER PT J AU He, B Lanz, RB Fiskus, W Geng, CD Yi, P Hartig, SM Rajapakshe, K Shou, J Wei, LP Shah, SS Foley, C Chew, SA Eedunuri, VK Bedoya, DJ Feng, Q Minami, T Mitsiades, CS Frolov, A Weigel, NL Hilsenbeck, SG Rosen, DG Palzkill, T Ittmann, MM Song, YC Coarfa, C O'Malley, BW Mitsiades, N AF He, Bin Lanz, Rainer B. Fiskus, Warren Geng, Chuandong Yi, Ping Hartig, Sean M. Rajapakshe, Kimal Shou, John Wei, Liping Shah, Shrijal S. Foley, Christopher Chew, Sue Anne Eedunuri, Vijay K. Bedoya, Diego J. Feng, Qin Minami, Takashi Mitsiades, Constantine S. Frolov, Anna Weigel, Nancy L. Hilsenbeck, Susan G. Rosen, Daniel G. Palzkill, Timothy Ittmann, Michael M. Song, Yongcheng Coarfa, Cristian O'Malley, Bert W. Mitsiades, Nicholas TI GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prostate cancer; small molecule inhibitor; AR signaling; GATA2; steroid receptor coactivator ID RESISTANT PROSTATE-CANCER; TRANSCRIPTION FACTORS; INCREASED SURVIVAL; GENE-EXPRESSION; GROWTH; ENZALUTAMIDE; ABIRATERONE; ENHANCERS; VARIANTS; TURNOVER AB The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC) and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent mechanisms (including constitutively active AR splice variants) highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA-binding protein 2 (GATA2) as a regulator of AR signaling and an actionable therapeutic target in PC. We demonstrate that GATA2 directly promotes expression of both full-length and splice-variant AR, resulting in a strong positive correlation between GATA2 and AR expression in both PC cell lines and patient specimens. Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of both fulllength and splice-variant AR. GATA2 colocalizes with AR and Forkhead box protein A1 on chromatin to enhance recruitment of steroid receptor coactivators and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of both full-length and splice-variant AR and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a firstin-field approach to target AR expression and function and improve outcomes in CRPC. C1 [He, Bin; Fiskus, Warren; Geng, Chuandong; Shou, John; Shah, Shrijal S.; Foley, Christopher; Chew, Sue Anne; Bedoya, Diego J.; Mitsiades, Nicholas] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [He, Bin; Lanz, Rainer B.; Fiskus, Warren; Yi, Ping; Hartig, Sean M.; Rajapakshe, Kimal; Foley, Christopher; Feng, Qin; Weigel, Nancy L.; Coarfa, Cristian; O'Malley, Bert W.; Mitsiades, Nicholas] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Wei, Liping; Palzkill, Timothy; Song, Yongcheng] Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. [Rosen, Daniel G.; Ittmann, Michael M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Frolov, Anna; Hilsenbeck, Susan G.] Baylor Coll Med, Dan L Duncan Canc Ctr Biostat, Houston, TX 77030 USA. [Rosen, Daniel G.; Ittmann, Michael M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Eedunuri, Vijay K.] Adrienne Helis Malvin Med Res Fdn, New Orleans, LA 70130 USA. [Minami, Takashi] Univ Tokyo, Res Ctr Adv Sci & Technol, Lab Syst Biol & Med, Tokyo 1538904, Japan. [Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Coarfa, C (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. EM coarfa@bcm.edu; berto@bcm.edu; mitsiade@bcm.edu RI EEDUNURI, VIJAY KUMAR /I-8507-2015; Rajapakshe, Kimal/P-1592-2015; EEDUNURI, VIJAY KUMAR/L-2213-2015 OI EEDUNURI, VIJAY KUMAR /0000-0003-3808-9875; FU National Cancer Institute (NCI) Cancer Center Support Grant [P30CA125123]; Prostate Cancer Foundation; Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator and Career Development Awards; Eunice Kennedy Shriver National Institute of Child Health and Human Development [8818]; Susan G. Komen for the Cure Foundation Promise Grant [221410]; National Institutes of Health [1K01DK096093]; Pilot/Feasibility Program of the Diabetes and Endocrinology Research Center at BCM [P30-DK079638]; Alkek Foundation for Molecular Discovery Pilot grant; Center for Drug Discovery at BCM FX We acknowledge the joint participation by the Adrienne Helis Malvin Medical Research Foundation through its direct engagement in the continuous, active conduct of medical research in conjunction with Baylor College of Medicine (BCM), and the assistance of the Shared Resources of the Dan L. Duncan Cancer Center [supported by National Cancer Institute (NCI) Cancer Center Support Grant P30CA125123]. This work was supported by the Prostate Cancer Foundation (B.W.O. and N.M.); Conquer Cancer Foundation of the American Society of Clinical Oncology Young Investigator and Career Development Awards (both to N.M.); Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant 8818 (to B.W.O.); Susan G. Komen for the Cure Foundation Promise Grant 221410 (to B.W.O.); National Institutes of Health Grant 1K01DK096093 (to S.M.H.); pilot grants (to S.M.H. and N.M.) from the Pilot/Feasibility Program of the Diabetes and Endocrinology Research Center at BCM (P30-DK079638); and an Alkek Foundation for Molecular Discovery Pilot grant (to C.C.). N.M. is a Dan L. Duncan Scholar, a Caroline Wiess Law Scholar, and a member of the Dan L. Duncan Cancer Center (supported by NCI Cancer Center Support Grant P30CA125123) and the Center for Drug Discovery at BCM. NR 35 TC 21 Z9 21 U1 0 U2 7 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 DEC 23 PY 2014 VL 111 IS 51 BP 18261 EP 18266 DI 10.1073/pnas.1421415111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX2IP UT WOS:000346767200052 PM 25489091 ER PT J AU Whitesell, L Santagata, S Mendillo, ML Lin, NU Proia, DA Lindquist, S AF Whitesell, Luke Santagata, Sandro Mendillo, Marc L. Lin, Nancy U. Proia, David A. Lindquist, Susan TI HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE estrogen receptor; antiestrogen; drug resistance; tumor progression; tamoxifen ID MOLECULAR CHAPERONE HSP90; HEAT-SHOCK; TARGETED INHIBITION; ANTITUMOR-ACTIVITY; MORPHOLOGICAL EVOLUTION; TUMOR-CELLS; GANETESPIB; EXPRESSION; CAPACITOR; PROFILE AB The efficacy of hormonal therapies for advanced estrogen receptor-positive breast cancers is limited by the nearly inevitable development of acquired resistance. Efforts to block the emergence of resistance have met with limited success, largely because the mechanisms underlying it are so varied and complex. Here, we investigate a new strategy aimed at the very processes by which cancers evolve resistance. From yeast to vertebrates, heat shock protein 90 (HSP90) plays a unique role among molecular chaperones by promoting the evolution of heritable new traits. It does so by regulating the folding of a diverse portfolio of metastable client proteins, many of which mediate adaptive responses that allow organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs. Guided by our previous work in pathogenic fungi, in which very modest HSP90 inhibition impairs resistance to mechanistically diverse antifungals, we examined the effect of similarly modest HSP90 inhibition on the emergence of resistance to antiestrogens in breast cancer models. Even though this degree of inhibition fell below the threshold for proteotoxic activation of the heat-shock response and had no overt anticancer activity on its own, it dramatically impaired the emergence of resistance to hormone antagonists both in cell culture and in mice. Our findings strongly support the clinical testing of combined hormone antagonist-low-level HSP90 inhibitor regimens in the treatment of metastatic estrogen receptor-positive breast cancer. At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics. C1 [Whitesell, Luke; Santagata, Sandro; Mendillo, Marc L.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Proia, David A.] Synta Pharmaceut, Lexington, MA 02421 USA. [Lindquist, Susan] MIT, Dept Biol, Cambridge, MA 02142 USA. [Lindquist, Susan] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA. RP Whitesell, L (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM whitesell@wi.mit.edu; lindquist_admin@wi.mit.edu FU NIH [K08NS064168]; National Cancer Institute of the NIH [K99CA175293]; Susan G. Komen Foundation [KG110450] FX We thank members of the S.L. laboratory for valuable discussions and comments on the manuscript. We also thank the Genome Technology Center and George Bell (Whitehead Institute/Bioinformatics and Research Computing) for help with expression profiling and statistical analysis. S.L. is a Howard Hughes Medical Institute Investigator. S.S. was supported by NIH Award K08NS064168. M.L.M. was supported by the National Cancer Institute of the NIH under Award K99CA175293. Support for this study was also provided by the Susan G. Komen Foundation [KG110450 (to L.W. and N.U.L.)]. NR 44 TC 24 Z9 25 U1 4 U2 20 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 DEC 23 PY 2014 VL 111 IS 51 BP 18297 EP 18302 DI 10.1073/pnas.1421323111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX2IP UT WOS:000346767200058 PM 25489079 ER PT J AU Perry, JA Kiezun, A Tonzi, P Van Allen, EM Carter, SL Baca, SC Cowley, GS Bhatt, AS Rheinbay, E Pedamallu, CS Helman, E Taylor-Weiner, A McKenna, A DeLuca, DS Lawrence, MS Ambrogio, L Sougnez, C Sivachenko, A Walensky, LD Wagle, N Mora, J de Torres, C Lavarino, C Aguiar, SD Yunes, JA Brandalise, SR Mercado-Celis, GE Melendez-Zajgla, J Cardenas-Cardos, R Velasco-Hidalgo, L Roberts, CWM Garraway, LA Rodriguez-Galindo, C Gabriel, SB Lander, ES Golub, TR Orkin, SH Getz, G Janeway, KA AF Perry, Jennifer A. Kiezun, Adam Tonzi, Peter Van Allen, Eliezer M. Carter, Scott L. Baca, Sylvan C. Cowley, Glenn S. Bhatt, Ami S. Rheinbay, Esther Pedamallu, Chandra Sekhar Helman, Elena Taylor-Weiner, Amaro McKenna, Aaron DeLuca, David S. Lawrence, Michael S. Ambrogio, Lauren Sougnez, Carrie Sivachenko, Andrey Walensky, Loren D. Wagle, Nikhil Mora, Jaume de Torres, Carmen Lavarino, Cinzia Aguiar, Simone Dos Santos Yunes, Jose Andres Brandalise, Silvia Regina Mercado-Celis, Gabriela Elisa Melendez-Zajgla, Jorge Cardenas-Cardos, Roco Velasco-Hidalgo, Liliana Roberts, Charles W. M. Garraway, Levi A. Rodriguez-Galindo, Carlos Gabriel, Stacey B. Lander, Eric S. Golub, Todd R. Orkin, Stuart H. Getz, Gad Janeway, Katherine A. TI Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE osteosarcoma; TP53; PI3K; mTOR; genomics ID RAPAMYCIN INHIBITOR RIDAFOROLIMUS; TUBEROUS SCLEROSIS COMPLEX; MOUSE OSTEOSARCOMA; MAMMALIAN TARGET; PAGETS-DISEASE; OSTEO-SARCOMA; CANCER-CELLS; MDM2 GENES; MUTATIONS; AMPLIFICATION AB Osteosarcoma is the most common primary bone tumor, yet there have been no substantial advances in treatment or survival in three decades. We examined 59 tumor/normal pairs by whole-exome, whole-genome, and RNA-sequencing. Only the TP53 gene was mutated at significant frequency across all samples. The mean nonsilent somatic mutation rate was 1.2 mutations per megabase, and there was a median of 230 somatic rearrangements per tumor. Complex chains of rearrangements and localized hypermutation were detected in almost all cases. Given the intertumor heterogeneity, the extent of genomic instability, and the difficulty in acquiring a large sample size in a rare tumor, we used several methods to identify genomic events contributing to osteosarcoma survival. Pathway analysis, a heuristic analytic algorithm, a comparative oncology approach, and an shRNA screen converged on the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a central vulnerability for therapeutic exploitation in osteosarcoma. Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo. C1 [Perry, Jennifer A.; Tonzi, Peter; Roberts, Charles W. M.; Rodriguez-Galindo, Carlos; Orkin, Stuart H.; Janeway, Katherine A.] Dana Farber Boston Childrens Canc, Dept Pediat Oncol, Boston, MA 02215 USA. [Perry, Jennifer A.; Tonzi, Peter; Roberts, Charles W. M.; Rodriguez-Galindo, Carlos; Orkin, Stuart H.; Janeway, Katherine A.] Blood Disorders Ctr, Boston, MA 02215 USA. [Kiezun, Adam; Van Allen, Eliezer M.; Carter, Scott L.; Baca, Sylvan C.; Cowley, Glenn S.; Bhatt, Ami S.; Rheinbay, Esther; Pedamallu, Chandra Sekhar; Helman, Elena; Taylor-Weiner, Amaro; McKenna, Aaron; DeLuca, David S.; Lawrence, Michael S.; Ambrogio, Lauren; Sougnez, Carrie; Sivachenko, Andrey; Wagle, Nikhil; Garraway, Levi A.; Gabriel, Stacey B.; Lander, Eric S.; Golub, Todd R.; Getz, Gad; Janeway, Katherine A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Van Allen, Eliezer M.; Baca, Sylvan C.; Bhatt, Ami S.; Pedamallu, Chandra Sekhar; Helman, Elena; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Walensky, Loren D.; Rodriguez-Galindo, Carlos; Golub, Todd R.; Orkin, Stuart H.; Janeway, Katherine A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wagle, Nikhil; Garraway, Levi A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Getz, Gad] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mora, Jaume; de Torres, Carmen; Lavarino, Cinzia] Hosp St Joan Deu, Dept Hematol & Oncol, Barcelona 08950, Spain. [Aguiar, Simone Dos Santos; Yunes, Jose Andres; Brandalise, Silvia Regina] Ctr Infantil Boldrini, Dept Pediat Oncol, BR-13083210 Campinas, SP, Brazil. [Aguiar, Simone Dos Santos] Univ Estadual Campinas, Fac Med Sci, Ctr Pediat Res, BR-13083887 Campinas, Brazil. [Yunes, Jose Andres] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, BR-13083887 Campinas, Brazil. [Mercado-Celis, Gabriela Elisa; Melendez-Zajgla, Jorge] Natl Inst Genom Med, Subdirect Basic Res, Mexico City 14610, DF, Mexico. [Cardenas-Cardos, Roco; Velasco-Hidalgo, Liliana] Natl Inst Pediat, Dept Oncol, Mexico City 04530, DF, Mexico. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Golub, Todd R.; Orkin, Stuart H.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Orkin, SH (reprint author), Dana Farber Boston Childrens Canc, Dept Pediat Oncol, Boston, MA 02215 USA. EM stuart_orkin@dfci.harvard.edu; gadgetz@broadinstitute.org; kjaneway@partners.org FU Carlos Slim Health Institute; Foster Foundation; Pedals for Pediatrics; Brazilian National Counsel of Technological and Scientific Development (CNPq); CNPq [401991/2010-5]; Alex Lemonade Stand Innovation Award; National Cancer Institute Grant [U01CA105423]; St. Baldrick's Foundation Career Development Award; Timothy O'Brien Osteosarcoma Research Fund FX We thank Ben Hubbell-Engler for technical support. This work was conducted as part of the Slim Initiative for Genomic Medicine in the Americas, a project funded by the Carlos Slim Health Institute. This work was supported in part by the Foster Foundation (J.A.P.), Pedals for Pediatrics (J.A.P.), a Productivity Fellowship from the Brazilian National Counsel of Technological and Scientific Development (CNPq, J.A.Y.), CNPq Grant 401991/2010-5 (to J.A.Y.), an Alex Lemonade Stand Innovation Award (to S.H.O.), National Cancer Institute Grant U01CA105423 (to S.H.O.), a St. Baldrick's Foundation Career Development Award (to K.A.J.), and the Timothy O'Brien Osteosarcoma Research Fund (K.A.J.). NR 65 TC 56 Z9 57 U1 3 U2 21 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 DEC 23 PY 2014 VL 111 IS 51 BP E5564 EP E5573 DI 10.1073/pnas.1419260111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX2IP UT WOS:000346767200013 PM 25512523 ER PT J AU Martz, CA Ottina, KA Singleton, KR Jasper, JS Wardell, SE Peraza-Penton, A Anderson, GR Winter, PS Wang, T Alley, HM Kwong, LN Cooper, ZA Tetzlaff, M Chen, PL Rathmell, JC Flaherty, KT Wargo, JA McDonnell, DP Sabatini, DM Wood, KC AF Martz, Colin A. Ottina, Kathleen A. Singleton, Katherine R. Jasper, Jeff S. Wardell, Suzanne E. Peraza-Penton, Ashley Anderson, Grace R. Winter, Peter S. Wang, Tim Alley, Holly M. Kwong, Lawrence N. Cooper, Zachary A. Tetzlaff, Michael Chen, Pei-Ling Rathmell, Jeffrey C. Flaherty, Keith T. Wargo, Jennifer A. McDonnell, Donald P. Sabatini, David M. Wood, Kris C. TI Systematic identification of signaling pathways with potential to confer anticancer drug resistance SO SCIENCE SIGNALING LA English DT Article ID POSITIVE BREAST-CANCER; ESTROGEN-RECEPTOR; METASTATIC MELANOMA; TUMOR MICROENVIRONMENT; TAMOXIFEN RESISTANCE; KINASE INHIBITORS; COLORECTAL-CANCER; RAF INHIBITION; LUNG-CANCER; BRAF AB Cancer cells can activate diverse signaling pathways to evade the cytotoxic action of drugs. Wecreated and screened a library of barcoded pathway-activating mutant complementary DNAs to identify those that enhanced the survival of cancer cells in the presence of 13 clinically relevant, targeted therapies. We found that activation of the RAS-MAPK (mitogen-activated protein kinase), Notch1, PI3K (phosphoinositide 3-kinase)-mTOR (mechanistic target of rapamycin), and ER (estrogen receptor) signaling pathways often conferred resistance to this selection of drugs. Activation of the Notch1 pathway promoted acquired resistance to tamoxifen (an ER-targeted therapy) in serially passaged breast cancer xenografts in mice, and treating mice with a g-secretase inhibitor to inhibit Notch signaling restored tamoxifen sensitivity. Markers of Notch1 activity in tumor tissue correlated with resistance to tamoxifen in breast cancer patients. Similarly, activation of Notch1 signaling promoted acquired resistance toMAPKinhibitors inBRAFV600Emelanoma cells in culture, and the abundance of Notch1 pathway markers was increased in tumors from a subset ofmelanoma patients. Thus, Notch1 signalingmay be a therapeutic target in some drug-resistant breast cancers and melanomas. Additionally, multiple resistance pathways were activated in melanoma cell lines with intrinsic resistance to MAPK inhibitors, and simultaneous inhibition of these pathways synergistically induced drug sensitivity. These data illustrate the potential for systematic identification of the signaling pathways controlling drug resistance that could inform clinical strategies and drug development for multiple types of cancer. This approach may also be used to advance clinical options in other disease contexts. C1 [Martz, Colin A.; Singleton, Katherine R.; Jasper, Jeff S.; Wardell, Suzanne E.; Peraza-Penton, Ashley; Anderson, Grace R.; Winter, Peter S.; Alley, Holly M.; Rathmell, Jeffrey C.; McDonnell, Donald P.; Wood, Kris C.] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Ottina, Kathleen A.; Wang, Tim; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Ottina, Kathleen A.; Wang, Tim; Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Wang, Tim; Sabatini, David M.] Broad Inst, Cambridge, MA 02142 USA. [Kwong, Lawrence N.; Cooper, Zachary A.; Tetzlaff, Michael; Chen, Pei-Ling; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM sabatini@wi.mit.edu; kris.wood@duke.edu OI Cooper, Zachary/0000-0003-1059-0940 FU Duke University School of Medicine start-up funds; Duke Cancer Institute; NIH Building Interdisciplinary Research Careers in Women's Health Program; Harry J. Lloyd Trust Translational Research Award; Golfers Against Cancer Research Award; Stewart Trust Fellowship; V Scholar Award from the V Foundation for Cancer Research; NIH [CA103866, AI07389, R37DK048807] FX This work was supported by Duke University School of Medicine start-up funds and by the Duke Cancer Institute (K.C.W.), the NIH Building Interdisciplinary Research Careers in Women's Health Program (K.C.W.), a Harry J. Lloyd Trust Translational Research Award (K.C.W.), a Golfers Against Cancer Research Award (K.C.W.), a Stewart Trust Fellowship (K.C.W.), a V Scholar Award from the V Foundation for Cancer Research (K.C.W.), and NIH grants CA103866 (D.M.S.), AI07389 (D.M.S.), and R37DK048807 (D.P.M.). D.M.S. is an investigator of the Howard Hughes Medical Institute. All cDNA constructs described here have been deposited in Addgene. NR 48 TC 34 Z9 35 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD DEC 23 PY 2014 VL 7 IS 357 AR ra121 DI 10.1126/scisignal.aaa1877 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AX3GA UT WOS:000346827000002 PM 25538079 ER PT J AU Winter, PS Sarosiek, KA Lin, KH Meggendorfer, M Schnittger, S Letai, A Wood, KC AF Winter, Peter S. Sarosiek, Kristopher A. Lin, Kevin H. Meggendorfer, Manja Schnittger, Susanne Letai, Anthony Wood, Kris C. TI RAS signaling promotes resistance to JAK inhibitors by suppressing BAD- mediated apoptosis SO SCIENCE SIGNALING LA English DT Article ID MYELOPROLIFERATIVE NEOPLASM CELLS; POLYCYTHEMIA-VERA; KINASE; PROTEIN; DEATH; PHOSPHORYLATION; BCL-2; BCL-X(L); MUTATION; THERAPY AB Myeloproliferative neoplasms (MPNs) frequently have an activating mutation in the gene encoding Janus kinase 2 (JAK2). Thus, targeting the pathway mediated by JAK and its downstream substrate, signal transducer and activator of transcription (STAT), may yield clinical benefit for patients with MPNs containing the JAK2V617F mutation. Although JAK inhibitor therapy reduces splenomegaly and improves systemic symptoms in patients, this treatment does not appreciably reduce the number of neoplastic cells. To identify potential mechanisms underlying this inherent resistance phenomenon, we performed pathway- centric, gain- of- function screens in JAK2V617F hematopoietic cells and found that the activation of the guanosine triphosphatase (GTPase) RAS or its effector pathways [ mediated by the kinases AKT and ERK (extracellular signal- regulated kinase)] renders cells insensitive to JAK inhibition. Resistant MPN cells became sensitized to JAK inhibitors when also exposed to inhibitors of the AKT or ERK pathways. Mechanistically, in JAK2V617F cells, a JAK2- mediated inactivating phosphorylation of the proapoptotic protein BAD [ B cell lymphoma 2 (BCL- 2)- associated death promoter] promoted cell survival. In sensitive cells, exposure to a JAK inhibitor resulted in dephosphorylation of BAD, enabling BAD to bind and sequester the prosurvival protein BCL- XL (BCL- 2- like 1), thereby triggering apoptosis. In resistant cells, RAS effector pathways maintained BAD phosphorylation in the presence of JAK inhibitors, yielding a specific dependence on BCL- XL for survival. In patients with MPNs, activating mutations in RAS co- occur with the JAK2V617F mutation in the malignant cells, suggesting that RAS effector pathways likely play an important role in clinically observed resistance. C1 [Winter, Peter S.; Lin, Kevin H.; Wood, Kris C.] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Sarosiek, Kristopher A.; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sarosiek, Kristopher A.; Letai, Anthony] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meggendorfer, Manja; Schnittger, Susanne] Munich Leukemia Lab, D-81377 Munich, Germany. RP Wood, KC (reprint author), Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. EM kris.wood@duke.edu FU Duke University start-up funds; NIH Building Interdisciplinary Research Careers in Women's Health Program; Stewart Trust; Golfers Against Cancer; Speer Memorial Fellowship; Duke Medical Scientist Training Program [T32 GM007171]; American Cancer Society Postdoctoral Fellowship [121360-PF-11-256-01-TBG]; National Cancer Institute [NCI 2R01 CA129974] FX This work was supported by Duke University start-up funds (K.C.W.), the NIH Building Interdisciplinary Research Careers in Women's Health Program (K.C.W.), the Stewart Trust (K.C.W.), Golfers Against Cancer (K.C.W.), the Speer Memorial Fellowship (P.S.W.), the Duke Medical Scientist Training Program (T32 GM007171 to K.H.L.), the American Cancer Society Postdoctoral Fellowship (121360-PF-11-256-01-TBG to K.A.S.), and the National Cancer Institute (NCI 2R01 CA129974 to A. L.). NR 47 TC 9 Z9 9 U1 2 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD DEC 23 PY 2014 VL 7 IS 357 AR ra122 DI 10.1126/scisignal.2005301 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AX3GA UT WOS:000346827000003 PM 25538080 ER PT J AU Jia, C Yu, D Lamarre, M Leopold, PL Teng, YD Wang, HJ AF Jia, Chao Yu, Dou Lamarre, Marven Leopold, Philip L. Teng, Yang D. Wang, Hongjun TI Patterned Electrospun Nanofiber Matrices Via Localized Dissolution: Potential for Guided Tissue Formation SO ADVANCED MATERIALS LA English DT Article ID STEM-CELLS; IN-VITRO; SCAFFOLDS; FIBERS; GROWTH; DIFFERENTIATION; MIGRATION; MEDICINE; SURFACES; GUIDANCE C1 [Jia, Chao; Lamarre, Marven; Leopold, Philip L.; Wang, Hongjun] Stevens Inst Technol, Hoboken, NJ 07030 USA. [Yu, Dou; Teng, Yang D.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Yu, Dou; Teng, Yang D.] Harvard Univ, Div SCI Res, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Wang, HJ (reprint author), Stevens Inst Technol, 1 Castle Point Hudson, Hoboken, NJ 07030 USA. EM Hongjun.wang@stevens.edu FU NSF-IIP [1338958, 1346430]; NSF-CBET [1033742]; NIAMS [1R21 AR056416]; VARR D; CIMIT-DoD FX The authors are grateful for the technical assistance from Mr. Yexin Gu and Dr. Tsengming Chou in SEM examination. Special thanks are also given to Dr. Shaohua Li (Rutgers-Robert Wood Johnson, NJ, USA), who provided GFP transfection to the mouse endothelial cells. Part of the work was financially supported by NSF-IIP (1338958, 1346430, Wang), NSF-CBET (1033742, Wang), NIAMS (1R21 AR056416, Wang), VARR& D (Teng) and CIMIT-DoD (Teng). NR 36 TC 10 Z9 10 U1 11 U2 67 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 EI 1521-4095 J9 ADV MATER JI Adv. Mater. PD DEC 23 PY 2014 VL 26 IS 48 BP 8192 EP 8197 DI 10.1002/adma.201403509 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AW7ZR UT WOS:000346480800017 PM 25352221 ER PT J AU Wasfy, JH Rao, SK Chittle, MD Gallen, KM Isselbacher, EM Ferris, TG AF Wasfy, Jason H. Rao, Sandhya K. Chittle, Melissa D. Gallen, Kathleen M. Isselbacher, Eric M. Ferris, Timothy G. TI Initial Results of a Cardiac E-Consult Pilot Program SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID COSTS C1 [Wasfy, Jason H.; Rao, Sandhya K.; Chittle, Melissa D.; Gallen, Kathleen M.; Isselbacher, Eric M.; Ferris, Timothy G.] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. RP Wasfy, JH (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Phys Org, BUL 205B 55 Fruit St, Boston, MA 02114 USA. EM jwasfy@mgh.harvard.edu NR 4 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 23 PY 2014 VL 64 IS 24 BP 2706 EP 2707 DI 10.1016/j.jacc.2014.09.061 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW5ZL UT WOS:000346349300019 PM 25524348 ER PT J AU Begg, CB Seshan, VE Zabor, EC Furberg, H Arora, A Shen, R Maranchie, JK Nielsen, ME Rathmell, WK Signoretti, S Tamboli, P Karam, JA Choueiri, TK Hakimi, AA Hsieh, JJ AF Begg, Colin B. Seshan, Venkatraman E. Zabor, Emily C. Furberg, Helena Arora, Arshi Shen, Ronglai Maranchie, Jodi K. Nielsen, Matthew E. Rathmell, W. Kimryn Signoretti, Sabina Tamboli, Pheroze Karam, Jose A. Choueiri, Toni K. Hakimi, A. Ari Hsieh, James J. TI Genomic investigation of etiologic heterogeneity: methodologic challenges SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article DE Etiologic heterogeneity; Kidney cancer; Tumor sub-types ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU GENE; CIGARETTE-SMOKING; CANCER; TRANSPORTERS; EPIDEMIOLOGY; METAANALYSIS; HYPERTENSION; MUTATIONS; DISEASE AB Background: The etiologic heterogeneity of cancer has traditionally been investigated by comparing risk factor frequencies within candidate sub-types, defined for example by histology or by distinct tumor markers of interest. Increasingly tumors are being profiled for molecular features much more extensively. This greatly expands the opportunities for defining distinct sub-types. In this article we describe an exploratory analysis of the etiologic heterogeneity of clear cell kidney cancer. Data are available on the primary known risk factors for kidney cancer, while the tumors are characterized on a genome-wide basis using expression, methylation, copy number and mutational profiles. Methods: We use a novel clustering strategy to identify sub-types. This is accomplished independently for the expression, methylation and copy number profiles. The goals are to identify tumor sub-types that are etiologically distinct, to identify the risk factors that define specific sub-types, and to endeavor to characterize the key genes that appear to represent the principal features of the distinct sub-types. Results: The analysis reveals strong evidence that gender represents an important factor that distinguishes disease sub-types. The sub-types defined using expression data and methylation data demonstrate considerable congruence and are also clearly correlated with mutations in important cancer genes. These sub-types are also strongly correlated with survival. The complexity of the data presents many analytical challenges including, prominently, the risk of false discovery. Conclusions: Genomic profiling of tumors offers the opportunity to identify etiologically distinct sub-types, paving the way for a more refined understanding of cancer etiology. C1 [Begg, Colin B.; Seshan, Venkatraman E.; Zabor, Emily C.; Furberg, Helena; Arora, Arshi; Shen, Ronglai] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Maranchie, Jodi K.] Univ Pittsburgh, Med Ctr, Dept Urol, Pittsburgh, PA USA. [Nielsen, Matthew E.] Univ N Carolina, Dept Urol, Chapel Hill, NC USA. [Nielsen, Matthew E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Nielsen, Matthew E.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Nielsen, Matthew E.] Univ N Carolina, Dept Surg, Chapel Hill, NC USA. [Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. [Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Signoretti, Sabina] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tamboli, Pheroze] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Karam, Jose A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Med Sch, Boston, MA 02115 USA. [Hakimi, A. Ari] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. [Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. RP Begg, CB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. EM beggc@mskcc.org OI Maranchie, Jodi/0000-0002-8534-9468 FU National Cancer Institute [CA163251, CA101942, CA008748] FX This research was supported by the National Cancer Institute (http://www.cancer.gov/), awards CA163251 to CBB and CA101942 to TKC; CBB, VES and ECZ are supported on CA008748. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 3 Z9 3 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD DEC 22 PY 2014 VL 14 AR 138 DI 10.1186/1471-2288-14-138 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ1IT UT WOS:000347993800002 PM 25532962 ER PT J AU Jain, RK Netti, PA AF Jain, Rakesh K. Netti, Paolo A. TI Letter to the editor regarding recent article by Wu et al. [J. Theor. Biol. 355 (2014) pp. 194-207] SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Editorial Material ID DRUG-DELIVERY; SOLID TUMORS; PRESSURE; EFFICACY; BLOOD; FLOW; INTERSTITIUM; STRATEGIES; TRANSPORT; COLLAGEN C1 [Jain, Rakesh K.] Harvard Univ, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Netti, Paolo A.] Univ Naples Federico II, Interdisciplinary Res Ctr Biomat, I-80125 Naples, Italy. RP Jain, RK (reprint author), Harvard Univ, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Sch Med, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI NETTI, PAOLO/0000-0002-2435-7181 NR 14 TC 0 Z9 0 U1 1 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 EI 1095-8541 J9 J THEOR BIOL JI J. Theor. Biol. PD DEC 21 PY 2014 VL 363 BP 453 EP 453 DI 10.1016/j.jtbi.2014.08.052 PG 1 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA AY2SE UT WOS:000347438600046 PM 25219622 ER PT J AU Vodovar, N Seronde, MF Laribi, S Gayat, E Lassus, J Boukef, R Nouira, S Manivet, P Samuel, JL Logeart, D Ishihara, S Solal, AC Januzzi, JL Richards, AM Launay, JM Mebazaa, A AF Vodovar, Nicolas Seronde, Marie-France Laribi, Said Gayat, Etienne Lassus, Johan Boukef, Riadh Nouira, Semir Manivet, Philippe Samuel, Jane-Lise Logeart, Damien Ishihara, Shiro Solal, Alain Cohen Januzzi, James L., Jr. Richards, A. Mark Launay, Jean-Marie Mebazaa, Alexandre CA GREAT Network TI Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure SO EUROPEAN HEART JOURNAL LA English DT Article DE Acute decompensated heart failure; ProBNP; BNP; NT-proBNP; Glycosylation; Furin activity ID BRAIN NATRIURETIC PEPTIDE; B-TYPE; TASK-FORCE; FURIN; CORIN; GLYCOSYLATION; CONVERTASES; GUIDELINES; PNEUMONIA; OVERLOAD AB Background Increases in plasma B-type natriuretic peptide (BNP) concentrations in those with acutely decompensated heart failure (ADHF) has been mainly attributed to an increase in NPPB gene transcription. Recently, proBNP glycosylation has emerged as a potential regulatory mechanism in the production of amino-terminal (NT)-proBNP and BNP. The aim of the present study was to investigate proBNP glycosylation, and corin and furin activities in ADHF patients. Methods and results Plasma levels of proBNP, NT-proBNP, BNP, as well as corin and furin concentration and activity were measured in a large cohort of 683 patients presenting with ADHF (n = 468), non-cardiac dyspnoea (non-ADHF: n = 169) and 46 patients with stable chronic heart failure (CHF); the degree of plasma proBNP glycosylation was assessed in a subset of these patients (ADHF: n = 49, non-ADHF: n = 50, CHF: n = 46). Our results showed a decrease in proBNP glycosylation in ADHF patients that paralleled NT-proBNP overproduction (rho = -0.62, P<0.001) but less so to BNP. In addition, we observed an increase in furin activity that is positively related to the plasma levels of proBNP, NT-proBNP and BNP overproduction (all P< 0.001, all rho>0.88), and negatively related to the degree of proBNP glycosylation (rho = 20.62, P<0.001). Conclusion These comprehensive results provide a paradigm for the post-translational modification of natriuretic peptides in ADHF: as proBNP glycosylation decreases, furin activity increases. This synergistically amplifies the processing of proBNP into BNP and NT-proBNP. C1 [Vodovar, Nicolas; Seronde, Marie-France; Laribi, Said; Gayat, Etienne; Manivet, Philippe; Samuel, Jane-Lise; Logeart, Damien; Ishihara, Shiro; Solal, Alain Cohen; Launay, Jean-Marie; Mebazaa, Alexandre] INSERM, UMRS 942, F-75010 Paris, France. [Vodovar, Nicolas; Logeart, Damien; Solal, Alain Cohen] Univ Hosp Jean Minjoz, DHU FIRE, Besancon, France. [Seronde, Marie-France] Univ Hosp Jean Minjoz, Dept Cardiol, EA3920, Besancon, France. [Laribi, Said] Lariboisiere Hosp, Dept Emergency Med, Paris, France. [Laribi, Said; Gayat, Etienne; Mebazaa, Alexandre] Hop Lariboisiere, DHU Neurovasc, F-75475 Paris 10, France. [Gayat, Etienne; Samuel, Jane-Lise; Mebazaa, Alexandre] Hop Lariboisiere, Dept Anesthesiol & Intens Care, F-75475 Paris 10, France. [Lassus, Johan] Helsinki Univ Cent Hosp, Div Cardiol, Heart & Lung Ctr, Helsinki, Finland. [Boukef, Riadh; Nouira, Semir] Fattouma Bourguiba Univ Hosp, Emergency Dept, Monastir, Tunisia. [Boukef, Riadh; Nouira, Semir] Fattouma Bourguiba Univ Hosp, Res Unit UR06SP21, Monastir, Tunisia. [Manivet, Philippe; Launay, Jean-Marie] Hop Lariboisiere, Dept Biochem, F-75475 Paris 10, France. [Manivet, Philippe; Launay, Jean-Marie] Lariboisiere Hosp, Ctr Biol Resources, Paris, France. [Logeart, Damien; Solal, Alain Cohen] Lariboisiere Hosp, Dept Cardiol, Paris, France. [Logeart, Damien; Solal, Alain Cohen; Mebazaa, Alexandre] Paris Diderot Univ, Sorbonne Paris Cite, F-75205 Paris, France. [Ishihara, Shiro] Nippon Med Sch, Cardiol & Intens Care Unit, Musashi Kosugi Hosp, Kawasaki, Kanagawa, Japan. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Richards, A. Mark] Univ Otago, Christchurch, New Zealand. [Richards, A. Mark] Natl Univ Hlth Syst, Singapore, Singapore. RP Launay, JM (reprint author), INSERM, UMRS 942, F-75010 Paris, France. EM alexandre.mebazaa@lrb.aphp.fr; alexandre.mebazaa@lrb.ap-hp.fr RI Laribi, said/S-3693-2016; OI Vodovar, Nicolas/0000-0001-8087-387X; Samuel, Jane-Lise/0000-0002-7346-2404; Nouira, Semir/0000-0002-0137-5491 NR 26 TC 28 Z9 30 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD DEC 21 PY 2014 VL 35 IS 48 BP 3434 EP 3441 DI 10.1093/eurheartj/ehu314 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX9JW UT WOS:000347220200014 PM 25157115 ER PT J AU Gori, M Senni, M Gupta, DK Charytan, DM Kraigher-Krainer, E Pieske, B Claggett, B Shah, AM Santos, ABS Zile, MR Voors, AA McMurray, JJV Packer, M Bransford, T Lefkowitz, M Solomon, SD AF Gori, Mauro Senni, Michele Gupta, Deepak K. Charytan, David M. Kraigher-Krainer, Elisabeth Pieske, Burkert Claggett, Brian Shah, Amil M. Santos, Angela B. S. Zile, Michael R. Voors, Adriaan A. McMurray, John J. V. Packer, Milton Bransford, Toni Lefkowitz, Martin Solomon, Scott D. CA PARAMOUNT Investigators TI Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction SO EUROPEAN HEART JOURNAL LA English DT Article DE Heart failure with preserved ejection fraction; Chronic kidney disease; Albuminuria; Glomerular filtration rate; Cardiovascular structure and function ID LEFT-VENTRICULAR HYPERTROPHY; URINARY ALBUMIN EXCRETION; CHRONIC KIDNEY-DISEASE; CARDIAC ABNORMALITIES; HYPERTENSIVE PATIENTS; CYSTATIN-C; PREVALENCE; MORTALITY; DYSFUNCTION; IMPAIRMENT AB Aim Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. Methods We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR)>30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. Results The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only lowe GFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higherNT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with lowe GFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P< 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P< 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Conclusion Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. C1 [Gori, Mauro; Gupta, Deepak K.; Claggett, Brian; Shah, Amil M.; Santos, Angela B. S.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02445 USA. [Senni, Michele] Azienda Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Charytan, David M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02445 USA. [Charytan, David M.] Brigham & Womens Hosp, Boston, MA 02445 USA. [Kraigher-Krainer, Elisabeth; Pieske, Burkert] Med Univ Graz, Graz, Austria. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael R.] Ralph H Johnson VA Med Ctr, US Dept Vet Affairs, Charleston, SC USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [McMurray, John J. V.] Univ Glasgow, Glasgow, Lanark, Scotland. [Packer, Milton] Univ Texas Southwestern, Dallas, TX USA. [Bransford, Toni; Lefkowitz, Martin] Novartis Pharmaceut, E Hanover, NJ USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02445 USA. EM ssolomon@rics.bwh.harvard.edu OI mcmurray, john/0000-0002-6317-3975 FU NHLBI NIH HHS [K08 HL116792, T32 HL094301] NR 39 TC 14 Z9 18 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD DEC 21 PY 2014 VL 35 IS 48 BP 3442 EP 3451 DI 10.1093/eurheartj/ehu254 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX9JW UT WOS:000347220200015 PM 24980489 ER PT J AU Li, TT Ogino, S Qian, ZR AF Li, Ting-Ting Ogino, Shuji Qian, Zhi Rong TI Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Toll-like receptor; Colorectal cancer; Carcinogenesis; Prognosis; Cancer therapy ID POOR-PROGNOSIS; COLON-CANCER; DNA-REPAIR; EXPRESSION; CELLS; INFLAMMATION; AGONIST; POLYMORPHISMS; PROTEIN; TUMOR AB Toll-like receptors (TLRs) are germ line encoded innate immune sensors that recognize conserved microbial structures and host alarmins, and signal expression of major histocompatibility complex proteins, costimulatory molecules, and inflammatory mediators by macrophages, neutrophils, dendritic cells, and other cell types. These protein receptors are characterized by their ability to respond to invading pathogens promptly by recognizing particular TLR ligands, including flagellin and lipopolysaccharide of bacteria, nucleic acids derived from viruses, and zymosan of fungi. There are 2 major TLR pathways; one is mediated by myeloid differentiation factor 88 (MYD88) adaptor proteins, and the other is independent of MYD88. The MYD88-dependent pathway involves early-phase activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-kappa B1) and all the TLRs, except TLR3, have been shown to activate this pathway. TLR3 and TLR4 act via MYD88-independent pathways with delayed activation of NF-kappa B signaling. TLRs play a vital role in activating immune responses. TLRs have been shown to mediate inflammatory responses and maintain epithelial barrier homeostasis, and are highly likely to be involved in the activation of a number of pathways following cancer therapy. Colorectal cancer (CRC) is one of the most common cancers, and accounts for almost half a million deaths annually worldwide. Inflammation is considered a risk factor for many common malignancies including cancers of the colorectum. The key molecules involved in inflammation-driven carcinogenesis include TLRs. As sensors of cell death and tissue remodeling, TLRs may have a universal role in cancer; stimulation of TLRs to activate the innate immune system has been a legitimate therapeutic strategy for some years. TLRs 3/4/7/8/9 are all validated targets for cancer therapy, and a number of companies are developing agonists and vaccine adjuvants. On the other hand, antagonists may favor inhibition of signaling responsible for autoimmune responses. In this paper, we review TLR signaling in CRC from carcinogenesis to cancer therapy. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Li, Ting-Ting] Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Gastroenterol, Beijing 100853, Peoples R China. [Li, Ting-Ting; Ogino, Shuji; Qian, Zhi Rong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Li, Ting-Ting; Ogino, Shuji; Qian, Zhi Rong] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Qian, ZR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M420, Boston, MA 02215 USA. EM zhirong_qian@dfci.harvard.edu FU United States National Institute of Health (NIH) [P01 CA87969, UM1 CA167552, P01 CA55075, R01 CA137178, P50 CA127003, R01 CA151993]; Bennett Family Fund for Targeted Therapies Research; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance FX Supported by grant from United States National Institute of Health (NIH), No. P01 CA87969 (to SE Hankinson), No. UM1 CA167552, and No. P01 CA55075 (to WC Willett), No. R01 CA137178 (to AT Chan), No. P50 CA127003 (to CS Fuchs), No. R01 CA151993 (to S Ogino); Bennett Family Fund for Targeted Therapies Research; and Entertainment Industry Foundation through National Colorectal Cancer Research Alliance NR 72 TC 11 Z9 12 U1 4 U2 19 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC 21 PY 2014 VL 20 IS 47 BP 17699 EP 17708 DI 10.3748/wjg.v20.i47.17699 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX1NE UT WOS:000346712800002 PM 25548469 ER PT J AU Lin, YT McMahon, SJ Scarpelli, M Paganetti, H Schuemann, J AF Lin, Yuting McMahon, Stephen J. Scarpelli, Matthew Paganetti, Harald Schuemann, Jan TI Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: a Monte Carlo simulation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE proton therapy; gold nanoparticles; Monte Carlo simulation; radiosensitizer; radiation therapy; Geant4-DNA; microscopic dose enhancement AB Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV photon spectrum, and a kilovoltage photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp photons and MV photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage photons have the longest range in water as compared to protons and MV photons, e. g. they cause a dose enhancement 20 times higher than the one caused by protons 10 mu m away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target. C1 [Lin, Yuting; McMahon, Stephen J.; Scarpelli, Matthew; Paganetti, Harald; Schuemann, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lin, Yuting; McMahon, Stephen J.; Scarpelli, Matthew; Paganetti, Harald; Schuemann, Jan] Harvard Univ, Sch Med, Boston, MA USA. [McMahon, Stephen J.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7AE, Antrim, North Ireland. [Scarpelli, Matthew] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Lin, YT (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM ylin20@partners.org NR 30 TC 28 Z9 29 U1 6 U2 17 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 21 PY 2014 VL 59 IS 24 BP 7675 EP 7689 DI 10.1088/0031-9155/59/24/7675 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA V41QB UT WOS:000209559600009 PM 25415297 ER PT J AU Park, SJ Jeon, HJ Kim, JY Kim, S Roh, S AF Park, Se Jin Jeon, Hong Jin Kim, Ju Young Kim, Sohye Roh, Sungwon TI Sociodemographic factors associated with the use of mental health services in depressed adults: results from the Korea National Health and Nutrition Examination Survey (KNHANES) SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Mental health service; Use; Depressive mood; Sociodemographic factor; Age; Education ID COMORBIDITY SURVEY REPLICATION; GENERAL-POPULATION SAMPLE; UNITED-STATES; SINGLE QUESTION; HELP-SEEKING; DISORDERS; GENDER; STIGMA; CARE; ANXIETY AB Background: The aims of this study were to determine the utilization of mental health services (MHSs) by adults with a depressive mood and to identify the influencing sociodemographic factors, using a nationwide representative Korean sample. Methods: The study included 2735 subjects, aged 19 years or older, who had experienced a depressive mood continuously for over 2 weeks within the previous year, using the data from the KNHANES IV (Fourth Korea National Health and Nutrition Examination Survey), which was performed between 2007 and 2009, and involved a nationally representative sample of the Korean community population who were visited at home. A multivariate logistic regression analysis was used to estimate the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for the use of MHSs, which was defined as using healthcare institutions, consulting services, and inpatient or outpatient treatments due to mental health problems. Results: MHSs had been used by 9.6% of the subjects with a depressive mood. The use of the MHSs was significantly associated with age, education level, and employment status, after adjusting for sociodemographic and health-related factors. Specifically, the OR for the nonuse of MHSs by the elderly (>= 65 years) relative to subjects aged 19-34 years was 2.55 (95% CI = 1.13-5.76), subjects with a lower education level were less likely to use MHSs compared to those with a higher education level (7-9 years, OR = 2.35, 95% CI = 1.19-4.64; 10-12 years, OR = 1.66, 95% CI = 1.07-2.56; >= 13 years, reference), and the OR of unemployed relative to employed was 0.47 (95% CI = 0.32-0.67). Conclusions: Among Korean adults with a depressive mood, the elderly, those with a lower education level, and the employed are less likely to use MHSs. These findings suggest that mental health policies should be made based on the characteristics of the population in order to reduce untreated patients with depression. Greater resources and attention to identifying and treating depression in older, less educated, and employed adults are warranted. C1 [Park, Se Jin; Roh, Sungwon] Seoul Natl Hosp, Dept Mental Hlth Res, Seoul 143711, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Depress Ctr,Dept Psychiat, Seoul 135710, South Korea. [Jeon, Hong Jin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. [Kim, Ju Young] Seoul Natl Univ, Bundang Hosp, Dept Family Med, Songnam 463707, Gyeonggi Do, South Korea. [Kim, Sohye] Kyung Hee Univ, Grad Sch East West Med Sci, Dept Med Nutr, Yongin 446701, Gyeonggi Do, South Korea. [Roh, Sungwon] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med,Dept Psychiat, Boston, MA 02114 USA. RP Roh, S (reprint author), Seoul Natl Hosp, Dept Mental Hlth Res, Seoul 143711, South Korea. EM swroh@korea.kr FU National Center for Mental Health Research and Education of Seoul National Hospital, Ministry of Health and Welfare, Korea FX This study was funded by the National Center for Mental Health Research and Education of Seoul National Hospital, Ministry of Health and Welfare, Korea. NR 37 TC 4 Z9 4 U1 4 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD DEC 20 PY 2014 VL 14 AR 645 DI 10.1186/s12913-014-0645-7 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ7WU UT WOS:000348426700001 PM 25527283 ER PT J AU Bradner, JE AF Bradner, James E. TI From transcriptional regulation to drugging the cancer epigenome SO GENOME MEDICINE LA English DT Letter AB Jay Bradner discusses the opportunities and challenges for the study and therapeutic targeting of the cancer epigenome, as well as innovative approaches to drug discovery. C1 [Bradner, James E.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD DEC 20 PY 2014 VL 6 AR 123 DI 10.1186/s13073-014-0123-1 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA AZ4AJ UT WOS:000348164500001 PM 25593599 ER PT J AU Qi, QB Kilpelainen, TO Downer, MK Tanaka, T Smith, CE Sluijs, I Sonestedtl, E Chull, AY Renstrom, F Lin, XC Angquist, LH Huang, JY Liu, ZH Li, YP Ali, MA Xu, M Ahluwalia, TS Boer, JMA Chen, P Daimon, M Eriksson, J Perola, M Friedlander, Y Gao, YT Heppe, DHM Holloway, JW Houston, DK Kanoni, S Kim, YM Laaksonen, MA Jaaskelainen, T Lee, NR Lehtimaki, T Lemaitre, RN Lu, W Luben, RN Manichaiku, A Mannisto, S Marques-Vidal, P Monda, KL Ngwa, JS Perusse, L van Rooij, FJA Xiang, YB Wen, WQ Wojczynski, MK Zhu, JW Borecki, IB Bouchard, C Cai, QY Cooper, C Dedoussis, GV Deloukas, P Ferrucci, L Forouhi, NG Hansen, T Christiansen, L Hofman, A Johansson, I Jorgensen, T Karasawa, S Khaw, KT Kim, MK Kristiansson, K Li, HX Lin, X Liu, YM Lohman, KK Long, JR Mikkila, V Mozaffarian, D North, K Pedersen, O Raitakari, O Rissanen, H Tuomilehto, J van der Schouw, YT Uitterlinden, AG Zillikens, MC Franco, OH Tai, ES Shu, XO Siscovick, DS Toft, U Verschuren, WMM Vollenweider, P Wareham, NJ Witteman, JCM Zheng, W Ridker, PM Kang, JH Liang, LM Jensen, MK Curhan, GC Pasquale, LR Hunter, DJ Mohlke, KL Uusitupa, M Cupples, LA Rankinen, T Orho-Melander, M Wang, T Chasman, DI Franks, PW Sorensen, TIA Hu, FB Loos, RJF Nettleton, JA Qi, L AF Qi, Qibin Kilpelainen, Tuomas O. Downer, Mary K. Tanaka, Toshiko Smith, Caren E. Sluijs, Ivonne Sonestedtl, Emily Chull, Audrey Y. Renstrom, Frida Lin, Xiaochen Angquist, Lars H. Huang, Jinyan Liu, Zhonghua Li, Yanping Ali, Muhammad Asif Xu, Min Ahluwalia, Tarunveer Singh Boer, Jolanda M. A. Chen, Peng Daimon, Makoto Eriksson, Johan Perola, Markus Friedlander, Yechiel Gao, Yu-Tang Heppe, Denise H. M. Holloway, John W. Houston, Denise K. Kanoni, Stavroula Kim, Yu-Mi Laaksonen, Maarit A. Jaaskelainen, Tiina Lee, Nanette R. Lehtimaki, Terho Lemaitre, Rozenn N. Lu, Wei Luben, Robert N. Manichaiku, Ani Mannisto, Satu Marques-Vidal, Pedro Monda, Keri L. Ngwa, Julius S. Perusse, Louis van Rooij, Frank J. A. Xiang, Yong-Bing Wen, Wanqing Wojczynski, Mary K. Zhu, Jingwen Borecki, Ingrid B. Bouchard, Claude Cai, Qiuyin Cooper, Cyrus Dedoussis, George V. Deloukas, Panos Ferrucci, Luigi Forouhi, Nita G. Hansen, Torben Christiansen, Lene Hofman, Albert Johansson, Ingegerd Jorgensen, Torben Karasawa, Shigeru Khaw, Kay-Tee Kim, Mi-Kyung Kristiansson, Kati Li, Huaixing Lin, Xu Liu, Yongmei Lohman, Kurt K. Long, Jirong Mikkila, Vera Mozaffarian, Dariush North, Kari Pedersen, Oluf Raitakari, Olli Rissanen, Harri Tuomilehto, Jaakko van der Schouw, Yvonne T. Uitterlinden, Andre G. Zillikens, M. Carola Franco, Oscar H. Tai, E. Shyong Shu, Xiao Ou Siscovick, David S. Toft, Ulla Verschuren, W. M. Monique Vollenweider, Peter Wareham, Nicholas J. Witteman, Jacqueline C. M. Zheng, Wei Ridker, Paul M. Kang, Jae H. Liang, Liming Jensen, Majken K. Curhan, Gary C. Pasquale, Louis R. Hunter, David J. Mohlke, Karen L. Uusitupa, Matti Cupples, L. Adrienne Rankinen, Tuomo Orho-Melander, Marju Wang, Tao Chasman, Daniel I. Franks, Paul W. Sorensen, Thorkild I. A. Hu, Frank B. Loos, Ruth J. F. Nettleton, Jennifer A. Qi, Lu TI FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals SO HUMAN MOLECULAR GENETICS LA English DT Article ID OBESITY-ASSOCIATED GENE; TIME PHYSICAL-ACTIVITY; FAT MASS; ENERGY-INTAKE; FOOD-INTAKE; METABOLIC-RATE; ASSOCIATION; CHILDREN; RS9939609; GENOTYPE AB FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BM I. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 x 10(-16)), and relative weak associations with lower total energy intake (-6.4 [- 10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [- 0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 x 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity. C1 [Qi, Qibin; Wang, Tao] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA. [Qi, Qibin; Downer, Mary K.; Li, Yanping; Ali, Muhammad Asif; Xu, Min; Mozaffarian, Dariush; Jensen, Majken K.; Hunter, David J.; Franks, Paul W.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lin, Xiaochen; Liu, Zhonghua; Mozaffarian, Dariush; Liang, Liming; Jensen, Majken K.; Curhan, Gary C.; Hunter, David J.; Franks, Paul W.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kilpelainen, Tuomas O.; Forouhi, Nita G.; Wareham, Nicholas J.; Loos, Ruth J. F.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Kilpelainen, Tuomas O.; Ahluwalia, Tarunveer Singh; Hansen, Torben; Pedersen, Oluf; Sorensen, Thorkild I. A.] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Ahluwalia, Tarunveer Singh] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Smith, Caren E.] Tufts Univ, Jean Mayer USDA HNRCA, Nutr & Genom Lab, Boston, MA 02111 USA. [Sluijs, Ivonne; van der Schouw, Yvonne T.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Sonestedtl, Emily; Renstrom, Frida; Orho-Melander, Marju; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Chull, Audrey Y.; Mozaffarian, Dariush; Kang, Jae H.; Curhan, Gary C.; Pasquale, Louis R.; Hunter, David J.; Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Mozaffarian, Dariush; Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Chasman, Daniel I.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA. [Angquist, Lars H.; Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark. [Huang, Jinyan] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200030, Peoples R China. [Ahluwalia, Tarunveer Singh] Gentofte Univ Hosp, Danish Pediat Asthma Ctr, Copenhagen, Denmark. [Boer, Jolanda M. A.; Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, NL-3720 BA Bilthoven, Netherlands. [Chen, Peng; Tai, E. Shyong] Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. [Tai, E. Shyong] Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore. [Daimon, Makoto] Hirosaki Univ, Grad Sch Med, Dept Endocrinol & Metab, Hirosaki, Aomori, Japan. [Daimon, Makoto; Karasawa, Shigeru] Yamagata Univ, Fac Med, Dept Neurol Hematol Metab Endocrinol & Diabetol, Yamagata 990, Japan. [Eriksson, Johan] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Perola, Markus] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Perola, Markus; Laaksonen, Maarit A.; Mannisto, Satu; Kristiansson, Kati; Rissanen, Harri; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Helsinki, Finland. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Friedlander, Yechiel] Hebrew Univ Jerusalem, Sch Publ Hlth, Jerusalem, Israel. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Heppe, Denise H. M.] Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands. [Heppe, Denise H. M.; van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Heppe, Denise H. M.] Erasmus MC, Dept Pediat, Rotterdam, Netherlands. [Uitterlinden, Andre G.; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Holloway, John W.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Houston, Denise K.] Wake Forest Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol, Winston Salem, NC USA. [Lohman, Kurt K.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Kanoni, Stavroula; Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Kim, Yu-Mi] Dong A Univ, Coll Med, Dept Prevent Med, Pusan, South Korea. [Jaaskelainen, Tiina; Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Lee, Nanette R.] Univ San Carlos, U5C Off Populat Studies Fdn Inc, Cebu, Philippines. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lemaitre, Rozenn N.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Lu, Wei] Shanghai Inst Prevent Med, Shanghai, Peoples R China. [Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Manichaiku, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaiku, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Marques-Vidal, Pedro] Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland. [Marques-Vidal, Pedro; Vollenweider, Peter] CHU Vaudois, Dept Med, CH-1011 Lausanne, Switzerland. [Monda, Keri L.; North, Kari] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Monda, Keri L.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Perusse, Louis] Univ Laval, Dept Kinesiol, Ste Foy, PQ, Canada. [van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Zillikens, M. Carola; Franco, Oscar H.; Witteman, Jacqueline C. M.] NGI NCHA, Leiden, Netherlands. [Wen, Wanqing; Cai, Qiuyin; Long, Jirong; Shu, Xiao Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr,Div Epidemiol, Nashville, TN 37212 USA. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Zhu, Jingwen; Li, Huaixing; Lin, Xu] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Zhu, Jingwen; Li, Huaixing; Lin, Xu] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China. [Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA. [Cooper, Cyrus] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England. [Cooper, Cyrus] Univ Southampton, Natl Inst Hlth Res Biomed Res Ctr, Southampton SO16 6YD, Hants, England. [Cooper, Cyrus] Univ Hosp Southampton NHS Fdn Trust, Southampton SO16 6YD, Hants, England. [Cooper, Cyrus] Univ Oxford, Natl Inst Hlth Res Musculoskeletal Biomed Res Uni, Oxford OX3 7LE, England. [Dedoussis, George V.] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Deloukas, Panos] PACER HD, Jeddah 21589, Saudi Arabia. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia. [Christiansen, Lene] Univ Southern Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark. [Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, Umea, Sweden. [Jorgensen, Torben; Toft, Ulla] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Kim, Mi-Kyung] Hanyang Univ, Coll Med, Dept Prevent Med, Seoul 133791, South Korea. [Mikkila, Vera; Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Raitakari, Olli] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, FIN-20520 Turku, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria. [Tuomilehto, Jaakko] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain. [Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Pasquale, Louis R.] Harvard Univ, Sch Med, Dept Ophthalmol, Mass Eye & Ear Infirm, Boston, MA USA. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Loos, Ruth J. F.] Mt Sinai Sch Med, Dept Prevent Med, Mindich Child Hlth & Dev Inst, Genet Obes & Related Metab Traits Program,Charles, New York, NY USA. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 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 Holloway, John/B-5424-2009; Colaus, PsyColaus/K-6607-2013; Chen, Peng/E-5546-2015; Lin, Xiaochen/P-6460-2015; Sonestedt, Emily/I-3814-2016; Bouchard, Claude/A-7637-2009; Deloukas, Panos/B-2922-2013 OI Forouhi, Nita/0000-0002-5041-248X; Jorgensen, Torben/0000-0001-9453-2830; Tai, E Shyong/0000-0003-2929-8966; Franks, Paul/0000-0002-0520-7604; Kristiansson, Kati/0000-0003-4688-107X; Mannisto, Satu/0000-0002-8668-3046; Holloway, John/0000-0001-9998-0464; Chen, Peng/0000-0002-1422-4641; Luben, Robert/0000-0002-5088-6343; Sonestedt, Emily/0000-0002-0747-4562; Deloukas, Panos/0000-0001-9251-070X FU Canadian Institutes of Health Research [GR-15187, MOP-77652]; Cancer Research UK [, 14136]; FIC NIH HHS [TW008288, TW05596]; Medical Research Council [, G0401527, G0701863, G1000143, MC_U106179471, MC_UP_A100_1003, MC_UP_A620_1014, MC_UU_12011/1, MC_UU_12015/1, MC_UU_12015/5]; NCATS NIH HHS [UL1 TR000124, UL1TR000124]; NCI NIH HHS [R01CA148667, CA047988, CA055075, CA49449, CA87969, P30 CA016086, R01CA064277, R01CA082729, R01CA092585, R01CA122364, R01CA124558, R01CA82729, R37CA070867, U54CA155626, UM1 CA173640, UM1 CA182910]; NCRR NIH HHS [RR-024156, RR20649, UL1RR025005]; NEI NIH HHS [EY015473, R01 EY015473]; NHGRI NIH HHS [U01 HG004728, U01HG004399, U01HG004402, U01HG004728-02]; NHLBI NIH HHS [5R01 HL08770003, 5R01 HL08821502, HL-45670, HL043851, HL071981, HL073168, HL080295, HL080467, HL085144, HL085251, HL087652, HL088521, HL103612, HL105756, HL120393, HL34594, K08 HL112845, N01-HC-25195, N01-HC-95159, N01-HC-95169, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N02-HL-6-4278, N02‐HL‐6‐4278, R01 HL034594, R01 HL105756, R01 HL120393, R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259, R01HL085710, R01HL086694, R01HL087641, R01HL59367]; NIA NIH HHS [AG023629, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG032098]; NIDDK NIH HHS [5P30DK46200, 5R01 DK06833603, 5R01 DK07568102, DK063491, DK078150, DK080140, DK091718, DK46200, DK56350, DK58845, DK70756, P30 DK046200, R01 DK078150, R01 DK089256, R01 DK091718]; NIEHS NIH HHS [ES10126, P30 ES010126]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164]; PHS HHS [HHSN268200625226C, HHSN268200782096C, HHSN268200800007C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C] NR 52 TC 24 Z9 24 U1 3 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 20 PY 2014 VL 23 IS 25 BP 6961 EP 6972 DI 10.1093/hmg/ddu411 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0GB UT WOS:000347923000023 PM 25104851 ER PT J AU Riesel, JN AF Riesel, Johanna N. TI On seeing Roses SO LANCET LA English DT Editorial Material C1 [Riesel, Johanna N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Riesel, JN (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jriesel@mgh.harvard.edu 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 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD DEC 20 PY 2014 VL 384 IS 9961 BP 2264 EP 2265 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AX0QC UT WOS:000346655700032 PM 25625400 ER PT J AU Sulmasy, D Moy, B AF Sulmasy, Daniel Moy, Beverly TI Debating the Oncologist's Role in Defining the Value of Cancer Care: Our Duty Is to Our Patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TOP 5 LIST; CLINICAL ONCOLOGY; AMERICAN SOCIETY; COST; OPPORTUNITIES; DISPARITIES C1 [Sulmasy, Daniel] Univ Chicago, Chicago, IL 60637 USA. [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sulmasy, D (reprint author), Univ Chicago, Chicago, IL 60637 USA. NR 24 TC 8 Z9 8 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2014 VL 32 IS 36 BP 4039 EP U234 DI 10.1200/JCO.2014.57.8716 PG 4 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500007 PM 25366686 ER PT J AU Hornbrook, MC Malin, J Weeks, JC Makgoeng, SB Keating, NL Potosky, AL AF Hornbrook, Mark C. Malin, Jennifer Weeks, Jane C. Makgoeng, Solomon B. Keating, Nancy L. Potosky, Arnold L. TI Did Changes in Drug Reimbursement After the Medicare Modernization Act Affect Chemotherapy Prescribing? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARE OUTCOMES RESEARCH; CANCER CARE; SURVEILLANCE CONSORTIUM; LOGISTIC-REGRESSION; COLORECTAL-CANCER; SAMPLE-SIZE; COMORBIDITY; PROJECTIONS; IMPACT AB Purpose The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs). Patients and Methods We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA. Results The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non-small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre-versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post-versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post-versus pre-MMA. Conclusion Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns. (C) 2014 by American Society of Clinical Oncology C1 [Hornbrook, Mark C.] Kaiser Permanente Northwest, Portland, OR 97227 USA. [Malin, Jennifer] Univ Calif Los Angeles, Vet Affairs Med Ctr, Los Angeles, CA USA. [Malin, Jennifer] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Weeks, Jane C.; Keating, Nancy L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Makgoeng, Solomon B.; Potosky, Arnold L.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Hornbrook, MC (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, 3800 North Interstate Ave, Portland, OR 97227 USA. EM mark.c.hornbrook@kpchr.org FU National Cancer Institute (NCI; Harvard University for the CanCORS Statistical Coordinating Center) [U01 CA093344]; NCI (Primary Data Collection and Research Centers of the Dana Farber Cancer Institute and the Cancer Research Network [U01 CA093332]; Harvard Medical School and Northern California Cancer Center [U01 CA093324]; RAND, University of California at Los Angeles [U01 CA093348]; University of Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA093339]; University of North Carolina [U01 CA093326]; Department of Veterans Affairs (Durham VA Medical Center) [CRS 02-164]; NCI [U19 CA79689, P30 CA051008]; Group Health Research Institute (Cancer Research Network Across Health Care Systems) FX Supported by Grants No. U01 CA093344 from the National Cancer Institute (NCI; Harvard University for the CanCORS Statistical Coordinating Center), No. U01 CA093332 from the NCI (Primary Data Collection and Research Centers of the Dana Farber Cancer Institute and the Cancer Research Network, No. U01 CA093324 (Harvard Medical School and Northern California Cancer Center), No. U01 CA093348 (RAND, University of California at Los Angeles), No. U01 CA093329 (University of Alabama at Birmingham), No. U01 CA093339 (University of Iowa), No. U01 CA093326 (University of North Carolina), and by Department of Veterans Affairs Grant No. CRS 02-164 (Durham VA Medical Center). Supported by Cooperative Agreement No. U19 CA79689 between the NCI and Group Health Research Institute (Cancer Research Network Across Health Care Systems; M.C.H.) and Grant No. P30 CA051008 from the NCI (A.L.P.). NR 24 TC 3 Z9 3 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2014 VL 32 IS 36 BP 4042 EP U247 DI 10.1200/JCO.2013.52.6780 PG 13 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500008 PM 25267762 ER PT J AU Polite, BN Griggs, JJ Moy, B Lathan, C duPont, NC Villani, G Wong, SL Halpern, MT AF Polite, Blase N. Griggs, Jennifer J. Moy, Beverly Lathan, Christopher duPont, Nefertiti C. Villani, Gina Wong, Sandra L. Halpern, Michael T. TI American Society of Clinical Oncology Policy Statement on Medicaid Reform SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INSURANCE STATUS; BREAST-CANCER; LYNCH-SYNDROME; PROPHYLACTIC MASTECTOMY; SURVIVAL DISPARITIES; COST-EFFECTIVENESS; DECISION-ANALYSIS; HEALTH-INSURANCE; LUNG-CANCER; EARLY-STAGE C1 [Polite, Blase N.] Univ Chicago, Chicago, IL 60637 USA. [Griggs, Jennifer J.; Wong, Sandra L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lathan, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. [duPont, Nefertiti C.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Villani, Gina] Ralph Lauren Ctr Canc Care & Prevent, New York, NY USA. [Halpern, Michael T.] RTI Int, Washington, DC USA. RP Polite, BN (reprint author), Univ Chicago, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM bpolite@medicine.bsd.uchicago.edu FU NCATS NIH HHS [UL1 TR000430] NR 47 TC 10 Z9 10 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2014 VL 32 IS 36 BP 4162 EP 4167 DI 10.1200/JCO.2014.56.3452 PG 6 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500024 PM 25403206 ER PT J AU Plimack, ER Hoffman-Censits, J Rosenberg, JE Wong, YN Bellmunt, J Choueiri, TK AF Plimack, Elizabeth R. Hoffman-Censits, Jean Rosenberg, Jonathan E. Wong, Yu-Ning Bellmunt, Joaquim Choueiri, Toni K. TI Neoadjuvant Phase II Studies of Modified Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CHEMOTHERAPY; SUBTYPES C1 [Plimack, Elizabeth R.; Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Hoffman-Censits, Jean] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bellmunt, Joaquim; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Plimack, ER (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 15 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2014 VL 32 IS 36 BP 4171 EP U408 DI 10.1200/JCO.2014.58.5281 PG 3 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500028 PM 25385730 ER PT J AU Matthay, KK London, WB Maris, J Adamson, PC Park, JR AF Matthay, Katherine K. London, Wendy B. Maris, John Adamson, Peter C. Park, Julie R. TI When Overall Survival Fails to Confirm Event-Free Survival, Should the Latter Be Used to Set the Standard of Care? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID HIGH-RISK NEUROBLASTOMA; 13-CIS-RETINOIC ACID; RANDOMIZED-TRIAL; CHEMOTHERAPY; THERAPY C1 [Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94117 USA. [London, Wendy B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [London, Wendy B.] Boston Childrens Canc & Blood Disorders, Boston, MA USA. [Maris, John; Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Park, Julie R.] Univ Washington, Sch Med, Seattle, WA USA. RP Matthay, KK (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94117 USA. FU NCI NIH HHS [U10 CA180899, U10 CA180886, U10 CA098413] NR 8 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2014 VL 32 IS 36 BP 4174 EP U417 DI 10.1200/JCO.2014.58.7006 PG 3 WC Oncology SC Oncology GA AW4JO UT WOS:000346247500031 PM 25403223 ER PT J AU Perez-Flores, G Castillo-Martinez, L Orea-Tejeda, A Keirns-Davis, C Lozano-Cruz, A Alcala-Davila, E Kauffman-Ortega, E Radilla-Davila, F AF Perez-Flores, Greta Castillo-Martinez, Lilia Orea-Tejeda, Arturo Keirns-Davis, Candace Lozano-Cruz, Arturo Alcala-Davila, Efrain Kauffman-Ortega, Eric Radilla-Davila, Fernando TI Frequency and clinical characteristics of acute heart failure patients at INCMNSZ, Mexico City, Mexico SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Acute heart failure; Emergency department; Clinical characteristics C1 [Perez-Flores, Greta; Castillo-Martinez, Lilia; Orea-Tejeda, Arturo; Lozano-Cruz, Arturo; Alcala-Davila, Efrain; Kauffman-Ortega, Eric; Radilla-Davila, Fernando] Inst Nacl Ciencias Med Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Keirns-Davis, Candace] Massachusetts Gen Hosp Interpreter Serv, Boston, MA 02114 USA. RP Orea-Tejeda, A (reprint author), Providencia 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. EM oreatart@gmail.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 10 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD DEC 20 PY 2014 VL 177 IS 3 BP 1085 EP 1086 DI 10.1016/j.ijcard.2014.10.003 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU6EX UT WOS:000345697200104 PM 25456704 ER PT J AU Long, SR Wang, ZQ Liu, RD Liu, LN Li, LG Jiang, P Zhang, X Zhang, ZF Shi, HN Cui, J AF Long, Shao Rong Wang, Zhong Quan Liu, Ruo Dan Liu, Li Na Li, Ling Ge Jiang, Peng Zhang, Xi Zhang, Zi Fang Shi, Hai Ning Cui, Jing TI Molecular identification of Trichinella spiralis nudix hydrolase and its induced protective immunity against trichinellosis in BALB/c mice SO PARASITES & VECTORS LA English DT Article DE Trichinella spiralis; Nudix hydrolases; Protective immunity; Vaccine ID INTESTINAL EPITHELIAL-CELLS; C9 BINDING DOMAIN; PROTEOMIC ANALYSIS; INFECTIVE LARVAE; VACCINE CANDIDATE; IN-VITRO; PROTEINS; CLONING; CHINA; GENE AB Background: Nudix hydrolases (Nd) is a widespread superfamily, which is found in all classes of organism, hydrolyse a wide range of organic pyrophosphates and has a 'housecleaning' function. The previous study showed that Trichinella spiralis Nd (TsNd) bound to intestinal epithelial cells (IECs), and the vaccination of mice with T7 phage-displayed TsNd polypeptides produced protective immunity. The aim of this study was to clone, express and identify the full-length TsNd and to investigate its immune protection against T. spiralis infection. Methods: The full-length cDNA sequence of TsNd gene encoding a 46 kDa protein from T. spiralis intestinal infective larvae (IIL) was cloned and identified. The antigenicity of rTsNd was analyzed by Western blot. Transcription and expression of TsNd at T. spiralis different stages were observed by RT-PCR and IFT. The levels of the specific total IgG, IgG1 and IgG2a antibodies to rTsNd were determined by ELISA. The immune protection of rTsNd against T. spiralis infection was investigated. Results: Sequence and phylogenetic analysis revealed that TsNd had a nudix motif located at 226-244aa, which had high homology and the closest evolutionary status with T. pseudospiralis. The rTsNd was obtained after expression and purification. Western blot analysis showed that anti-rTsNd serum recognized the native TsNd protein in crude antigens of muscle larvae (ML), IIL, adult worms (AW) and newborn larvae (NBL), and ES antigens of ML. Transcription and expression of TsNd gene was observed in all developmental stages of T. spiralis (ML, IIL, AW and NBL), with high level expression in IIL. An immunolocalization analysis identified TsNd in the cuticle, stichocytes and reproductive organs of the parasite. Following immunization, anti-rTsNd IgG levels were increased, and the levels of IgG1 were more significantly higher than that of IgG2a. After a challenge infection with T. spiralis, mice immunized with the rTsNd displayed a 57.7% reduction in adult worms and a 56.9% reduction in muscle larval burden. Conclusions: TsNd induced a partial protective immunity in mice and could be considered as a novel candidate vaccine antigen against trichinellosis. C1 [Long, Shao Rong; Wang, Zhong Quan; Liu, Ruo Dan; Liu, Li Na; Li, Ling Ge; Jiang, Peng; Zhang, Xi; Zhang, Zi Fang; Cui, Jing] Zhengzhou Univ, Dept Parasitol, Coll Med, Zhengzhou 450052, Peoples R China. [Shi, Hai Ning] Massachusetts Gen Hosp, Dept Immunol, Charlestown, MA 02129 USA. [Shi, Hai Ning] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wang, ZQ (reprint author), Zhengzhou Univ, Dept Parasitol, Coll Med, Zhengzhou 450052, Peoples R China. EM wangzq@zzu.edu.cn; cuij@zzu.edu.cn FU National Natural Science Foundation of China [81371843, 81271860, 81471981] FX This work was supported by the National Natural Science Foundation of China (No. 81371843, 81271860, and 81471981). NR 40 TC 11 Z9 11 U1 0 U2 107 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-3305 J9 PARASITE VECTOR JI Parasites Vectors PD DEC 19 PY 2014 VL 7 AR 600 DI 10.1186/s13071-014-0600-9 PG 10 WC Parasitology SC Parasitology GA CA5KD UT WOS:000348946400001 PM 25522912 ER PT J AU Crawley, DJ Holmberg, L Melvin, JC Loda, M Chowdhury, S Rudman, SM Van Hemelrijck, M AF Crawley, Danielle J. Holmberg, Lars Melvin, Jennifer C. Loda, Massimo Chowdhury, Simon Rudman, Sarah M. Van Hemelrijck, Mieke TI Serum glucose and risk of cancer: a meta-analysis SO BMC CANCER LA English DT Article DE Glucose; Cancer; Metabolic syndrome; Meta-analysis; Diabetes ID GROWTH-FACTOR-I; INCIDENT COLORECTAL-CANCER; PROSTATE-CANCER; INSULIN-RESISTANCE; BREAST-CANCER; METABOLIC SYNDROME; ENDOMETRIAL CANCER; PANCREATIC-CANCER; DIABETES-MELLITUS; BLOOD-GLUCOSE AB Background: Raised serum glucose has been linked to increased risk of many solid cancers. We performed a meta-analysis to quantify and summarise the evidence for this link. Methods: Pubmed and Embase were reviewed, using search terms representing serum glucose and cancer. Inclusion and exclusion criteria focused on epidemiological studies with clear definitions of serum glucose levels, cancer type, as well as well-described statistical methods with sufficient data available. We used 6.1 mmol/L as the cut-off for high glucose, consistent with the WHO definition of metabolic syndrome. Random effects analyses were performed to estimate the pooled relative risk (RR). Results: Nineteen studies were included in the primary analysis, which showed a pooled RR of 1.32 (95% CI: 1.20 - 1.45). Including only those individuals with fasting glucose measurements did not have a large effect on the pooled RR (1.32 (95% CI: 1.11-1.57). A stratified analysis showed a pooled RR of 1.34 (95% CI: 1.02-1.77) for hormonally driven cancer and 1.21 (95% CI: 1.09-1.36) for cancers thought to be driven by Insulin Growth Factor-1. Conclusion: A positive association between serum glucose and risk of cancer was found. The underlying biological mechanisms remain to be elucidated but our subgroup analyses suggest that the insulin- IGF-1 axis does not fully explain the association. These findings are of public health importance as measures to reduce serum glucose via lifestyle and dietary changes could be implemented in the context of cancer mortality. C1 [Crawley, Danielle J.; Holmberg, Lars; Melvin, Jennifer C.; Van Hemelrijck, Mieke] Kings Coll London, Sch Med, Div Canc Studies, Canc Epidemiol Grp, London, England. [Holmberg, Lars] Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden. [Holmberg, Lars] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Loda, Massimo] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Crawley, Danielle J.; Chowdhury, Simon; Rudman, Sarah M.] Guys & St Thomas NHS Fdn Trust, Dept Oncol, London, England. RP Crawley, DJ (reprint author), Kings Coll London, Sch Med, Div Canc Studies, Canc Epidemiol Grp, London, England. EM Danielle.crawley@kcl.ac.uk OI Van Hemelrijck, Mieke/0000-0002-7317-0858; Crawley, Danielle/0000-0001-7294-5634 FU Experimental Cancer Medicine Centre at King's College London; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; King's College London FX This research was supported by the Experimental Cancer Medicine Centre at King's College London and also by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. NR 96 TC 3 Z9 3 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 19 PY 2014 VL 14 AR 985 DI 10.1186/1471-2407-14-985 PG 11 WC Oncology SC Oncology GA AZ0XG UT WOS:000347964700001 PM 25526881 ER PT J AU Jones, A Kainz, D Khan, F Lee, C Carrithers, MD AF Jones, Alexis Kainz, Danielle Khan, Faatima Lee, Cara Carrithers, Michael D. TI Human Macrophage SCN5A Activates an Innate Immune Signaling Pathway for Antiviral Host Defense SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Adenylate Cyclase; Double-stranded RNA (dsRNA); Innate Immunity; Interferon; Sodium Channel ID SODIUM-CHANNEL NAV1.5; EXPRESSION; PROTEIN; RECOGNITION; INFECTION; NUCLEAR; BINDING; SYSTEM; CELLS AB Pattern recognition receptors contain a binding domain for pathogen-associated molecular patterns coupled to a signaling domain that regulates transcription of host immune response genes. Here, a novel mechanism that links pathogen recognition to channel activation and downstream signaling is proposed. We demonstrate that an intracellular sodium channel variant, human macrophage SCN5A, initiates signaling and transcription through a calcium-dependent isoform of adenylate cyclase, ADCY8, and the transcription factor, ATF2. Pharmacological stimulation with a channel agonist or treatment with cytoplasmic poly(I:C), a mimic of viral dsRNA, activates this pathway to regulate expression of SP100-related genes and interferon . Electrophysiological analysis reveals that the SCN5A variant mediates nonselective outward currents and a small, but detectable, inward current. Intracellular poly(I:C) markedly augments an inward voltage-sensitive sodium current and inhibits the outward nonselective current. These results suggest human macrophage SCN5A initiates signaling in an innate immune pathway relevant to antiviral host defense. It is postulated that SCN5A is a novel pathogen sensor and that this pathway represents a channel activation-dependent mechanism of transcriptional regulation. C1 [Jones, Alexis; Kainz, Danielle; Khan, Faatima; Lee, Cara; Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53706 USA. [Jones, Alexis; Kainz, Danielle; Khan, Faatima; Lee, Cara; Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, Program Cellular & Mol Pathol, Madison, WI 53706 USA. [Carrithers, Michael D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Carrithers, MD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 1300 Univ Ave,Rm 2679, Madison, WI 53706 USA. EM carrithers@neurology.wisc.edu OI Lee, Cara/0000-0003-0614-9060 FU Department of Veterans Affairs; University of Wisconsin at Madison FX This work was supported by a Merit Award from the Department of Veterans Affairs and the University of Wisconsin at Madison. NR 24 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35326 EP 35340 DI 10.1074/jbc.M114.611962 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200024 PM 25368329 ER PT J AU Mariappan, MM Prasad, S D'Silva, K Cedillo, E Sataranatarajan, K Barnes, JL Choudhury, GG Kasinath, BS AF Mariappan, Meenalakshmi M. Prasad, Sanjay D'Silva, Kristin Cedillo, Esteban Sataranatarajan, Kavithalakshmi Barnes, Jeffrey L. Choudhury, Goutam Ghosh Kasinath, Balakuntalam S. TI Activation of Glycogen Synthase Kinase 3 beta Ameliorates Diabetes-induced Kidney Injury SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cell Signaling; Eukaryotic Translation Initiation; Extracellular Matrix Protein; Glycogen Synthase Kinase 3 (GSK-3); Kidney; Mammalian Target of Rapamycin (mTOR); Type 1 Diabetes; Diabetic Nephropathy; Sodium Nitroprusside; Kidney Hypertrophy ID MESSENGER-RNA TRANSLATION; RENAL EPITHELIAL-CELLS; PROTEIN-SYNTHESIS; HIGH GLUCOSE; HIGH INSULIN; AKT KINASE; PHOSPHORYLATION; NEPHROPATHY; INITIATION; GROWTH AB Increase in protein synthesis contributes to kidney hypertrophy and matrix protein accumulation in diabetes. We have previously shown that high glucose-induced matrix protein synthesis is associated with inactivation of glycogen synthase kinase 3 (GSK3) in renal cells and in the kidneys of diabetic mice. We tested whether activation of GSK3 by sodium nitroprusside (SNP) mitigates kidney injury in diabetes. Studies in kidney-proximal tubular epithelial cells showed that SNP abrogated high glucose-induced laminin increment by stimulating GSK3 and inhibiting Akt, mTORC1, and events in mRNA translation regulated by mTORC1 and ERK. NONOate, an NO donor, also activated GSK3, indicating that NO may mediate SNP stimulation of GSK3. SNP administered for 3 weeks to mice with streptozotocin-induced type 1 diabetes ameliorated kidney hypertrophy, accumulation of matrix proteins, and albuminuria without changing blood glucose levels. Signaling studies showed that diabetes caused inactivation of GSK3 by activation of Src, Pyk2, Akt, and ERK; GSK3 inhibition activated mTORC1 and downstream events in mRNA translation in the kidney cortex. These reactions were abrogated by SNP. We conclude that activation of GSK3 by SNP ameliorates kidney injury induced by diabetes. C1 [Mariappan, Meenalakshmi M.; Prasad, Sanjay; D'Silva, Kristin; Cedillo, Esteban; Sataranatarajan, Kavithalakshmi; Barnes, Jeffrey L.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78245 USA. [Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. [Mariappan, Meenalakshmi M.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU Veterans Affairs Merit Review Program; National Institutes of Health [DK077295, RC2AG036613, DK050190]; American Diabetes Association; Juvenile Diabetes Research Foundation; Veterans Affairs Merit Review Grant [5I01BX000926]; Veterans Affairs Senior Research Career Scientist Award FX This work was supported, in whole or in part, by the Veterans Affairs Merit Review Program (to B. S. K.), National Institutes of Health Grants DK077295 (to B. S. K.) and RC2AG036613 (to B. S. K.). This work was also supported by the American Diabetes Association (to B. S. K.) and the Juvenile Diabetes Research Foundation (to M. M. M.).; Supported by National Institutes of Health R01 Grant DK050190 and Veterans Affairs Merit Review Grant 5I01BX000926; recipient of a Veterans Affairs Senior Research Career Scientist Award. NR 51 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2014 VL 289 IS 51 BP 35363 EP 35375 DI 10.1074/jbc.M114.587840 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AX0RT UT WOS:000346660200027 PM 25339176 ER PT J AU Crystal, AS Shaw, AT Sequist, LV Friboulet, L Niederst, MJ Lockerman, EL Frias, RL Gainor, JF Amzallag, A Greninger, P Lee, D Kalsy, A Gomez-Caraballo, M Elamine, L Howe, E Hur, W Lifshits, E Robinson, HE Katayama, R Faber, AC Awad, MM Ramaswamy, S Mino-Kenudson, M Iafrate, AJ Benes, CH Engelman, JA AF Crystal, Adam S. Shaw, Alice T. Sequist, Lecia V. Friboulet, Luc Niederst, Matthew J. Lockerman, Elizabeth L. Frias, Rosa L. Gainor, Justin F. Amzallag, Arnaud Greninger, Patricia Lee, Dana Kalsy, Anuj Gomez-Caraballo, Maria Elamine, Leila Howe, Emily Hur, Wooyoung Lifshits, Eugene Robinson, Hayley E. Katayama, Ryohei Faber, Anthony C. Awad, Mark M. Ramaswamy, Sridhar Mino-Kenudson, Mari Iafrate, A. John Benes, Cyril H. Engelman, Jeffrey A. TI Patient-derived models of acquired resistance can identify effective drug combinations for cancer SO SCIENCE LA English DT Article ID CELL LUNG-CANCER; KINASE INHIBITION; BYPASS MECHANISMS; ALK; CRIZOTINIB; MUTATIONS; GEFITINIB; CHEMOTHERAPY; ACTIVATION; CERITINIB AB Targeted cancer therapies have produced substantial clinical responses, but most tumors develop resistance to these drugs. Here, we describe a pharmacogenomic platform that facilitates rapid discovery of drug combinations that can overcome resistance. We established cell culture models derived from biopsy samples of lung cancer patients whose disease had progressed while on treatment with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors and then subjected these cells to genetic analyses and a pharmacological screen. Multiple effective drug combinations were identified. For example, the combination of ALK and MAPK kinase (MEK) inhibitors was active in an ALK-positive resistant tumor that had developed a MAP2K1 activating mutation, and the combination of EGFR and fibroblast growth factor receptor (FGFR) inhibitors was active in an EGFR mutant resistant cancer with a mutation in FGFR3. Combined ALK and SRC (pp60c-src) inhibition was effective in several ALK-driven patient-derived models, a result not predicted by genetic analysis alone. With further refinements, this strategy could help direct therapeutic choices for individual patients. C1 [Crystal, Adam S.; Shaw, Alice T.; Sequist, Lecia V.; Friboulet, Luc; Niederst, Matthew J.; Lockerman, Elizabeth L.; Frias, Rosa L.; Gainor, Justin F.; Amzallag, Arnaud; Greninger, Patricia; Lee, Dana; Kalsy, Anuj; Gomez-Caraballo, Maria; Elamine, Leila; Howe, Emily; Lifshits, Eugene; Katayama, Ryohei; Faber, Anthony C.; Awad, Mark M.; Ramaswamy, Sridhar; Benes, Cyril H.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Crystal, Adam S.; Shaw, Alice T.; Sequist, Lecia V.; Friboulet, Luc; Niederst, Matthew J.; Lockerman, Elizabeth L.; Frias, Rosa L.; Gainor, Justin F.; Amzallag, Arnaud; Greninger, Patricia; Lee, Dana; Kalsy, Anuj; Gomez-Caraballo, Maria; Elamine, Leila; Howe, Emily; Lifshits, Eugene; Robinson, Hayley E.; Katayama, Ryohei; Faber, Anthony C.; Awad, Mark M.; Ramaswamy, Sridhar; Mino-Kenudson, Mari; Iafrate, A. John; Benes, Cyril H.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Robinson, Hayley E.; Mino-Kenudson, Mari; Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [Hur, Wooyoung] Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hur, Wooyoung] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hur, Wooyoung] Korea Inst Sci & Technol, Chem Kin Res Ctr, Seoul 136791, South Korea. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. EM cbenes@partners.org; jengelman@partners.org RI friboulet, luc/N-7276-2015 OI Crystal, Adam/0000-0002-2302-2654; friboulet, luc/0000-0002-1129-4978 FU NIH [R01CA137008, R01CA164273, 1U54HG006097-01]; Wellcome Trust [086357, 102696]; National Cancer Institute Lung SPORE [P50CA090578]; Department of Defense; Conquer Cancer Foundation Young Investigator Award; Uniting Against Lung Cancer; Free to Breathe; Lungevity; National Foundation for Cancer Research; Be a Piece of the Solution; Novartis; Sanofi-Aventis; AstraZeneca; Chugai; Amgen; Genentech; GSK; Merck; Pfizer; Boehringer Ingelheim; Ariad; Roche; Ignyta FX We thank L. H. Park for direction, redirection, and support; S. R. Vora for continual critical discussion and support; W. Michaud for providing feeder cells and training for the development of patient-derived cell lines; and N. Gray for providing several kinase inhibitors. This study was funded by support from the NIH R01CA137008 (J.A.E.), R01CA164273 (A.T.S. and J.A.E.), 1U54HG006097-01 (C.H.B.), the Wellcome Trust (086357 and 102696, C.H.B.), the National Cancer Institute Lung SPORE P50CA090578 (A.S.C., A.J.I., and J.A.E.), the Department of Defense (L.V.S. and J.A.E.), Conquer Cancer Foundation Young Investigator Award (A.S.C.), Uniting Against Lung Cancer (A.S.C. and A.T.S.), Free to Breathe (A.S.C.), Lungevity (L.V.S. and J.A.E.), National Foundation for Cancer Research (A.T.S.), and Be a Piece of the Solution. J.A.E. is a paid consultant for Novartis, Sanofi-Aventis, AstraZeneca, Chugai, Amgen, Genentech, GSK, Merck, and Pfizer, and he holds equity in Gatekeeper Pharmaceuticals, which has a potential equity interest in T790M inhibitors. J.A.E. also receives research support from Novartis. J.F.G. is a paid consultant for Boehringer Ingelheim. A.T.S. is a paid consultant for Pfizer, Novartis, Ariad, Chugai, Genentech, Roche, and Ignyta. A.J.I. is a Senior Advisory Board member and holds equity in Enzymatics Inc. For gene expression analyses, the raw data are deposited in ArrayExpress (accession number is E-MTAB-783). The normalized data are available at www.cancerrxgene.org/downloads. NR 27 TC 148 Z9 152 U1 7 U2 66 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 DEC 19 PY 2014 VL 346 IS 6216 BP 1480 EP 1486 DI 10.1126/science.1254721 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8UI UT WOS:000346536500056 PM 25394791 ER PT J AU Nelson, BA Kaplan, JL El Saleeby, CM Lu, MT Mark, EJ AF Nelson, Benjamin A. Kaplan, Jess L. El Saleeby, Chadi M. Lu, Michael T. Mark, Eugene J. TI Case 39-2014: A 9-Year-Old Girl with Crohn's Disease and Pulmonary Nodules SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; WEGENERS-GRANULOMATOSIS; LUNG LESIONS; PATIENT; AZATHIOPRINE; CHILDREN; BIOPSY C1 [Nelson, Benjamin A.; Kaplan, Jess L.; El Saleeby, Chadi M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Lu, Michael T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nelson, Benjamin A.; Kaplan, Jess L.; El Saleeby, Chadi M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lu, Michael T.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nelson, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 24 TC 3 Z9 3 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 18 PY 2014 VL 371 IS 25 BP 2418 EP 2427 DI 10.1056/NEJMcpc1410938 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AW7DX UT WOS:000346425800013 PM 25517709 ER PT J AU Lu, EP McLellan, M Ding, L Fulton, R Mardis, ER Wilson, RK Miller, CA Westervelt, P DiPersio, JF Link, DC Walter, MJ Ley, TJ Graubert, TA AF Lu, Elise Peterson McLellan, Michael Ding, Li Fulton, Robert Mardis, Elaine R. Wilson, Richard K. Miller, Christopher A. Westervelt, Peter DiPersio, John F. Link, Daniel C. Walter, Matthew J. Ley, Timothy J. Graubert, Timothy A. TI Caspase-9 is required for normal hematopoietic development and protection from alkylator-induced DNA damage in mice SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; NON-HODGKIN-LYMPHOMA; STEM-CELL FUNCTION; GENE-EXPRESSION; HUMAN CANCER; REPAIR; APOPTOSIS; RISK; DIFFERENTIATION; SUSCEPTIBILITY AB Apoptosis and the DNA damage responses have been implicated in hematopoietic development and differentiation, as well as in the pathogenesis of myelodysplastic syndromes (MDS) and leukemia. However, the importance of late-stage mediators of apoptosis in hematopoiesis and leukemogenesis has not been elucidated. Here, we examine the role of caspase-9 (Casp9), the initiator caspase of the intrinsic apoptotic cascade, in murine fetal and adult hematopoiesis. Casp9 deficiency resulted in decreased erythroid and B-cell progenitor abundance and impaired function of hematopoietic stem cells after transplantation. Mouse bone marrow chimeras lacking Casp9 or its cofactor Apaf1 developed low white blood cell counts, decreased B-cell numbers, anemia, and reduced survival. Defects in apoptosis have also been previously implicated in susceptibility to therapy-related leukemia, a disease caused by exposure to DNA-damaging chemotherapy. We found that the burden of DNA damage was increased in Casp9-deficient cells after exposure to the alkylator, N-ethyl-nitrosourea (ENU). Furthermore, exome sequencing revealed that oligoclonal hematopoiesis emerged in Casp9-deficient bone marrow chimeras after alkylator exposure. Taken together, these findings suggest that defects in apoptosis could be a key step in the pathogenesis of alkylator-associated secondary malignancies. C1 [Lu, Elise Peterson; Westervelt, Peter; DiPersio, John F.; Link, Daniel C.; Walter, Matthew J.; Ley, Timothy J.; Graubert, Timothy A.] Washington Univ, Dept Med, Div Oncol, St Louis, MO USA. [McLellan, Michael; Ding, Li; Fulton, Robert; Mardis, Elaine R.; Wilson, Richard K.; Miller, Christopher A.; Ley, Timothy J.] Washington Univ, Genome Inst, St Louis, MO USA. [Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Westervelt, Peter; DiPersio, John F.; Link, Daniel C.; Walter, Matthew J.; Ley, Timothy J.; Graubert, Timothy A.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Mardis, Elaine R.; Wilson, Richard K.; Walter, Matthew J.; Ley, Timothy J.] Washington Univ, Dept Genet, St Louis, MO 63110 USA. RP Graubert, TA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 North Grove St,Lawrence House 204, Boston, MA 02114 USA. EM tgraubert@partners.org OI Graubert, Timothy/0000-0002-7710-1171 FU National Institutes of Health, National Cancer Institute [P01CA101937]; National Institutes of Health, National Heart, Lung, and Blood Institute [F30HL114316] FX This work was supported by the National Institutes of Health, National Cancer Institute grant P01CA101937 and National Heart, Lung, and Blood Institute grant F30HL114316. NR 34 TC 4 Z9 5 U1 0 U2 5 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 DEC 18 PY 2014 VL 124 IS 26 BP 3887 EP 3895 DI 10.1182/blood-2014-06-582551 PG 9 WC Hematology SC Hematology GA AY3EU UT WOS:000347468200011 PM 25349173 ER PT J AU Burgess, MR Hwang, E Firestone, AJ Huang, TN Xu, J Zuber, J Bohin, N Wen, T Kogan, SC Haigis, KM Sampath, D Lowe, S Shannon, K Li, Q AF Burgess, Michael R. Hwang, Eugene Firestone, Ari J. Huang, Tannie Xu, Jin Zuber, Johannes Bohin, Natacha Wen, Tiffany Kogan, Scott C. Haigis, Kevin M. Sampath, Deepak Lowe, Scott Shannon, Kevin Li, Qing TI Preclinical efficacy of MEK inhibition in Nras-mutant AML SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; SMALL-MOLECULE INHIBITION; HEMATOPOIETIC STEM; MYELODYSPLASTIC SYNDROME; HYPERACTIVE RAS; TARGETING RAS; PHASE-I; MUTATIONS; CANCER; GENE AB Oncogenic NRAS mutations are highly prevalent in acute myeloid leukemia (AML). Genetic analysis supports the hypothesis that NRAS mutations cooperate with antecedent molecular lesions in leukemogenesis, but have limited independent prognostic significance. Using short hairpin RNA-mediated knockdown in human cell lines and primary mouse leukemias, we show that AML cells with NRAS/Nras mutations are dependent on continued oncogene expression in vitro and in vivo. Using the Mx1-Cre transgene to inactivate a conditional mutant Nras allele, we analyzed hematopoiesis and hematopoietic stem and progenitor cells (HSPCs) under normal and stressed conditions and found that HSPCs lacking Nras expression are functionally equivalent to normal HSPCs in the adult mouse. Treating recipient mice transplanted with primary Nras(G12D) AMLs with 2 potent allosteric mitogen-activated protein kinase kinase (MEK) inhibitors (PD0325901 or trametinib/GlaxoSmithKline 1120212) significantly prolonged survival and reduced proliferation but did not induce apoptosis, promote differentiation, or drive clonal evolution. The phosphatidylinositol 3-kinase inhibitor GDC-0941 was ineffective as a single agent and did not augment the activity of PD0325901. All mice ultimately succumbed to progressive leukemia. Together, these data validate oncogenic N-Ras signaling as a therapeutic target in AML and support testing combination regimens that include MEK inhibitors. C1 [Burgess, Michael R.] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94158 USA. [Hwang, Eugene; Firestone, Ari J.; Huang, Tannie; Xu, Jin; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA. [Zuber, Johannes] Res Inst Mol Pathol, A-1030 Vienna, Austria. [Bohin, Natacha; Wen, Tiffany; Li, Qing] Univ Michigan, Dept Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Kogan, Scott C.; Shannon, Kevin] Univ Calif San Francisco, San Francisco, CA 94158 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Sampath, Deepak] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA. [Lowe, Scott] Howard Hughes Med Inst, New York, NY USA. [Lowe, Scott] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shannon, Kevin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. RP Shannon, K (reprint author), Univ Calif San Francisco, Helen Diller Family Canc Res Bldg,1450 3rd St, San Francisco, CA 94158 USA. EM shannonk@peds.ucsf.edu; lqing@med.umich.edu FU Rally Foundation for Childhood Cancer Research; Leukemia and Lymphoma Society of America Specialized Center of Research [LLS 7019-04]; National Institutes of Health, National Cancer Institute [R37 CA72614, T32 CA108462, K01 CA118425, K08 CA134649]; American Cancer Society-Hillcrest Committee Postdoctoral Fellowship [PF-14-146-01-LIB]; Damon Runyon Cancer Research Foundation Fellowship [DRG-2149-13] FX This work was supported by the Rally Foundation for Childhood Cancer Research and The Truth 365; the Leukemia and Lymphoma Society of America Specialized Center of Research (LLS 7019-04); the National Institutes of Health, National Cancer Institute grants R37 CA72614 (K.S.), and T32 CA108462 (M.R.B.), grant K01 CA118425 (K.M.H.), and grant K08 CA134649 (Q.L.); an American Cancer Society-Hillcrest Committee Postdoctoral Fellowship (PF-14-146-01-LIB) (M.R.B.); and a Damon Runyon Cancer Research Foundation Fellowship (DRG-2149-13) (A.J.F.) S.L. is an Investigator of the Howard Hughes Medical Institute, and K.S. is an American Cancer Society Research Professor. NR 49 TC 18 Z9 18 U1 0 U2 6 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 DEC 18 PY 2014 VL 124 IS 26 BP 3947 EP 3955 DI 10.1182/blood-2014-05-574582 PG 9 WC Hematology SC Hematology GA AY3EU UT WOS:000347468200018 PM 25361812 ER PT J AU Petersdorf, EW Gooley, TA Malkki, M Bacigalupo, AP Cesbron, A Du Toit, E Ehninger, G Egeland, T Fischer, GF Gervais, T Haagenson, MD Horowitz, MM Hsu, K Jindra, P Madrigal, A Oudshoorn, M Ringden, O Schroeder, ML Spellman, SR Tiercy, JM Velardi, A Witt, CS O'Huigin, C Apps, R Carrington, M AF Petersdorf, Effie W. Gooley, Theodore A. Malkki, Mari Bacigalupo, Andrea P. Cesbron, Anne Du Toit, Ernette Ehninger, Gerhard Egeland, Torstein Fischer, Gottfried F. Gervais, Thibaut Haagenson, Michael D. Horowitz, Mary M. Hsu, Katharine Jindra, Pavel Madrigal, Alejandro Oudshoorn, Machteld Ringden, Olle Schroeder, Marlis L. Spellman, Stephen R. Tiercy, Jean-Marie Velardi, Andrea Witt, Campbell S. O'Huigin, Colm Apps, Richard Carrington, Mary CA Int Histocompatibility Working Grp TI HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; KIR LIGAND INCOMPATIBILITY; VERSUS-HOST-DISEASE; CLASS-I MOLECULES; UNRELATED DONOR; HIV CONTROL; ALLELE; IDENTIFICATION; SUBSTITUTIONS; ENVIRONMENT AB Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-Cexpression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-Cexpression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-Callotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease. C1 [Petersdorf, Effie W.; Gooley, Theodore A.; Malkki, Mari] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Petersdorf, Effie W.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Bacigalupo, Andrea P.] Azienda Osped Univ San Martino, Ist Ricovero & Cura Carattere Sci, Genoa, Italy. [Cesbron, Anne] Etab Francais Sang Pays de Loire, Lab Histocompatibilit & Immunogenet, Nantes, France. [Du Toit, Ernette] Univ Cape Town, Cape Town, South Africa. [Du Toit, Ernette] South African Bone Marrow Registry, Cape Town, South Africa. [Ehninger, Gerhard] Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Egeland, Torstein] Oslo Univ Hosp, Dept Immunol, Oslo, Norway. [Fischer, Gottfried F.] Med Univ Vienna, Dept Blood Grp Serol & Transfus Med, Vienna, Austria. [Gervais, Thibaut] Catholic Univ Louvain, Clin St Luc, Brussels, Belgium. [Haagenson, Michael D.; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Hsu, Katharine] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Jindra, Pavel] Univ Hosp, Plzen, Czech Republic. [Madrigal, Alejandro] Royal Free Hampstead NHS Trust, Anthony Nolan Res Inst, London, England. [Oudshoorn, Machteld] Leiden Univ, Med Ctr, Leiden, Netherlands. [Oudshoorn, Machteld] Europdonor Fdn, Leiden, Netherlands. [Ringden, Olle] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Div Therapeut Immunol, Huddinge, Sweden. [Schroeder, Marlis L.] Univ Manitoba, Canc Care Manitoba, Winnipeg, MB, Canada. [Tiercy, Jean-Marie] Univ Hosp Geneva, Dept Genet & Lab Med, Natl Reference Lab Histocompatibil, Geneva, Switzerland. [Velardi, Andrea] European Grp Blood & Marrow Transplantat, Perugia, Italy. [Velardi, Andrea] Univ Perugia, I-06100 Perugia, Italy. [Witt, Campbell S.] Royal Perth Hosp, Dept Clin Immunol, Perth, WA 6001, Australia. [O'Huigin, Colm; Apps, Richard; Carrington, Mary] SAIC Frederick Inc, Frederick Natl Labs Canc Res, Canc & Inflammat Program, Frederick, MD USA. [Apps, Richard; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Apps, Richard; Carrington, Mary] Harvard Univ, Boston, MA 02115 USA. RP Petersdorf, EW (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,D4-115,POB 19024, Seattle, WA 98109 USA. EM epetersd@fhcrc.org FU National Institute of Allergy and Infectious Diseases (NIAID) [AI069197]; National Cancer Institute (NCI) [CA18029]; NCI [CA76518, U24-CA76518, 5U01HL069294]; Health Resources and Services Administration [HHSH234200637015C]; National Heart, Lung and Blood Institute (NHLBI); NIAID; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Associazione Italiana Ricerca sul Cancro (Milano, Italy); European Regional Development Fund [ED2.1.00/03.0076]; Swedish Cancer Society; Swedish Research Council; Children's Cancer Foundation; Cancer Society in Stockholm; Karolinska Institutet (Stockholm, Sweden); Swiss National Science Foundation [310030-146306/1]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; National Institutes of Health, Frederick National Laboratory, Center for Cancer Research; [T.A. C.R TA01010342]; [GACRNT/12454-5] FX E.W.P., T.A.G., M.M., S.R.S., M.D.H., and M.M.H. are supported by National Institute of Allergy and Infectious Diseases (NIAID) grant AI069197; E.W.P., T.A.G., and M.M. are supported by National Cancer Institute (NCI) grant CA18029; M.M.H. is supported by NCI grant CA76518 and Health Resources and Services Administration grant HHSH234200637015C; S.R.S., M.D.H., and M.M.H. are supported by NCI grant U24-CA76518, the National Heart, Lung and Blood Institute (NHLBI), NIAID, NHLBI and NCI grant 5U01HL069294, and Office of Naval Research grants N00014-12-1-0142 and N00014-13-1-0039; A.P.B. was supported by The Associazione Italiana Ricerca sul Cancro (Milano, Italy); P.J. was supported by Project ED2.1.00/03.0076 from the European Regional Development Fund, T.A. C.R TA01010342, and GACRNT/12454-5, Czech Republic; O.R. was supported by The Swedish Cancer Society, The Swedish Research Council, The Children's Cancer Foundation, The Cancer Society in Stockholm, and Karolinska Institutet (Stockholm, Sweden); J.-M.T. was supported by Swiss National Science Foundation grant 310030-146306/1; and M.C. was supported by Frederick National Laboratory for Cancer Research contract HHSN261200800001E and the Intramural Research Program of the National Institutes of Health, Frederick National Laboratory, Center for Cancer Research. NR 35 TC 27 Z9 27 U1 1 U2 5 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 DEC 18 PY 2014 VL 124 IS 26 BP 3996 EP 4003 DI 10.1182/blood-2014-09-599969 PG 8 WC Hematology SC Hematology GA AY3EU UT WOS:000347468200025 PM 25323824 ER PT J AU Meng, FL Du, Z Federation, A Hu, JZ Wang, Q Kieffer-Kwon, KR Meyers, RM Amor, C Wasserman, CR Neuberg, D Casellas, R Nussenzweig, MC Bradner, JE Liu, XS Alt, FW AF Meng, Fei-Long Du, Zhou Federation, Alexander Hu, Jiazhi Wang, Qiao Kieffer-Kwon, Kyong-Rim Meyers, Robin M. Amor, Corina Wasserman, Caitlyn R. Neuberg, Donna Casellas, Rafael Nussenzweig, Michel C. Bradner, James E. Liu, X. Shirley Alt, Frederick W. TI Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability SO CELL LA English DT Article ID RNA-POLYMERASE-II; INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; B-CELL LYMPHOMA; SOMATIC HYPERMUTATION; SEQUENCING REVEALS; CHROMOSOMAL TRANSLOCATIONS; NONCODING TRANSCRIPTION; IG GENES; C-MYC AB Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single-stranded DNA targets. Though largely specific for immunoglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing mystery. Based on deep GRO-seq studies of mouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target translocations occur within highly focal regions of target genes in which sense and antisense transcription converge. Moreover, we found that such AID-targeting "convergent'' transcription arises from antisense transcription that emanates from super-enhancers within sense transcribed gene bodies. Our findings provide an explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells. C1 [Meng, Fei-Long; Du, Zhou; Hu, Jiazhi; Meyers, Robin M.; Amor, Corina; Wasserman, Caitlyn R.; Alt, Frederick W.] Harvard Univ, Boston Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med,Med Sch, Boston, MA 02115 USA. [Meng, Fei-Long; Du, Zhou; Hu, Jiazhi; Meyers, Robin M.; Amor, Corina; Wasserman, Caitlyn R.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Du, Zhou] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Federation, Alexander; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Federation, Alexander; Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Qiao; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10065 USA. [Kieffer-Kwon, Kyong-Rim; Casellas, Rafael] NCI, NIAMS, NIH, Bethesda, MD 20892 USA. [Kieffer-Kwon, Kyong-Rim; Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Neuberg, Donna; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neuberg, Donna; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu; alt@enders.tch.harvard.edu FU NIH grants [R01AI077595, P01CA109901]; Leukemia and Lymphoma Society (LLS) SCOR grant; NIH grant [1R01GM099409]; Leukemia and Lymphoma Society SCOR; National Science Foundation; NIH [1R01 CA176745-01, P01 CA109901, AI072529, AI037526]; intramural research program of NIAMS, NIH; Robertson Foundation/Cancer Research Institute Irvington Fellowship; National Science Foundation of China [NSFC 31329003] FX F.W.A was supported by NIH grants R01AI077595 and P01CA109901, and a Leukemia and Lymphoma Society (LLS) SCOR grant, and he is an investigator of the Howard Hughes Medical Institute. X.S.L was supported by NIH grant 1R01GM099409. A.F. and J.E.B. were supported by a Leukemia and Lymphoma Society SCOR, the National Science Foundation, and NIH grants 1R01 CA176745-01 and P01 CA109901. M.C.N. was supported by NIH grants AI072529 and AI037526 and is an investigator of the Howard Hughes Medical Institute. K.K. and R.C. were supported by the intramural research program of NIAMS, NIH. F.L.M. is a Lymphoma Research Foundation postdoctoral fellow and was a Cancer Research Institute postdoctoral fellow. J.Z. is supported by a Robertson Foundation/Cancer Research Institute Irvington Fellowship. Z.D. was supported by the National Science Foundation of China grant NSFC 31329003. The authors thank Drs. Yi Zhang and Li Shen for assistance with DNA sequencing and Dr. David Schatz (Yale University) for providing primers for GC SHM targets. Dr. Bradner is a scientific founder of Syros Pharmaceuticals, which is developing drugs targeting super-enhancers. NR 53 TC 55 Z9 56 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 18 PY 2014 VL 159 IS 7 BP 1538 EP 1548 DI 10.1016/j.cell.2014.11.014 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AZ0FW UT WOS:000347922500009 PM 25483776 ER PT J AU Woo, JM Jeon, HJ Noh, E Kim, HJ Lee, SW Lee, KK Kim, SH Hong, JP AF Woo, Jong-Min Jeon, Hong Jin Noh, Eunsun Kim, Hyo-Jin Lee, Sun Woo Lee, Kyung Kyu Kim, Sung Hwan Hong, Jin Pyo TI Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article DE Major depressive disorder; Quality of life; EQ-5D; Q-LES-Q-SF ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PAINFUL PHYSICAL SYMPTOMS; MENTAL-HEALTH; DSM-IV; OUTCOMES; VALIDATION; SCALE; ASSOCIATION; POPULATION; IMIPRAMINE AB Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 0.10, while it was 0.57 0.23 in the non-remitted group and 0.58 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 16.6 and 50.9 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 8.8, whereas tho se with non-remission reported 36.7 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 0.24) than those with mild/moderate somatic symptoms (0.75 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD. C1 [Woo, Jong-Min] Inje Univ, Sch Med, Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea. [Woo, Jong-Min] Inje Univ, Stress Res Inst, Seoul, South Korea. [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Noh, Eunsun] Vet Affairs Med Ctr, Providence, RI USA. [Noh, Eunsun] Univ Rhode Isl, Coll Pharm, Dept Pharm Practice, Kingston, RI 02881 USA. [Kim, Hyo-Jin] Pfizer Pharmaceut Korea Ltd, Hlth & Value Div, OR RWD Team, Seoul, South Korea. [Lee, Sun Woo] Chungnam Natl Univ, Sch Med, Dept Psychiat, Chungnam, South Korea. [Lee, Kyung Kyu] Dankook Univ, Sch Med, Dept Psychiat, Cheonan, South Korea. [Kim, Sung Hwan] Dong A Univ, Sch Med, Dept Psychiat, Pusan, South Korea. [Hong, Jin Pyo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, Seoul 138736, South Korea. RP Hong, JP (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Psychiat, 388-1 Pungnap 2dong, Seoul 138736, South Korea. EM jphong@amc.seoul.kr FU Pfizer Pharmaceuticals Korea Ltd.; Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology [2011-0013064] FX This study was supported by Pfizer Pharmaceuticals Korea Ltd. and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (No. 2011-0013064). NR 43 TC 7 Z9 7 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD DEC 18 PY 2014 VL 12 AR 188 DI 10.1186/s12955-014-0188-y PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AY2NG UT WOS:000347426300001 PM 25519704 ER PT J AU Gaiha, GD McKim, KJ Woods, M Pertel, T Rohrbach, J Barteneva, N Chin, CR Liu, DF Soghoian, DZ Cesa, K Wilton, S Waring, MT Chicoine, A Doering, T Wherry, EJ Kaufmann, DE Lichterfeld, M Brass, AL Walker, BD AF Gaiha, Gaurav D. McKim, Kevin J. Woods, Matthew Pertel, Thomas Rohrbach, Janine Barteneva, Natasha Chin, Christopher R. Liu, Dongfang Soghoian, Damien Z. Cesa, Kevin Wilton, Shannon Waring, Michael T. Chicoine, Adam Doering, Travis Wherry, E. John Kaufmann, Daniel E. Lichterfeld, Mathias Brass, Abraham L. Walker, Bruce D. TI Dysfunctional HIV-Specific CD8(+) T Cell Proliferation Is Associated with Increased Caspase-8 Activity and Mediated by Necroptosis SO IMMUNITY LA English DT Article ID GENE-EXPRESSION DATA; NF-KAPPA-B; HUMAN-IMMUNODEFICIENCY; PROGRAMMED NECROSIS; DISEASE PROGRESSION; ACTIVATION; INFECTION; DEATH; EXHAUSTION; APOPTOSIS AB Decreased HIV-specific CD8(+) T cell proliferation is a hallmark of chronic infection, but the mechanisms of decline are unclear. We analyzed gene expression profiles from antigen-stimulated HIV-specific CD8(+) T cells from patients with controlled and uncontrolled infection and identified caspase-8 as a correlate of dysfunctional CD8(+) T cell proliferation. Caspase-8 activity was upregulated in HIV-specific CD8(+) T cells from progressors and correlated positively with disease progression and programmed cell death-1 (PD-1) expression, but negatively with proliferation. In addition, progressor cells displayed a decreased ability to upregulate membrane-associated caspase-8 activity and increased necrotic cell death following antigenic stimulation, implicating the programmed cell death pathway necroptosis. In vitro necroptosis blockade rescued HIV-specific CD8(+) T cell proliferation in progressors, as did silencing of necroptosis mediator RIPK3. Thus, chronic stimulation leading to upregulated caspase-8 activity contributes to dysfunctional HIV-specific CD8(+) T cell proliferation through activation of necroptosis and increased cell death. C1 [Gaiha, Gaurav D.; McKim, Kevin J.; Woods, Matthew; Rohrbach, Janine; Chin, Christopher R.; Soghoian, Damien Z.; Cesa, Kevin; Wilton, Shannon; Waring, Michael T.; Chicoine, Adam; Kaufmann, Daniel E.; Lichterfeld, Mathias; Brass, Abraham L.; Walker, Bruce D.] Ragon Inst MGH, Cambridge, MA 02139 USA. [Pertel, Thomas] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Barteneva, Natasha] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Chin, Christopher R.; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst MaPS, Worcester, MA 01655 USA. [Liu, Dongfang] Baylor Coll Med, Texas Childrens Hosp, Ctr Human Immunobiol, Houston, TX 77030 USA. [Waring, Michael T.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Doering, Travis] Hofstra North Shore LIJ Sch Med, Hempstead, NY 11549 USA. [Wherry, E. John] Univ Penn, Perelman Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Kaufmann, Daniel E.] Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, Montreal, PQ H2X 0A9, Canada. [Lichterfeld, Mathias; Walker, Bruce D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Walker, BD (reprint author), Ragon Inst MGH, Cambridge, MA 02139 USA. EM bwalker@partners.org FU Howard Hughes Medical Institute; Ragon Institute; NIH [AI30914, AI105343, AI112521, AI082630, AI095608, HHSN266200500030C]; Bill and Melinda Gates Foundation; NIH-funded Center for AIDS Research grant [P30 AI060354]; NIH Co-Funding and Participating Institute and Center: NIAID; NIH Co-Funding and Participating Institute and Center: NCI; NIH Co-Funding and Participating Institute and Center: NICHD; NIH Co-Funding and Participating Institute and Center: NHLBI; NIH Co-Funding and Participating Institute and Center: NIDA; NIH Co-Funding and Participating Institute and Center: NIMH; NIH Co-Funding and Participating Institute and Center: NIA; NIH Co-Funding and Participating Institute and Center: FIC; NIH Co-Funding and Participating Institute and Center: OAR FX We are grateful to Judy Lieberman and Jennifer Sims for comments on the manuscript and to Deanna Nguyen for assistance with experiments. This study was supported by funds from the Howard Hughes Medical Institute, the Ragon Institute, the NIH (AI30914, AI105343, AI112521, AI082630, AI095608, HHSN266200500030C), the Bill and Melinda Gates Foundation, and an NIH-funded Center for AIDS Research grant (P30 AI060354), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. NR 61 TC 11 Z9 11 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD DEC 18 PY 2014 VL 41 IS 6 BP 1001 EP 1012 DI 10.1016/j.immuni.2014.12.011 PG 12 WC Immunology SC Immunology GA AX0PM UT WOS:000346654100017 PM 25526311 ER PT J AU Tschopp, P Sherratt, E Sanger, TJ Groner, AC Aspiras, AC Hu, JK Pourquie, O Gros, J Tabin, CJ AF Tschopp, Patrick Sherratt, Emma Sanger, Thomas J. Groner, Anna C. Aspiras, Ariel C. Hu, Jimmy K. Pourquie, Olivier Gros, Jerome Tabin, Clifford J. TI A relative shift in cloacal location repositions external genitalia in amniote evolution SO NATURE LA English DT Article ID GENE-EXPRESSION; MESENCHYMAL TRANSITION; VERTEBRATE EMBRYOS; HOMOLOGY; PACKAGE; LIMB; ONTOLOGY; PROGRAM; BIOLOGY; TISSUES AB The move of vertebrates to a terrestrial lifestyle required major adaptations in their locomotory apparatus and reproductive organs. While the fin-to-limb transition has received considerable attention(1,2), little is known about the developmental and evolutionary origins of external genitalia. Similarities in gene expression have been interpreted as a potential evolutionary link between the limb and genitals(3-6); however, no underlying developmental mechanism has been identified. We re-examined this question using micro-computed tomography, lineage tracing in three amniote clades, and RNA-sequencing-based transcriptional profiling. Here we show that the developmental origin of external genitalia has shifted through evolution, and in some taxa limbs and genitals share a common primordium. In squamates, the genitalia develop directly from the budding hindlimbs, or the remnants thereof, whereas in mice the genital tubercle originates from the ventral and tail bud mesenchyme. The recruitment of different cell populations for genital outgrowth follows a change in the relative position of the cloaca, the genitalia organizing centre. Ectopic grafting of the cloaca demonstrates the conserved ability of different mesenchymal cells to respond to these genitalia-inducing signals. Our results support a limb-like developmental origin of external genitalia as the ancestral condition. Moreover, they suggest that a change in the relative position of the cloacal signalling centre during evolution has led to an altered developmental route for external genitalia in mammals, while preserving parts of the ancestral limb molecular circuitry owing to a common evolutionary origin. C1 [Tschopp, Patrick; Aspiras, Ariel C.; Hu, Jimmy K.; Pourquie, Olivier; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Sherratt, Emma; Sanger, Thomas J.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Groner, Anna C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pourquie, Olivier] IGBMC, F-67400 Illkirch Graffenstaden, France. [Pourquie, Olivier] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gros, Jerome] Inst Pasteur, Dev & Stem Cell Biol Dept, F-75724 Paris 15, France. RP Tabin, CJ (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM jgros@pasteur.fr; tabin@genetics.med.harvard.edu RI Sherratt, Emma/A-9931-2011; OI Sherratt, Emma/0000-0003-2164-7877; Pourquie, Olivier/0000-0001-5189-1227; Gros, Jerome/0000-0002-2264-2851 FU National Science Foundation [ECS-0335765]; Swiss National Science Foundation; EMBO; Human Frontiers Science Program; National Institutes of Health [R37-HD032443] FX The authors thank D. Duboule, H. Kaessmann, A. Necsulea, B. Okaty, G. Rey and G. P. Wagner for discussions, M. A. de Bakker for the snake Tbx5 probe and A. M. Herrera and M. J. Cohn for discussing and sharing unpublished results. mu CT scans were performed at the Center for Nanoscale Systems, Harvard University (supported by National Science Foundation award ECS-0335765) and at the Museum of Comparative Zoology. Next-generation sequencing was performed at the HMS Biopolymers Facility and computational analyses were run on the Orchestra Cluster, HMS Research Computing. P.T. was supported by post-doctoral fellowships from the Swiss National Science Foundation, EMBO and the Human Frontiers Science Program. A.C.G. was supported by a post-doctoral fellowship from the Swiss National Science Foundation. This work was supported by National Institutes of Health grant R37-HD032443 to C.J.T. NR 48 TC 25 Z9 25 U1 10 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 18 PY 2014 VL 516 IS 7531 BP 391 EP + DI 10.1038/nature13819 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8BE UT WOS:000346484800046 PM 25383527 ER PT J AU Pellegrino, MW Nargund, AM Kirienko, NV Gillis, R Fiorese, CJ Haynes, CM AF Pellegrino, Mark W. Nargund, Amrita M. Kirienko, Natalia V. Gillis, Reba Fiorese, Christopher J. Haynes, Cole M. TI Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection SO NATURE LA English DT Article ID UNFOLDED PROTEIN RESPONSE; CAENORHABDITIS-ELEGANS; C. ELEGANS; TRANSLATIONAL INHIBITION; LIFE-SPAN; GENES; CELLS; DEGRADATION; ACTIVATION; PATHWAYS AB Metazoans identify and eliminate bacterial pathogens in microbe-rich environments such as the intestinal lumen; however, the mechanisms are unclear. Host cells could potentially use intracellular surveillance or stress response programs to detect pathogens that target monitored cellular activities and then initiate innate immune responses(1-3). Mitochondrial function is evaluated by monitoring mitochondrial protein import efficiency of the transcription factor ATFS-1, which mediates the mitochondrial unfolded protein response (UPRmt). During mitochondrial stress, mitochondrial import is impaired(4), allowing ATFS-1 to traffic to the nucleus where it mediates a transcriptional response to re-establish mitochondrial homeostasis(5). Here we examined the role of ATFS-1 in Caenorhabditis elegans during pathogen exposure, because during mitochondrial stress ATFS-1 induced not only mitochondrial protective genes but also innate immune genes that included a secreted lysozyme and anti-microbial peptides. Exposure to the pathogen Pseudomonas aeruginosa caused mitochondrial dysfunction and activation of the UPRmt. C. elegans lacking atfs-1 were susceptible to P. aeruginosa, whereas hyper-activation of ATFS-1 and the UPRmt improved clearance of P. aeruginosa from the intestine and prolonged C. elegans survival in a manner mainly independent of known innate immune pathways(6,7). We propose that ATFS-1 import efficiency and the UPRmt is a means to detect pathogens that target mitochondria and initiate a protective innate immune response. C1 [Pellegrino, Mark W.; Nargund, Amrita M.; Gillis, Reba; Haynes, Cole M.] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA. [Kirienko, Natalia V.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kirienko, Natalia V.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Fiorese, Christopher J.; Haynes, Cole M.] Weill Cornell Med Coll, BCMB Allied Program, New York, NY 10065 USA. RP Haynes, CM (reprint author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, 1275 York Ave, New York, NY 10065 USA. EM haynesc@mskcc.org FU Ellison Medical Foundation; Lucille Castori Center for Microbes, Inflammation and Cancer at MSKCC; National Institutes of Health [R01AG040061, F32AI100501, R01AI085581] FX We thank E. Troemel, M. Pilon, S. Mitani of the National Bioresource Project, and the Caenorhabditis Genetics Center for providing C. elegans strains. We thank D. Kim and J. Xavier for providing P. aeruginosa strains, and T. Langer and S. Troeder for mammalian reagents. This work was supported by the Ellison Medical Foundation, the Lucille Castori Center for Microbes, Inflammation and Cancer at MSKCC and the National Institutes of Health (R01AG040061) to C.M.H., (F32AI100501) to N.V.K. and (R01AI085581) to F. Ausubel. NR 36 TC 44 Z9 45 U1 5 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 18 PY 2014 VL 516 IS 7531 BP 414 EP + DI 10.1038/nature13818 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW8BE UT WOS:000346484800051 PM 25274306 ER PT J AU Kreuels, B Wichmann, D Emmerich, P Schmidt-Chanasit, J de Heer, G Kluge, S Sow, A Renne, T Gunther, S Lohse, AW Addo, MM Schmiedel, S AF Kreuels, Benno Wichmann, Dominic Emmerich, Petra Schmidt-Chanasit, Jonas de Heer, Geraldine Kluge, Stefan Sow, Abdourahmane Renne, Thomas Guenther, Stephan Lohse, Ansgar W. Addo, Marylyn M. Schmiedel, Stefan TI A Case of Severe Ebola Virus Infection Complicated by Gram-Negative Septicemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article AB Ebola virus disease (EVD) developed in a patient who contracted the disease in Sierra Leone and was airlifted to an isolation facility in Hamburg, Germany, for treatment. During the course of the illness, he had numerous complications, including septicemia, respiratory failure, and encephalopathy. Intensive supportive treatment consisting of high-volume fluid resuscitation (approximately 10 liters per day in the first 72 hours), broad-spectrum antibiotic therapy, and ventilatory support resulted in full recovery without the use of experimental therapies. Discharge was delayed owing to the detection of viral RNA in urine (day 30) and sweat (at the last assessment on day 40) by means of polymerase-chain-reaction (PCR) assay, but the last positive culture was identified in plasma on day 14 and in urine on day 26. This case shows the challenges in the management of EVD and suggests that even severe EVD can be treated effectively with routine intensive care. C1 [Kreuels, Benno; Lohse, Ansgar W.; Addo, Marylyn M.; Schmiedel, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Div Trop Med, D-20246 Hamburg, Germany. [Wichmann, Dominic; de Heer, Geraldine; Kluge, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Intens Care Med, D-20246 Hamburg, Germany. [Renne, Thomas] Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, D-20246 Hamburg, Germany. [Schmiedel, Stefan] Univ Med Ctr Hamburg Eppendorf, Infect Dis Unit Outpatient Care, D-20246 Hamburg, Germany. [Kreuels, Benno; Schmidt-Chanasit, Jonas; Guenther, Stephan; Lohse, Ansgar W.; Addo, Marylyn M.; Schmiedel, Stefan] German Ctr Infect Res, Hamburg, Germany. [Kreuels, Benno] Bernhard Nocht Inst Trop Med, Res Grp Infect Dis Epidemiol, D-20359 Hamburg, Germany. [Emmerich, Petra; Schmidt-Chanasit, Jonas; Guenther, Stephan] Bernhard Nocht Inst Trop Med, World Hlth Org Collaborating Ctr Arbovirus & Hemo, D-20359 Hamburg, Germany. [Sow, Abdourahmane] Inst Pasteur, Arboviruses & Hemorrhag Fever Viruses Unit, Dakar, Senegal. [Sow, Abdourahmane] Cheikh Anta Diop Univ, Publ Hlth & Dev Inst, Dakar, Senegal. [Sow, Abdourahmane] Bordeaux Univ, INSERM, U897, Bordeaux Publ Hlth Inst, Bordeaux, France. [Renne, Thomas] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Addo, Marylyn M.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Addo, MM (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Martinistr 52, D-20246 Hamburg, Germany. EM m.addo@uke.de; s.schmiedel@uke.de NR 8 TC 129 Z9 139 U1 4 U2 48 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 18 PY 2014 VL 371 IS 25 BP 2394 EP 2401 DI 10.1056/NEJMoa1411677 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AW7DX UT WOS:000346425800008 PM 25337633 ER PT J AU Rigotti, NA AF Rigotti, Nancy A. TI Cytisine - A Tobacco Treatment Hiding in Plain Sight SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SMOKING-CESSATION; METAANALYSIS; TRIAL C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 18 PY 2014 VL 371 IS 25 BP 2429 EP 2430 DI 10.1056/NEJMe1412313 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AW7DX UT WOS:000346425800014 PM 25517710 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Increasing obesity and comorbidity in patients undergoing primary total hip arthroplasty in the US: A 13-year study of time trends SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Total hip replacement; Time trends; Arthroplasty; Joint replacement; Diagnosis; Obesity; Comorbidity; Osteoarthritis ID TOTAL KNEE ARTHROPLASTY; TOTAL JOINT ARTHROPLASTY; MODIFYING ANTIRHEUMATIC DRUGS; RHEUMATOID-ARTHRITIS; UNITED-STATES; PAIN MEDICATIONS; DEMOGRAPHICS; REPLACEMENT; POPULATION; MORBIDITY AB Background: Few, if any data are available are available regarding the time-trends in characteristics of patients who have undergone primary THA. Our objective was to examine the time-trends in key demographic and clinical characteristics of patients undergoing primary total hip arthroplasty (THA). Methods: We used the data from the Mayo Clinic Total Joint Registry from 1993-2005 to examine the time-trends in demographics (age, body mass index (BMI)), medical (Deyo-Charlson index) and psychological comorbidity (anxiety, depression) and underlying diagnosis of patients undergoing primary THA. Chi-square test and analysis for variance were used. Multivariable-adjusted logistic regression (age, sex, comorbidity-adjusted) compared 1993-95 to other study periods. Odds ratio (OR) and 95% confidence interval (CI) are presented. Results: The primary THA cohort consisted of 6,168 patients with 52% women. In unadjusted analyses, compared to 1993-95, significantly more patients (by > 2-times for most) in 2002-05 had: BMI >= 40, 2.3% vs. 6.3%; depression, 4.1% vs. 9.8%; and anxiety, 3.4% vs. 5.7%; and significantly fewer had an underlying diagnosis of rheumatoid/inflammatory arthritis, 3.7% vs. 1.5% (p <= 0.01 for all). In multivariable-adjusted models, compared to 1993-95, significantly more patients in 2003-05 had (all p-values <= 0.01): BMI >= 40, OR, 2.79 (95% CI: 1.85, 4.22); Deyo-Charlson Index >= 3, 1.32 (1.07, 1.63); depression, 2.25 (1.66, 3.05); and anxiety, 1.71 (1.19, 2.15). Respectively, fewer patients had a diagnosis of RA/inflammatory arthritis: 0.28 (0.17, 0.46; p < 0.01). Over the 13-year study period, Deyo-Charlson index increased by 22% (0.9 to 1.1) and the mean age decreased by 0.7 years (65.0 to 64.3) (p < 0.01 for both). Conclusions: Obesity, medical and psychological comorbidity increased and the underlying diagnosis of RA/inflammatory arthritis decreased rapidly in primary THA patients over 13-years. Our cohort characteristics are similar to previously described characteristics of national U. S. cohort, suggesting that these trends may be national rather than local trends. This is important information for policy makers to take into account for resource allocation. Studies of THA outcomes and utilization should take these rapidly changing patient characteristics into account. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.com FU Mayo Clinic Orthopedic Surgery research funds; Birmingham VA Medical Center, Alabama, USA; Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631] FX This material is the result of work supported Mayo Clinic Orthopedic Surgery research funds and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891, National Institute of Aging (NIA) U01 AG018947, and National Cancer Institute (NCI) U10 CA149950, and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute (PCORI). NR 46 TC 6 Z9 6 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD DEC 17 PY 2014 VL 15 AR 441 DI 10.1186/1471-2474-15-441 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AZ8JI UT WOS:000348461200001 PM 25519434 ER PT J AU Jin, ZC Wu, C Zhou, XH He, J AF Jin, Zhi-Chao Wu, Cheng Zhou, Xiao-Hua He, Jia TI A modified regression method to test publication bias in meta-analyses with binary outcomes SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article DE Meta-analysis; Observational studies; Publication bias; Smoothed variance; Weighted regression ID STATISTICAL TESTS; CLINICAL-RESEARCH; CONTROLLED-TRIALS AB Background: The tendency towards publication bias is greater for observational studies than for randomized clinical trials. Several statistical methods have been developed to test the publication bias. However, almost all existing methods exhibit rather low power or have inappropriate type I error rates. Methods: We propose a modified regression method, which used a smoothed variance to estimate the precision of a study, to test for publication bias in meta-analyses of observational studies. A comprehensive simulation study is carried out, and a real-world example is considered. Results: The simulation results indicate that the performance of tests varies with the number of included studies, level of heterogeneity, event rates, and sample size ratio between two groups. Neither the existing tests nor the newly developed method is particularly powerful in all simulation scenarios. However, our proposed method has a more robust performance across different settings. In the presence of heterogeneity, the arcsine-Thompson test is a suitable alternative, and Peters' test can be considered as a complementary method when mild or no heterogeneity is present. Conclusions: Several factors should be taken into consideration when employing asymmetry tests for publication bias. Based on our simulation results, we provide a concise table to show the appropriate use of regression methods to test for publication bias based on our simulation results. C1 [Jin, Zhi-Chao; Wu, Cheng; He, Jia] Second Mil Med Univ, Dept Hlth Stat, Shanghai 200433, Peoples R China. [Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, Biostat Unit, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Zhou, XH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Biostat Unit, HSR&D Ctr Excellence, Seattle, WA 98101 USA. EM azhou@u.washington.edu; hejia63@yahoo.com FU Department of Veterans Affairs, Veterans Health Administration, Health Service Research and Development [RCS 05-196]; National Natural Science Foundation, China [81001287]; key discipline construction of evidence-based public health in Shanghai [12GWZX0602]; Ministry of Science and Technology of China [2009ZX09312-025, 2008ZX09312-007, 2008ZX10002-018]; China Scholarship Council FX This work was supported by Department of Veterans Affairs, Veterans Health Administration, Health Service Research and Development [Research Career Scientist Award RCS 05-196]; National Natural Science Foundation [grant number 81001287], China; the key discipline construction of evidence-based public health in Shanghai [grant number 12GWZX0602]; The Ministry of Science and Technology of China [grant number 2009ZX09312-025, 2008ZX09312-007, 2008ZX10002-018]. We thank China Scholarship Council for sponsoring the first author's visiting in University of Washington. NR 33 TC 2 Z9 2 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD DEC 17 PY 2014 VL 14 AR 132 DI 10.1186/1471-2288-14-132 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ1IM UT WOS:000347993100001 PM 25516509 ER PT J AU Takahashi, Y Maki, T Liang, AC Itoh, K Lok, J Osumi, N Arai, K AF Takahashi, Yoko Maki, Takakuni Liang, Anna C. Itoh, Kanako Lok, Josephine Osumi, Nariko Arai, Ken TI p38 MAP kinase mediates transforming-growth factor-beta 1-induced upregulation of matrix metalloproteinase-9 but not-2 in human brain pericytes SO BRAIN RESEARCH LA English DT Article DE Pericyte; MMP-9; p38 MAP kinase; Neurovascular unit ID GROWTH-FACTOR-BETA-1 INDUCES MATRIX-METALLOPROTEINASE-9; NERVOUS-SYSTEM DEVELOPMENT; SMOOTH-MUSCLE-CELLS; KAPPA-B PATHWAYS; TGF-BETA; MATRIX METALLOPROTEINASES; NEUROVASCULAR UNIT; ISCHEMIC-STROKE; IN-VITRO; EXPRESSION AB Pericytes are vascular mural cells embedded within the basal lamina of blood microvessels. Within the neurovascular unit, pericytes play important roles in regulating neurovascular homeostasis by secreting soluble factors, such as matrix metalloproteinases (MMPs). However, little is known about the regulatory signaling pathways in brain pericytes. Here we show that transforming growth factor-beta 1 (TGF-beta 1) induces MMP-9 upregulation in pericytes via p38 mitogen-activated protein (MAP) kinase signaling. Cultured human brain vascular pericytes were used in this study. When the brain pericytes were treated with purified human TGF-beta 1 (0.1-10 ng/mL for 24 h), the levels of MMP-2 and MMP-9 in culture media were significantly increased in a concentration dependent manner as measured by gelatin zymography. WST assay confirmed that TGF-beta 1 did not affect cell survival of the brain pericytes. A TGF-beta-receptor inhibitor SB431542 (0.5-5 mu M) decreased the TGF-beta 1-induced upregulation of MMP-2 and MMP-9. To assess the underlying intracellular mechanisms, we focused on p38 MAP kinase signaling, which is one of the major downstream kinases for TGF-beta 1. A well-validated p38 MAP kinase inhibitor SB203580 (0.5-5 mu M) cancelled the effect of TGF-beta 1 in upregulation of MMP-9 but not MMP-2. Western blotting confirmed that TGF-beta 1 treatment increased the level of p38 MAP kinase phosphorylation in pericytes, and again, the TGF-beta-receptor inhibitor SB431542 (0.5-5 mu M) blocked the TGF-beta 1-induced phosphorylation of p38 MAP kinase. Both TGF-beta 1 and MMP-9 are major neurovascular mediators, and therefore, our current finding may suggest a novel mechanism for how pericytes regulate neurovascular homeostasis. (C) 2014 Elsevier B.V. All rights reserved. C1 [Takahashi, Yoko; Osumi, Nariko] Tohoku Univ, Sch Med, United Ctr Adv Res & Translat Med, Dept Dev Neurosci, Sendai, Miyagi 980, Japan. [Takahashi, Yoko; Maki, Takakuni; Liang, Anna C.; Itoh, Kanako; Lok, Josephine; Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Takahashi, Yoko; Maki, Takakuni; Liang, Anna C.; Itoh, Kanako; Lok, Josephine; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Takahashi, Yoko; Maki, Takakuni; Liang, Anna C.; Itoh, Kanako; Lok, Josephine; Arai, Ken] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU National Institutes of Health [R01 NS065089, P01 NS055104]; Research Abroad from the Uehara Memorial Foundation FX Supported in part by National Institutes of Health (Grant nos. R01 NS065089, P01 NS055104) and Research Abroad from the Uehara Memorial Foundation. NR 45 TC 8 Z9 8 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 17 PY 2014 VL 1593 BP 1 EP 8 DI 10.1016/j.brainres.2014.10.029 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AX5FJ UT WOS:000346951900001 PM 25451097 ER PT J AU Yip, S McCall, K Aristophanous, M Chen, AB Aerts, HJWL Berbeco, R AF Yip, Stephen McCall, Keisha Aristophanous, Michalis Chen, Aileen B. Aerts, Hugo J. W. L. Berbeco, Ross TI Comparison of Texture Features Derived from Static and Respiratory-Gated PET Images in Non-Small Cell Lung Cancer SO PLOS ONE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; DUAL TIME-POINT; STANDARDIZED UPTAKE VALUES; F-18-FDG PET; FDG-PET; UPTAKE HETEROGENEITY; PULMONARY NODULES; PROGNOSTIC VALUE; CT; CHEMORADIOTHERAPY AB Background: PET-based texture features have been used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by comparing static (3D) and respiratory-gated (4D) PET imaging. Methods: Twenty-six patients (34 lesions) received 3D and 4D [F-18] FDG-PET scans before the chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Texture features, including Maximal correlation coefficient (MCC), Long run low gray (LRLG), Coarseness, Contrast, and Busyness, were computed within the physician-defined tumor volume. The relative difference (delta(3D-4D)) in each texture between the 3D-and 4D-PET imaging was calculated. Coefficient of variation (CV) was used to determine the variability in the textures between all 4D-PET phases. Correlations between tumor volume, motion amplitude, and delta(3D-4D) were also assessed. Results: 4D-PET increased LRLG (=1%-2%, p<0.02), Busyness (=7%-19%, p<0.01), and decreased MCC (=1%-2%, p<7.5x10(-3)), Coarseness (=5%-10%, p<0.05) and Contrast (=4%-6%, p>0.08) compared to 3D-PET. Nearly negligible variability was found between the 4D phase bins with CV<5% for MCC, LRLG, and Coarseness. For Contrast and Busyness, moderate variability was found with CV=9% and 10%, respectively. No strong correlation was found between the tumor volume and delta(3D-4D) for the texture features. Motion amplitude had moderate impact on delta for MCC and Busyness and no impact for LRLG, Coarseness, and Contrast. Conclusions: Significant differences were found in MCC, LRLG, Coarseness, and Busyness between 3D and 4D PET imaging. The variability between phase bins for MCC, LRLG, and Coarseness was negligible, suggesting that similar quantification can be obtained from all phases. Texture features, blurred out by respiratory motion during 3D-PET acquisition, can be better resolved by 4D-PET imaging. 4D-PET textures may have better prognostic value as they are less susceptible to tumor motion. C1 [Yip, Stephen; Chen, Aileen B.; Aerts, Hugo J. W. L.; Berbeco, Ross] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yip, Stephen; McCall, Keisha; Chen, Aileen B.; Aerts, Hugo J. W. L.; Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA USA. [McCall, Keisha] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Aristophanous, Michalis] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Div Radiat Oncol, Houston, TX 77030 USA. [Aerts, Hugo J. W. L.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Yip, S (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM syip@lroc.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 NR 51 TC 18 Z9 18 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 17 PY 2014 VL 9 IS 12 AR e115510 DI 10.1371/journal.pone.0115510 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX9IA UT WOS:000347215600070 PM 25517987 ER PT J AU Schwab, JH Lozano-Calderon, SA Mankin, HJ Raskin, KA Hornicek, FJ AF Schwab, Joseph H. Lozano-Calderon, Santiago A. Mankin, Henry J. Raskin, Kevin A. Hornicek, Francis J. TI What's New in Primary Bone Tumors SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID SOFT-TISSUE SARCOMAS; CHONDROSARCOMA CELLS; AFFECT SURVIVAL; EWING SARCOMA; GLUCOSE-METABOLISM; PROGNOSTIC-FACTORS; EXPRESSION; OSTEOSARCOMA; MANAGEMENT; INHIBITION C1 [Schwab, Joseph H.; Lozano-Calderon, Santiago A.; Mankin, Henry J.; Raskin, Kevin A.; Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Schwab, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM JHSCHWAB@mgh.harvard.edu NR 63 TC 2 Z9 2 U1 0 U2 9 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC 17 PY 2014 VL 96A IS 24 BP 2099 EP 2104 DI 10.2106/JBJS.N.01014 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AW7WI UT WOS:000346471900015 PM 25520345 ER PT J AU Hu, WF Pomp, O Ben-Omran, T Kodani, A Henke, K Mochida, GH Yu, TW Woodworth, MB Bonnard, C Raj, GS Tan, TT Hamamy, H Masri, A Shboul, M Al Saffar, M Partlow, JN Al-Dosari, M Alazami, A Alowain, M Alkuraya, FS Reiter, JF Harris, MP Reversade, B Walsh, CA AF Hu, Wen F. Pomp, Oz Ben-Omran, Tawfeg Kodani, Andrew Henke, Katrin Mochida, Ganeshwaran H. Yu, Timothy W. Woodworth, Mollie B. Bonnard, Carine Raj, Grace Selva Tan, Thong Teck Hamamy, Hanan Masri, Amira Shboul, Mohammad Al Saffar, Muna Partlow, Jennifer N. Al-Dosari, Mohammed Alazami, Anas Alowain, Mohammed Alkuraya, Fowzan S. Reiter, Jeremy F. Harris, Matthew P. Reversade, Bruno Walsh, Christopher A. TI Katanin p80 Regulates Human Cortical Development by Limiting Centriole and Cilia Number SO NEURON LA English DT Article ID MICROTUBULE-SEVERING PROTEIN; DE-NOVO FORMATION; SONIC HEDGEHOG; CENTROSOME DUPLICATION; NEURAL PROGENITORS; NERVOUS-SYSTEM; SPINDLE LENGTH; CELL-DIVISION; MUTATIONS; CDK5RAP2 AB Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development. C1 [Hu, Wen F.; Mochida, Ganeshwaran H.; Yu, Timothy W.; Woodworth, Mollie B.; Al Saffar, Muna; Partlow, Jennifer N.; Walsh, Christopher A.] Boston Childrens Hosp, Dept Med, Div Genet & Genom, Boston, MA 02115 USA. [Hu, Wen F.; Mochida, Ganeshwaran H.; Woodworth, Mollie B.; Al Saffar, Muna; Partlow, Jennifer N.; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Hu, Wen F.; Woodworth, Mollie B.; Partlow, Jennifer N.; Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Henke, Katrin; Harris, Matthew P.] Boston Childrens Hosp, Dept Orthoped Res, Boston, MA 02115 USA. [Hu, Wen F.; Walsh, Christopher A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Hu, Wen F.; Walsh, Christopher A.] Harvard Univ, Sch Med, Harvard MD PhD MSTP Program, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.; Yu, Timothy W.; Woodworth, Mollie B.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Henke, Katrin; Harris, Matthew P.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. [Yu, Timothy W.] Broad Inst MIT & Harvard Univ, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Ben-Omran, Tawfeg] Hamad Med Corp, Dept Pediat, Clin & Metab Genet Div, Doha 3050, Qatar. [Al Saffar, Muna] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Pediat, Al Ain, U Arab Emirates. [Alazami, Anas; Alkuraya, Fowzan S.] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Alowain, Mohammed] King Faisal Specialist Hosp & Res Ctr, Dept Med Genet, Riyadh 11211, Saudi Arabia. [Alowain, Mohammed; Alkuraya, Fowzan S.] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh 11533, Saudi Arabia. [Al-Dosari, Mohammed] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh 11451, Saudi Arabia. [Kodani, Andrew; Reiter, Jeremy F.] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Biochem & Biophys, San Francisco, CA 94158 USA. [Pomp, Oz; Bonnard, Carine; Raj, Grace Selva; Tan, Thong Teck; Shboul, Mohammad; Reversade, Bruno] ASTAR, Human Genet & Embryol Lab, Med Biol Inst, Singapore 138648, Singapore. [Reversade, Bruno] ASTAR, Inst Mol & Cellular Biol, Singapore 138648, Singapore. [Hamamy, Hanan] Univ Geneva, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Reversade, Bruno] Natl Univ Singapore, Dept Paediat, Singapore 119260, Singapore. [Masri, Amira] Univ Jordan, Fac Med, Dept Paediat, Amman 11942, Jordan. RP Harris, MP (reprint author), Boston Childrens Hosp, Dept Orthoped Res, Boston, MA 02115 USA. EM harris@genetics.med.harvard.edu; bruno@reversade.com; christopher.walsh@childrens.harvard.edu RI ASTAR, IMCB/E-2320-2012; OI Woodworth, Mollie/0000-0003-2130-2289; Yu, Timothy/0000-0003-2988-7701 FU NIH NINDS [F31NS083111, R01NS035129]; NIH NIGMS [T32GM007753, R01GM095941]; NIH NHLBI [T32HL007731]; Manton Center for Orphan Disease Research; F. Hoffman-La Roche Ltd.; Clinical Investigator Training Program at Harvard-MIT Health Sciences and Technology; BIDMC; Pfizer, Inc.; Merck Company, Inc; Nancy Lurie Marks Junior Faculty MeRIT Fellowship; Leonard and Isabelle Goldenson Research Fellowship; KACST [09-MED941-20]; NIH NIAMS [R01AR054396]; Burroughs Wellcome Fund; Packard Foundation; Sandler Family Supporting Foundation; Strategic Positioning Fund for Genetic Orphan Diseases; A*STAR Investigatorship from the Agency for Science, Technology and Research in Singapore; A*STAR; EMBO; NIH NIDCR [1U01DE024434-01]; BCH Orthopedic Surgical Foundation; NIH NIMH [RC2MH089952]; Qatar National Research Fund National Priorities Research Program FX We thank the individuals and their families for their participation. We thank Boston Children's Hospital (BCH) Transgenic Core Laboratory, Dana-Farber/Harvard Cancer Center Rodent Histopathology Core, Dana-Farber Cancer Institute Neoplasia Flow Cytometry Core, Beth Israel Deaconess Medical Center (BIDMC) Histology Core Laboratory, Harvard Medical School Electron Microscopy Facility, and Genome Institute of Singapore for use of facilities. We thank Tamara Caspary, Erich Nigg, Suzie Scales, and James Sillibourne for kind gifts of reagents. This research was supported by NIH NINDS F31NS083111 and NIGMS T32GM007753 (W.F.H.); NIH NHLBI T32HL007731 (A.K.); Manton Center for Orphan Disease Research and F. Hoffman-La Roche Ltd. (G.H.M.); Clinical Investigator Training Program at Harvard-MIT Health Sciences and Technology and BIDMC in collaboration with Pfizer, Inc. and Merck & Company, Inc, and the Nancy Lurie Marks Junior Faculty MeRIT Fellowship (T.W.Y.); Leonard and Isabelle Goldenson Research Fellowship (M.B.W.); KACST grant 09-MED941-20 (F.S.A.); NIH NIAMS R01AR054396, NIGMS R01GM095941, Burroughs Wellcome Fund, Packard Foundation, and Sandler Family Supporting Foundation (J.F.R.); Strategic Positioning Fund for Genetic Orphan Diseases, A*STAR Investigatorship from the Agency for Science, Technology and Research in Singapore, Branco Weiss Foundation fellow, and A*STAR and EMBO Young Investigator (B.R.); NIH NIDCR 1U01DE024434-01 and BCH Orthopedic Surgical Foundation (K.H. and M.P.H.); and NIH NINDS R01NS035129 and NIMH RC2MH089952, the Qatar National Research Fund National Priorities Research Program, and the Manton Center for Orphan Disease Research (C.A.W.). C.A.W. is an Investigator of the Howard Hughes Medical Institute. NR 78 TC 15 Z9 17 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD DEC 17 PY 2014 VL 84 IS 6 BP 1240 EP 1257 DI 10.1016/j.neuron.2014.12.017 PG 18 WC Neurosciences SC Neurosciences & Neurology GA AW9JY UT WOS:000346574500016 PM 25521379 ER PT J AU Abramson, JS Chung, RT AF Abramson, Jeremy S. Chung, Raymond T. TI Optimal Antiviral Prophylaxis Against Hepatitis B Reactivation in Patients Receiving Rituximab-Based Chemotherapy for Lymphoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID VIRUS HBV REACTIVATION; CELL LYMPHOMA; CYTOTOXIC CHEMOTHERAPY; CANCER-PATIENTS; LAMIVUDINE; ENTECAVIR; THERAPY; RISK; METAANALYSIS; INFECTION C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. [Abramson, Jeremy S.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Ctr Liver, Div Gastroenterol, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, 55 Fruit St, Boston, MA 02114 USA. EM jabramson@mgh.harvard.edu NR 22 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 17 PY 2014 VL 312 IS 23 BP 2505 EP 2507 DI 10.1001/jama.2014.16095 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YN UT WOS:000346346900012 PM 25514300 ER PT J AU Bekelman, JE Sylwestrzak, G Barron, J Liu, JA Epstein, AJ Freedman, G Malin, J Emanuel, EJ AF Bekelman, Justin E. Sylwestrzak, Gosia Barron, John Liu, Jinan Epstein, Andrew J. Freedman, Gary Malin, Jennifer Emanuel, Ezekiel J. TI Uptake and Costs of Hypofractionated vs Conventional Whole Breast Irradiation After Breast Conserving Surgery in the United States, 2008-2013 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED-TRIAL; RADIOTHERAPY HYPOFRACTIONATION; UK STANDARDIZATION; RADIATION-THERAPY; CANCER; FRACTIONATION; WOMEN; MASTECTOMY AB IMPORTANCE Based on randomized evidence, expert guidelines in 2011 endorsed shorter, hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients. OBJECTIVES To examine the uptake and costs of hypofractionated WBI among commercially insured patients in the United States. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational cohort study, using administrative claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013, we classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n = 8924) included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement. EXPOSURES Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks of treatment). MAIN OUTCOMES AND MEASURES Use of hypofractionated and conventional WBI, total and radiotherapy-related health care expenditures, and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment, age, comorbid disease, prior chemotherapy, axillary lymph node involvement, intensity-modulated radiotherapy, practice setting, and other contextual variables. RESULTS Hypofractionated WBI increased from 10.6% (95% Cl, 8.8%-12.5%) in 2008 to 34.5% (95% Cl, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% Cl, 6.0%-10.2%) in 2008 to 21.2% (95% Cl, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were $28 747 for hypofractionated and $31 641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; 95% Cl, $1610-$4234; P < .001) and $64 273 for hypofractionated and $72 860 for conventional WBI in the hypofractionation-permitted cohort (difference, $8587; 95% Cl, $5316-$12 017; P < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBlin either cohort. CONCLUSIONS AND RELEVANCE Hypofractionated WBI after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However, only 34.5% of patients with hypofractionation-endorsed and 21.2% with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013. C1 [Bekelman, Justin E.; Freedman, Gary] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Sylwestrzak, Gosia; Barron, John; Liu, Jinan] HealthCore, Wilmington, DE USA. [Epstein, Andrew J.] Univ Penn, Div Gen Internal Med, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Malin, Jennifer] WellPoint Inc, Indianapolis, IN USA. RP Bekelman, JE (reprint author), Univ Penn, Perelman Ctr Adv Med, Dept Radiat Oncol, Perelman Sch Med, 3400 Civ Ctr Blvd,4 West, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU National Cancer Institute [K07-CA163616]; WellPoint FX Dr Bekelman received support from grant K07-CA163616 from the National Cancer Institute. WellPoint provided funds to support research at HealthCore, a wholly-owned WellPoint subsidiary. NR 27 TC 39 Z9 39 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 17 PY 2014 VL 312 IS 23 BP 2542 EP 2550 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YN UT WOS:000346346900017 PM 25494006 ER PT J AU Chen, ZX Yang, W Liu, QZ Yang, JY Li, J Yang, MQ AF Chen, Zhongxue Yang, William Liu, Qingzhong Yang, Jack Y. Li, Jing Yang, Mary Qu TI A new statistical approach to combining p-values using gamma distribution and its application to genome-wide association study SO BMC BIOINFORMATICS LA English DT Article ID DIFFERENTIALLY METHYLATED LOCI; WEIGHTED Z-TEST; INDEPENDENT TESTS; MULTIPLE DISEASES; PROBABILITIES; COMBINATION AB Background: Combining information from different studies is an important and useful practice in bioinformatics, including genome-wide association study, rare variant data analysis and other set-based analyses. Many statistical methods have been proposed to combine p-values from independent studies. However, it is known that there is no uniformly most powerful test under all conditions; therefore, finding a powerful test in specific situation is important and desirable. Results: In this paper, we propose a new statistical approach to combining p-values based on gamma distribution, which uses the inverse of the p-value as the shape parameter in the gamma distribution. Conclusions: Simulation study and real data application demonstrate that the proposed method has good performance under some situations. C1 [Chen, Zhongxue; Li, Jing] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Yang, William] Univ Arkansas, Dept Comp Sci, George W Donaghey Coll Engn & Informat Technol, Little Rock, AR 72204 USA. [Liu, Qingzhong] Sam Houston State Univ, Dept Comp Sci, Huntsville, TX 77341 USA. [Yang, Jack Y.] Indiana Univ Sch Med, Ctr Compuat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Div Biostat & Biomath, Boston, MA 02114 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Mary Qu] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Informat Sci, MidSouth Bioinformat Ctr, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas, Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas Med Sci, Little Rock, AR 72204 USA. RP Chen, ZX (reprint author), Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 1025 E 7th St,PH C104, Bloomington, IN 47405 USA. EM zc3@indiana.edu FU Indiana University Institutional Research Awards; National Institutes of Health (NIH); Indiana University Bloomington School of Public Health; NIH/NIGMS [5P20GM10342913]; ASTA [15-B-23] FX The research was supported by Indiana University Institutional Research Awards and National Institutes of Health (NIH). ZC would like to thank the institutional faculty research grant awards from the Indiana University Bloomington School of Public Health. MQY would like to thank the support from NIH/NIGMS 5P20GM10342913 and ASTA Award # 15-B-23. NR 29 TC 3 Z9 3 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 16 PY 2014 VL 15 SU 17 AR S3 DI 10.1186/1471-2105-15-S17-S3 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4AS UT WOS:000353973500004 PM 25559433 ER PT J AU Liu, C Lu, LL Kong, Q Li, Y Wu, HH Yang, W Xu, SD Yang, XY Song, XL Yang, JY Yang, MQ Deng, YP AF Liu, Chang Lu, Lili Kong, Quan Li, Yan Wu, Haihua Yang, William Xu, Shandan Yang, Xinyu Song, Xiaolei Yang, Jack Y. Yang, Mary Qu Deng, Youping TI Developing discriminate model and comparative analysis of differentially expressed genes and pathways for bloodstream samples of diabetes mellitus type 2 SO BMC BIOINFORMATICS LA English DT Article ID GENOME-WIDE ASSOCIATION; IMPAIRED FASTING GLUCOSE; PREVALENCE; PROFILES; ETIOLOGY; INSIGHTS; RISK AB Background: Diabetes mellitus of type 2 (T2D), also known as noninsulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes, is a common disease. It is estimated that more than 300 million people worldwide suffer from T2D. In this study, we investigated the T2D, pre-diabetic and healthy human (no diabetes) bloodstream samples using genomic, genealogical, and phonemic information. We identified differentially expressed genes and pathways. The study has provided deeper insights into the development of T2D, and provided useful information for further effective prevention and treatment of the disease. Results: A total of 142 bloodstream samples were collected, including 47 healthy humans, 22 pre-diabetic and 73 T2D patients. Whole genome scale gene expression profiles were obtained using the Agilent Oligo chips that contain over 20,000 human genes. We identified 79 significantly differentially expressed genes that have fold change >= 2. We mapped those genes and pinpointed locations of those genes on human chromosomes. Amongst them, 3 genes were not mapped well on the human genome, but the rest of 76 differentially expressed genes were well mapped on the human genome. We found that most abundant differentially expressed genes are on chromosome one, which contains 9 of those genes, followed by chromosome two that contains 7 of the 76 differentially expressed genes. We performed gene ontology (GO) functional analysis of those 79 differentially expressed genes and found that genes involve in the regulation of cell proliferation were among most common pathways related to T2D. The expression of the 79 genes was combined with clinical information that includes age, sex, and race to construct an optimal discriminant model. The overall performance of the model reached 95.1% accuracy, with 91.5% accuracy on identifying healthy humans, 100% accuracy on pre-diabetic patients and 95.9% accuract on T2D patients. The higher performance on identifying pre-diabetic patients was resulted from more significant changes of gene expressions among this particular group of humans, which implicated that patients were having profound genetic changes towards disease development. Conclusion: Differentially expressed genes were distributed across chromosomes, and are more abundant on chromosomes 1 and 2 than the rest of the human genome. We found that regulation of cell proliferation actually plays an important role in the T2D disease development. The predictive model developed in this study has utilized the 79 significant genes in combination with age, sex, and racial information to distinguish pre-diabetic, T2D, and healthy humans. The study not only has provided deeper understanding of the disease molecular mechanisms but also useful information for pathway analysis and effective drug target identification. C1 [Liu, Chang; Lu, Lili; Kong, Quan; Xu, Shandan; Song, Xiaolei; Deng, Youping] Wuhan Univ Sci & Technol, Wuhan, Peoples R China. [Li, Yan; Deng, Youping] Rush Univ, Ctr Canc, Chicago, IL 60612 USA. [Li, Yan; Deng, Youping] Rush Univ, Dept Internal Med, Med Ctr, Chicago, IL 60612 USA. [Li, Yan; Deng, Youping] Rush Univ, Dept Biochem, Med Ctr, Chicago, IL 60612 USA. [Wu, Haihua] Guangxi Armed Police Gen Hosp, Nanning, Guangxi Autonom, Peoples R China. [Yang, William] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Comp Sci, Little Rock, AR 72204 USA. [Yang, Xinyu] Natl 48610 Hosp Armed Police Force, Panjin, Liaoning, Peoples R China. [Yang, Jack Y.] Massachusetts Gen Hosp, Div Biostat & Biomath, Boston, MA 02114 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Jack Y.] Indiana Univ Purdue Univ, Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Yang, Mary Qu] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Informat Sci, MidSouth Bioinformat Ctr, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas, Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Lu, LL (reprint author), Wuhan Univ Sci & Technol, Wuhan, Peoples R China. EM lulili@wust.edu.cn; youping_deng@rush.edu FU Natural Science Foundation Hubei Province of China [2011CDB236, 2012FFB04903]; Open Research Fund Program of the State Key Laboratory of Virology of China [2012002]; United States National Institutes of Health (NIH); NIH [5P20GM10342913, R21CA164764]; ASTA [15-B-23] FX The research and publication of the research were supported by the Natural Science Foundation Hubei Province of China (2011CDB236 and 2012FFB04903), Open Research Fund Program of the State Key Laboratory of Virology of China (2012002) and United States National Institutes of Health (NIH). MQY was supported by NIH 5P20GM10342913 and ASTA Award #15-B-23, and YD was supported by NIH R21CA164764. NR 22 TC 1 Z9 1 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 16 PY 2014 VL 15 SU 17 AR S5 DI 10.1186/1471-2105-15-S17-S5 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4AS UT WOS:000353973500006 PM 25559614 ER PT J AU Yang, JY Dunker, AK Liu, JS Qin, X Arabnia, HR Yang, W Niemierko, A Chen, ZX Luo, ZJ Wang, LJ Liu, YL Xu, D Deng, YP Tong, WD Yang, MQ AF Yang, Jack Y. Dunker, A. Keith Liu, Jun S. Qin, Xiang Arabnia, Hamid R. Yang, William Niemierko, Andrzej Chen, Zhongxue Luo, Zuojie Wang, Liangjiang Liu, Yunlong Xu, Dong Deng, Youping Tong, Weida Yang, Mary Qu TI Advances in translational bioinformatics facilitate revealing the landscape of complex disease mechanisms SO BMC BIOINFORMATICS LA English DT Editorial Material AB Advances of high-throughput technologies have rapidly produced more and more data from DNAs and RNAs to proteins, especially large volumes of genome-scale data. However, connection of the genomic information to cellular functions and biological behaviours relies on the development of effective approaches at higher systems level. In particular, advances in RNA-Seq technology has helped the studies of transcriptome, RNA expressed from the genome, while systems biology on the other hand provides more comprehensive pictures, from which genes and proteins actively interact to lead to cellular behaviours and physiological phenotypes. As biological interactions mediate many biological processes that are essential for cellular function or disease development, it is important to systematically identify genomic information including genetic mutations from GWAS (genome-wide association study), differentially expressed genes, bidirectional promoters, intrinsic disordered proteins (IDP) and protein interactions to gain deep insights into the underlying mechanisms of gene regulations and networks. Furthermore, bidirectional promoters can co-regulate many biological pathways, where the roles of bidirectional promoters can be studied systematically for identifying co-regulating genes at interactive network level. Combining information from different but related studies can ultimately help revealing the landscape of molecular mechanisms underlying complex diseases such as cancer. C1 [Yang, Jack Y.] Univ Arkansas, George W Dougherty Coll Engn & Informat Technol, Joint Bioinformat PhD Program, Little Rock, AR 72204 USA. [Yang, Jack Y.] Univ Arkansas Med Sci, Little Rock, AR 72204 USA. [Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat & Biomath, Boston, MA 02114 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Dunker, A. Keith] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Qin, Xiang] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Qin, Xiang] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. [Yang, William] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Comp Sci, Little Rock, AR 72204 USA. [Chen, Zhongxue] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Luo, Zuojie] Guangxi Med Univ, Affiliated Hosp 1, Dept Endocrinol, Nanning 530021, Guangxi, Peoples R China. [Wang, Liangjiang] Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. [Liu, Yunlong; Deng, Youping] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA. [Xu, Dong] Rush Univ, Ctr Canc, Chicago, IL 60612 USA. [Xu, Dong] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Xu, Dong] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Tong, Weida] US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tong, Weida] US FDA, Div Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yang, Mary Qu] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, MidSouth Bioinformat Ctr, Dept Informat Sci, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas, Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas Med Sci, Little Rock, AR 72204 USA. RP Arabnia, HR (reprint author), Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. EM hra@uga.edu; youping_deng@rush.edu FU PHS HHS [NIH/NIGMS 5P20GM10342913, NIH/NHGRI 5U54HG003273-11] NR 6 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 16 PY 2014 VL 15 SU 17 AR I1 DI 10.1186/1471-2105-15-S17-I1 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4AS UT WOS:000353973500001 PM 25559210 ER PT J AU Yang, W Yoshigoe, K Qin, X Liu, JS Yang, JY Niemierko, A Deng, YP Liu, YL Dunker, AK Chen, ZX Wang, LJ Xu, D Arabnia, HR Tong, WD Yang, MQ AF Yang, William Yoshigoe, Kenji Qin, Xiang Liu, Jun S. Yang, Jack Y. Niemierko, Andrzej Deng, Youping Liu, Yunlong Dunker, A. Keith Chen, Zhongxue Wang, Liangjiang Xu, Dong Arabnia, Hamid R. Tong, Weida Yang, Mary Qu TI Identification of genes and pathways involved in kidney renal clear cell carcinoma SO BMC BIOINFORMATICS LA English DT Article ID HISTONE DEMETHYLASE RBP2; CANCER; NEPHRECTOMY; METASTASIS; ACTIVATION; INFECTION; DISEASE AB Background: Kidney Renal Clear Cell Carcinoma (KIRC) is one of fatal genitourinary diseases and accounts for most malignant kidney tumours. KIRC has been shown resistance to radiotherapy and chemotherapy. Like many types of cancers, there is no curative treatment for metastatic KIRC. Using advanced sequencing technologies, The Cancer Genome Atlas (TCGA) project of NIH/NCI-NHGRI has produced large-scale sequencing data, which provide unprecedented opportunities to reveal new molecular mechanisms of cancer. We combined differentially expressed genes, pathways and network analyses to gain new insights into the underlying molecular mechanisms of the disease development. Results: Followed by the experimental design for obtaining significant genes and pathways, comprehensive analysis of 537 KIRC patients' sequencing data provided by TCGA was performed. Differentially expressed genes were obtained from the RNA-Seq data. Pathway and network analyses were performed. We identified 186 differentially expressed genes with significant p-value and large fold changes (P < 0.01, |log(FC)| > 5). The study not only confirmed a number of identified differentially expressed genes in literature reports, but also provided new findings. We performed hierarchical clustering analysis utilizing the whole genome-wide gene expressions and differentially expressed genes that were identified in this study. We revealed distinct groups of differentially expressed genes that can aid to the identification of subtypes of the cancer. The hierarchical clustering analysis based on gene expression profile and differentially expressed genes suggested four subtypes of the cancer. We found enriched distinct Gene Ontology (GO) terms associated with these groups of genes. Based on these findings, we built a support vector machine based supervised-learning classifier to predict unknown samples, and the classifier achieved high accuracy and robust classification results. In addition, we identified a number of pathways (P < 0.04) that were significantly influenced by the disease. We found that some of the identified pathways have been implicated in cancers from literatures, while others have not been reported in the cancer before. The network analysis leads to the identification of significantly disrupted pathways and associated genes involved in the disease development. Furthermore, this study can provide a viable alternative in identifying effective drug targets. Conclusions: Our study identified a set of differentially expressed genes and pathways in kidney renal clear cell carcinoma, and represents a comprehensive computational approach to analysis large-scale next-generation sequencing data. The pathway and network analyses suggested that information from distinctly expressed genes can be utilized in the identification of aberrant upstream regulators. Identification of distinctly expressed genes and altered pathways are important in effective biomarker identification for early cancer diagnosis and treatment planning. Combining differentially expressed genes with pathway and network analyses using intelligent computational approaches provide an unprecedented opportunity to identify upstream disease causal genes and effective drug targets. C1 [Yang, William; Yoshigoe, Kenji] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Comp Sci, Little Rock, AR 72204 USA. [Qin, Xiang] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Qin, Xiang] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat & Biomath, Boston, MA 02114 USA. [Yang, Jack Y.; Niemierko, Andrzej] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Deng, Youping] Rush Univ, Med Ctr, Ctr Canc, Chicago, IL 60612 USA. [Deng, Youping] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Deng, Youping] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Yang, Jack Y.; Liu, Yunlong; Dunker, A. Keith] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Chen, Zhongxue] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Wang, Liangjiang] Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. [Xu, Dong] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. [Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yang, Mary Qu] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Informat Sci, MidSouth Bioinformat Ctr, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas, Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas Med Sci, Little Rock, AR 72204 USA. RP Yang, MQ (reprint author), Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, Dept Informat Sci, MidSouth Bioinformat Ctr, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM mqyang@ualr.edu FU National Institutes of Health (NIH); Arkansas Science and Technology Authority (ASTA); National Science Foundation (NSF); NIH/NIGMS [5P20GM10342913]; ASTA [15-B-23]; NIH/NHGRI [5U54HG003273-11]; NSF [1359323, 1429160] FX The research was supported by the National Institutes of Health (NIH), Arkansas Science and Technology Authority (ASTA), and National Science Foundation (NSF). Specifically, MQY was supported by NIH/NIGMS 5P20GM10342913 and ASTA Award # 15-B-23. XQ was supported by NIH/NHGRI 5U54HG003273-11. KY and WY were supported by NSF Award # 1359323 and NSF Award # 1429160. NR 23 TC 14 Z9 14 U1 6 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 16 PY 2014 VL 15 SU 17 AR S2 DI 10.1186/1471-2105-15-S17-S2 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA CH4AS UT WOS:000353973500003 PM 25559354 ER PT J AU Yang, MQ Yoshigoe, K Yang, W Tong, WD Qin, X Dunker, AK Chen, ZX Arbania, HR Liu, JS Niemierko, A Yang, JY AF Yang, Mary Qu Yoshigoe, Kenji Yang, William Tong, Weida Qin, Xiang Dunker, A. Keith Chen, Zhongxue Arbania, Hamid R. Liu, Jun S. Niemierko, Andrzej Yang, Jack Y. TI The emerging genomics and systems biology research lead to systems genomics studies SO BMC GENOMICS LA English DT Article AB Synergistically integrating multi-layer genomic data at systems level not only can lead to deeper insights into the molecular mechanisms related to disease initiation and progression, but also can guide pathway-based biomarker and drug target identification. With the advent of high-throughput next-generation sequencing technologies, sequencing both DNA and RNA has generated multi-layer genomic data that can provide DNA polymorphism, non-coding RNA, messenger RNA, gene expression, isoform and alternative splicing information. Systems biology on the other hand studies complex biological systems, particularly systematic study of complex molecular interactions within specific cells or organisms. Genomics and molecular systems biology can be merged into the study of genomic profiles and implicated biological functions at cellular or organism level. The prospectively emerging field can be referred to as systems genomics or genomic systems biology. The Mid-South Bioinformatics Centre (MBC) and Joint Bioinformatics Ph.D. Program of University of Arkansas at Little Rock and University of Arkansas for Medical Sciences are particularly interested in promoting education and research advancement in this prospectively emerging field. Based on past investigations and research outcomes, MBC is further utilizing differential gene and isoform/exon expression from RNA-seq and co-regulation from the ChiP-seq specific for different phenotypes in combination with protein-protein interactions, and protein-DNA interactions to construct high-level gene networks for an integrative genome-phoneme investigation at systems biology level. C1 [Yang, Mary Qu] Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, MidSouth Bioinformat Ctr, Dept Informat Sci, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas, Joint Bioinformat Grad Program, Little Rock, AR 72204 USA. [Yang, Mary Qu] Univ Arkansas Med Sci, Little Rock, AR 72204 USA. [Yoshigoe, Kenji; Yang, William] Univ Arkansas, Dept Comp Sci, George W Donaghey Coll Engn & Informat Technol, Little Rock, AR 72204 USA. [Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Qin, Xiang] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Qin, Xiang] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Dunker, A. Keith; Yang, Jack Y.] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Chen, Zhongxue] Indiana Univ, Sch Med, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Arbania, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. [Liu, Jun S.; Yang, Jack Y.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Biostat & Biomath, Boston, MA 02114 USA. [Niemierko, Andrzej] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yang, MQ (reprint author), Univ Arkansas, George W Donaghey Coll Engn & Informat Technol, MidSouth Bioinformat Ctr, Dept Informat Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM mqyang@ualr.edu FU National Institutes of Health (NIH); Arkansas Science and Technology Authority (ASTA); National Science Foundation (NSF); NIH/NIGMS [5P20GM10342913]; ASTA [15-B-23]; NIH/NHGRI [5U54HG003273-11]; NSF [1359323, 1429160] FX The research at MBC was supported by the National Institutes of Health (NIH), Arkansas Science and Technology Authority (ASTA), and National Science Foundation (NSF). MQY was supported by NIH/NIGMS 5P20GM10342913 and ASTA Award # 15-B-23. XQ was supported by NIH/NHGRI 5U54HG003273-11. KY and WY were supported by NSF Award # 1359323 and NSF Award # 1429160. NR 4 TC 0 Z9 0 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 16 PY 2014 VL 15 SU 11 AR I1 DI 10.1186/1471-2164-15-S11-I1 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CH4CE UT WOS:000353978200001 PM 25558922 ER PT J AU Cunningham, MA Wirth, JR Freeman, LR Boger, HA Granholm, AC Gilkeson, GS AF Cunningham, Melissa A. Wirth, Jena R. Freeman, Linnea R. Boger, Heather A. Granholm, Ann-Charlotte Gilkeson, Gary S. TI Estrogen receptor alpha deficiency protects against development of cognitive impairment in murine lupus SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Estrogen receptor alpha (ERa); Neuropsychiatric lupus (NP-SLE); Microglia ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RADIAL-ARM MAZE; DENDRITIC CELL-DIFFERENTIATION; MEMORY LOAD INCREASES; MRL-LPR MICE; NEUROPSYCHIATRIC SYNDROMES; OBJECT-RECOGNITION; WORKING-MEMORY; GLUTAMATE-RECEPTOR; DNA ANTIBODIES AB Background: One of the more profound features of systemic lupus erythematosus (SLE) is that females have a 9: 1 prevalence of this disease over males. Up to 80% of SLE patients have cognitive defects or affective disorders. The mechanism of CNS injury responsible for cognitive impairment is unknown. We previously showed that ERa deficiency significantly reduced renal disease and increased survival in lupus-prone mice. We hypothesized that ERa deficiency would be similarly protective in the brain, and that ERa may play a role in modulating blood-brain barrier (BBB) integrity and/or neuroinflammation in lupus-prone mice. Methods: MRL/lpr ERa+/+ and ERaKO mice (n = 46) were ovariectomized, received 17 beta-estradiol pellets, and underwent radial arm water maze (WRAM) and novel object recognition (NOR) testing starting at eight weeks of age. Mice were sacrificed and brains were hemisected and processed for either immunohistochemistry, or hippocampus and parietal cortex dissection for Western blotting. Results: MRL/lpr ERaKO mice (n = 21) performed significantly better in WRAM testing than wild-type MRL/lpr mice (n = 25). There was a significant reduction in reference memory errors (P < 0.007), working memory errors (P < 0.05), and start arm errors (P < 0.02) in ERaKO mice. There were significant differences in NOR testing, particularly total exploration time, with ERa deficiency normalizing behavior. No significant differences were seen in markers of tight junction, astrogliosis, or microgliosis in the hippocampus or cortex by Western blot, however, there was a significant reduction in numbers of Iba1+ activated microglia in the hippocampus of ERaKO mice, as evidenced by immunohistochemietry (IHC). Conclusion: ERa deficiency provides significant protection against cognitive deficits in MRL/lpr mice as early as eight weeks of age. Additionally, the significant reduction in Iba1+ activated microglia in the MRL/lpr ERaKO mice was consistent with reduced inflammation, and may represent a biological mechanism for the cognitive improvement observed. C1 [Cunningham, Melissa A.] Med Univ S Carolina, Dept Neurosci, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29425 USA. RP Cunningham, MA (reprint author), Med Univ S Carolina, Dept Neurosci, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 814,MSC637, Charleston, SC 29425 USA. EM cunnima@musc.edu OI Wirth, Jena/0000-0001-6094-8336; Cunningham, Melissa/0000-0002-9207-1986 FU Office of Research on Women's Health: Specialized Centers of Research on Sex and Gender Factors Affecting Women's Health (NIH/NIAMS - National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin diseases) [P50 DA016511]; South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina (NIH/NCRR - National Instititutes of Health/National Center for Research Resources) [UL1 RR029880, UL1 RR029882]; VA Medical Research Service merit award [1I01BX000470-01] FX The authors wish to thank Ms Claudia Umphlet and Dr Michael Smith for help with tissue processing. This publication was supported by the Office of Research on Women's Health: Specialized Centers of Research on Sex and Gender Factors Affecting Women's Health (NIH/NIAMS - National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin diseases, grant number: P50 DA016511); The South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina (NIH/NCRR - National Instititutes of Health/National Center for Research Resources, grant numbers: UL1 RR029880 and UL1 RR029882); and a VA Medical Research Service merit award (grant number: 1I01BX000470-01). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NCRR. NR 76 TC 3 Z9 3 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD DEC 16 PY 2014 VL 11 AR 171 DI 10.1186/s12974-014-0171-x PG 15 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CC5ZS UT WOS:000350444700001 PM 25510908 ER PT J AU Guo, AY Stevens, BW Wilson, RG Russell, CN Cohen, MA Sturgeon, HC Thornton, A Giallourakis, C Khalili, H Nguyen, DD Sauk, J Yajnik, V Xavier, RJ Ananthakrishnan, AN AF Guo, Abra Y. Stevens, Betsy W. Wilson, Robin G. Russell, Caitlin N. Cohen, Melissa A. Sturgeon, Holly C. Thornton, Anna Giallourakis, Cosmas Khalili, Hamed Nguyen, Deanna D. Sauk, Jenny Yajnik, Vijay Xavier, Ramnik J. Ananthakrishnan, Ashwin N. TI Early life environment and natural history of inflammatory bowel diseases SO BMC GASTROENTEROLOGY LA English DT Article DE Breastfeeding; Early life; Microbiome; Crohn's disease; Surgery ID CROHNS-DISEASE; ULCERATIVE-COLITIS; RISK-FACTORS; INTESTINAL MICROBIOTA; CIGARETTE-SMOKING; PASSIVE SMOKING; GUT MICROBIOTA; COHORT; IBD; TOBACCO AB Background: Early life exposures may modify risk of inflammatory bowel diseases (IBD; Crohn's disease (CD), ulcerative colitis (UC)). However, the relationship between early life exposures and natural history of IBD has not been previously examined. Methods: This single center study included patients with CD or UC recruited in a prospective IBD registry. Enrolled patients completed a detailed environmental questionnaire that assessed various early life environmental exposures. Our primary outcome was requirement for disease-related surgery in CD and UC. Logistic regression models defined independent effect of early life exposures, adjusting for potential confounders. Results: Our study included 333 CD and 270 UC patients. Just over half were female with a median age at diagnosis of 25 years. One-third of the cohort had history of bowel surgery (31%) and nearly half had used at least one biologic agent (47%). Among those with CD, being breastfed was associated with reduced risk of CD-related surgery (34% vs. 55%), while childhood cigarette smoke exposure was associated with increased risk. On multivariate analysis, history of being breastfed (odds ratio (OR) 0.21, 95% confidence interval [CI] 0.09-0.46) and cigarette smoke exposure as a child (OR 2.17, 95% CI 1.10-4.29) remained independently associated with surgery. None of the early life variables influenced disease phenotype or outcome in UC. Conclusion: A history of being breastfed was associated with a decreased risk while childhood cigarette smoke exposure was associated with an increased risk of surgery in patients with CD. Further investigation to examine biological mechanisms is warranted. C1 [Guo, Abra Y.; Stevens, Betsy W.; Wilson, Robin G.; Russell, Caitlin N.; Cohen, Melissa A.; Sturgeon, Holly C.; Thornton, Anna; Giallourakis, Cosmas; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Giallourakis, Cosmas; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU National Institutes of Health (NIH) [P30 DK043351]; National Institutes of Health [K23 DK097142] FX We acknowledge the valuable contributions of the participants and the research staff of our registry. This work is supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). NR 47 TC 3 Z9 3 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-230X J9 BMC GASTROENTEROL JI BMC Gastroenterol. PD DEC 16 PY 2014 VL 14 AR 216 DI 10.1186/s12876-014-0216-8 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AZ1EN UT WOS:000347983100001 PM 25510175 ER PT J AU Xia, W Springer, TA AF Xia, Wei Springer, Timothy A. TI Metal ion and ligand binding of integrin alpha(5)beta(1) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CRYSTAL-STRUCTURE; STRUCTURAL BASIS; EXTENDED CONFORMATIONS; FIBRONECTIN RECEPTOR; LEUKOCYTE INTEGRIN; A-DOMAIN; I DOMAIN; SUBUNIT; RECOGNITION; ACTIVATION AB Integrin alpha(5)beta(1) binds to an Arg-Gly-Asp (RGD) motif in its ligand fibronectin. We report high-resolution crystal structures of a four-domain alpha(5)beta(1) headpiece fragment, alone or with RGD peptides soaked into crystals, and RGD peptide affinity measurements. The headpiece crystallizes in a closed conformation essentially identical to that seen previously for alpha(5)beta(1) complexed with a Fab that allosterically inhibits ligand binding by stabilizing the closed conformation. Soaking experiments show that binding of cyclic RGD peptide with 20-fold higher affinity than a linear RGD peptide induces conformational change in the beta(1)-subunit beta I domain to a state that is intermediate between closed (low affinity) and open (high affinity). In contrast, binding of a linear RGD peptide induces no shape shifting. However, linear peptide binding induces shape shifting when Ca2+ is depleted during soaking. Ca2+ bound to the adjacent to metal ion-dependent adhesion site (ADMIDAS), at the locus of shape shifting, moves and decreases in occupancy, correlating with an increase in affinity for RGD measured when Ca2+ is depleted. The results directly demonstrate that Ca2+ binding to the ADMIDAS stabilizes integrins in the low-affinity, closed conformation. Comparisons in affinity between four-domain and six-domain headpiece constructs suggest that flexible integrin leg domains contribute to conformational equilibria. High-resolution views of the hybrid domain interface with the plexin-semaphorin-integrin (PSI) domain in different orientations show a ball-and-socket joint with a hybrid domain Arg side chain that rocks in a PSI domain socket lined with carbonyl oxygens. C1 [Xia, Wei; Springer, Timothy A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Xia, Wei; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM timothy.springer@childrens.harvard.edu FU NIH [HL-108248] FX We thank beamline 24ID at the Advanced Photon Source and Jianghai Zhu, Xianchi Dong, and Li-Zhi Mi for help with data collection and refinement. Supported by NIH Grant HL-108248. NR 41 TC 16 Z9 16 U1 2 U2 19 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 DEC 16 PY 2014 VL 111 IS 50 BP 17863 EP 17868 DI 10.1073/pnas.1420645111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500058 PM 25475857 ER PT J AU Balasubramanian, R Choi, JH Francescatto, L Willer, J Horton, ER Asimacopoulos, EP Stankovic, KM Plummer, L Buck, CL Quinton, R Nebesio, TD Mericq, V Merino, PM Meyer, BF Monies, D Gusella, JF Al Tassan, N Katsanis, N Crowley, WF AF Balasubramanian, Ravikumar Choi, Jin-Ho Francescatto, Ludmila Willer, Jason Horton, Edward R. Asimacopoulos, Eleni P. Stankovic, Konstantina M. Plummer, Lacey Buck, Cassandra L. Quinton, Richard Nebesio, Todd D. Mericq, Veronica Merino, Paulina M. Meyer, Brian F. Monies, Dorota Gusella, James F. Al Tassan, Nada Katsanis, Nicholas Crowley, William F., Jr. TI Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHD7; Kallmann syndrome; idiopathic hypogonadotropic hypogondism; CHARGE syndrome; missense mutations ID CHARGE-SYNDROME; KALLMANN-SYNDROME; HYPOGONADOTROPIC HYPOGONADISM; MOUSE MODEL; MUTATIONS; GENE; IDENTIFICATION; MISSENSE; NEURONS; BIOLOGY AB Inactivating mutations in chromodomain helicase DNA binding protein 7 (CHD7) cause CHARGE syndrome, a severe multiorgan system disorder of which Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a minor feature. Recent reports have described predominantly missense CHD7 alleles in IGD patients, but it is unclear if these alleles are relevant to causality or overall genetic burden of Kallmann syndrome (KS) and normosmic form of IGD. To address this question, we sequenced CHD7 in 783 well-phenotyped IGD patients lacking full CHARGE features; we identified nonsynonymous rare sequence variants in 5.2% of the IGD cohort (73% missense and 27% splice variants). Functional analyses in zebrafish using a surrogate otolith assay of a representative set of these CHD7 alleles showed that rare sequence variants observed in controls showed no altered function. In contrast, 75% of the IGD-associated alleles were deleterious and resulted in both KS and normosmic IGD. In two families, pathogenic mutations in CHD7 coexisted with mutations in other known IGD genes. Taken together, our data suggest that rare deleterious CHD7 alleles contribute to the mutational burden of patients with both KS and normosmic forms of IGD in the absence of full CHARGE syndrome. These findings (i) implicate a unique role or preferential sensitivity for CHD7 in the ontogeny of GnRH neurons, (ii) reiterate the emerging genetic complexity of this family of IGD disorders, and (iii) demonstrate how the coordinated use of well-phenotyped cohorts, families, and functional studies can inform genetic architecture and provide insights into the developmental biology of cellular systems. C1 [Balasubramanian, Ravikumar; Choi, Jin-Ho; Horton, Edward R.; Plummer, Lacey; Buck, Cassandra L.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr & Reprod Endocri, Dept Med, Boston, MA 02114 USA. [Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Balasubramanian, Ravikumar; Crowley, William F., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Asimacopoulos, Eleni P.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Choi, Jin-Ho] Univ Ulsan, Coll Med, Asan Med Ctr Childrens Hosp, Dept Pediat, Seoul 138736, South Korea. [Francescatto, Ludmila; Willer, Jason; Katsanis, Nicholas] Duke Univ, Dept Cell Biol & Pediat, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Asimacopoulos, Eleni P.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Quinton, Richard] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Nebesio, Todd D.] Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA. [Mericq, Veronica; Merino, Paulina M.] Univ Chile, Inst Maternal & Child Res, Santiago 2263, Chile. [Meyer, Brian F.; Monies, Dorota; Al Tassan, Nada] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr & Reprod Endocri, Dept Med, Boston, MA 02114 USA. EM wcrowley@partners.org OI Mericq, Veronica/0000-0003-2287-0181; Katsanis, Nicholas/0000-0002-2480-0171 FU National Institutes of Health [U54 HD028138, P50 DK096415, K23 HD077043, K08 DC010419]; Bertarelli Foundation; National Institutes of Health (Developmental Genome Anatomy Project) [P01 GM061354] FX This study was supported by the National Institutes of Health Grants U54 HD028138 (to W.F.C.) and P50 DK096415 (to N.K.). R.B. is supported by the National Institutes of Health Grant K23 HD077043. K.M.S. is supported by National Institutes of Health Grant K08 DC010419 and the Bertarelli Foundation. J.F.G. is supported by National Institutes of Health Grant P01 GM061354 (Developmental Genome Anatomy Project). NR 34 TC 6 Z9 6 U1 1 U2 7 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 DEC 16 PY 2014 VL 111 IS 50 BP 17953 EP 17958 DI 10.1073/pnas.1417438111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500073 PM 25472840 ER PT J AU Landman, R Sharma, J Sur, M Desimone, R AF Landman, Rogier Sharma, Jitendra Sur, Mriganka Desimone, Robert TI Effect of distracting faces on visual selective attention in the monkey SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE attention; faces; oxytocin; social; vision ID EMOTIONAL FACIAL EXPRESSIONS; PSYCHOPHYSICS TOOLBOX; PERCEPTUAL LOAD; RHESUS MACAQUES; EYE TRACKING; OXYTOCIN; AMYGDALA; CAPTURE; THREAT; STIMULI AB In primates, visual stimuli with social and emotional content tend to attract attention. Attention might be captured through rapid, automatic, subcortical processing or guided by slower, more voluntary cortical processing. Here we examined whether irrelevant faces with varied emotional expressions interfere with a covert attention task in macaque monkeys. In the task, the monkeys monitored a target grating in the periphery for a subtle color change while ignoring distracters that included faces appearing elsewhere on the screen. The onset time of distracter faces before the target change, as well as their spatial proximity to the target, was varied from trial to trial. The presence of faces, especially faces with emotional expressions interfered with the task, indicating a competition for attentional resources between the task and the face stimuli. However, this interference was significant only when faces were presented for greater than 200 ms. Emotional faces also affected saccade velocity and reduced pupillary reflex. Our results indicate that the attraction of attention by emotional faces in the monkey takes a considerable amount of processing time, possibly involving cortical-subcortical interactions. Intranasal application of the hormone oxytocin ameliorated the interfering effects of faces. Together these results provide evidence for slow modulation of attention by emotional distracters, which likely involves oxytocinergic brain circuits. C1 [Landman, Rogier; Desimone, Robert] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Sharma, Jitendra; Sur, Mriganka] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Sharma, Jitendra] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sharma, Jitendra] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sur, Mriganka] Simons Ctr Social Brain, Cambridge, MA 02139 USA. RP Landman, R (reprint author), MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. EM landman@mit.edu; desimone@mit.edu FU Simons Foundation; National Institutes of Health [EY017292] FX We thank Dr. David Amaral for kindly providing us with the stimuli used, Dr. David Osher for helpful discussions, and Emma Myers for training the animals and setting up the training rig. This research was supported in part by grants from The Simons Foundation (to M.S.) and National Institutes of Health Grant EY017292 (to R.D.). NR 64 TC 9 Z9 9 U1 0 U2 19 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 DEC 16 PY 2014 VL 111 IS 50 BP 18037 EP 18042 DI 10.1073/pnas.1420167111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500079 PM 25472846 ER PT J AU Merlo, P Frost, B Peng, SY Yang, YWJ Park, PJ Feany, M AF Merlo, Paola Frost, Bess Peng, Shouyong Yang, Yawei J. Park, Peter J. Feany, Mel TI p53 prevents neurodegeneration by regulating synaptic genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE p53 transcriptional function; ChIP-chip; neurodegeneration; tauopathy; synaptic genes ID ALZHEIMERS-DISEASE; DNA-DAMAGE; NEUROFIBRILLARY TANGLES; DROSOPHILA-MELANOGASTER; CELL-DEATH; TAUOPATHY; ISOFORMS; MODEL; P73; DIFFERENTIATION AB DNA damage has been implicated in neurodegenerative disorders, including Alzheimer's disease and other tauopathies, but the consequences of genotoxic stress to postmitotic neurons are poorly understood. Here we demonstrate that p53, a key mediator of the DNA damage response, plays a neuroprotective role in a Drosophila model of tauopathy. Further, through a whole-genome ChIP-chip analysis, we identify genes controlled by p53 in postmitotic neurons. We genetically validate a specific pathway, synaptic function, in p53-mediated neuroprotection. We then demonstrate that the control of synaptic genes by p53 is conserved in mammals. Collectively, our results implicate synaptic function as a central target in p53-dependent protection from neurodegeneration. C1 [Merlo, Paola; Frost, Bess; Feany, Mel] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Peng, Shouyong; Park, Peter J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Peng, Shouyong; Park, Peter J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Peng, Shouyong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yang, Yawei J.] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. [Yang, Yawei J.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Yang, Yawei J.] Broad Inst & Harvard, Cambridge, MA 02142 USA. [Yang, Yawei J.] Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. RP Feany, M (reprint author), Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM mel_feany@hms.harvard.edu RI Merlo, Paola/K-5330-2014 OI Merlo, Paola/0000-0003-0105-7044 FU NIH [P40OD018537]; Vienna Drosophila RNAi Center; Transgenic RNAi Project at Harvard Medical School (NIH/National Institute of General Medical Sciences) [R01GM084947]; National Institute of Child Health and Human Development; National Institute on Aging; Ellison Medical Foundation; American Health Assistance Foundation FX We thank Art Alekseyenko and C. John Luckey for reagents and helpful discussions. Drosophila stocks were obtained from the Bloomington Drosophila Stock Center (NIH Grant P40OD018537), the Vienna Drosophila RNAi Center, the Transgenic RNAi Project at Harvard Medical School (NIH/National Institute of General Medical Sciences Grant R01GM084947), Nancy Bonini, and Thomas Neufeld. Antibodies were from the DSHB, developed under the auspices of the National Institute of Child Health and Human Development and maintained by the University of Iowa; and from the University of California Davis/NIH NeuroMab Facility. This work was supported by grants from the National Institute on Aging, the Ellison Medical Foundation, and the American Health Assistance Foundation (to M. F.). NR 45 TC 7 Z9 7 U1 0 U2 5 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 DEC 16 PY 2014 VL 111 IS 50 BP 18055 EP 18060 DI 10.1073/pnas.1419083111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500082 PM 25453105 ER PT J AU Ba, DB Babadi, B Purdon, PL Brown, EN AF Ba, Demba Babadi, Behtash Purdon, Patrick L. Brown, Emery N. TI Robust spectrotemporal decomposition by iteratively reweighted least squares SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE structured sparsity; spectral decomposition; dynamics; recursive estimation; neural signal processing ID CONVERGENCE; ALGORITHMS; REGRESSION; SELECTION; NETWORKS; PROPOFOL; SPECTRUM; MODEL AB Classical nonparametric spectral analysis uses sliding windows to capture the dynamic nature of most real-world time series. This universally accepted approach fails to exploit the temporal continuity in the data and is not well-suited for signals with highly structured time-frequency representations. For a time series whose time-varying mean is the superposition of a small number of oscillatory components, we formulate nonparametric batch spectral analysis as a Bayesian estimation problem. We introduce prior distributions on the time-frequency plane that yield maximum a posteriori (MAP) spectral estimates that are continuous in time yet sparse in frequency. Our spectral decomposition procedure, termed spectrotemporal pursuit, can be efficiently computed using an iteratively reweighted least-squares algorithm and scales well with typical data lengths. We show that spectrotemporal pursuit works by applying to the time series a set of data-derived filters. Using a link between Gaussian mixture models, l(1) minimization, and the expectation-maximization algorithm, we prove that spectrotemporal pursuit converges to the global MAP estimate. We illustrate our technique on simulated and real human EEG data as well as on human neural spiking activity recorded during loss of consciousness induced by the anesthetic propofol. For the EEG data, our technique yields significantly denoised spectral estimates that have significantly higher time and frequency resolution than multitaper spectral estimates. For the neural spiking data, we obtain a new spectral representation of neuronal firing rates. Spectrotemporal pursuit offers a robust spectral decomposition framework that is a principled alternative to existing methods for decomposing time series into a small number of smooth oscillatory components. C1 [Ba, Demba; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ba, Demba; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Babadi, Behtash] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20740 USA. [Purdon, Patrick L.; Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Ba, DB (reprint author), MIT, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM demba@mit.edu FU National Institutes of Health Transformative Research Award [GM 104948]; [DP2-OD006454]; [R01-EB006385] FX This work was partially supported by National Institutes of Health Transformative Research Award GM 104948 (to E.N.B.) and by New Innovator Awards DP2-OD006454 (to P.L.P.) and R01-EB006385 (to E.N.B. and P.L.P.). NR 39 TC 5 Z9 5 U1 2 U2 12 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 DEC 16 PY 2014 VL 111 IS 50 BP E5336 EP E5345 DI 10.1073/pnas.1320637111 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500005 PM 25468968 ER PT J AU Payne, R Muenchhoff, M Mann, J Roberts, HE Matthews, P Adland, E Hempenstall, A Huang, KH Brockman, M Brumme, Z Sinclair, M Miura, T Frater, J Essex, M Shapiro, R Walker, BD Ndung'u, T McLean, AR Carlson, JM Goulder, PJR AF Payne, Rebecca Muenchhoff, Maximilian Mann, Jaclyn Roberts, Hannah E. Matthews, Philippa Adland, Emily Hempenstall, Allison Huang, Kuan-Hsiang Brockman, Mark Brumme, Zabrina Sinclair, Marc Miura, Toshiyuki Frater, John Essex, Myron Shapiro, Roger Walker, Bruce D. Ndung'u, Thumbi McLean, Angela R. Carlson, Jonathan M. Goulder, Philip J. R. TI Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HLA; HIV; adaptation; antiretroviral therapy; virulence ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL LOAD; REPLICATION CAPACITY; CLASS-I; ESCAPE MUTATIONS; IMMUNE CONTROL; GAG-PROTEASE; CHRONIC INFECTION; COITAL ACT; SET-POINT AB It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity. We here investigate the impact on HIV virulence of HIV adaptation to HLA molecules that protect against disease progression, such as HLA-B*57 and HLA-B*58:01. We analyzed cohorts in Botswana and South Africa, two countries severely affected by the HIV epidemic. In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 x 10(-82)), the protective effect of HLA-B*57/58: 01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03). These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time. The potential role in this process played by increasing antiretroviral therapy (ART) access is also explored. Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation. C1 [Payne, Rebecca; Muenchhoff, Maximilian; Matthews, Philippa; Adland, Emily; Hempenstall, Allison; Sinclair, Marc; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. [Mann, Jaclyn; Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip J. R.] Univ Oxford, Oxford Martin Sch, Inst Emerging Infect, Oxford OX1 3BD, England. [Roberts, Hannah E.; Huang, Kuan-Hsiang; Frater, John; McLean, Angela R.] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. [Roberts, Hannah E.; Huang, Kuan-Hsiang; Frater, John] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Brockman, Mark; Brumme, Zabrina] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. [Brockman, Mark; Brumme, Zabrina] ViiV Healthcare KK, Shibuya Ku, Tokyo 1518566, Japan. [Miura, Toshiyuki] Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX1 3SY, England. [Frater, John] Botswana Harvard AIDS Inst Partnership, BO-320 Gaborone, Botswana. [Essex, Myron; Shapiro, Roger] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02215 USA. [Essex, Myron; Shapiro, Roger] Massachusetts Gen Hosp, MIT, Ragon Inst, Cambridge, MA 02139 USA. [Walker, Bruce D.; Ndung'u, Thumbi] Harvard Univ, Cambridge, MA 02139 USA. [Walker, Bruce D.; Ndung'u, Thumbi] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [McLean, Angela R.] Microsoft Res, ESci Grp, Los Angeles, CA 90024 USA. RP Goulder, PJR (reprint author), Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. EM philip.goulder@paediatrics.ox.ac.uk OI Matthews, Philippa/0000-0002-4036-4269; Ndung'u, Thumbi/0000-0003-2962-3992; Brockman, Mark/0000-0001-6432-1426 FU National Institutes of Health [R01AI46995]; Wellcome Trust; Medical Research Council UK; New Investigator Award (Canadian Institutes of Health); Michael Smith Foundation for Health Research FX This work is funded by grants from the National Institutes of Health [R01AI46995 (to P.J.R.G.)], the Wellcome Trust (to P.J.R.G.), and the Medical Research Council UK. Z.B. is supported by a New Investigator Award (Canadian Institutes of Health) and the Michael Smith Foundation for Health Research. M.B. holds a Canada Research Chair, Tier 2, in Viral Pathogenesis and Immunity. NR 52 TC 24 Z9 24 U1 1 U2 16 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 DEC 16 PY 2014 VL 111 IS 50 BP E5393 EP E5400 DI 10.1073/pnas.1413339111 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6GA UT WOS:000346366500011 PM 25453107 ER PT J AU Wojtaszek, JL Wang, S Kim, H Wu, QL D'Andrea, AD Zhou, P AF Wojtaszek, Jessica L. Wang, Su Kim, Hyungjin Wu, Qinglin D'Andrea, Alan D. Zhou, Pei TI Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CROSS-LINK REPAIR; ANEMIA CORE COMPLEX; FANCONI-ANEMIA; BINDING DOMAINS; ZINC-FINGER; PROTEIN; PATHWAY; RABEX-5 AB FAAP20 is an integral component of the Fanconi anemia core complex that mediates the repair of DNA interstrand crosslinks. The ubiquitin-binding capacity of the FAAP20 UBZ is required for recruitment of the Fanconi anemia complex to interstrand DNA crosslink sites and for interaction with the translesion synthesis machinery. Although the UBZ-ubiquitin interaction is thought to be exclusively encapsulated within the beta beta alpha module of UBZ, we show that the FAAP20-ubiquitin interaction extends beyond such a canonical zinc-finger motif. Instead, ubiquitin binding by FAAP20 is accompanied by transforming a disordered tail C-terminal to the UBZ of FAAP20 into a rigid, extended beta-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44(Ub) for enhanced binding specificity and affinity. Substitution of the C-terminal tryptophan with alanine in FAAP20 not only abolishes FAAP20-ubiquitin binding in vitro, but also causes profound cellular hypersensitivity to DNA interstrand crosslink lesions in vivo, highlighting the indispensable role of the C-terminal tail of FAAP20, beyond the compact zinc finger module, toward ubiquitin recognition and Fanconi anemia complex-mediated DNA interstrand crosslink repair. C1 [Wojtaszek, Jessica L.; Wang, Su; Wu, Qinglin; Zhou, Pei] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Kim, Hyungjin; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP Zhou, P (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. EM peizhou@biochem.duke.edu OI Zhou, Pei/0000-0002-7823-3416 FU National Institutes of Health [NIGMS 51310, R01DK43889, R37HL52725, 2P01HL048546]; Duke Bridge Fund; Leukemia and Lymphoma Society FX National Institutes of Health [NIGMS 51310 to P.Z.; R01DK43889, R37HL52725 and 2P01HL048546 to A.D.D.]; Duke Bridge Fund [to P.Z.]; Leukemia and Lymphoma Society [to H.K.]. Funding for open access charge: National Institutes of Health [NIGMS 51310 to P.Z.; R01DK43889, R37HL52725 and 2P01HL048546 to A.D.D.]; Duke Bridge Fund [to P.Z.]; Leukemia and Lymphoma Society [to H.K.]. NR 28 TC 2 Z9 2 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 16 PY 2014 VL 42 IS 22 BP 13997 EP 14005 DI 10.1093/nar/gku1153 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AZ0DQ UT WOS:000347916900053 PM 25414354 ER PT J AU Backus, LI Belperio, PS Loomis, TP Han, SH Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Loomis, Timothy P. Han, Steven-Huy Mole, Larry A. TI Screening for and Prevalence of Hepatitis B Virus Infection Among High-Risk Veterans Under the Care of the US Department of Veterans Affairs: A Case Report SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID UNITED-STATES C1 [Backus, Lisa I.; Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.] Vet Affairs Palo Alto Hlth Care Syst, Off Publ Hlth Populat Hlth, Palo Alto, CA 94304 USA. [Mole, Larry A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Hlthcare Syst, Los Angeles, CA 90095 USA. [Mole, Larry A.] Univ Calif Los Angeles, David Geffen Sch Med, Pfleger Liver Inst, Los Angeles, CA 90095 USA. RP Backus, LI (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Off Publ Hlth Populat Hlth, Palo Alto, CA 94304 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 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 DEC 16 PY 2014 VL 161 IS 12 BP 926 EP 928 DI 10.7326/L14-5036 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AX9UW UT WOS:000347248400046 PM 25506867 ER PT J AU Hentrich, C Szostak, JW AF Hentrich, Christian Szostak, Jack W. TI Controlled Growth of Filamentous Fatty Acid Vesicles under Flow SO LANGMUIR LA English DT Article ID MEMBRANE; LIFE; PROLIFERATION; MICROTUBULE; PROTOCELL; MICELLES; DYNAMICS; BINDING; SURFACE; SYSTEM AB The earliest forms of cellular life would have required a membrane compartment capable of growth and division. Fatty acid vesicles are an attractive model of protocell membranes, as they can grow into filamentous vesicles that readily divide while retaining their contents. In order to study vesicle growth, we have developed a method for immobilizing multilamellar fatty acid vesicles on modified glass surfaces and inducing filamentous membrane growth under flow. Filament formation strictly depended on the presence of freshly neutralized fatty acid micelles in the flow chamber. Using light microscopy, we observed a strong dependence of initial growth velocity on initial vesicle size, suggesting that new fatty acid molecules were incorporated into the membrane over the entire external surface of the vesicle. We examined the influences of flow rate, fatty acid concentration, and salt concentration on filamentous growth and observed drastic shape changes, including membrane pearling, of preexisting membrane tubules in response to osmotic stress. These results illustrate the versatility of flow studies for exploring the process of fatty acid vesicle growth following exposure to free fatty acids. C1 [Hentrich, Christian; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Hentrich, Christian; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Hentrich, Christian; Szostak, Jack W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Szostak, Jack W.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NASA Exobiology Program [EXB02-0031-0018] FX We thank Brian Lee and Lakshminarayanan Mahadevan for helpful discussions. We also thank Aaron Engelhart, Aaron Larsen, Anders Bjorkbom, Neha Kamat, Noam Prywes, Tony Z. Jia, and Victor Lelyveld for critical reading of the manuscript. J.W.S. is an investigator of the Howard Hughes Medical Institute. This research was supported in part by Grant EXB02-0031-0018 from the NASA Exobiology Program to J.W.S. NR 47 TC 4 Z9 4 U1 6 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD DEC 16 PY 2014 VL 30 IS 49 BP 14916 EP 14925 DI 10.1021/la503933x PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA AX1CE UT WOS:000346685100025 PM 25402759 ER PT J AU Fan, TT Fang, SC Cavallari, JM Barnett, IJ Wang, ZX Su, L Byun, HM Lin, XH Baccarelli, AA Christiani, DC AF Fan, Tianteng Fang, Shona C. Cavallari, Jennifer M. Barnett, Ian J. Wang, Zhaoxi Su, Li Byun, Hyang-Min Lin, Xihong Baccarelli, Andrea A. Christiani, David C. TI Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study SO BMC PUBLIC HEALTH LA English DT Article ID BOILERMAKER CONSTRUCTION WORKERS; PARTICULATE AIR-POLLUTION; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; PROMOTER METHYLATION; PERIPHERAL-BLOOD; OXIDATIVE STRESS; WELDING FUMES; MATTER; ASSOCIATION AB Background: In occupational settings, boilermakers are exposed to high levels of metallic fine particulate matter (PM2.5) generated during the welding process. The effect of welding PM2.5 on heart rate variability (HRV) has been described, but the relationship between PM2.5, DNA methylation, and HRV is not known. Methods: In this repeated-measures panel study, we recorded resting HRV and measured DNA methylation levels in transposable elements Alu and long interspersed nuclear element-1 (LINE-1) in peripheral blood leukocytes under ambient conditions (pre-shift) and right after a welding task (post-shift) among 66 welders. We also monitored personal PM2.5 level in the ambient environment and during the welding procedure. Results: The concentration of welding PM2.5 was significantly higher than background levels in the union hall (0.43 mg/m(3) vs. 0.11 mg/m(3), p < 0.0001). The natural log of transformed power in the high frequency range (ln HF) had a significantly negative association with PM2.5 exposure (beta = -0.76, p = 0.035). pNN10 and pNN20 also had a negative association with PM2.5 exposure (beta = -0.16%, p = 0.006 and beta = -0.13%, p = 0.030, respectively). PM2.5 was positively associated with LINE-1 methylation [beta = 0.79%, 5-methylcytosince (% mC), p = 0.013]; adjusted for covariates. LINE-1 methylation did not show an independent association with HRV. Conclusions: Acute decline of HRV was observed following exposure to welding PM2.5 and evidence for an epigenetic response of transposable elements to short-term exposure to high-level metal-rich particulates was reported. C1 [Fan, Tianteng; Fang, Shona C.; Cavallari, Jennifer M.; Wang, Zhaoxi; Su, Li; Byun, Hyang-Min; Baccarelli, Andrea A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Fang, Shona C.; Lin, Xihong] New England Res Inst, Watertown, MA 02172 USA. [Cavallari, Jennifer M.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Barnett, Ian J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Baccarelli, Andrea A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640; Byun, Hyang-Min/0000-0002-6278-3165 FU National Institute of Environmental Health Sciences (NIEHS) [R01ES009860, P50ES000002] FX This research was supported by the National Institute of Environmental Health Sciences (NIEHS) grant numbers R01ES009860 and P50ES000002. We thank the participants and the leadership of Local 29 of the International Brotherhood of Boilermakers, Iron Ship Builders, Blacksmiths, Forgers and Helpers in Quincy, MA. NR 44 TC 6 Z9 6 U1 1 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD DEC 16 PY 2014 VL 14 AR 1279 DI 10.1186/1471-2458-14-1279 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX4AE UT WOS:000346875800001 PM 25512264 ER PT J AU Slow, S Florkowski, CM Chambers, ST Priest, PC Stewart, AW Jennings, LC Livesey, JH Camargo, CA Scragg, R Murdoch, DR AF Slow, Sandy Florkowski, Christopher M. Chambers, Stephen T. Priest, Patricia C. Stewart, Alistair W. Jennings, Lance C. Livesey, John H. Camargo, Carlos A., Jr. Scragg, Robert Murdoch, David R. TI CHRISTMAS 2014: GOING TO EXTREMES Effect of monthly vitamin D-3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; DEPRESSION; CHRISTCHURCH; SYMPTOMS; ANXIETY; IMPACT; AREAS AB Objective To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Design Opportunistic addition to an established randomised double blind placebo controlled trial. Setting Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. Participants 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Intervention Participants were randomised to receive an oral dose of either 200 000 IU vitamin D-3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. Main outcome measure This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. Results 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (X-2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; X-2 P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly higher after the earthquake (X-2 P=0.007) but did not differ between treatment groups. Conclusion In this trial, vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults. Trial registration Australian New Zealand Clinical C1 [Slow, Sandy; Florkowski, Christopher M.; Chambers, Stephen T.; Jennings, Lance C.; Murdoch, David R.] Univ Otago, Dept Pathol, Christchurch, New Zealand. [Florkowski, Christopher M.; Jennings, Lance C.; Livesey, John H.; Murdoch, David R.] Canterbury Hlth Labs, Christchurch, New Zealand. [Chambers, Stephen T.] Christchurch Hosp, Dept Infect Dis, Christchurch, New Zealand. [Priest, Patricia C.] Univ Otago, Dept Prevent & Social Med, Dunedin, New Zealand. [Stewart, Alistair W.; Scragg, Robert] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Slow, S (reprint author), Univ Otago, Dept Pathol, POB 4345, Christchurch, New Zealand. EM sandy.slow@otago.ac.nz FU Health Research Council of New Zealand FX The study was funded by the Health Research Council of New Zealand. The Health Research Council was not involved in the design or conduct of the study, the collection, management, analysis and interpretation of the data, or the preparation, review or approval of the manuscript. All authors were independent from the funders. NR 26 TC 0 Z9 0 U1 1 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD DEC 16 PY 2014 VL 349 AR g7260 DI 10.1136/bmj.g7260 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AX2HK UT WOS:000346763900006 PM 25516139 ER PT J AU Hsu, A Conell-Price, J Cenzer, IS Eng, C Huang, AJ Rice-Trumble, K Lee, SJ AF Hsu, Amy Conell-Price, Jessamyn Cenzer, Irena Stijacic Eng, Catherine Huang, Alison J. Rice-Trumble, Kathy Lee, Sei J. TI Predictors of urinary incontinence in communityd-welling frail older adults with diabetes mellitus in a cross-sectional study SO BMC GERIATRICS LA English DT Article DE Urinary incontinence; Frail older adults; Diabetes mellitus ID QUALITY-OF-LIFE; NURSING-HOME RESIDENTS; POSTMENOPAUSAL WOMEN; GERIATRIC SYNDROMES; OVERACTIVE BLADDER; UNITED-STATES; HEALTH; RISK; PREVALENCE; CARE AB Background: Diabetes mellitus is a potent risk factor for urinary incontinence. Previous studies of incontinence in patients with diabetes have focused on younger, healthier patients. Our objective was to characterize risk factors for urinary incontinence among frail older adults with diabetes mellitus in a real-world clinical setting. Methods: We performed a cross-sectional analysis on enrollees at On Lok (the original Program for All-Inclusive Care of the Elderly) between October 2004 and December 2010. Enrollees were community-dwelling, nursing home-eligible older adults with diabetes mellitus (N = 447). Our outcome was urinary incontinence measures (n = 2602) assessed every 6 months as "never incontinent", "seldom incontinent" (occurring less than once per week), or "often incontinent" (occurring more than once per week). Urinary incontinence was dichotomized ("never" versus "seldom" and "often" incontinent). We performed multivariate mixed effects logistic regression analysis with demographic (age, gender and ethnicity), geriatric (dependence on others for ambulation or transferring; cognitive impairment), diabetes-related factors (hemoglobin A1c level; use of insulin and other glucose-lowering medications; presence of renal, ophthalmologic, neurological and peripheral vascular complications), depressive symptoms and diuretic use. Results: The majority of participants were 75 years or older (72%), Asian (65%) and female (66%). Demographic factors independently associated with incontinence included older age (OR for age >85, 3.13, 95% CI: 2.15-4.56; Reference: Age <75) and African American or other race (OR 2.12, 95% CI: 1.14-3.93; Reference: Asian). Geriatric factors included: dependence on others for ambulation (OR 1.48, 95% CI: 1.19-1.84) and transferring (OR 2.02, 95% CI: 1.58-2.58) and being cognitively impaired (OR 1.41, 95% CI: 1.15-1.73). Diabetes-related factors associated included use of insulin (OR 2.62, 95% CI: 1.67-4.13) and oral glucose-lowering agents (OR 1.81, 95% CI: 1.33-2.45). Urinary incontinence was not associated with gender, hemoglobin A1c level or depressive symptoms. Conclusions: Geriatric factors such as the inability to ambulate or transfer independently are important predictors of urinary incontinence among frail older adults with diabetes mellitus. Clinicians should address mobility and cognitive impairment as much as diabetes-related factors in their assessment of urinary incontinence in this population. C1 [Hsu, Amy; Cenzer, Irena Stijacic; Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA 94122 USA. [Hsu, Amy; Cenzer, Irena Stijacic; Eng, Catherine; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Conell-Price, Jessamyn] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eng, Catherine; Rice-Trumble, Kathy] On Lok Lifeways, San Francisco, CA USA. [Huang, Alison J.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Hsu, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St,181G, San Francisco, CA 94122 USA. EM Amy.Hsu@ucsf.edu FU Beeson Career Development Award - National Institution on Aging [K23AG040779]; American Federation of Aging Research FX This material is the result of work supported with resources and the use of facilities at the San Francisco VA Medical Center. Dr. Sei Lee's effort was supported by the Beeson Career Development Award (K23AG040779) funded by the National Institution on Aging and the American Federation of Aging Research. NR 36 TC 2 Z9 3 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PD DEC 16 PY 2014 VL 14 AR 137 DI 10.1186/1471-2318-14-137 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AX2AU UT WOS:000346746300001 PM 25514968 ER PT J AU Rosenson, RS Davidson, MH Hirsh, BJ Kathiresan, S Gaudet, D AF Rosenson, Robert S. Davidson, Michael H. Hirsh, Benjamin J. Kathiresan, Sekar Gaudet, Daniel TI Genetics and Causality of Triglyceride-Rich Lipoproteins in Atherosclerotic Cardiovascular Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE atherosclerosis; cardiovascular disease; genetics; triglyceride; triglyceride-rich lipoproteins ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; APOLIPOPROTEIN C-III; ALIPOGENE TIPARVOVEC AAV1-LPLS447X; PAPER GLOBAL RECOMMENDATIONS; TISSUE-SPECIFIC EXPRESSION; CYTOSOLIC LIPID DROPLETS; GENOME-WIDE ASSOCIATION; EXTENDED-RELEASE NIACIN; OF-FUNCTION MUTATIONS AB Triglycerides represent 1 component of a heterogeneous pool of triglyceride-rich lipoproteins (TGRLs). The reliance on triglycerides or TGRLs as cardiovascular disease (CVD) risk biomarkers prompted investigations into therapies that lower plasma triglycerides as a means to reduce CVD events. Genetic studies identified TGRL components and pathways involved in their synthesis and metabolism. We advocate that only a subset of genetic mechanisms regulating TGRLs contribute to the risk of CVD events. This " omic" approach recently resulted in new targets for reducing CVD events. (C) 2014 by the American College of Cardiology Foundation. C1 [Rosenson, Robert S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Davidson, Michael H.] Univ Chicago, Pritzker Sch Med, Div Cardiol, Chicago, IL 60637 USA. [Hirsh, Benjamin J.] Mt Sinai Hosp, New York, NY 10029 USA. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gaudet, Daniel] Univ Montreal, Dept Med, ECOGENE 21, Chicoutimi, PQ, Canada. [Gaudet, Daniel] Univ Montreal, Dept Med, Lipid Clin, Chicoutimi, PQ, Canada. RP Rosenson, RS (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM robert.rosenson@mssm.edu NR 154 TC 32 Z9 34 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 16 PY 2014 VL 64 IS 23 BP 2525 EP 2540 DI 10.1016/j.jacc.2014.09.042 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW0EF UT WOS:000345962400013 PM 25500239 ER PT J AU Lamming, DW AF Lamming, Dudley W. TI Diminished mTOR signaling: a common mode of action for endocrine longevity factors SO SPRINGERPLUS LA English DT Review DE Calorie restriction; Rapamycin; Insulin resistance; Longevity ID AMES DWARF MICE; GLUCAGON-LIKE PEPTIDE-1; IMPROVES INSULIN SENSITIVITY; BETA-CELL PROLIFERATION; MAMMALIAN LIFE-SPAN; CALORIC RESTRICTION; DIETARY RESTRICTION; FAT-METABOLISM; EXTENDS LIFE; ALZHEIMERS-DISEASE AB Since the initial observation that a calorie-restricted (CR) diet can extend rodent lifespan, many genetic and pharmaceutical interventions that also extend lifespan in mammals have been discovered. The mechanism by which CR and these other interventions extend lifespan is the subject of significant debate and research. One proposed mechanism is that CR promotes longevity by increasing insulin sensitivity, but recent findings that dissociate longevity and insulin sensitivity cast doubt on this hypothesis. These findings can be reconciled if longevity is promoted not via increased insulin sensitivity, but instead via decreased PI3K/Akt/mTOR pathway signaling. This review presents a unifying hypothesis that explains the lifespan-extending effects of a variety of genetic mutations and pharmaceutical interventions and points towards new molecular pathways which may also be leveraged to promote healthy aging. C1 [Lamming, Dudley W.] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53706 USA. [Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Lamming, DW (reprint author), Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI 53706 USA. EM dlamming@medicine.wisc.edu OI Lamming, Dudley/0000-0002-0079-4467 FU National Institute of Health [AG041765]; UW-Madison School of Medicine and Public Health; UW-Madison Department of Medicine; William S. Middleton Memorial Veterans Hospital FX This review benefited greatly from the advice of D.E. Cohen, and we also thank A.K. Linnemann for helpful suggestions about CCK and E.L. Baar for critical reading of the manuscript. The Lamming lab is supported by a grant from the National Institute of Health (AG041765) and startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government. NR 112 TC 13 Z9 15 U1 1 U2 4 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PD DEC 15 PY 2014 VL 3 AR 735 DI 10.1186/2193-1801-3-735 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CO4HY UT WOS:000359123000002 PM 25674466 ER PT J AU Jin, L Datta, PK AF Jin, Lin Datta, Pran K. TI Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21(Cip1) by modulating the transcription factor Sp1 SO CELL CYCLE LA English DT Article DE STRAP; Sp1; transcription factor; cell cycle; ubiquitination; STRAP; serine threonine kinase receptor-associated protein; Sp1; specificity protein 1; Sp; KLF; specificity protein; Kruppel-like factor; SWI; SNF; SWItch; Sucrose nonfermentable; p300; CBP; p300; CREB-binding protein; TSS; transcription start site; MEF; mouse embryonic fibroblast; HNF4; hepatocyte nuclear factor 4; TSA; trichostatin A; HDAC1; histone deacetylase 1; HDAC2; histone deacetylase 2; HDAC3; histone deacetylase 3; NF-YA; nuclear transcription factor Y subunit alpha; TR I; II; TGF- receptor I; II; RNase; A ribonuclease A; CDK2; cyclin-dependent kinase 2; CDK4; cyclin-dependent kinase 4; PARP; poly (ADP-ribose) polymerase; RhoA; Ras homolog gene family; member A ID GENE-TRANSCRIPTION; CANCER-CELLS; LUNG-CANCER; EXPRESSION; PROTEINS; PROMOTER; BINDING; OVEREXPRESSION; PROGRESSION; INHIBITION AB We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21(Cip1). However, the functional mechanism of regulation of E-cadherin and p21(Cip1) by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21(Cip1) by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21(Cip1) promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21(Cip1) by >4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21(Cip1) by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21(Cip1) and to tumor progression. C1 [Jin, Lin; Datta, Pran K.] Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. [Jin, Lin; Datta, Pran K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Datta, PK (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. EM prandatta@uabmc.edu FU Veterans Affairs Merit Review Award; [R01 CA095195] FX This study was supported by R01 CA095195, and Veterans Affairs Merit Review Award (to PK Datta). NR 36 TC 4 Z9 4 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2014 VL 13 IS 24 BP 3909 EP 3920 DI 10.4161/15384101.2014.973310 PG 12 WC Cell Biology SC Cell Biology GA AZ6KU UT WOS:000348329600020 PM 25483064 ER PT J AU Wang, ZM Zhu, B Zhang, MF Parikh, H Jia, JP Chung, CC Sampson, JN Hoskins, JW Hutchinson, A Burdette, L Ibrahim, A Hautman, C Raj, PS Abnet, CC Adjei, AA Ahlbom, A Albanes, D Allen, NE Ambrosone, CB Aldrich, M Amiano, P Amos, C Andersson, U Andriole, G Andrulis, IL Arici, C Arslan, AA Austin, MA Baris, D Barkauskas, DA Bassig, BA Freeman, LEB Berg, CD Berndt, SI Bertazzi, PA Biritwum, RB Black, A Blot, W Boeing, H Boffetta, P Bolton, K Boutron-Ruault, MC Bracci, PM Brennan, P Brinton, LA Brotzman, M Bueno-de-Mesquita, HB Buring, JE Butler, MA Cai, QY Cancel-Tassin, G Canzian, F Cao, GW Caporaso, NE Carrato, A Carreon, T Carta, A Chang, GC Chang, IS Chang-Claude, J Che, X Chen, CJ Chen, CY Chen, CH Chen, C Chen, KY Chen, YM Chokkalingam, AP Chu, LW Clavel-Chapelon, F Colditz, GA Colt, JS Conti, D Cook, MB Cortessis, VK Crawford, ED Cussenot, O Davis, FG De Vivo, I Deng, X Ding, T Dinney, CP Di Stefano, AL Diver, WR Duell, EJ Elena, JW Fan, JH Feigelson, HS Feychting, M Figueroa, JD Flanagan, AM Fraumeni, JF Freedman, ND Fridley, BL Fuchs, CS Gago-Dominguez, M Gallinger, S Gao, YT Gapstur, SM Garcia-Closas, M Garcia-Closas, R Gastier-Foster, JM Gaziano, JM Gerhard, DS Giffen, CA Giles, GG Gillanders, EM Giovannucci, EL Goggins, M Gokgoz, N Goldstein, AM Gonzalez, C Gorlick, R Greene, MH Gross, M Grossman, HB Grubb, R Gu, J Guan, P Haiman, CA Hallmans, G Hankinson, SE Harris, CC Hartge, P Hattinger, C Hayes, RB He, QC Helman, L Henderson, BE Henriksson, R Hoffman-Bolton, J Hohensee, C Holly, EA Hong, YC Hoover, RN Hosgood, HD Hsiao, CF Hsing, AW Hsiung, CA Hu, N Hu, W Hu, ZB Huang, MS Hunter, DJ Inskip, PD Ito, H Jacobs, EJ Jacobs, KB Jenab, M Ji, BT Johansen, C Johansson, M Johnson, A Kaaks, R Kamat, AM Kamineni, A Karagas, M Khanna, C Khaw, KT Kim, C Kim, IS Kim, JH Kim, YH Kim, YC Kim, YT Kang, CH Jung, YJ Kitahara, CM Klein, AP Klein, R Kogevinas, M Koh, WP Kohno, T Kolonel, LN Kooperberg, C Kratz, CP Krogh, V Kunitoh, H Kurtz, RC Kurucu, N Lan, Q Lathrop, M Lau, CC Lecanda, F Lee, KM Lee, MP Le Marchand, L Lerner, SP Li, DH Liao, LM Lim, WY Lin, DX Lin, J Lindstrom, S Linet, MS Lissowska, J Liu, JJ Ljungberg, B Lloreta, J Lu, DR Ma, J Malats, N Mannisto, S Marina, N Mastrangelo, G Matsuo, K McGlynn, KA McKean-Cowdin, R McNeill, LH McWilliams, RR Melin, BS Meltzer, PS Mensah, JE Miao, XP Michaud, DS Mondul, AM Moore, LE Muir, K Niwa, S Olson, SH Orr, N Panico, S Park, JY Patel, AV Patino-Garcia, A Pavanello, S Peeters, PHM Peplonska, B Peters, U Petersen, GM Picci, P Pike, MC Porru, S Prescott, J Pu, X Purdue, MP Qiao, YL Rajaraman, P Riboli, E Risch, HA Rodabough, RJ Rothman, N Ruder, AM Ryu, JS Sanson, M Schned, A Schumacher, FR Schwartz, AG Schwartz, KL Schwenn, M Scotlandi, K Seow, A Serra, C Serra, M Sesso, HD Severi, G Shen, HB Shen, M Shete, S Shiraishi, K Shu, XO Siddiq, A Sierrasesumaga, L Sierri, S Sihoe, ADL Silverman, DT Simon, M Southey, MC Spector, L Spitz, M Stampfer, M Stattin, P Stern, MC Stevens, VL Stolzenberg-Solomon, RZ Stram, DO Strom, SS Su, WC Sund, M Sung, SW Swerdlow, A Tan, W Tanaka, H Tang, W Tang, ZZ Tardon, A Tay, E Taylor, PR Tettey, Y Thomas, DM Tirabosco, R Tjonneland, A Tobias, GS Toro, JR Travis, RC Trichopoulos, D Troisi, R Truelove, A Tsai, YH Tucker, MA Tumino, R Van Den Berg, D Van Den Eeden, SK Vermeulen, R Vineis, P Visvanathan, K Vogel, U Wang, CY Wang, CF Wang, JW Wang, SS Weiderpass, E Weinstein, SJ Wentzensen, N Wheeler, W White, E Wiencke, JK Wolk, A Wolpin, BM Wong, MP Wrensch, M Wu, C Wu, TC Wu, XF Wu, YL Wunder, JS Xiang, YB Xu, J Yang, HP Yang, PC Yatabe, Y Ye, YQ Yeboah, ED Yin, ZH Ying, C Yu, CJ Yu, K Yuan, JM Zanetti, KA Zeleniuch-Jacquotte, A Zheng, W Zhou, BS Mirabello, L Savage, SA Kraft, P Chanock, SJ Yeager, M Landi, MT Shi, JX Chatterjee, N Amundadottir, LT AF Wang, Zhaoming Zhu, Bin Zhang, Mingfeng Parikh, Hemang Jia, Jinping Chung, Charles C. Sampson, Joshua N. Hoskins, Jason W. Hutchinson, Amy Burdette, Laurie Ibrahim, Abdisamad Hautman, Christopher Raj, Preethi S. Abnet, Christian C. Adjei, Andrew A. Ahlbom, Anders Albanes, Demetrius Allen, Naomi E. Ambrosone, Christine B. Aldrich, Melinda Amiano, Pilar Amos, Christopher Andersson, Ulrika Andriole, Gerald, Jr. Andrulis, Irene L. Arici, Cecilia Arslan, Alan A. Austin, Melissa A. Baris, Dalsu Barkauskas, Donald A. Bassig, Bryan A. Freeman, Laura E. Beane Berg, Christine D. Berndt, Sonja I. Bertazzi, Pier Alberto Biritwum, Richard B. Black, Amanda Blot, William Boeing, Heiner Boffetta, Paolo Bolton, Kelly Boutron-Ruault, Marie-Christine Bracci, Paige M. Brennan, Paul Brinton, Louise A. Brotzman, Michelle Bueno-de-Mesquita, H. Bas Buring, Julie E. Butler, Mary Ann Cai, Qiuyin Cancel-Tassin, Geraldine Canzian, Federico Cao, Guangwen Caporaso, Neil E. Carrato, Alfredo Carreon, Tania Carta, Angela Chang, Gee-Chen Chang, I-Shou Chang-Claude, Jenny Che, Xu Chen, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chokkalingam, Anand P. Chu, Lisa W. Clavel-Chapelon, Francoise Colditz, Graham A. Colt, Joanne S. Conti, David Cook, Michael B. Cortessis, Victoria K. Crawford, E. David Cussenot, Olivier Davis, Faith G. De Vivo, Immaculata Deng, Xiang Ding, Ti Dinney, Colin P. Di Stefano, Anna Luisa Diver, W. Ryan Duell, Eric J. Elena, Joanne W. Fan, Jin-Hu Feigelson, Heather Spencer Feychting, Maria Figueroa, Jonine D. Flanagan, Adrienne M. Fraumeni, Joseph F., Jr. Freedman, Neal D. Fridley, Brooke L. Fuchs, Charles S. Gago-Dominguez, Manuela Gallinger, Steven Gao, Yu-Tang Gapstur, Susan M. Garcia-Closas, Montserrat Garcia-Closas, Reina Gastier-Foster, Julie M. Gaziano, J. Michael Gerhard, Daniela S. Giffen, Carol A. Giles, Graham G. Gillanders, Elizabeth M. Giovannucci, Edward L. Goggins, Michael Gokgoz, Nalan Goldstein, Alisa M. Gonzalez, Carlos Gorlick, Richard Greene, Mark H. Gross, Myron Grossman, H. Barton Grubb, Robert, III Gu, Jian Guan, Peng Haiman, Christopher A. Hallmans, Goran Hankinson, Susan E. Harris, Curtis C. Hartge, Patricia Hattinger, Claudia Hayes, Richard B. He, Qincheng Helman, Lee Henderson, Brian E. Henriksson, Roger Hoffman-Bolton, Judith Hohensee, Chancellor Holly, Elizabeth A. Hong, Yun-Chul Hoover, Robert N. Hosgood, H. Dean Hsiao, Chin-Fu Hsing, Ann W. Hsiung, Chao Agnes Hu, Nan Hu, Wei Hu, Zhibin Huang, Ming-Shyan Hunter, David J. Inskip, Peter D. Ito, Hidemi Jacobs, Eric J. Jacobs, Kevin B. Jenab, Mazda Ji, Bu-Tian Johansen, Christoffer Johansson, Mattias Johnson, Alison Kaaks, Rudolf Kamat, Ashish M. Kamineni, Aruna Karagas, Margaret Khanna, Chand Khaw, Kay-Tee Kim, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kang, Chang Hyun Jung, Yoo Jin Kitahara, Cari M. Klein, Alison P. Klein, Robert Kogevinas, Manolis Koh, Woon-Puay Kohno, Takashi Kolonel, Laurence N. Kooperberg, Charles Kratz, Christian P. Krogh, Vittorio Kunitoh, Hideo Kurtz, Robert C. Kurucu, Nilgun Lan, Qing Lathrop, Mark Lau, Ching C. Lecanda, Fernando Lee, Kyoung-Mu Lee, Maxwell P. Le Marchand, Loic Lerner, Seth P. Li, Donghui Liao, Linda M. Lim, Wei-Yen Lin, Dongxin Lin, Jie Lindstrom, Sara Linet, Martha S. Lissowska, Jolanta Liu, Jianjun Ljungberg, Boerje Lloreta, Josep Lu, Daru Ma, Jing Malats, Nuria Mannisto, Satu Marina, Neyssa Mastrangelo, Giuseppe Matsuo, Keitaro McGlynn, Katherine A. McKean-Cowdin, Roberta McNeill, Lorna H. McWilliams, Robert R. Melin, Beatrice S. Meltzer, Paul S. Mensah, James E. Miao, Xiaoping Michaud, Dominique S. Mondul, Alison M. Moore, Lee E. Muir, Kenneth Niwa, Shelley Olson, Sara H. Orr, Nick Panico, Salvatore Park, Jae Yong Patel, Alpa V. Patino-Garcia, Ana Pavanello, Sofia Peeters, Petra H. M. Peplonska, Beata Peters, Ulrike Petersen, Gloria M. Picci, Piero Pike, Malcolm C. Porru, Stefano Prescott, Jennifer Pu, Xia Purdue, Mark P. Qiao, You-Lin Rajaraman, Preetha Riboli, Elio Risch, Harvey A. Rodabough, Rebecca J. Rothman, Nathaniel Ruder, Avima M. Ryu, Jeong-Seon Sanson, Marc Schned, Alan Schumacher, Fredrick R. Schwartz, Ann G. Schwartz, Kendra L. Schwenn, Molly Scotlandi, Katia Seow, Adeline Serra, Consol Serra, Massimo Sesso, Howard D. Severi, Gianluca Shen, Hongbing Shen, Min Shete, Sanjay Shiraishi, Kouya Shu, Xiao-Ou Siddiq, Afshan Sierrasesumaga, Luis Sierri, Sabina Sihoe, Alan Dart Loon Silverman, Debra T. Simon, Matthias Southey, Melissa C. Spector, Logan Spitz, Margaret Stampfer, Meir Stattin, Par Stern, Mariana C. Stevens, Victoria L. Stolzenberg-Solomon, Rachael Z. Stram, Daniel O. Strom, Sara S. Su, Wu-Chou Sund, Malin Sung, Sook Whan Swerdlow, Anthony Tan, Wen Tanaka, Hideo Tang, Wei Tang, Ze-Zhang Tardon, Adonina Tay, Evelyn Taylor, Philip R. Tettey, Yao Thomas, David M. Tirabosco, Roberto Tjonneland, Anne Tobias, Geoffrey S. Toro, Jorge R. Travis, Ruth C. Trichopoulos, Dimitrios Troisi, Rebecca Truelove, Ann Tsai, Ying-Huang Tucker, Margaret A. Tumino, Rosario Van Den Berg, David Van Den Eeden, Stephen K. Vermeulen, Roel Vineis, Paolo Visvanathan, Kala Vogel, Ulla Wang, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S. Weiderpass, Elisabete Weinstein, Stephanie J. Wentzensen, Nicolas Wheeler, William White, Emily Wiencke, John K. Wolk, Alicja Wolpin, Brian M. Wong, Maria Pik Wrensch, Margaret Wu, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wunder, Jay S. Xiang, Yong-Bing Xu, Jun Yang, Hannah P. Yang, Pan-Chyr Yatabe, Yasushi Ye, Yuanqing Yeboah, Edward D. Yin, Zhihua Ying, Chen Yu, Chong-Jen Yu, Kai Yuan, Jian-Min Zanetti, Krista A. Zeleniuch-Jacquotte, Anne Zheng, Wei Zhou, Baosen Mirabello, Lisa Savage, Sharon A. Kraft, Peter Chanock, Stephen J. Yeager, Meredith Landi, Maria Terese Shi, Jianxin Chatterjee, Nilanjan Amundadottir, Laufey T. TI Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33 SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISM; POSTMENOPAUSAL BREAST-CANCER; TERT PROMOTER MUTATIONS; 2 SUSCEPTIBILITY LOCI; TELOMERE LENGTH; LUNG-CANCER; PROSTATE-CANCER; PANCREATIC-CANCER; DNA METHYLATION AB Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and P-Conditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and P-Conditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and P-Conditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10 215 and P-Conditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene(Region 2: rs451360; P = 1.90 x 10(-18) and P-Conditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. C1 [Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Albanes, Demetrius; Baris, Dalsu; Bassig, Bryan A.; Freeman, Laura E. Beane; Berndt, Sonja I.; Black, Amanda; Bolton, Kelly; Brinton, Louise A.; Caporaso, Neil E.; Colt, Joanne S.; Cook, Michael B.; Deng, Xiang; Figueroa, Jonine D.; Fraumeni, Joseph F., Jr.; Freedman, Neal D.; Garcia-Closas, Montserrat; Goldstein, Alisa M.; Greene, Mark H.; Hartge, Patricia; Hayes, Richard B.; Hoover, Robert N.; Hu, Nan; Hu, Wei; Inskip, Peter D.; Ji, Bu-Tian; Kim, Christopher; Kitahara, Cari M.; Kratz, Christian P.; Lan, Qing; Liao, Linda M.; Linet, Martha S.; McGlynn, Katherine A.; Mondul, Alison M.; Moore, Lee E.; Purdue, Mark P.; Rajaraman, Preetha; Rothman, Nathaniel; Shen, Min; Silverman, Debra T.; Stolzenberg-Solomon, Rachael Z.; Tang, Wei; Taylor, Philip R.; Tobias, Geoffrey S.; Toro, Jorge R.; Troisi, Rebecca; Tucker, Margaret A.; Wang, Chaoyu; Wang, Junwen; Weinstein, Stephanie J.; Wentzensen, Nicolas; Yang, Hannah P.; Yu, Kai; Mirabello, Lisa; Savage, Sharon A.; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. 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[Lee, Kyoung-Mu] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea. RP Amundadottir, LT (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM amundadottirl@mail.nih.gov RI Serra, Massimo/J-4878-2016; Tobias, Geoffrey/M-4135-2016; Weiderpass, Elisabete/M-4029-2016; Wang, Junwen/D-3700-2011; Hattinger, Claudia/Q-1212-2016; Kitahara, Cari/R-8267-2016; Jung, Yoojin/G-2519-2015; Kogevinas, Manolis/C-3918-2017; Vermeulen, Roel/F-8037-2011; bertazzi, pietro alberto/D-5039-2017; Vogel, Ulla/I-5048-2012; Abnet, Christian/C-4111-2015; Malats, Nuria/H-7041-2015; Chen, Chien-Jen/C-6976-2008; Patino-Garcia, Ana/I-4299-2012; Tucker, Margaret/B-4297-2015; Simon, Matthias/F-3046-2014; Cook, Michael/A-5641-2009; Purdue, Mark/C-9228-2016; Savage, Sharon/B-9747-2015; Tanaka, Hideo/A-8145-2016; Krogh, Vittorio/K-2628-2016; Panico, Salvatore/K-6506-2016; Amundadottir, Laufey/L-7656-2016; Gallinger, Steven/E-4575-2013; Garcia-Closas, Montserrat /F-3871-2015; Chang, I-Shou/D-2084-2010; Hsiao, Chin-Fu/E-3993-2010; Boutron-Ruault, Marie-Christine/H-3936-2014; Albanes, Demetrius/B-9749-2015; Beane Freeman, Laura/C-4468-2015; Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; miao, xiaoping/C-4336-2011; Andrulis, Irene/E-7267-2013; Fridley, Brooke/D-8315-2015; Hsiung, Chao Agnes/E-3994-2010 OI Qiao, You-Lin/0000-0001-6380-0871; Spector, Logan/0000-0003-2516-0222; Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Cancel-Tassin, Geraldine/0000-0002-9583-6382; Liao, Linda/0000-0002-1923-5294; Mondul, Alison/0000-0002-8843-1416; Hoskins, Jason/0000-0001-6944-1996; Hayes, Richard/0000-0002-0918-661X; Serra, Massimo/0000-0003-0742-1177; Tobias, Geoffrey/0000-0002-2878-8253; Weiderpass, Elisabete/0000-0003-2237-0128; Wang, Junwen/0000-0002-4432-4707; Hattinger, Claudia/0000-0002-9316-5095; Vermeulen, Roel/0000-0003-4082-8163; bertazzi, pietro alberto/0000-0003-3475-2449; Duell, Eric J/0000-0001-5256-0163; Vogel, Ulla/0000-0001-6807-1524; Abnet, Christian/0000-0002-3008-7843; Malats, Nuria/0000-0003-2538-3784; Cook, Michael/0000-0002-0533-7302; Purdue, Mark/0000-0003-1177-3108; Savage, Sharon/0000-0001-6006-0740; Krogh, Vittorio/0000-0003-0122-8624; Panico, Salvatore/0000-0002-5498-8312; Amundadottir, Laufey/0000-0003-1859-8971; Garcia-Closas, Montserrat /0000-0003-1033-2650; Beane Freeman, Laura/0000-0003-1294-4124; Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098; miao, xiaoping/0000-0002-6818-9722; Fridley, Brooke/0000-0001-7739-7956; FU US National Institutes of Health (NIH), National Cancer Institute [HHSN261200800001E]; Intramural Research Program FX This work was supported by the Intramural Research Program and by contract number HHSN261200800001E of the US National Institutes of Health (NIH), National Cancer Institute. 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 U.S. Government. Additional funding acknowledgements are listed in Supplementary Material. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 89 TC 25 Z9 25 U1 4 U2 59 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2014 VL 23 IS 24 BP 6616 EP 6633 DI 10.1093/hmg/ddu363 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0FP UT WOS:000347921900017 PM 25027329 ER PT J AU Georgieva, L Rees, E Moran, JL Chambert, KD Milanova, V Craddock, N Purcell, S Sklar, P McCarroll, S Holmans, P O'Donovan, MC Owen, MJ Kirov, G AF Georgieva, Lyudmila Rees, Elliott Moran, Jennifer L. Chambert, Kimberly D. Milanova, Vihra Craddock, Nicholas Purcell, Shaun Sklar, Pamela McCarroll, Steven Holmans, Peter O'Donovan, Michael C. Owen, Michael J. Kirov, George TI De novo CNVs in bipolar affective disorder and schizophrenia SO HUMAN MOLECULAR GENETICS LA English DT Article ID COPY-NUMBER VARIANTS; CASE-CONTROL SAMPLE; ASSOCIATION; DUPLICATIONS; DELETIONS; DEPRESSION; GENETICS; 16P11.2; RISK AB An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all their parents. Copy number variants were called by PennCNV and filtered for frequency (<1%) and size (>10 kb). Putative de novo CNVs were validated with the z-score algorithm, manual inspection of log R ratios (LRR) and qPCR probes. We found 15 de novo CNVs in BD (4.1% rate) and 6 in SZ (7.9% rate). Combining results with previous studies and using a cut-off of > 100 kb, the rate of de novo CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were significant. The median size of de novo CNVs in BD (448 kb) was also intermediate between SZ (613 kb) and controls (338 kb), but only the comparison between SZ and controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus (16p11.2). Sporadic or early onset cases were not more likely to have de novo CNVs. We conclude that de novo CNVs play a smaller role in BD compared with SZ. Patients with a positive family history can also harbour de novo mutations. C1 [Georgieva, Lyudmila; Rees, Elliott; Craddock, Nicholas; Holmans, Peter; O'Donovan, Michael C.; Owen, Michael J.; Kirov, George] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. [Moran, Jennifer L.; Chambert, Kimberly D.; McCarroll, Steven] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Milanova, Vihra] Med Univ, Dept Psychiat, Sofia, Bulgaria. [Purcell, Shaun; Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [Purcell, Shaun; Sklar, Pamela] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Kirov, G (reprint author), Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. EM kirov@cardiff.ac.uk RI Holmans, Peter/F-4518-2015; OI Holmans, Peter/0000-0003-0870-9412; Moran, Jennifer/0000-0002-5664-4716 FU Medical Research Council (MRC) Centre [G0800509, G0801418]; MRC PhD Studentship; Janssen Research Foundation [045856]; Wellcome Trust [045856]; Research Councils UK FX The work at Cardiff University was funded by Medical Research Council (MRC) Centre (G0800509) and Program Grants (G0801418) and an MRC PhD Studentship to E.R. Funding for the recruitment of trios in Bulgaria was provided by the Janssen Research Foundation in 1999-2004, Ref: 045856. Funding for the recruitment of BD samples in the UK was provided by the Wellcome Trust as a Training Fellowship to G.K. in 1996-1999, Ref: 045856. The samples were genotyped at the Broad Institute, USA, funded by a philanthropic gift to the Stanley Center for Psychiatric Research. Funding to pay the Open Access publication charges for this article was provided by Research Councils UK. NR 35 TC 14 Z9 14 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2014 VL 23 IS 24 BP 6677 EP 6683 DI 10.1093/hmg/ddu379 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AZ0FP UT WOS:000347921900022 PM 25055870 ER PT J AU Bisio, A Zamborszky, J Zaccara, S Lion, M Tebaldi, T Sharma, V Raimondi, I Alessandrini, F Ciribilli, Y Inga, A AF Bisio, Alessandra Zamborszky, Judit Zaccara, Sara Lion, Mattia Tebaldi, Toma Sharma, Vasundhara Raimondi, Ivan Alessandrini, Federica Ciribilli, Yari Inga, Alberto TI Cooperative interactions between p53 and NF kappa B enhance cell plasticity SO ONCOTARGET LA English DT Article DE p53; NFkB; chemotherapy; doxorubicin; TNF alpha; EMT; synergy; breast cancer ID ESTROGEN-RECEPTOR-ALPHA; BREAST-CANCER CELLS; TRANSCRIPTION FACTORS; PROMOTES METASTASIS; MICROARRAY DATA; AP-1 ACTIVITY; ACTIVATION; GENES; IDENTIFICATION; RESPONSES AB The p53 and NF kappa B sequence-specific transcription factors play crucial roles in cell proliferation and survival with critical, even if typically opposite, effects on cancer progression. To investigate a possible crosstalk between p53 and NF kappa B driven by chemotherapy-induced responses in the context of an inflammatory microenvironment, we performed a proof of concept study using MCF7 cells. Transcriptome analyses upon single or combined treatments with doxorubicin (Doxo, 1.5 mu M) and the NF kappa B inducer TNF-alpha (TNF alpha, 5ng/ml) revealed 432 upregulated (log(2) FC>2), and 390 repressed genes (log(2) FC<-2) for the Doxo+TNF alpha treatment. 239 up-regulated and 161 repressed genes were synergistically regulated by the double treatment. Annotation and pathway analyses of Doxo+TNF alpha selectively up-regulated genes indicated strong enrichment for cell migration terms. A panel of genes was examined by qPCR coupled to p53 activation by Doxo, 5-Fluoruracil and Nutlin-3a, or to p53 or NF kappa B inhibition. Transcriptome data were confirmed for 12 of 15 selected genes and seven (PLK3, LAMP3, ETV7, UNC5B, NTN1, DUSP5, SNAI1) were synergistically up-regulated after Doxo+TNF alpha and dependent both on p53 and NF kappa B. Migration assays consistently showed an increase in motility for MCF7 cells upon Doxo+TNF alpha. A signature of 29 Doxo+TNF alpha highly synergistic genes exhibited prognostic value for luminal breast cancer patients, with adverse outcome correlating with higher relative expression. We propose that the crosstalk between p53 and NF kappa B can lead to the activation of specific gene expression programs that may impact on cancer phenotypes and potentially modify the efficacy of cancer therapy. C1 [Bisio, Alessandra; Zamborszky, Judit; Zaccara, Sara; Lion, Mattia; Sharma, Vasundhara; Raimondi, Ivan; Alessandrini, Federica; Ciribilli, Yari; Inga, Alberto] Univ Trento, Ctr Integrat Biol, Lab Transcript Networks, CIBIO, I-38123 Trento, Italy. [Tebaldi, Toma] Univ Trento, Ctr Integrat Biol, Lab Translat Genom, CIBIO, I-38123 Trento, Italy. [Zamborszky, Judit] Res Ctr Nat Sci, Inst Enzymol, Budapest, Hungary. [Lion, Mattia] Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. RP Ciribilli, Y (reprint author), Univ Trento, Ctr Integrat Biol, Lab Transcript Networks, CIBIO, I-38123 Trento, Italy. EM ciribilli@science.unitn.it; inga@science.unitn.it FU Italian Association for Cancer Research, AIRC (IG) [12869]; Pezcoller Foundation FX We thank Dr. Valentina Adami (CIBIO High-throughput screening facility), Dr. Isabella Pesce (CIBIO Cell Separation facility), Ms. Sonia Leonardelli, Mr. Dennis Pedri for technical support. This work was supported by the Italian Association for Cancer Research, AIRC (IG grant # 12869 to AI). IR is supported by a Fellowship from the Pezcoller Foundation. NR 63 TC 7 Z9 7 U1 3 U2 8 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 15 PY 2014 VL 5 IS 23 BP 12111 EP 12125 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AT UT WOS:000348037700026 PM 25401416 ER PT J AU Baldwin, LA Hoff, JT Lefringhouse, J Zhang, M Jia, CH Liu, ZY Erfani, S Jin, HY Xu, M She, QB Van Nagell, JR Wang, C Chen, L Plattner, R Kaetzel, DM Luo, J Lu, M West, D Liu, CM Ueland, FR Drapkin, R Zhou, BP Yang, XWH AF Baldwin, Lauren A. Hoff, John T. Lefringhouse, Jason Zhang, Michael Jia, Changhe Liu, Zeyi Erfani, Sonia Jin, Hongyan Xu, Mei She, Qing-Bai Van Nagell, John R. Wang, Chi Chen, Li Plattner, Rina Kaetzel, David M. Luo, Jia Lu, Michael West, Dava Liu, Chunming Ueland, Fred R. Drapkin, Ronny Zhou, Binhua P. Yang, Xiuwei H. TI CD151-alpha 3 beta 1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling SO ONCOTARGET LA English DT Article DE CD151 integrin EMT tumor growth ovarian cancer ID EPITHELIAL-MESENCHYMAL TRANSITION; TETRASPANIN CD151; CELL-ADHESION; BREAST-CANCER; SEROUS CARCINOMA; PROSTATE-CANCER; GENE-EXPRESSION; COLON-CANCER; LOW-GRADE; METASTASIS AB Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-alpha 3 beta 1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or alpha 3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-alpha 3 beta 1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of beta-catenin and Axin-2 as well as resistance to the inhibition in beta-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-alpha 3 beta 1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling. C1 [Baldwin, Lauren A.; Hoff, John T.; Lefringhouse, Jason; Zhang, Michael; Jia, Changhe; Liu, Zeyi; Erfani, Sonia; Jin, Hongyan; Xu, Mei; She, Qing-Bai; Wang, Chi; Chen, Li; Plattner, Rina; Luo, Jia; Liu, Chunming; Zhou, Binhua P.; Yang, Xiuwei H.] Univ Kentucky, Dept Mol & Cellular Biochem, Dept Pharmacol & Nutr Sci, Lexington, KY 40506 USA. [Baldwin, Lauren A.; Hoff, John T.; Lefringhouse, Jason; Zhang, Michael; Jia, Changhe; Liu, Zeyi; Erfani, Sonia; Jin, Hongyan; Xu, Mei; She, Qing-Bai; Van Nagell, John R.; Wang, Chi; Chen, Li; Plattner, Rina; Luo, Jia; West, Dava; Liu, Chunming; Ueland, Fred R.; Zhou, Binhua P.; Yang, Xiuwei H.] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA. [Baldwin, Lauren A.; Hoff, John T.; Lefringhouse, Jason; Van Nagell, John R.; West, Dava; Ueland, Fred R.] Univ Kentucky, Coll Med, Dept Pathol & Lab Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Lexington, KY USA. [Kaetzel, David M.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Lu, Michael] Florida Atlantic Univ, Dept Biomed Sci, Boca Raton, FL 33431 USA. [Drapkin, Ronny] Dana Farber Canc Inst, Dept Canc Biol & Pathol, Boston, MA 02115 USA. [Drapkin, Ronny] Harvard Univ, Sch Med, Boston, MA USA. RP Yang, XWH (reprint author), Univ Kentucky, Dept Mol & Cellular Biochem, Dept Pharmacol & Nutr Sci, Lexington, KY 40506 USA. EM xiuwei-yang@uky.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU DOD Ovarian Cancer Research Program [W81XWH-08-1-0120]; Franchi Investigator Award/Dana-Farber Cancer Institute; S.G. Komen for the Cure career catalyst award; NIH COBRE/pilot project fund; American Cancer Society [IRG85-001-25] FX This study was supported in part through DOD Ovarian Cancer Research Program W81XWH-08-1-0120, Franchi Investigator Award/Dana-Farber Cancer Institute, S.G. Komen for the Cure career catalyst award, NIH COBRE/pilot project fund and A pilot project grant from American Cancer Society #IRG85-001-25 to X.H. Yang. NR 65 TC 17 Z9 20 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC 15 PY 2014 VL 5 IS 23 BP 12203 EP 12217 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ2AT UT WOS:000348037700033 PM 25356755 ER PT J AU Cho, I Slight, SP Nanji, KC Seger, DL Maniam, N Dykes, PC Bates, DW AF Cho, Insook Slight, Sarah P. Nanji, Karen C. Seger, Diane L. Maniam, Nivethietha Dykes, Patricia C. Bates, David W. TI Understanding physicians' behavior toward alerts about nephrotoxic medications in outpatients: a cross-sectional analysis SO BMC NEPHROLOGY LA English DT Article DE Medication safety; Clinical decision support system; Renal insufficiency; Drug prescribing; Chronic kidney disease ID CHRONIC KIDNEY-DISEASE; DECISION-SUPPORT ALERTS; RENAL-INSUFFICIENCY; ORDER ENTRY; CARE; QUALITY; SAFETY; SYSTEM; TRIAL AB Background: Although most outpatients are relatively healthy, many have chronic renal insufficiency, and high override rates for suggestions on renal dosing have been observed. To better understand the override of renal dosing alerts in an outpatient setting, we conducted a study to evaluate which patients were more frequently prescribed contraindicated medications, to assess providers' responses to suggestions, and to examine the drugs involved and the reasons for overrides. Methods: We obtained data on renal alert overrides and the coded reasons for overrides cited by providers at the time of prescription from outpatient clinics and ambulatory hospital-based practices at a large academic health care center over a period of 3 years, from January 2009 to December 2011. For detailed chart review, a group of 6 trained clinicians developed the appropriateness criteria with excellent inter-rater reliability (kappa = 0.93). We stratified providers by override frequency and then drew samples from the high-and low-frequency groups. We measured the rate of total overrides, rate of appropriate overrides, medications overridden, and the reason(s) for override. Results: A total of 4120 renal alerts were triggered by 584 prescribers in the study period, among which 78.2% (3,221) were overridden. Almost half of the alerts were triggered by 40 providers and one-third was triggered by high-frequency overriders. The appropriateness rates were fairly similar, at 28.4% and 31.6% for high-and low frequency overriders, respectively. Metformin, glyburide, hydrochlorothiazide, and nitrofurantoin were the most common drugs overridden. Physicians' appropriateness rates were higher than the rates for nurse practitioners (32.9% vs. 22.1%). Physicians with low frequency override rates had higher levels of appropriateness for metformin than the high frequency overriders (P = 0.005). Conclusion: A small number of providers accounted for a large fraction of overrides, as was the case with a small number of drugs. These data suggest that a focused intervention targeting primarily these providers and medications has the potential to improve medication safety. C1 [Cho, Insook; Slight, Sarah P.; Dykes, Patricia C.; Bates, David W.] Brigham & Womens Hosp, Ctr Patient Safety Res & Practice, Div Gen Internal Med, Boston, MA 02115 USA. [Cho, Insook] Inha Univ, Dept Nursing, Inchon, South Korea. [Cho, Insook; Slight, Sarah P.; Nanji, Karen C.; Dykes, Patricia C.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Seger, Diane L.; Maniam, Nivethietha; Bates, David W.] Partners Healthcare Syst Inc, Wellesley, MA USA. [Slight, Sarah P.] Univ Nottingham, Div Primary Care, Nottingham, England. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cho, I (reprint author), Brigham & Womens Hosp, Ctr Patient Safety Res & Practice, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. EM insook.cho@inha.ac.kr FU Centers for Education and Research on Therapeutics (CERT), Agency for Healthcare Research and Quality, Rockville, MD, USA [U19HS021094]; Korea Research Foundation - Korean Government (MOEHRD) [KRF-2013R1A1A2006387] FX This research was sponsored by the Centers for Education and Research on Therapeutics (CERT Grant # U19HS021094), Agency for Healthcare Research and Quality, Rockville, MD, USA. I.C. was also supported by a Korea Research Foundation Grant, which was funded by the Korean Government (MOEHRD; No. KRF-2013R1A1A2006387). NR 22 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2369 J9 BMC NEPHROL JI BMC Nephrol. PD DEC 15 PY 2014 VL 15 AR 200 DI 10.1186/1471-2369-15-200 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AY6AC UT WOS:000347649200002 PM 25511564 ER PT J AU Fogelgren, B Zuo, XF Buonato, JM Vasilyev, A Baek, JI Choi, SY Chacon-Heszele, MF Palmyre, A Polgar, N Drummond, I Park, KM Lazzara, MJ Lipschutz, JH AF Fogelgren, Ben Zuo, Xiaofeng Buonato, Janine M. Vasilyev, Aleksandr Baek, Jeong-In Choi, Soo Young Chacon-Heszele, Maria F. Palmyre, Aurelien Polgar, Noemi Drummond, Iain Park, Kwon Moo Lazzara, Matthew J. Lipschutz, Joshua H. TI Exocyst Sec10 protects renal tubule cells from injury by EGFR/MAPK activation and effects on endocytosis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE AKI; EGFR; exocyst; MAPK ID GROWTH-FACTOR RECEPTOR; ACUTE KIDNEY INJURY; CRITICALLY-ILL PATIENTS; EPITHELIAL-CELLS; PRIMARY CILIOGENESIS; EARLY PHASE; IN-VITRO; FAILURE; RECOVERY; COMPLEX AB Acute kidney injury is common and has a high mortality rate, and no effective treatment exists other than supportive care. Using cell culture models, we previously demonstrated that exocyst Sec10 overexpression reduced damage to renal tubule cells and speeded recovery and that the protective effect was mediated by higher basal levels of mitogen-activated protein kinase (MAPK) signaling. The exocyst, a highly-conserved eight-protein complex, is known for regulating protein trafficking. Here we show that the exocyst biochemically interacts with the epidermal growth factor receptor (EGFR), which is upstream of MAPK, and Sec10-overexpressing cells express greater levels of phosphorylated (active) ERK, the final step in the MAPK pathway, in response to EGF stimulation. EGFR endocytosis, which has been linked to activation of the MAPK pathway, increases in Sec10-overexpressing cells, and gefitinib, a specific EGFR inhibitor, and Dynasore, a dynamin inhibitor, both reduce EGFR endocytosis. In turn, inhibition of the MAPK pathway reduces ligand-mediated EGFR endocytosis, suggesting a potential feedback of elevated ERK activity on EGFR endocytosis. Gefitinib also decreases MAPK signaling in Sec10-overexpressing cells to levels seen in control cells and, demonstrating a causal role for EGFR, reverses the protective effect of Sec10 overexpression following cell injury in vitro. Finally, using an in vivo zebrafish model of acute kidney injury, morpholino-induced knockdown of sec10 increases renal tubule cell susceptibility to injury. Taken together, these results suggest that the exocyst, acting through EGFR, endocytosis, and the MAPK pathway is a candidate therapeutic target for acute kidney injury. C1 [Fogelgren, Ben; Polgar, Noemi] Univ Hawaii, Dept Anat, Dept Biochem & Physiol, Honolulu, HI 96822 USA. [Zuo, Xiaofeng; Baek, Jeong-In; Choi, Soo Young; Lipschutz, Joshua H.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Buonato, Janine M.] Univ Penn, Dept Chem & Biomol Engn, Philadelphia, PA USA. [Vasilyev, Aleksandr; Palmyre, Aurelien] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chacon-Heszele, Maria F.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Drummond, Iain] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Drummond, Iain] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Park, Kwon Moo] Kyungpook Natl Univ, Sch Med, Dept Anat & Plus BK21, Taegu, South Korea. [Lipschutz, Joshua H.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. RP Lipschutz, JH (reprint author), Med Univ S Carolina, Clin Sci Bldg 829,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM Lipschut@musc.edu OI Polgar, Noemi/0000-0002-8400-162X FU Veterans Affairs (Merit Award); National Institute of Diabetes and Digestive and Kidney Diseases [DK-069909, DK-070980, K01-DK-087852, R0-3DK-100738] FX This work was supported in part by grants from the Veterans Affairs (Merit Award to J. H. Lipschutz), National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-069909 and DK-070980 (to J. H. Lipschutz) and K01-DK-087852 and R0-3DK-100738 (to B. Fogelgren F.), Satellite Healthcare (Norman S. Coplon Extramural Research Grant to J. H. Lipschutz), Hawaii Community Foundation (12ADVC-51347 to B. F.), March of Dimes (Basil O'Connor No. 5-FY14-56 to B. Fogelgren), University of Hawaii RCMI-BRIDGES (5G12MD007601, Pilot Award to B. Fogelgren), Hepato/Renal Fibrocystic Diseases Core Center at the University of Alabama at Birmingham (5P30-DK-074038, Pilot Award to B. Fogelgren), National Science Foundation (Graduate Research Fellowship Award to J. M. Buonato), and the Korean Government (National Research Foundation Grant NRF-2011-220-E00001 to K. Park). NR 52 TC 3 Z9 3 U1 1 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC 15 PY 2014 VL 307 IS 12 BP F1334 EP F1341 DI 10.1152/ajprenal.00032.2014 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AW7ZS UT WOS:000346480900003 PM 25298525 ER PT J AU Zheng, P Wang, YY Li, HB AF Zheng, Peng Wang, Yanyan Li, Hongbin TI Reversible Unfolding-Refolding of Rubredoxin: A Single-Molecule Force Spectroscopy Study SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE force spectroscopy; iron priming; metalloproteins; protein folding; single-molecule studies ID FERRIC-THIOLATE BONDS; MECHANICAL STABILITY; PYROCOCCUS-FURIOSUS; PROTEIN AB In metalloproteins, metal centers serve as active sites for a range of functional purposes and as important structural elements to facilitate protein folding and assembly. It is challenging to observe the reversible unfolding and refolding of metalloproteins because of a loss or decomposition of the metal center. Here, the reversible unfolding-refolding of the iron-sulfur protein rubredoxin was observed directly using single-molecule force spectroscopy. The results demonstrate that the iron can remain attached to the CXXC motif when rubredoxin is unfolded. Upon relaxation, the unfolded rubredoxin can refold into its native holo state with the reconstituted FeS4 center. The possible loss of iron from the unfolded protein prevents rubredoxin from refolding into its native holo state. These results demonstrated that unfolding of rubredoxin is reversible, as long as the iron remains attached, and provide experimental evidence for the iron-priming mechanism for the folding of rubredoxin. C1 [Wang, Yanyan; Li, Hongbin] Tianjin Univ, State Key Lab Precis Measurements Technol & Instr, Sch Precis Instrument & Optoelect Engn, Tianjin 300072, Peoples R China. [Zheng, Peng; Li, Hongbin] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. [Zheng, Peng] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA USA. [Zheng, Peng] Harvard Univ, Sch Med, Dept Biol Chem & Mol Med, Boston, MA USA. RP Li, HB (reprint author), Tianjin Univ, State Key Lab Precis Measurements Technol & Instr, Sch Precis Instrument & Optoelect Engn, Tianjin 300072, Peoples R China. EM Hongbin@chem.ubc.ca RI Li, Hongbin/G-2949-2012 OI Li, Hongbin/0000-0001-7813-1332 FU Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation; Canada Research Chairs program; Tianjin University FX We thank Chengzhi He and Ashlee Jollymore for technical assistance. This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, the Canada Research Chairs program, and Tianjin University. NR 23 TC 6 Z9 6 U1 4 U2 38 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD DEC 15 PY 2014 VL 53 IS 51 BP 14060 EP 14063 DI 10.1002/anie.201408105 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AW8BA UT WOS:000346484400015 PM 25314323 ER PT J AU Priolo, C Pyne, S Rose, J Regan, ER Zadra, G Photopoulos, C Cacciatore, S Schultz, D Scaglia, N McDunn, J De Marzo, AM Loda, M AF Priolo, Carmen Pyne, Saumyadipta Rose, Joshua Regan, Erzsebet Ravasz Zadra, Giorgia Photopoulos, Cornelia Cacciatore, Stefano Schultz, Denise Scaglia, Natalia McDunn, Jonathan De Marzo, Angelo M. Loda, Massimo TI AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer SO CANCER RESEARCH LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; EXPRESSION; PATHWAYS; GROWTH; CELLS AB Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostatespecific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics. C1 [Priolo, Carmen; Pyne, Saumyadipta; Rose, Joshua; Zadra, Giorgia; Photopoulos, Cornelia; Cacciatore, Stefano; Scaglia, Natalia; Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Regan, Erzsebet Ravasz] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Schultz, Denise; De Marzo, Angelo M.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [McDunn, Jonathan] Metabolon Inc, Durham, NC USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. RP Loda, M (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1536, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu OI Cacciatore, Stefano/0000-0001-7052-7156 FU Nuclea Biomarkers; Lank Center/Dana-Farber Cancer Institute; DBT, India; MoSPI, India; DST, India [SR/SA/MS: 516/07, 21/04/2008]; Fondazione Italiana per la Ricerca sul Cancro, Italy; Prostate Cancer Foundation; Friends of Dana-Farber fund; Patrick C. Walsh Prostate Cancer Research Fund Award; [R01CA131945]; [P50 CA90381]; Associazione Italiana per la Ricerca sul Cancro FX This work was supported by R01CA131945, P50 CA90381, the Prostate Cancer Foundation, and philanthropic funds from Nuclea Biomarkers (Pittsfield, MA; M. Loda); the P.A.R.T. Investigatorship in Prostate Cancer Award from the Lank Center/Dana-Farber Cancer Institute and a Friends of Dana-Farber fund (C. Priolo); the Ramalingswami Fellowship from DBT, MoS&PI and DST (CMS Project SR/SA/MS: 516/07; 21/04/2008), India (S. Pyne); the Patrick C. Walsh Prostate Cancer Research Fund Award (A. M. De Marzo); and the Fondazione Italiana per la Ricerca sul Cancro, Italy (S. Cacciatore). NR 20 TC 14 Z9 14 U1 0 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2014 VL 74 IS 24 BP 7198 EP 7204 DI 10.1158/0008-5472.CAN-14-1490 PG 7 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900007 PM 25322691 ER PT J AU Bersani, F Lee, J Yu, M Morris, R Desai, R Ramaswamy, S Toner, M Haber, DA Parekkadan, B AF Bersani, Francesca Lee, Jungwoo Yu, Min Morris, Robert Desai, Rushil Ramaswamy, Sridhar Toner, Mehmet Haber, Daniel A. Parekkadan, Biju TI Bioengineered Implantable Scaffolds as a Tool to Study Stromal-Derived Factors in Metastatic Cancer Models SO CANCER RESEARCH LA English DT Article ID INVERTED COLLOIDAL CRYSTALS; TISSUE-ENGINEERED BONE; PROSTATE-CANCER; BREAST-CANCER; PRIMARY TUMORS; STEM-CELLS; IN-VITRO; PROGRESSION; EXPRESSION; MICROENVIRONMENTS AB Modeling the hematogenous spread of cancer cells to distant organs poses one of the greatest challenges in the study of human metastasis. Both tumor cell-intrinsic properties as well as interactions with reactive stromal cells contribute to this process, but identification of relevant stromal signals has been hampered by the lack of models allowing characterization of the metastatic niche. Here, we describe an implantable bioengineered scaffold, amenable to in vivo imaging, ex vivo manipulation, and serial transplantation for the continuous study of human metastasis in mice. Orthotopic or systemic inoculation of tagged human cancer cells into the mouse leads to the release of circulating tumor cells into the vasculature, which seed the scaffold, initiating a metastatic tumor focus. Mouse stromal cells can be readily recovered and profiled, revealing differential expression of cytokines, such as IL1 beta, from tumor-bearing versus unseeded scaffolds. Finally, this platform can be used to test the effect of drugs on suppressing initiation of metastatic lesions. This generalizable model to study cancer metastasis may thus identify key stromal-derived factors with important implications for basic and translational cancer research. C1 [Bersani, Francesca; Yu, Min; Morris, Robert; Desai, Rushil; Ramaswamy, Sridhar; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Bersani, Francesca; Yu, Min; Morris, Robert; Desai, Rushil; Ramaswamy, Sridhar; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. [Lee, Jungwoo; Toner, Mehmet; Parekkadan, Biju] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. [Lee, Jungwoo; Toner, Mehmet; Parekkadan, Biju] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA USA. [Lee, Jungwoo; Toner, Mehmet; Parekkadan, Biju] Shriners Hosp Children, Boston, MA USA. [Yu, Min; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Parekkadan, Biju] Harvard Stem Cell Inst, Boston, MA USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu; biju_parekkadan@hms.harvard.edu FU NIH [R01EB012521, K01DK087770, K99CA163671, R01CA129933]; Shriners Hospitals for Children; National Foundation for Cancer Research; Howard Hughes Medical Institute FX This work was supported in part by NIH grants R01EB012521 (B. Parekkadan), K01DK087770 (B. Parekkadan), K99CA163671 (J. Lee), R01CA129933 (D. A. Haber and F. Bersani), the Shriners Hospitals for Children (J. Lee and B. Parekkadan), the National Foundation for Cancer Research (D. A. Haber), and the Howard Hughes Medical Institute (D. A. Haber). NR 43 TC 5 Z9 5 U1 1 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2014 VL 74 IS 24 BP 7229 EP 7238 DI 10.1158/0008-5472.CAN-14-1809 PG 10 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900010 PM 25339351 ER PT J AU Samkoe, KS Tichauer, KM Gunn, JR Wells, WA Hasan, T Pogue, BW AF Samkoe, Kimberley S. Tichauer, Kenneth M. Gunn, Jason R. Wells, Wendy A. Hasan, Tayyaba Pogue, Brian W. TI Quantitative In Vivo Immunohistochemistry of Epidermal Growth Factor Receptor Using a Receptor Concentration Imaging Approach SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; SITU HYBRIDIZATION; DRUG DISCOVERY; QUANTIFICATION; BINDING; EXPRESSION; THERAPY; PET; UTILITY; MODELS AB As receptor-targeted therapeutics become increasingly used in clinical oncology, the ability to quantify protein expression and pharmacokinetics in vivo is imperative to ensure successful individualized treatment plans. Current standards for receptor analysis are performed on extracted tissues. These measurements are static and often physiologically irrelevant; therefore, only a partial picture of available receptors for drug targeting in vivo is provided. Until recently, in vivo measurements were limited by the inability to separate delivery, binding, and retention effects, but this can be circumvented by a dual-tracer approach for referencing the detected signal. We hypothesized that in vivo receptor concentration imaging (RCI) would be superior to ex vivo immunohistochemistry (IHC). Using multiple xenograft tumor models with varying EGFR expression, we determined the EGFR concentration in each model using a novel targeted agent (anti-EGFR affibody-IRDye800CW conjugate) along with a simultaneously delivered reference agent (control affibody-IRDye680RD conjugate). The RCI-calculated in vivo receptor concentration was strongly correlated with ex vivo pathologist-scored IHC and computer-quantified ex vivo immunofluorescence. In contrast, no correlation was observed with ex vivo Western blot analysis or in vitro flow-cytometry assays. Overall, our results argue that in vivo RCI provides a robust measure of receptor expression equivalent to ex vivo immunostaining, with implications for use in noninvasive monitoring of therapy or therapeutic guidance during surgery. (C)2014 AACR. C1 [Samkoe, Kimberley S.; Pogue, Brian W.] Dartmouth Coll, Geisel Sch Med, Dept Surg, Lebanon, NH 03756 USA. [Samkoe, Kimberley S.; Gunn, Jason R.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Tichauer, Kenneth M.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Wells, Wendy A.] Dartmouth Coll, Dartmouth Hitchcock Med Ctr, Dept Pathol, Geisel Sch Med, Lebanon, NH 03756 USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Samkoe, KS (reprint author), Dartmouth Coll, Dartmouth Hitchcock Med Ctr, Dept Surg, Geisel Sch Med, One Med Ctr Dr, Lebanon, NH 03756 USA. EM Kimberley.S.Samkoe@Dartmouth.edu FU NIH [R01CA156177, U54CA151662, P01CA84201] FX This work has been supported by NIH grants R01CA156177 (K.S. Samkoe, B.W. Pogue, and T. Hasan), U54CA151662 (B.W. Pogue, J.R. Gunn, and K.S. Samkoe), and P01CA84201 (K.S. Samkoe, J.R. Gunn, and B.W. Pogue) NR 44 TC 13 Z9 14 U1 1 U2 19 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2014 VL 74 IS 24 BP 7465 EP 7474 DI 10.1158/0008-5472.CAN-14-0141 PG 10 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900030 PM 25344226 ER PT J AU Chan, CT Qi, J Smith, W Paranol, R Mazitschek, R West, N Reeves, R Chiosis, G Schreiber, SL Bradner, JE Paulmurugan, R Gambhir, SS AF Chan, C. T. Qi, J. Smith, W. Paranol, R. Mazitschek, R. West, N. Reeves, R. Chiosis, G. Schreiber, S. L. Bradner, J. E. Paulmurugan, R. Gambhir, S. S. TI Syntheses and Discovery of a Novel Class of Cinnamic Hydroxamates as Histone Deacetylase Inhibitors by Multimodality Molecular Imaging in Living Subjects SO CANCER RESEARCH LA English DT Article ID CANCER-THERAPY; HEAT-SHOCK-PROTEIN-90 INHIBITORS; CHAPERONE FUNCTION; ANTICANCER AGENTS; RECEPTOR; VORINOSTAT; EXPRESSION; CELLS; ACID; IDENTIFICATION AB Histone deacetylases (HDAC) that regulate gene expression are being explored as cancer therapeutic targets. In this study, we focused on HDAC6 based on its ability to inhibit cancerous Hsp90 chaperone activities by disrupting Hsp90/p23 interactions. To identify novel HDAC6 inhibitors, we used a dual-luciferase reporter system in cell culture and living mice by bioluminescence imaging (BLI). On the basis of existing knowledge, a library of hydrazone compounds was generated for screening by coupling cinnamic hydroxamates with aldehydes and ketones. Potency and selectivity were determined by in vitro HDAC profiling assays, with further evaluation to inhibit Hsp90(alpha/beta)/p23 interactions by BLI. In this manner, we identified compound 1A12 as a dose-dependent inhibitor of Hsp90(alpha/beta)/p23 interactions, UKE-1 myeloid cell proliferation, p21(waf1) upregulation, and acetylated histone H3 levels. 1A12 was efficacious in tumor xenografts expressing Hsp90(alpha)/p23 reporters relative to carrier control-treated mice as determined by BLI. Small animal F-18-FDG PET/CT imaging on the same cohort showed that 1A12 also inhibited glucose metabolism relative to control subjects. Ex vivo analyses of tumor lysates showed that 1A12 administration upregulated acetylated-H3 by approximately 3.5-fold. Taken together, our results describe the discovery and initial preclinical validation of a novel selective HDAC inhibitor. C1 [Chan, C. T.; Reeves, R.; Paulmurugan, R.; Gambhir, S. S.] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. [Chan, C. T.; Reeves, R.; Paulmurugan, R.; Gambhir, S. S.] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Chan, C. T.; Reeves, R.; Paulmurugan, R.; Gambhir, S. S.] Stanford Univ, Sch Med, Bio X Program, Stanford, CA 94305 USA. [Qi, J.; Smith, W.; Paranol, R.; West, N.; Bradner, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mazitschek, R.; Bradner, J. E.] Harvard Univ, Sch Med, Boston, MA USA. [Mazitschek, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mazitschek, R.; Schreiber, S. L.; Bradner, J. E.] Broad Inst, Cambridge, MA USA. [Chiosis, G.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Chiosis, G.] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Med Chem, New York, NY 10021 USA. [Gambhir, S. S.] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA. [Gambhir, S. S.] Stanford Univ, Sch Med, Div Nucl Med, Stanford, CA 94305 USA. RP Gambhir, SS (reprint author), Stanford Univ, 318 Campus Dr,Clark Ctr Room E150, Stanford, CA 94305 USA. EM sgambhir@stanford.edu FU NIH [NCI RO1 CA082214, NCI ICMIC P50CA114747, P50CA086355]; Susan Komen Postdoctoral Fellowship FX This research was supported by the NIH (grant number NCI RO1 CA082214), NCI ICMIC P50CA114747 at Stanford University (S.S. Gambhir), and the Susan Komen Postdoctoral Fellowship (C.T. Chan) and NIH P50CA086355 (R. Mazitschek) NR 49 TC 4 Z9 4 U1 1 U2 25 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2014 VL 74 IS 24 BP 7475 EP 7486 DI 10.1158/0008-5472.CAN-14-0197 PG 12 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900031 PM 25320008 ER PT J AU Kawasumi, M Bradner, JE Tolliday, N Thibodeau, R Sloan, H Brummond, KM Nghiem, P AF Kawasumi, Masaoki Bradner, James E. Tolliday, Nicola Thibodeau, Renee Sloan, Heather Brummond, Kay M. Nghiem, Paul TI Identification of ATR-Chk1 Pathway Inhibitors That Selectively Target p53-Deficient Cells without Directly Suppressing ATR Catalytic Activity SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGE RESPONSE; ATAXIA-TELANGIECTASIA; CANCER-CELLS; RADIOSENSITIZING AGENT; CYCLE CHECKPOINTS; PROTEIN-KINASE; G(2) ARREST; CHK1; P53; ACTIVATION AB Resistance to DNA-damaging chemotherapy is a barrier to effective treatment that appears to be augmented by p53 functional deficiency in many cancers. In p53-deficient cells in which the G(1)-S checkpoint is compromised, cell viability after DNA damage relies upon intact intra-S and G(2)-M checkpoints mediated by the ATR (ataxia telangiectasia and Rad3 related) and Chk1 kinases. Thus, a logical rationale to sensitize p53-deficient cancers to DNA-damaging chemotherapy is through the use of ATP-competitive inhibitors of ATR or Chk1. To discover small molecules that may act on uncharacterized components of the ATR pathway, we performed a phenotype-based screen of 9,195 compounds for their ability to inhibit hydroxyurea-induced phosphorylation of Ser345 on Chk1, known to be a critical ATR substrate. This effort led to the identification of four small-molecule compounds, three of which were derived from known bioactive library (anthothecol, dihydrocelastryl, and erysolin) and one of which was a novel synthetic compound termed MARPIN. These compounds all inhibited ATR-selective phosphorylation and sensitized p53-deficient cancer cells to DNA-damaging agents in vitro and in vivo. Notably, these compounds did not inhibit ATR catalytic activity in vitro, unlike typical ATP-competitive inhibitors, but acted in a mechanistically distinct manner to disable ATR-Chk1 function. Our results highlight a set of novel molecular probes to further elucidate druggable mechanisms to improve cancer therapeutic responses produced by DNA-damaging drugs. (C)2014 AACR. C1 [Kawasumi, Masaoki; Thibodeau, Renee; Sloan, Heather; Nghiem, Paul] Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98109 USA. [Bradner, James E.; Tolliday, Nicola] Broad Inst MIT & Harvard, Cambridge, MA USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Brummond, Kay M.] Univ Pittsburgh, Ctr Chem Methodol & Lib Dev, Pittsburgh, PA USA. [Nghiem, Paul] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Kawasumi, M (reprint author), Univ Washington, Dept Med, Div Dermatol, 850 Republ St,Room 242, Seattle, WA 98109 USA. EM kawasumi@uw.edu; pnghiem@uw.edu RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X FU NIH [R01-AR049832]; Dermatology Foundation; Michael Piepkorn Endowment for Dermatology Research at University of Washington FX This work was supported by the NIH (R01-AR049832; P. Nghiem), a Dermatology Foundation Career Development Award (M. Kawasumi), and the Michael Piepkorn Endowment for Dermatology Research at University of Washington. NR 50 TC 5 Z9 6 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2014 VL 74 IS 24 BP 7534 EP 7545 DI 10.1158/0008-5472.CAN-14-2650 PG 12 WC Oncology SC Oncology GA AW6FC UT WOS:000346363900036 PM 25336189 ER PT J AU Groeneweg, JW Hernandez, SF Byron, VF DiGloria, CM Lopez, H Scialabba, V Kim, M Zhang, L Borger, DR Tambouret, R Foster, R Rueda, BR Growdon, WB AF Groeneweg, Jolijn W. Hernandez, Silvia F. Byron, Virginia F. DiGloria, Celeste M. Lopez, Hector Scialabba, Vanessa Kim, Minji Zhang, Ling Borger, Darrell R. Tambouret, Rosemary Foster, Rosemary Rueda, Bo R. Growdon, Whitfield B. TI Dual HER2 Targeting Impedes Growth of HER2 Gene-Amplified Uterine Serous Carcinoma Xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; METASTATIC BREAST-CANCER; PHASE-III TRIAL; ENDOMETRIAL CARCINOMA; PROGNOSTIC INDICATOR; TRASTUZUMAB; LAPATINIB; RECEPTOR; AMPLIFICATION; THERAPY AB Purpose: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. We investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in vitro and in xenografts derived from USC cell lines and USC patient-derived xenografts. Experimental Design: Immunohistochemistry and FISH were performed to assess HER2 expression in 42 primary USC specimens. ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab or lapatinib. Cohorts of mice harboring xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human USC samples were treated with either vehicle, trastuzumab, lapatinib, or the combination of trastuzumab and lapatinib. Acute and chronic posttreatment tumor samples were assessed for downstream signaling alterations and examined for apoptosis and proliferation. Results: HER2 gene amplification (24%) correlated significantly with HER2 protein overexpression (55%). All models were impervious to single-agent trastuzumab treatment. Lapatinib decreased in vitro proliferation of all cell lines and in vivo growth of HER2-amplified xenografts (ARK2, EnCa1). In addition, dual therapy with trastuzumab and lapatinib resulted in significant antitumor activity only in ARK2 and EnCa1 tumors. Dual HER2 therapy induced on target alteration of downstream MAPK and PI3K pathway mediators only in HER2-amplified models, and was associated with increased apoptosis and decreased proliferation. Conclusions: Although trastuzumab alone did not impact USC growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2-amplified USC and may be a promising avenue for future investigation. (C) 2014 AACR. C1 [Groeneweg, Jolijn W.; Hernandez, Silvia F.; Byron, Virginia F.; DiGloria, Celeste M.; Kim, Minji; Zhang, Ling; Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Groeneweg, Jolijn W.; Hernandez, Silvia F.; Tambouret, Rosemary; Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Hector; Scialabba, Vanessa; Borger, Darrell R.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Tambouret, Rosemary] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, THR901,55 Fruit St, Boston, MA 02114 USA. EM wgrowdon@partners.org FU institutional K12 Proton Share NCI Grant [C06 CA059267]; Advanced Medical Research Foundation; Vincent Department of Obstetrics and Gynecology Research Funds FX This research was funded by an institutional K12 Proton Share NCI Grant C06 CA059267 (to W.B. Growdon), and funding from the Advanced Medical Research Foundation (to B.R. Rueda) and Vincent Department of Obstetrics and Gynecology Research Funds (to B.R. Rueda). NR 50 TC 6 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2014 VL 20 IS 24 BP 6517 EP 6528 DI 10.1158/1078-0432.CCR-14-1647 PG 12 WC Oncology SC Oncology GA AW7AZ UT WOS:000346418100031 PM 25294905 ER PT J AU Capelletti, M Dodge, ME Ercan, D Hammerman, PS Park, SI Kim, J Sasaki, H Jablons, DM Lipson, D Young, L Stephens, PJ Miller, VA Lindeman, NI Munir, KJ Richards, WG Janne, PA AF Capelletti, Marzia Dodge, Michael E. Ercan, Dalia Hammerman, Peter S. Park, Seung-Il Kim, Jhingook Sasaki, Hidefumi Jablons, David M. Lipson, Doron Young, Lauren Stephens, Phil J. Miller, Vincent A. Lindeman, Neal I. Munir, Kiara J. Richards, William G. Jaenne, Pasi A. TI Identification of Recurrent FGFR3-TACC3 Fusion Oncogenes from Lung Adenocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID NEVER SMOKERS; GENE FUSIONS; EGFR MUTATIONS; PHASE-II; CANCER; RET; ERLOTINIB; FEATURES; ALK; CHEMOTHERAPY AB Purpose: Targetable oncogenic alterations are detected more commonly in patients with non-small cell lung cancer (NSCLC) who never smoked cigarettes. For such patients, specific kinase inhibitors have emerged as effective clinical treatments. However, the currently known oncogenic alterations do not account for all never smokers who develop NSCLC. We sought to identify additional oncogenic alterations from patients with NSCLC to define additional treatment options. Experimental Design: We analyzed 576 lung adenocarcinomas from patients of Asian and Caucasian ethnicity. We identified a subset of cancers that did not harbor any known oncogenic alteration. We performed targeted next-generation sequencing (NGS) assay on 24 patients from this set with >75% tumor cell content. Results: EGFR mutations were the most common oncogenic alteration from both Asian (53%) and Caucasian (41.6%) patients. No known oncogenic alterations were present in 25.7% of Asian and 31% of Caucasian tumor specimens. We identified a FGFR3-TACC3 fusion event in one of 24 patients from this subset using targeted NGS. Two additional patients harboring FGFR3-TACC3 were identified by screening our entire cohort (overall prevalence, 0.5%). Expression of FGFR3-TACC3 led to IL3 independent growth in Ba/F3 cells. These cells were sensitive to pan-fibroblast growth factor receptor (pan-FGFR) inhibitors but not the epidermal growth factor (EGFR) inhibitor gefitinib. Conclusions: FGFR3-TACC3 rearrangements occur in a subset of patients with lung adenocarcinoma. Such patients should be considered for clinical trials featuring FGFR inhibitors. (C) 2014 AACR. C1 [Capelletti, Marzia; Dodge, Michael E.; Ercan, Dalia; Hammerman, Peter S.; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Park, Seung-Il] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Thorac Surg, Seoul, South Korea. [Kim, Jhingook] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Thorac Surg, Seoul, South Korea. [Sasaki, Hidefumi] Nagoya City Univ, Grad Sch Med Sci, Dept Oncol Immunol & Surg, Nagoya, Aichi, Japan. [Jablons, David M.] Univ Calif San Francisco, Dept Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Lipson, Doron; Young, Lauren; Stephens, Phil J.; Miller, Vincent A.] Fdn Med Inc, Cambridge, MA USA. [Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lindeman, Neal I.] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, Boston, MA 02115 USA. [Munir, Kiara J.; Richards, William G.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,HIM 223, Boston, MA 02215 USA. EM pasi_janne@dfci.harvard.edu FU Cammarata Family Foundation Research Fund; Nirenberg Fellowship at the Dana-Farber Cancer Institute; V Foundation Scholar Award; Scientific Research, Japan Society for the Promotion of Science (JSPS) [24592097] FX This work was supported by the Cammarata Family Foundation Research Fund (to M. Capelletti and P.A.Janne), the Nirenberg Fellowship at the Dana-Farber Cancer Institute (to M. Capelletti and P.A.Janne). P.S. Hammerman is supported by a V Foundation Scholar Award. H. Sasaki is supported by Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science (JSPS; No. 24592097). NR 41 TC 21 Z9 22 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2014 VL 20 IS 24 BP 6551 EP 6558 DI 10.1158/1078-0432.CCR-14-1337 PG 8 WC Oncology SC Oncology GA AW7AZ UT WOS:000346418100034 PM 25294908 ER PT J AU Sucker, A Zhao, F Real, B Heeke, C Bielefeld, N Massen, S Horn, S Moll, I Maltaner, R Horn, PA Schilling, B Sabbatino, F Lennerz, V Kloor, M Ferrone, S Schadendorf, D Falk, CS Griewank, K Paschen, A AF Sucker, Antje Zhao, Fang Real, Birgit Heeke, Christina Bielefeld, Nicola Massen, Stefan Horn, Susanne Moll, Iris Maltaner, Raffaela Horn, Peter A. Schilling, Bastian Sabbatino, Francesco Lennerz, Volker Kloor, Matthias Ferrone, Soldano Schadendorf, Dirk Falk, Christine S. Griewank, Klaus Paschen, Annette TI Genetic Evolution of T-cell Resistance in the Course of Melanoma Progression SO CLINICAL CANCER RESEARCH LA English DT Article ID EMBEDDED TISSUE-SECTIONS; I ANTIGEN-EXPRESSION; METASTATIC MELANOMA; TUMOR-ANTIGENS; IMMUNE ESCAPE; CANCER; IMMUNOTHERAPY; MUTATIONS; ANTIBODY; EPITOPE AB Purpose: CD8(+) T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells. Experimental Design: One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell-stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alterations affecting the tumor-T-cell interaction. Results: Metastases Ma-Mel-48a and Ma-Mel-48b, in contrast with Ma-Mel-48c, were infiltrated by T cells. The T-cell-stimulatory capacity was found to be strong for Ma-Mel-48a, lower for Ma-Mel-48b, and completely abrogated for Ma-Mel-48c cells. The latter proved to be HLA class I-negative due to an inactivating mutation in one allele of the beta-2-microglobulin (B2M) gene and concomitant loss of the other allele by a deletion on chromosome 15q. The same deletion was already present in Ma-Mel-48a and Ma-Mel-48b cells, pointing to an early acquired genetic event predisposing to development of beta 2m deficiency. Notably, the same chronology of genetic alterations was also observed in a second beta 2m-deficient melanoma model. Conclusion: Our study reveals a progressive loss in melanoma immunogenicity during the course of metastatic disease. The genetic evolvement of T-cell resistance suggests screening tumors for genetic alterations affecting immunogenicity could be clinically relevant in terms of predicting patient responses to T-cell-based immunotherapy. (C) 2014 AACR. C1 [Sucker, Antje; Zhao, Fang; Real, Birgit; Heeke, Christina; Bielefeld, Nicola; Horn, Susanne; Moll, Iris; Maltaner, Raffaela; Schilling, Bastian; Schadendorf, Dirk; Griewank, Klaus; Paschen, Annette] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Essen, Germany. [Sucker, Antje; Zhao, Fang; Real, Birgit; Heeke, Christina; Bielefeld, Nicola; Horn, Susanne; Moll, Iris; Maltaner, Raffaela; Horn, Peter A.; Schilling, Bastian; Schadendorf, Dirk; Griewank, Klaus; Paschen, Annette] German Canc Consortium DKTK, Heidelberg, Germany. [Massen, Stefan; Falk, Christine S.] Hannover Med Sch, Inst Transplantat Immunol, IFB Tx, Hannover, Germany. [Horn, Peter A.] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Essen, Germany. [Sabbatino, Francesco; Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lennerz, Volker] Johannes Gutenberg Univ Mainz, Univ Med Ctr, D-55122 Mainz, Germany. [Kloor, Matthias] Heidelberg Univ, Inst Pathol, Dept Appl Tumor Biol, Heidelberg, Germany. RP Paschen, A (reprint author), Univ Hosp Essen, Hufelandstr 55, D-45122 Essen, Germany. EM annette.paschen@uk-essen.de RI Sabbatino, Francesco/F-4992-2014; Griewank, Klaus/A-9097-2017 OI Sabbatino, Francesco/0000-0001-6431-8278; FU Helmholtz Alliance on Cancer Immunotherapy; NRW/EU-Ziel2-Programm [005-1006-0057]; DFG [TRR77]; Integrated Research and Treatment Centre Transplantation (IFB-Tx, BMBF) [01EO1302]; National Cancer Institute [RO1CA138188, RO1CA110249] FX This study was supported in part by the Helmholtz Alliance on Cancer Immunotherapy and by the NRW/EU-Ziel2-Programm 2007-2013 (005-1006-0057; to A. Paschen and D. Schadendorf); the DFG TRR77 and Integrated Research and Treatment Centre Transplantation (IFB-Tx, BMBF 01EO1302; to C.S. Falk); and PHS grants RO1CA138188 and RO1CA110249 awarded by the National Cancer Institute (to S. Ferrone). NR 47 TC 12 Z9 12 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2014 VL 20 IS 24 BP 6593 EP 6604 DI 10.1158/1078-0432.CCR-14-0567 PG 12 WC Oncology SC Oncology GA AW7AZ UT WOS:000346418100038 PM 25294904 ER PT J AU Emmanuel, C Chiew, YE George, J Etemadmoghadam, D Anglesio, MS Sharma, R Russell, P Kennedy, C Fereday, S Hung, JL Galletta, L Hogg, R Wain, GV Brand, A Balleine, R MacConaill, L Palescandolo, E Hunter, SM Campbell, I Dobrovic, A Wong, SQ Do, HD Clarke, CL Harnett, PR Bowtell, DDL deFazio, A AF Emmanuel, Catherine Chiew, Yoke-Eng George, Joshy Etemadmoghadam, Dariush Anglesio, Michael S. Sharma, Raghwa Russell, Peter Kennedy, Catherine Fereday, Sian Hung, Jillian Galletta, Laura Hogg, Russell Wain, Gerard V. Brand, Alison Balleine, Rosemary MacConaill, Laura Palescandolo, Emanuele Hunter, Sally M. Campbell, Ian Dobrovic, Alexander Wong, Stephen Q. Do, Hongdo Clarke, Christine L. Harnett, Paul R. Bowtell, David D. L. deFazio, Anna CA Australian Ovarian Canc Study AOCS TI Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-GRADE CARCINOMAS; BRAF MUTATIONS; OPEN-LABEL; KRAS; EXPRESSION; PROFILES; ACTIVATION; MELANOMA; SURVIVAL; WOMEN AB Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. (C) 2014 AACR. C1 [Emmanuel, Catherine; Chiew, Yoke-Eng; Kennedy, Catherine; Hung, Jillian; Hogg, Russell; Wain, Gerard V.; Brand, Alison; deFazio, Anna] Univ Sydney, Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW 2145, Australia. [Emmanuel, Catherine; Chiew, Yoke-Eng; Kennedy, Catherine; Hung, Jillian; Hogg, Russell; Wain, Gerard V.; Brand, Alison; Harnett, Paul R.; deFazio, Anna] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia. [Emmanuel, Catherine; Sharma, Raghwa; Kennedy, Catherine; Hogg, Russell; Wain, Gerard V.; Brand, Alison; Balleine, Rosemary; Clarke, Christine L.; Harnett, Paul R.; deFazio, Anna] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. [Emmanuel, Catherine; Chiew, Yoke-Eng; Kennedy, Catherine; Hung, Jillian; Balleine, Rosemary; Clarke, Christine L.; Harnett, Paul R.; deFazio, Anna] Westmead Hosp, Westmead Inst Canc Res, Westmead Millennium Inst, Sydney, NSW, Australia. [George, Joshy; Etemadmoghadam, Dariush; Anglesio, Michael S.; Fereday, Sian; Galletta, Laura; Hunter, Sally M.; Campbell, Ian; Dobrovic, Alexander; Wong, Stephen Q.; Do, Hongdo; Bowtell, David D. L.] Peter MacCallum Canc Inst, Canc Genom Program, East Melbourne, Vic, Australia. [Etemadmoghadam, Dariush; Bowtell, David D. L.] Univ Melbourne, Sir Peter MacCallum Canc Ctr, Dept Oncol, Parkville, Vic 3052, Australia. [Etemadmoghadam, Dariush; Campbell, Ian; Dobrovic, Alexander; Wong, Stephen Q.; Bowtell, David D. L.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Sharma, Raghwa; Balleine, Rosemary] Pathol West ICPMR Westmead, Sydney, NSW, Australia. [Sharma, Raghwa] Univ Western Sydney, Westmead Hosp, Westmead, NSW, Australia. [Russell, Peter] Univ Sydney, Dept Obstet Gynaecol & Neonatal, Camperdown, NSW, Australia. [Russell, Peter] Douglass Hanly Moir Pathol, Macquarie Pk, NSW, Australia. [MacConaill, Laura; Palescandolo, Emanuele] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dobrovic, Alexander; Wong, Stephen Q.] La Trobe Univ, Sch Canc Med, Bundoora, Vic, Australia. [Bowtell, David D. L.] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3052, Australia. [Bowtell, David D. L.] Univ London Imperial Coll Sci Technol & Med, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England. RP deFazio, A (reprint author), Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia. EM anna.defazio@sydney.edu.au RI deFazio, Anna/D-3939-2013; Bowtell, David/H-1007-2016; Harnett, Paul/D-4090-2014; OI deFazio, Anna/0000-0003-0057-4744; Bowtell, David/0000-0001-9089-7525; Harnett, Paul/0000-0001-7021-0642; Anglesio, Michael/0000-0003-1639-5003; Dobrovic, Alexander/0000-0003-3414-112X FU U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729] FX The Australian Ovarian Cancer Study was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer CouncilNew South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia, The Cancer Council Tasmania, and the National Health and Medical Research Council of Australia (NHMRC; ID400413, ID400281). The Gynaecological Oncology Biobank at Westmead is funded by Cancer Institute NSW and is amember bank of the Australasian Biospecimens Network-Oncology, funded byNHMRC(ID310670, ID628903). A. de Fazio is funded by the University of Sydney Cancer Research Fund, and A. de Fazio and P. R. Harnett are funded by the Cancer Institute NSW through the Sydney-West Translational Cancer Research Centre. This work was also supported by a grant from the Cancer Council of New South Wales (CCNSW RG10-05). This work was also supported by the Victorian Breast Cancer Research Consortium (VBCRC), the NHMRC (ID 628630), Cancer Australia (1004673), and theEmer Casey Foundation. H. Do was funded by a fellowship from the Cancer Council of Victoria, and S. Q. Wong was supported by the Melbourne Melanoma Project, funded by the Victorian Cancer Agency Translational Research Program. L. MacConaill and E. Palescandolo were funded by the Dana-Farber Cancer Institute. NR 50 TC 16 Z9 16 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2014 VL 20 IS 24 BP 6618 EP 6630 DI 10.1158/1078-0432.CCR-14-1292 PG 13 WC Oncology SC Oncology GA AW7AZ UT WOS:000346418100040 PM 25316818 ER PT J AU Knudson, IM Shera, CA Melcher, JR AF Knudson, Inge M. Shera, Christopher A. Melcher, Jennifer R. TI Increased contralateral suppression of otoacoustic emissions indicates a hyperresponsive medial olivocochlear system in humans with tinnitus and hyperacusis SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE DPOAE; efferent feedback; loudness discomfort level; cochlear efferents; posteroventral cochlear nucleus; anteroventral cochlear nucleus; dorsal cochlear nucleus ID EFFERENT AUDITORY-SYSTEM; VENTRAL COCHLEAR NUCLEUS; ACOUSTIC DISTORTION PRODUCTS; NORMAL-HEARING SENSITIVITY; NOISE-INDUCED TINNITUS; INFERIOR COLLICULUS; BRAIN-STEM; PSYCHOMETRIC PROPERTIES; GUINEA-PIG; NEURONS AB Atypical medial olivocochlear (MOC) feedback from brain stem to cochlea has been proposed to play a role in tinnitus, but even well-constructed tests of this idea have yielded inconsistent results. In the present study, it was hypothesized that low sound tolerance (mild to moderate hyperacusis), which can accompany tinnitus or occur on its own, might contribute to the inconsistency. Sound-level tolerance (SLT) was assessed in subjects (all men) with clinically normal or near-normal thresholds to form threshold-, age-, and sex-matched groups: 1) no tinnitus/high SLT, 2) no tinnitus/low SLT, 3) tinnitus/high SLT, and 4) tinnitus/low SLT. MOC function was measured from the ear canal as the change in magnitude of distortion-product otoacoustic emissions (DPOAE) elicited by broadband noise presented to the contralateral ear. The noise reduced DPOAE magnitude in all groups ("contralateral suppression"), but significantly more reduction occurred in groups with tinnitus and/or low SLT, indicating hyperresponsiveness of the MOC system compared with the group with no tinnitus/high SLT. The results suggest hyperresponsiveness of the interneurons of the MOC system residing in the cochlear nucleus and/or MOC neurons themselves. The present data, combined with previous human and animal data, indicate that neural pathways involving every major division of the cochlear nucleus manifest hyperactivity and/or hyperresponsiveness in tinnitus and/or low SLT. The overactivation may develop in each pathway separately. However, a more parsimonious hypothesis is that top-down neuromodulation is the driving force behind ubiquitous overactivation of the auditory brain stem and may correspond to attentional spotlighting on the auditory domain in tinnitus and hyperacusis. C1 [Knudson, Inge M.; Shera, Christopher A.; Melcher, Jennifer R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Knudson, Inge M.; Shera, Christopher A.; Melcher, Jennifer R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Shera, Christopher A.; Melcher, Jennifer R.] Harvard Div Med Sci, Speech & Hearing Biosci & Technol Program, Boston, MA USA. RP Knudson, IM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM inge_knudson@meei.harvard.edu FU Tinnitus Research Consortium; National Institute of Deafness and Other Communications Disorders [P30 DC005209] FX Support for this work was provided by the Tinnitus Research Consortium and National Institute of Deafness and Other Communications Disorders Grant P30 DC005209. NR 70 TC 9 Z9 10 U1 3 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC 15 PY 2014 VL 112 IS 12 BP 3197 EP 3208 DI 10.1152/jn.00576.2014 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AW7WB UT WOS:000346471200016 PM 25231612 ER PT J AU Song, DR Jun, CS Do Lim, S Kim, BY AF Song, Du-Ri Jun, Chang Su Do Lim, Sun Kim, Byoung Yoon TI Effect of metal coating in all-fiber acousto-optic tunable filter using torsional wave SO OPTICS EXPRESS LA English DT Article ID SILICA OPTICAL FIBERS; MODE; BIREFRINGENCE; MODULATION; STRENGTH AB Torsional mode acousto-optic tunable filter (AOTF) is demonstrated using a metal-coated birefringent optical fiber for an improved robustness. The changes in acoustic and optical properties of a metal-coated birefringent optical fiber induced by the thin metal coating were analyzed experimentally and theoretically. The filter wavelength shift is successfully explained as a result of combined effect of acoustic wavelength change and optical birefringence change. We also demonstrated a small form-factor configuration by coiling the fiber with 6 cm diameter without performance degradation. The center wavelength of the filter can be tuned >35 nm by changing the applied frequency, and the coupling efficiency is higher than 92% with <5 nm 3-dB bandwidth. (C)2014 Optical Society of America C1 [Song, Du-Ri; Kim, Byoung Yoon] Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea. [Jun, Chang Su] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Jun, Chang Su] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Do Lim, Sun] Korea Res Inst Stand & Sci, Ctr Photometry & Radiometry, Div Phys Metrol, Taejon 305340, South Korea. RP Song, DR (reprint author), Korea Adv Inst Sci & Technol, Dept Phys, 373-1 Guseong Dong, Taejon 305701, South Korea. EM cherry22@kaist.ac.kr RI Kim, Byoung Yoon/C-2008-2011 FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2013R1A1A2064061] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A2064061). The authors thank Dr. Sejeong Kim (KAIST) for the SEM image. NR 26 TC 1 Z9 1 U1 1 U2 14 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 15 PY 2014 VL 22 IS 25 BP 30873 EP 30881 DI 10.1364/OE.22.030873 PG 9 WC Optics SC Optics GA AW6GW UT WOS:000346368800080 PM 25607036 ER PT J AU Oh, HJ Gather, MC Song, JJ Yun, SH AF Oh, Heon Jeong Gather, Malte C. Song, Ji-Joon Yun, Seok Hyun TI Lasing from fluorescent protein crystals SO OPTICS EXPRESS LA English DT Article AB We investigated fluorescent protein crystals for potential photonic applications, for the first time to our knowledge. Rod-shaped crystals of enhanced green fluorescent protein (EGFP) were synthesized, with diameters of 0.5-2 mu m and lengths of 100-200 mu m. The crystals exhibit minimal light scattering due to their ordered structure and generate substantially higher fluorescence intensity than EGFP or dye molecules in solutions. The magnitude of concentration quenching in EGFP crystals was measured to be about 7-10 dB. Upon optical pumping at 485 nm, individual EGFP crystals located between dichroic mirrors generated laser emission with a single-mode spectral line at 513 nm. Our results demonstrate the potential of protein crystals as novel optical elements for self-assembled, micro- or nano-lasers and amplifiers in aqueous environment. (C) 2014 Optical Society of America C1 [Oh, Heon Jeong; Gather, Malte C.; Yun, Seok Hyun] Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Oh, Heon Jeong; Gather, Malte C.; Yun, Seok Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Oh, Heon Jeong; Song, Ji-Joon] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. [Gather, Malte C.] Univ St Andrews, Sch Phys & Astron, SUPA, St Andrews KY16 9SS, Fife, Scotland. [Song, Ji-Joon; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea. RP Yun, SH (reprint author), Wellman Ctr Photomed, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA. EM songj@kaist.ac.kr; syun@hms.harvard.edu RI Song, Ji-Joon/C-1721-2011; OI Gather, Malte/0000-0002-4857-5562 FU National Science Foundation [ECCS-1101947, EEC-1358296]; Korea National Research Foundation [R31-2008-000-10071-0]; KAIST-MGH Summer Internship Program; European Union Marie Curie Career Integration Grant [PCIG12-GA-2012-334407] FX We thank Uhn-Soo Cho for discussion about crystal handling and Myunghwan Choi for taking two-photon fluorescence images of the crystals. This work was funded by the National Science Foundation (ECCS-1101947, EEC-1358296), the Korea National Research Foundation (R31-2008-000-10071-0), the KAIST-MGH Summer Internship Program, and the European Union Marie Curie Career Integration Grant (PCIG12-GA-2012-334407). NR 13 TC 3 Z9 3 U1 3 U2 31 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 15 PY 2014 VL 22 IS 25 BP 31411 EP 31416 DI 10.1364/OE.22.031411 PG 6 WC Optics SC Optics GA AW6GW UT WOS:000346368800134 PM 25607090 ER PT J AU Iftimia, N Maguluri, G Chang, EW Chang, S Magill, J Brugge, W AF Iftimia, Nicusor Maguluri, Gopi Chang, Ernest W. Chang, Shing Magill, John Brugge, William TI Hand scanning optical coherence tomography imaging using encoder feedback SO OPTICS LETTERS LA English DT Article ID TRACKING; BIOPSY AB We present a new method for generating micron-scale OCT images of interstitial tissue with a hand scanning probe and a linear optical encoder that senses probe movement relative to a fixed reference point, i.e., tissue surface. Based on this approach, we demonstrate high resolution optical imaging of biological tissues through a very long biopsy needle. Minor artifacts caused by tissue noncompliance are corrected using a software algorithm which detects the simple repetition of the adjacent A-scans. This hand-scanning OCT imaging approach offers the physician the freedom to access imaging sites of interest repeatedly. (C) 2014 Optical Society of America C1 [Iftimia, Nicusor; Maguluri, Gopi; Chang, Ernest W.; Chang, Shing; Magill, John] Phys Sci Inc, Andover, MA 01810 USA. [Brugge, William] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.com FU NCI [5R44CA117218] FX This work was supported by the NCI Grant 5R44CA117218. NR 16 TC 2 Z9 2 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD DEC 15 PY 2014 VL 39 IS 24 BP 6807 EP 6810 DI 10.1364/OL.39.006807 PG 4 WC Optics SC Optics GA AW5YX UT WOS:000346347900011 PM 25503002 ER PT J AU Fung, TT Kashambwa, R Sato, K Chiuve, SE Fuchs, CS Wu, KN Giovannucci, E Ogino, S Hu, FB Meyerhardt, JA AF Fung, Teresa T. Kashambwa, Rutendo Sato, Kaori Chiuve, Stephanie E. Fuchs, Charles S. Wu, Kana Giovannucci, Edward Ogino, Shuji Hu, Frank B. Meyerhardt, Jeffrey A. TI Post Diagnosis Diet Quality and Colorectal Cancer Survival in Women SO PLOS ONE LA English DT Article ID SYSTEMIC INFLAMMATORY RESPONSE; FOOD-FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; III COLON-CANCER; MEDITERRANEAN DIET; PROSPECTIVE COHORT; ALL-CAUSE; RISK; MORTALITY AB Background: Dietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival. Methods: 1201 women diagnosed with stage I-III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western (unhealthy) and prudent (healthy), by principal component analysis for each woman. Results: During follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles=0.71, 95% CI 0.52-0.98, p trend=0.01) as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1=0.72, 95% CI=0.43-1.21, p trend=0.07). When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5-15 g/d=1.30, 95% CI=1.05-1.61) and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving=1.11, 95% CI=1.01-1.23). No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality. Conclusion: Higher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations. C1 [Fung, Teresa T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. [Kashambwa, Rutendo] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chiuve, Stephanie E.; Wu, Kana; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Surg, Boston, MA 02115 USA. [Fuchs, Charles S.; Hu, Frank B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Fung, TT (reprint author), Simmons Coll, Dept Nutr, Boston, MA 02115 USA. EM fung@simmons.edu FU National Institute of Health [CA87969, CA127003, CA149222, CA95589, CA151993, CA169141, CA 118553, UM1CA167552, U54CA155626, UM1 CA167552] FX This work is funded by the National Institute of Health research grants CA87969, CA127003, CA149222, CA95589, CA151993, CA169141, CA 118553, UM1CA167552, U54CA155626, UM1 CA167552. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 9 Z9 9 U1 2 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 15 PY 2014 VL 9 IS 12 AR e115377 DI 10.1371/journal.pone.0115377 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW9WY UT WOS:000346607100072 PM 25506700 ER PT J AU Paweletz, CP Janne, PA AF Paweletz, Cloud P. Jaenne, Pasi A. TI Monitoring Cancer Through the Blood SO CANCER LA English DT Editorial Material ID PLASMA DNA; ACQUIRED-RESISTANCE; COLORECTAL-CANCER; MUTATIONS; THERAPY AB Tumor biopsies remain the gold standard for the evaluation of genetic changes in tumors either at diagnosis or after treatment with targeted therapies. However, this is not always feasible and can seldom be performed more than once. Noninvasive techniques that measure the allelic burden in blood have the potential to realize genotype-directed cancer therapy. These technologies can potentially be used for noninvasive tumor genotyping and also provide an opportunity for disease monitoring. Several non-invasive genotyping technologies are currently under development and being evaluated in patients treated with targeted therapies. C1 [Paweletz, Cloud P.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Paweletz, Cloud P.; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Jaenne, Pasi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,HIM223, Boston, MA 02215 USA. EM pasi_janne@dfci.harvard.edu FU NCI NIH HHS [R01 CA135257, R01-CA135257] NR 14 TC 0 Z9 0 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2014 VL 120 IS 24 BP 3859 EP 3861 DI 10.1002/cncr.28967 PG 3 WC Oncology SC Oncology GA AW1TX UT WOS:000346074300006 PM 25103496 ER PT J AU Viswanathan, AN Lee, LJ Eswara, JR Horowitz, NS Konstantinopoulos, PA Mirabeau-Beale, KL Rose, BS von Keudell, AG Wo, JY AF Viswanathan, Akila N. Lee, Larissa J. Eswara, Jairam R. Horowitz, Neil S. Konstantinopoulos, Panagiotis A. Mirabeau-Beale, Kristina L. Rose, Brent S. von Keudell, Arvind G. Wo, Jennifer Y. TI Complications of Pelvic Radiation in Patients Treated for Gynecologic Malignancies SO CANCER LA English DT Review DE radiation; morbidity; toxicity; gynecologic cancer ID ADVANCED CERVICAL-CANCER; DOSE-RATE BRACHYTHERAPY; QUALITY-OF-LIFE; PHASE-III TRIAL; RANDOMIZED-CONTROLLED-TRIAL; ACUTE HEMATOLOGIC TOXICITY; HYPERBARIC-OXYGEN THERAPY; RISK ENDOMETRIAL CANCER; TERM FOLLOW-UP; INSUFFICIENCY FRACTURES AB Radiation therapy is a critical treatment modality in the management of patients with gynecologic tumors. New highly conformal external-beam and brachytherapy techniques have led to important reductions in recurrence and patient morbidity and mortality. However, patients who receive pelvic radiation for gynecologic malignancies may experience a unique constellation of toxicity because of the anatomic locations, combination with concurrent chemotherapy and/or surgery, as well as potential surgical interventions. Although side effects are often categorized into acute versus late toxicities, several late toxicities represent continuation and evolution of the same pathologic process. Comorbidities and radiation dose can significantly increase the risk of morbidity. Current understanding of the incidence of various morbidities in patients treated with current radiation techniques for gynecologic malignancies, the impact of chemotherapy and surgery, treatment options for those effects, and future areas of research are highlighted. Cancer 2014;120:3870-3883. (c) 2014 American Cancer Society. Modern radiotherapy techniques, including highly conformal radiation and image-guided conformal brachytherapy, may reduce the risk of radiation-related side effects. The management of side effects, including surgical and chemotherapeutic implications, is discussed. C1 [Viswanathan, Akila N.; Lee, Larissa J.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Akila N.; Lee, Larissa J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Eswara, Jairam R.] Washington Univ, Sch Med, Div Urol, St Louis, MO USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. [Konstantinopoulos, Panagiotis A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mirabeau-Beale, Kristina L.; Rose, Brent S.] Harvard Radiat Oncol Residency Program, Boston, MA USA. [von Keudell, Arvind G.] Harvard Orthoped Combined Residency Program, Boston, MA USA. [Wo, Jennifer Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU National Institutes of Health [R21 CA 167800] FX Dr. Viswanathan receives funding from the National Institutes of Health (grant R21 CA 167800). NR 115 TC 10 Z9 10 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2014 VL 120 IS 24 BP 3870 EP 3883 DI 10.1002/cncr.28849 PG 14 WC Oncology SC Oncology GA AW1TX UT WOS:000346074300009 PM 25056522 ER PT J AU Garrido, MM Harrington, ST Prigerson, HG AF Garrido, Melissa M. Harrington, Shannon T. Prigerson, Holly G. TI End-of-Life Treatment Preferences: A Key to Reducing Ethnic/Racial Disparities in Advance Care Planning? SO CANCER LA English DT Article DE health care disparities; end-of-life care; do-not-resuscitate orders; cardiopulmonary resuscitation; advance care planning ID ADVANCED CANCER; RACIAL-DIFFERENCES; HOSPICE CARE; OLDER-ADULTS; NEAR-DEATH; DIRECTIVES; RACE/ETHNICITY; RESUSCITATION; VALIDATION; PREDICTORS AB BACKGROUNDThe objective of this study was to identify targets for interventions to reduce end-of-life care disparities among patients with advanced cancer. To do this, the authors evaluated the degree to which end-of-life care values and preferences are associated with advance care planning within racial/ethnic minority groups. METHODSThe Coping with Cancer study recruited patients with advanced cancer from outpatient clinics in 5 states from 2002 to 2008. Then, the rates of 1 type of advance care planningdo-not-resuscitate (DNR) ordersreported at baseline interviews by 606 patients were investigated. Bivariate tests determined associations among DNR order completion, religious values, and treatment preferences within racial/ethnic groups. RESULTSNon-Latino white patients were significantly more likely to have a DNR order (45%) than black (25%) and Latino (20%) patients (P<.001). A preference against specific life-prolonging treatment (eg, chemotherapy, ventilation) was the only factor significantly associated with higher DNR order likelihood in each group, with non-Latino white patients more likely than Latino or black patients to express preferences against life-prolonging care (eg, 26% of non-Latino white patients, 46% of black patients, and 41% of Latino patients wanted a feeding tube if it would extend life for 1 more day; P<.001). CONCLUSIONSPreferences against life-prolonging care differ dramatically by race/ethnicity, but they have a uniform significant association with DNR order completion rates across racial/ethnic groups of patients with advanced cancer. Advance care planning interventions that target preferences associated with DNR orders across racial/ethnic groups may reach a broad patient population and reduce end-of-life care disparities. Cancer 2014;120:3981-3986. (c) 2014 American Cancer Society. Patient interview data are used to demonstrate that, although patient preferences against life-prolonging care differ dramatically by race/ethnicity, they are uniformly significantly associated with do-not-resuscitate order completion rates across racial/ethnic groups of patients with advanced cancer. C1 [Garrido, Melissa M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, New York, NY USA. [Garrido, Melissa M.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Harrington, Shannon T.] Dana Farber Canc Inst, Phillis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Harrington, Shannon T.] Univ Massachusetts, Boston, MA 02125 USA. [Prigerson, Holly G.] Weill Cornell Med Coll, Ctr Res End Life Care, New York, NY 10065 USA. RP Prigerson, HG (reprint author), Weill Cornell Med Coll, Ctr Res End Life Care, 525 East 68th St,Box 39, New York, NY 10065 USA. EM hgp2001@med.cornell.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA156732]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [CDA 11-201/CDP 12-255] FX This research was supported in part by the following grants to Dr. Prigerson: grant MH63892 from the National Institute of Mental Health, grants CA106370 and CA156732 from the National Cancer Institute. Dr. Garrido is supported by grant CDA 11-201/CDP 12-255 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service. NR 31 TC 14 Z9 14 U1 4 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2014 VL 120 IS 24 BP 3981 EP 3986 DI 10.1002/cncr.28970 PG 6 WC Oncology SC Oncology GA AW1TX UT WOS:000346074300021 PM 25145489 ER PT J AU George, S Muto, MG AF George, Suzanne Muto, Michael G. TI Reply to In-Bag Morcellation for Presumed Myoma Retrieval at Laparoscopy SO CANCER LA English DT Letter C1 [George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Muto, Michael G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP George, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2014 VL 120 IS 24 BP 4005 EP 4005 DI 10.1002/cncr.28957 PG 1 WC Oncology SC Oncology GA AW1TX UT WOS:000346074300027 PM 25102828 ER PT J AU Koo, S Thomas, HR Daniels, SD Lynch, RC Fortier, SM Shea, MM Rearden, P Comolli, JC Baden, LR Marty, FM AF Koo, Sophia Thomas, Horatio R. Daniels, S. David Lynch, Robert C. Fortier, Sean M. Shea, Margaret M. Rearden, Preshious Comolli, James C. Baden, Lindsey R. Marty, Francisco M. TI A Breath Fungal Secondary Metabolite Signature to Diagnose Invasive Aspergillosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE aspergillosis; diagnostics; volatile organic compounds; breath; fungal infection ID VOLATILE ORGANIC-COMPOUNDS; SURVEILLANCE NETWORK TRANSNET; CELL TRANSPLANT RECIPIENTS; INFECTIOUS-DISEASES; FUMIGATUS; METAANALYSIS; BERGAMOTENE; PROGRESS AB Background. Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. Methods. Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. Results. The monoterpenes camphene, alpha- and beta-pinene, and limonene, and the sesquiterpene compounds alpha- and beta-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of alpha-trans-bergamotene, beta-trans-bergamotene, a beta-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). Conclusions. In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia. C1 [Koo, Sophia; Thomas, Horatio R.; Daniels, S. David; Lynch, Robert C.; Fortier, Sean M.; Shea, Margaret M.; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Koo, Sophia; Baden, Lindsey R.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Koo, Sophia; Thomas, Horatio R.; Baden, Lindsey R.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA. [Rearden, Preshious; Comolli, James C.] Draper Lab, Cambridge, MA USA. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM skoo@partners.org OI Koo, Sophia/0000-0002-4973-7439 FU Harvard Catalyst Pilot Grant Program [UL1 RR 025758]; National Institute of Allergy and Infectious Diseases at the National Institutes of Health [K23 AI097225, R21 AI085454] FX This work was supported by the Harvard Catalyst Pilot Grant Program (grant number UL1 RR 025758) and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant numbers K23 AI097225 to S. K. and R21 AI085454). NR 40 TC 14 Z9 15 U1 2 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2014 VL 59 IS 12 BP 1733 EP 1740 DI 10.1093/cid/ciu725 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AU9KM UT WOS:000345911500018 PM 25342502 ER PT J AU Cherayil, BJ AF Cherayil, Bobby J. TI Response to Comment on "Intestinal Inflammation Modulates Expression of the Iron-Regulating Hormone Hepcidin Depending on Erythropoietic Activity and the Commensal Microbiota" SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 [Cherayil, Bobby J.] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02129 USA. [Cherayil, Bobby J.] Harvard Univ, Sch Med, Boston, MA USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Room 3600,MGH East,Bldg 114,16th St, Boston, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK040561] NR 1 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2014 VL 193 IS 12 BP 5763 EP 5763 DI 10.4049/jimmunol.1402567 PG 1 WC Immunology SC Immunology GA AW1XQ UT WOS:000346082400002 PM 25480954 ER PT J AU Playa, H Lewis, TA Ting, A Suh, BC Munoz, B Matuza, R Passer, BJ Schreiber, SL Buolamwini, JK AF Playa, Hilaire Lewis, Timothy A. Ting, Amal Suh, Byung-Chul Munoz, Benito Matuza, Robert Passer, Brent J. Schreiber, Stuart L. Buolamwini, John K. TI Dilazep analogues for the study of equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2) SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Equilibrative nucleoside transporters (ENTs); hENT1; hENT2; rENT2; Dilazep ID PROTEINS; FAMILY; VIRUS AB As ENT inhibitors including dilazep have shown efficacy improving oHSV1 targeted oncolytic cancer therapy, a series of dilazep analogues was synthesized and biologically evaluated to examine both ENT1 and ENT2 inhibition. The central diamine core, alkyl chains, ester linkage and substituents on the phenyl ring were all varied. Compounds were screened against ENT1 and ENT2 using a radio-ligand cell-based assay. Dilazep and analogues with minor structural changes are potent and selective ENT1 inhibitors. No selective ENT2 inhibitors were found, although some analogues were more potent against ENT2 than the parent dilazep. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Playa, Hilaire; Buolamwini, John K.] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. [Lewis, Timothy A.; Ting, Amal; Suh, Byung-Chul; Munoz, Benito; Schreiber, Stuart L.] Broad Inst MIT & Harvard, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Matuza, Robert; Passer, Brent J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Buolamwini, JK (reprint author), Rosalind Franklin Univ Med & Sci, Coll Pharm, Dept Pharmaceut Sci, 3333 Green Bay Rd, N Chicago, IL 60064 USA. EM john.buolamwini@rosalindfranklin.edu FU NIH-MLPCN program [1 U54 HG005032-1]; NIH [RO1GM10405, RO1CA102139] FX This work was funded in part by the NIH-MLPCN program (1 U54 HG005032-1 awarded to S.L.S.) as well as NIH RO1GM10405 (J.K.B.) and Grant RO1CA102139 (R.L.M.). NR 15 TC 2 Z9 2 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 15 PY 2014 VL 24 IS 24 BP 5801 EP 5804 DI 10.1016/j.bmcl.2014.10.026 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA AU4LA UT WOS:000345581300053 PM 25454272 ER PT J AU Lapidus, KAB Levitch, CF Perez, AM Brallier, JW Parides, MK Soleimani, L Feder, A Iosifescu, DV Charney, DS Murrough, JW AF Lapidus, Kyle A. B. Levitch, Cara F. Perez, Andrew M. Brallier, Jess W. Parides, Michael K. Soleimani, Laili Feder, Adriana Iosifescu, Dan V. Charney, Dennis S. Murrough, James W. TI A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Antidepressant; depression; glutamate; intranasal; ketamine; treatment resistant ID TREATMENT-RESISTANT DEPRESSION; D-ASPARTATE ANTAGONIST; MAGNETIC-RESONANCE-SPECTROSCOPY; RAPID ANTIDEPRESSANT RESPONSE; ADD-ON TRIAL; UNIPOLAR DEPRESSION; BIPOLAR DEPRESSION; GLUTAMATE; EFFICACY; PREMEDICATION AB Background: The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods: In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results: Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p < .001; estimated mean Montgomery-Asberg Depression Rating Scale score difference of 7.6 +/- 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p = .033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions: This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. C1 [Lapidus, Kyle A. B.; Levitch, Cara F.; Soleimani, Laili; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.] Icahn Sch Med Mt Sinai, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Lapidus, Kyle A. B.; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Perez, Andrew M.; Brallier, Jess W.] Icahn Sch Med Mt Sinai, Dept Anesthesiol, New York, NY 10029 USA. [Parides, Michael K.] Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, New York, NY 10029 USA. [Charney, Dennis S.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Iosifescu, Dan V.; Murrough, James W.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Soleimani, Laili] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Murrough, JW (reprint author), 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM james.murrough@mssm.edu RI Murrough, James/J-7129-2013 OI Murrough, James/0000-0001-6286-1242 FU National Institutes of Health [UL1TR000067, K23MH094707]; National Alliance for Research on Schizophrenia and Depression Young Investigator Award from the Brain and Behavior Research Foundation; National Institutes of Health; National Institute of Mental Health; Department of Veterans Affairs; Doris Duke Charitable Foundation; American Foundation for Suicide Prevention; Brain and Behavior Research Foundation; Janssen Research and Development; Avanir Pharmaceuticals; American Psychiatric Institute for Research and Education Janssen Resident Psychiatric Research Scholars; Le Foundation; LCN Consulting; Icahn School of Medicine at Mount Sinai from AstraZeneca; Brainsway; Euthymics Bioscience; NeoSync; Roche; Shire; CNS Response; Otsuka Pharmaceutical Co, Ltd; Servier Laboratories; Sunovion Pharmaceuticals, Inc.; United States Department of Defense; National Alliance for Research on Schizophrenia and Depression; United States Army Medical Research Acquisition Activity; CNS Spectrums FX This work was supported by National Institutes of Health Grant Nos. UL1TR000067 (Mount Sinai Clinical and Translational Science Award) and K23MH094707 (JWM) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award from the Brain and Behavior Research Foundation (KABL). A portion of the data from the current study was previously presented at the 52nd annual meeting of the American College of Neuropsychopharmacology.; The content of this article is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other sponsoring entity. In the past 2 years, JWM has received research support from the National Institutes of Health, the National Institute of Mental Health, the Department of Veterans Affairs, the Doris Duke Charitable Foundation, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation, Janssen Research and Development, and Avanir Pharmaceuticals; he has served on advisory boards for Janssen Research and Development and Genentech and has provided consultation services for ProPhase, LLC, and Impel NeuroPharma. KABL has received research support from the Brain and Behavior Research Foundation, American Psychiatric Institute for Research and Education Janssen Resident Psychiatric Research Scholars, and the Le Foundation; he has received consulting fees from LCN Consulting and serves on the advisory board for Halo Neuro Inc. DVI has received research funding through Icahn School of Medicine at Mount Sinai from AstraZeneca, Brainsway, Euthymics Bioscience, NeoSync, Roche, and Shire; he has received consulting fees for Avanir Pharmaceuticals, CNS Response, Otsuka Pharmaceutical Co, Ltd, Servier Laboratories, and Sunovion Pharmaceuticals, Inc. DSC has received consulting fees or research support from the United States Department of Defense, National Institutes of Health, National Institute of Mental Health, National Alliance for Research on Schizophrenia and Depression, United States Army Medical Research Acquisition Activity, and CNS Spectrums; he a member of the Advisory and Editorial Boards of the Institute of Medicine Committee on Department of Homeland Security Workforce Resilience. DSC (Dean of Icahn School of Medicine at Mount Sinai and coinvestigator on this study) and Icahn School of Medicine at Mount Sinai have been named on a use patent on ketamine for the treatment of depression. The Icahn School of Medicine has entered into a licensing agreement for the use of ketamine as therapy for treatment-resistant depression. DSC and Icahn School of Medicine at Mount Sinai could potentially benefit from the results of this study. DSC and AF (a coinvestigator on this study) are named coinventors on a use patent application filed by Mount Sinai for the use of ketamine as a treatment for posttraumatic stress disorder. If ketamine were shown to be effective in the treatment of posttraumatic stress disorder and received approval from the U.S. Food and Drug Administration for this indication, DSC, AF, and the Icahn School of Medicine at Mount Sinai could benefit financially. All other authors report no biomedical financial interests or potential conflicts of interest. NR 38 TC 69 Z9 71 U1 9 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2014 VL 76 IS 12 BP 970 EP 976 DI 10.1016/j.biopsych.2014.03.026 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU2DY UT WOS:000345427500009 PM 24821196 ER PT J AU Gros, DF AF Gros, Daniel F. TI Development and initial evaluation of Transdiagnostic Behavior Therapy (TBT) for veterans with affective disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Transdiagnostic Behavior Therapy TBT; Anxiety disorders; Depression; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH PROBLEMS; PRIMARY-CARE CLINICS; DSM-IV DISORDERS; EMOTIONAL DISORDERS; ANXIETY DISORDER; UNIFIED PROTOCOL; PANIC DISORDER AB Considerable attention has focused on the growing need for evidence-based psychotherapy for veterans with affective disorders within the Department of Veteran Affairs. Despite, and possibly due to, the large number of evidence-based protocols available, several obstacles remain in their widespread delivery within Veterans Affairs Medical Centers. In part as an effort to address these concerns, newer transdiagnostic approaches to psychotherapy have been developed to provide a single treatment that is capable of addressing several, related disorders. The goal of the present investigation was to develop and evaluate a transdiagnostic psychotherapy, Transdiagnostic Behavior Therapy (TBT), in veterans with affective disorders. Study 1 provided initial support for transdiagnostic presentation of evidence-based psychotherapy components in veterans with principal diagnoses of affective disorders (n=15). These findings were used to inform the development of the TBT protocol. In Study 2, an initial evaluation of TBT was completed in a second sample of veterans with principal diagnoses of affective disorders (n=29). The findings of Study 2 demonstrated significant improvements in symptoms of depression, anxiety, stress, posttraumatic stress, and related impairment across participants with various principal diagnoses. Together, the investigation provided preliminary support for effectiveness of TBT in veterans with affective disorders. Published by Elsevier Ireland Ltd. C1 [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU CSRD VA [IK2 CX000845] NR 42 TC 9 Z9 9 U1 3 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 15 PY 2014 VL 220 IS 1-2 BP 275 EP 282 DI 10.1016/j.psychres.2014.08.018 PG 8 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400044 PM 25193379 ER PT J AU Park, JM Lewin, AB Storch, EA AF Park, Jennifer M. Lewin, Adam B. Storch, Eric A. TI Adult offspring perspectives on parental hoarding behaviors SO PSYCHIATRY RESEARCH LA English DT Article DE Hoarding; Family; Parent-offspring relationships; Parental psychopathology; Path analysis ID OBSESSIVE-COMPULSIVE DISORDER; FAMILY ASSESSMENT DEVICE; SOCIAL SUPPORT; FIT INDEXES; ACCOMMODATION; CHILDREN; BURDEN; HEALTH; SCALE; VALIDATION AB Hoarding disorder (HD) is characterized by difficulty discarding unneeded items and the accumulation of items within living spaces and is associated with significant functional impairment and distress. Along with the negative impact of hoarding on the individual, HD is substantially impairing for family members, and linked to disruptions in family functioning. The present study utilized a path model analysis to examine the associations between an array of hoarding variables hypothesized to impact family functioning and parent-offspring relationships in 150 adult-aged children of hoarders who responded to online requests to participate in a research study. It was hypothesized that increased hoarding severity, decreased insight, and increased family accommodation (i.e., act of family members facilitating or assisting in hoarding behaviors) would be associated with decreased family functioning, decreased quality of parent-offspring relationships, and increased offspring impairment. Results from the path model revealed that family functioning mediated the relationship between hoarding severity and parent-offspring relationship. Diminished insight in the hoarding parent (as reported by the offspring) was associated with increased familial conflict and family functioning partially mediated the relationship between insight and quality of parent-offspring relationship. Increased family accommodation was significantly associated with increased impairment (work, social, and family domains) in offspring of hoarders. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Park, Jennifer M.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Child CBT Program, Boston, MA 02114 USA. [Lewin, Adam B.; Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Lewin, Adam B.; Storch, Eric A.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Lewin, Adam B.; Storch, Eric A.] Univ S Florida, Dept Psychiat, Tampa, FL 33620 USA. [Lewin, Adam B.; Storch, Eric A.] Univ S Florida, Dept Behav Neurosci, Tampa, FL 33620 USA. RP Park, JM (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Child CBT Program, 151 Merrimac St,3rd Floor, Boston, MA 02114 USA. EM jpark12@partners.org NR 57 TC 3 Z9 3 U1 7 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 15 PY 2014 VL 220 IS 1-2 BP 328 EP 334 DI 10.1016/j.psychres.2014.07.061 PG 7 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400052 PM 25129564 ER PT J AU Kasckow, J Morse, J Begley, A Anderson, S Bensasi, S Thomas, S Quinn, SC Reynolds, CF AF Kasckow, John Morse, Jennifer Begley, Amy Anderson, Stewart Bensasi, Salem Thomas, Stephen Quinn, Sandra C. Reynolds, Charles F., III TI Treatment of post traumatic stress disorder symptoms in emotionally distressed individuals SO PSYCHIATRY RESEARCH LA English DT Article DE Post traumatic stress disorder; Dietary education; Problem solving therapy ID RANDOMIZED CONTROLLED-TRIAL; PROBLEM-SOLVING THERAPY; PRIMARY-CARE PATIENTS; SUBSYNDROMAL DEPRESSION; MAJOR DEPRESSION; RATING-SCALE; PREVENTION; VETERANS; PTSD; INTERVENTION AB Older individuals with emotional distress and a history of psychologic trauma are at risk for post traumatic stress disorder (PTSD) and major depression. This study was an exploratory, secondary analysis of data from the study "Prevention of Depression in Older African Americans". It examined whether Problem Solving Therapy-Primary Care (PST-PC) would lead to improvement in PTSD symptoms in patients with subsyndromal depression and a history of psychologic trauma. The control condition was dietary education (DIET). Participants (n=60) were age 50 or older with scores on the Center for Epidemiologic Studies -Depression scale of 11 or greater and history of psychologic trauma. Exclusions stipulated no major depression and substance dependence within a year. Participants were randomized to 6-8 sessions of either PST-PC or DIET and followed 2 years with booster sessions every 6 months; 29 participants were in the PST-PC group and 31 were in the DIET group. Mixed effects models showed that improvement of PTSD Check List scores was significantly greater in the DIET group over two years than in the PST-PC group (based on a group time interaction). We observed no intervention*time interactions in Beck Depression Inventory or Brief Symptom Inventory-Anxiety subscale scores. Published by Elsevier Ireland Ltd. C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth, Pittsburgh, PA 15240 USA. [Kasckow, John; Morse, Jennifer; Begley, Amy; Bensasi, Salem; Reynolds, Charles F., III] UPMC Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Anderson, Stewart] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Thomas, Stephen; Quinn, Sandra C.] Univ Maryland, Ctr Hlth Equ, College Pk, MD 20742 USA. [Thomas, Stephen] Univ Maryland, Dept Hlth Serv Adm, Sch Publ Hlth, College Pk, MD 20742 USA. [Quinn, Sandra C.] Univ Maryland, Dept Family Sci, Sch Publ Hlth, College Pk, MD 20742 USA. RP Kasckow, J (reprint author), VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth, Univ Dr C, Pittsburgh, PA 15240 USA. EM kasckowjw@upmc.edu OI Anderson, Stewart/0000-0001-8948-0650 FU NCATS NIH HHS [UL1 TR000005]; NIMH NIH HHS [P30 MH090333, P30MH090333]; NIMHD NIH HHS [P20 MD006737, P60 MD000207, P60MD000207] NR 36 TC 1 Z9 1 U1 1 U2 28 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 15 PY 2014 VL 220 IS 1-2 BP 370 EP 375 DI 10.1016/j.psychres.2014.06.043 PG 6 WC Psychiatry SC Psychiatry GA AT6OJ UT WOS:000345058400058 PM 25107318 ER PT J AU Brack, AS AF Brack, Andrew S. TI Pax7 is back SO SKELETAL MUSCLE LA English DT Editorial Material DE Pax7; Satellite cell; Skeletal muscle; Regeneration; Lineage tracing; Cre ID MYOGENIC SATELLITE CELLS; ADULT SKELETAL-MUSCLE; STEM-CELLS; SPECIFICATION; PROGENITORS; RESIDENT; FIBERS AB Two recent studies have reinvigorated the conversation regarding the role of Pax7 in adult satellite. Studies by Gunther et al (Cell Stem Cell 13: 590 601, 2013) and Von Maltzhen et al (Proc Natl Acad Sci U S A 110: 16474 16479) show that Pax7 is critical for adult satellite cell function and their contribution to muscle repair. Previously, Lepper et al (Nature 460: 627 631, 2009) demonstrated that Pax7 was dispensable for adult muscle repair. In this commentary I have summarized the results from these studies, focusing on the differences in experimental paradigms that led the authors to different conclusions. I also take this opportunity to discuss the potential limitations and hurdles of Cre-lox technology that are responsible for the discrepant results. C1 [Brack, Andrew S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Brack, Andrew S.] HSCI, Boston, MA 02114 USA. [Brack, Andrew S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brack, AS (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM brack.andrew@mgh.harvard.edu FU NIAMS NIH HHS [R01 AR060868, R01 AR061002] NR 18 TC 2 Z9 2 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2044-5040 J9 SKELET MUSCLE JI Skeletal Muscle PD DEC 14 PY 2014 VL 4 AR 24 DI 10.1186/s13395-014-0024-4 PG 5 WC Cell Biology SC Cell Biology GA CL9YL UT WOS:000357334900001 PM 25546147 ER PT J AU McLaughlin, HM Ceyhan-Birsoy, O Christensen, KD Kohane, IS Krier, J Lane, WJ Lautenbach, D Lebo, MS Machini, K MacRae, CA Azzariti, DR Murray, MF Seidman, CE Vassy, JL Green, RC Rehm, HL AF McLaughlin, Heather M. Ceyhan-Birsoy, Ozge Christensen, Kurt D. Kohane, Isaac S. Krier, Joel Lane, William J. Lautenbach, Denise Lebo, Matthew S. Machini, Kalotina MacRae, Calum A. Azzariti, Danielle R. Murray, Michael F. Seidman, Christine E. Vassy, Jason L. Green, Robert C. Rehm, Heidi L. CA MedSeq Project TI A systematic approach to the reporting of medically relevant findings from whole genome sequencing SO BMC MEDICAL GENETICS LA English DT Review DE Clinical genome sequencing; Incidental findings; MedSeq Project; Clinical report formatting ID GENETIC-VARIANTS; ACMG RECOMMENDATIONS; CLINICAL EXOME; PRIMARY-CARE; KNOWLEDGE; RISK; PHYSICIANS; MEDICINE; CARRIERS; CANCER AB Background: The MedSeq Project is a randomized clinical trial developing approaches to assess the impact of integrating genome sequencing into clinical medicine. To facilitate the return of results of potential medical relevance to physicians and patients participating in the MedSeq Project, we sought to develop a reporting approach for the effective communication of such findings. Methods: Genome sequencing was performed on the Illumina HiSeq platform. Variants were filtered, interpreted, and validated according to methods developed by the Laboratory for Molecular Medicine and consistent with current professional guidelines. The GeneInsight software suite, which is integrated with the Partners HealthCare electronic health record, was used for variant curation, report drafting, and delivery. Results: We developed a concise 5-6 page Genome Report (GR) featuring a single-page summary of results of potential medical relevance with additional pages containing structured variant, gene, and disease information along with supporting evidence for reported variants and brief descriptions of associated diseases and clinical implications. The GR is formatted to provide a succinct summary of genomic findings, enabling physicians to take appropriate steps for disease diagnosis, prevention, and management in their patients. Conclusions: Our experience highlights important considerations for the reporting of results of potential medical relevance and provides a framework for interpretation and reporting practices in clinical genome sequencing. C1 [McLaughlin, Heather M.; Ceyhan-Birsoy, Ozge; Christensen, Kurt D.; Kohane, Isaac S.; Krier, Joel; Lane, William J.; Lebo, Matthew S.; MacRae, Calum A.; Seidman, Christine E.; Vassy, Jason L.; Green, Robert C.; Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [McLaughlin, Heather M.; Ceyhan-Birsoy, Ozge; Lebo, Matthew S.; Machini, Kalotina; Azzariti, Danielle R.; Rehm, Heidi L.] Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA USA. [McLaughlin, Heather M.; Lane, William J.; Lebo, Matthew S.; Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Christensen, Kurt D.; Krier, Joel; Lautenbach, Denise; MacRae, Calum A.; Green, Robert C.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [MacRae, Calum A.; Seidman, Christine E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Seidman, Christine E.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Kohane, Isaac S.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Murray, Michael F.] Geisinger Hlth Syst, Danville, PA USA. [MacRae, Calum A.; Seidman, Christine E.; Green, Robert C.; Rehm, Heidi L.] Broad Inst, Cambridge, MA USA. [Vassy, Jason L.] VA Boston HealthCare Syst, Sect Gen Internal Med, Boston, MA USA. [Vassy, Jason L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. RP Rehm, HL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM hrehm@partners.org OI Christensen, Kurt/0000-0003-4068-776X; Lebo, Matthew/0000-0002-9733-5207 FU [U01 HG006500]; [U19 HD077671]; [U41 HG006834-01A1]; [L30 DK089597]; [F32 HG006993] FX We would like to thank MedSeq Project patients and physicians for their participation in this study. We would like to acknowledge Elizabeth Duffy Hynes, Lisa Mahanta, and Laura Hutchinson for their work on laboratory process improvement, Siva Gowrisankar and Rimma Shakhbatyan for their bioinformatics contributions, and Bob Hurley, Matt Varugheese, Mike Oates, and Tom Venman for their work on developing the GeneInsight report templates. This work was supported by U01 HG006500, U19 HD077671, U41 HG006834-01A1, L30 DK089597, and F32 HG006993. Members of the MedSeq Project are as follows: David W Bates, Alexis D Carere, Allison Cirino, Lauren Connor, Kurt D Christensen, Jake Duggan, Robert C Green, Carolyn Y Ho, Joel B Krier, William J Lane, Denise M Lautenbach, Lisa Lehmann, Christina Liu, Calum A MacRae, Rachel Miller, Cynthia C Morton, Christine E Seidman, Shamil Sunyaev, Jason L Vassy, Sandy Aronson, Ozge Ceyhan-Birsoy, Siva Gowrisankar, Matthew S Lebo, Ignat Leschiner, Kalotina Machini, Heather M McLaughlin, Danielle R Metterville, Heidi L Rehm, Jennifer Blumenthal-Barby, Lindsay Zausmer Feuerman, Amy L McGuire, Sarita Panchang, Jill Oliver Robinson, Melody J Slashinski, Stewart C Alexander, Kelly Davis, Peter A Ubel, Peter Kraft, J Scott Roberts, Judy E Garber, Tina Hambuch, Michael F Murray, Isaac Kohane, Sek Won Kong. NR 35 TC 19 Z9 19 U1 6 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD DEC 14 PY 2014 VL 15 AR 134 DI 10.1186/s12881-014-0134-1 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CB0UV UT WOS:000349343900001 PM 25714468 ER PT J AU Breithardt, G Baumgartner, H Berkowitz, SD Hellkamp, AS Piccini, JP Stevens, SR Lokhnygina, Y Patel, MR Halperin, JL Singer, DE Hankey, GJ Hacke, W Becker, RC Nessel, CC Mahaffey, KW Fox, KAA Califf, RM AF Breithardt, Gunter Baumgartner, Helmut Berkowitz, Scott D. Hellkamp, Anne S. Piccini, Jonathan P. Stevens, Susanna R. Lokhnygina, Yuliya Patel, Manesh R. Halperin, Jonathan L. Singer, Daniel E. Hankey, Graeme J. Hacke, Werner Becker, Richard C. Nessel, Christopher C. Mahaffey, Kenneth W. Fox, Keith A. A. Califf, Robert M. CA Rocket AF Steering Comm Investigat TI Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Fibrillation; Anticoagulants; Heart diseases; Regurgitation; Stenosis ID MANAGEMENT; RATIONALE; DESIGN; STROKE; REGISTRY; PREVENTION; APIXABAN; EVENTS; RISK; GUIDELINES AB We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. C1 [Breithardt, Gunter] Univ Hosp Munster, Dept Cardiovasc Med, Div Electrophysiol, D-48149 Munster, Germany. [Baumgartner, Helmut] Univ Hosp Munster, Dept Cardiovasc Med, Div Adult Congenital & Valvular Heart Dis, D-48149 Munster, Germany. [Berkowitz, Scott D.] Bayer Healthcare Pharmaceut LP, Whippany, NJ USA. [Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Piccini, Jonathan P.] Mt Sinai Med Ctr, Ctr Cardiovasc, New York, NY 10029 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. RP Breithardt, G (reprint author), Univ Hosp Munster, Dept Cardiovasc Med, Div Electrophysiol, Von Esmarch Str 117, D-48149 Munster, Germany. EM g.breithardt@uni-muenster.de RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 25 TC 37 Z9 38 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD DEC 14 PY 2014 VL 35 IS 47 BP 3377 EP 3385 DI 10.1093/eurheartj/ehu305 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW6WS UT WOS:000346406800016 PM 25148838 ER PT J AU Hayano, K Fujishiro, T Sahani, DV Satoh, A Aoyagi, T Ohira, G Tochigi, T Matsubara, H Shuto, K AF Hayano, Koichi Fujishiro, Takeshi Sahani, Dushyant V. Satoh, Asami Aoyagi, Tomoyoshi Ohira, Gaku Tochigi, Toru Matsubara, Hisahiro Shuto, Kiyohiko TI Computed tomography perfusion imaging as a potential imaging biomarker of colorectal cancer SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Colorectal cancer; Angiogenesis; Computed tomography perfusion; Antiangiogenic therapy; Chemoradiation therapy ID TUMOR BLOOD-FLOW; INTERSTITIAL FLUID PRESSURE; INDIVIDUAL PATIENT DATA; 18 RANDOMIZED-TRIALS; RECTAL-CANCER; CT PERFUSION; POSTOPERATIVE CHEMORADIOTHERAPY; HEPATIC METASTASES; PROGNOSTIC-FACTORS; RADIATION-THERAPY AB Neovascularization was reported to arise early in the adenoma- carcinoma sequence in colorectal cancer (CRC), and the importance of angiogenesis in cancer progression has been established. Computed tomography (CT) perfusion (CTP) based on high temporal resolution CT images enables evaluation of hemodynamics of tissue in vivo by modeling tracer kinetics. CTP has been reported to characterize tumor angiogenesis, and to be a sensitive marker for predicting recurrence or survival in CRC. In this review, we will discuss the biomarker value of CTP in the management of CRC patients. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Hayano, Koichi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Fujishiro, Takeshi; Satoh, Asami; Aoyagi, Tomoyoshi; Ohira, Gaku; Tochigi, Toru; Matsubara, Hisahiro] Chiba Univ, Grad Sch Med, Dept Frontier Surg, Chiba 2608677, Japan. [Shuto, Kiyohiko] Teikyo Univ, Med Ctr, Dept Surg, Ichihara, Chiba 2990111, Japan. RP Hayano, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM khayano@partners.org NR 49 TC 3 Z9 3 U1 2 U2 3 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC 14 PY 2014 VL 20 IS 46 BP 17345 EP 17351 DI 10.3748/wjg.v20.i46.17345 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW6NN UT WOS:000346386300009 PM 25516645 ER PT J AU Wong, JC Fernandes, KA Amin, S Lwin, Z Krzyzanowska, MK AF Wong, Janice C. Fernandes, Kimberly A. Amin, Shubarna Lwin, Zarnie Krzyzanowska, Monika K. TI Involvement of low- and middle-income countries in randomized controlled trial publications in oncology SO GLOBALIZATION AND HEALTH LA English DT Article DE Randomized controlled trials; Publications; Cancer; Low and middle income countries; Authorship; Sponsorship ID BREAST HEALTH-CARE; GUIDELINE IMPLEMENTATION; CLINICAL-TRIALS; RESOURCE-ALLOCATION; CANCER; BURDEN; DISEASE; AFRICA; WORLD AB Background: We describe trends in participation by investigators from low- and middle-income countries (LMCs) in publications describing oncology randomized control trials (RCTs) over a decade. Methods: We used Medline to identify RCTs published in English from 1998 to 2008 evaluating treatment in lung, breast, colorectal, stomach and liver cancers. Data on author affiliations, authorship roles, trial characteristics, funding and interventions were extracted from each article. Countries were stratified as low-, middle-or high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression was used to identify factors associated with authorship by investigators from LMCs. Results: 454 publications were identified. Proportion of articles with at least one LMC author increased over time from 20% in 1998 to 29% in 2008 (p = 0.01), but almost all LMC authors were from middle-income countries. Proportion of articles with at least one LMC author was higher among articles that explicitly reported recruitment in at least one LMC vs those that did not (76% vs 13%). Among 87 articles (19%) that involved authors from LMCs, 17% had LMC authors as first or corresponding authors, and 67% evaluated interventions requiring enhanced or maximal resources. Factors associated with LMC authorship included industry funding (OR = 3.54, p = 0.0001), placebo comparator arm (OR = 2.57, p = 0.02) and palliative intent treatment (OR = 4.00, p = 0.0003). Conclusion: An increasing number of publications describing oncology RCTs involve authors from LMC countries but primarily in non-leadership roles in industry-funded trials. C1 [Wong, Janice C.] Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. [Wong, Janice C.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fernandes, Kimberly A.; Krzyzanowska, Monika K.] Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [Amin, Shubarna; Krzyzanowska, Monika K.] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. [Lwin, Zarnie] Univ Queensland, Royal Brisbane & Womens Hosp, Sch Med, Dept Med Oncol, Brisbane, Qld 4029, Australia. [Krzyzanowska, Monika K.] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada. RP Krzyzanowska, MK (reprint author), Inst Clin Evaluat Sci, G1 44,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM monika.krzyzanowska@uhn.ca NR 29 TC 0 Z9 0 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8603 J9 GLOBALIZATION HEALTH JI Global. Health PD DEC 13 PY 2014 VL 10 AR 83 DI 10.1186/s12992-014-0083-7 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AY7EI UT WOS:000347723700001 PM 25498958 ER PT J AU Steckling, N Bose-O'Reilly, S Pinheiro, P Plass, D Shoko, D Drasch, G Bernaudat, L Siebert, U Hornberg, C AF Steckling, Nadine Bose-O'Reilly, Stephan Pinheiro, Paulo Plass, Dietrich Shoko, Dennis Drasch, Gustav Bernaudat, Ludovic Siebert, Uwe Hornberg, Claudia TI The burden of chronic mercury intoxication in artisanal small-scale gold mining in Zimbabwe: data availability and preliminary estimates SO ENVIRONMENTAL HEALTH LA English DT Article DE Environmental burden of disease; Disability-adjusted life years; Artisanal small-scale gold mining; Mercury; Occupational health; Zimbabwe ID HUMAN BIOMONITORING COMMISSION; ADJUSTED LIFE YEARS; ELEMENTAL MERCURY; GLOBAL BURDEN; OCCUPATIONAL-EXPOSURE; ENVIRONMENTAL-HEALTH; CHLORALKALI WORKERS; SYSTEMATIC ANALYSIS; 21 REGIONS; MINERS AB Background: Artisanal small-scale gold mining (ASGM) is a poverty-driven activity practiced in over 70 countries worldwide. Zimbabwe is amongst the top ten countries using large quantities of mercury to extract gold from ore. This analysis was performed to check data availability and derive a preliminary estimate of disability-adjusted life years (DALYs) due to mercury use in ASGM in Zimbabwe. Methods: Cases of chronic mercury intoxication were identified following an algorithm using mercury-related health effects and mercury in human specimens. The sample prevalence amongst miners and controls (surveyed by the United Nations Industrial Development Organization in 2004 and the University of Munich in 2006) was determined and extrapolated to the entire population of Zimbabwe. Further epidemiological and demographic data were taken from the literature and missing data modeled with DisMod II to quantify DALYs using the methods from the Global Burden of Disease (GBD) 2004 update published by the World Health Organization (WHO). While there was no disability weight (DW) available indicating the relative disease severity of chronic mercury intoxication, the DW of a comparable disease was assigned by following the criteria 1) chronic condition, 2) triggered by a substance, and 3) causing similar health symptoms. Results: Miners showed a sample prevalence of 72% while controls showed no cases of chronic mercury intoxication. Data availability is very limited why it was necessary to model data and make assumptions about the number of exposed population, the definition of chronic mercury intoxication, DW, and epidemiology. If these assumptions hold, the extrapolation would result in around 95,400 DALYs in Zimbabwe's total population in 2004. Conclusions: This analysis provides a preliminary quantification of the mercury-related health burden from ASGM based on the limited data available. If the determined assumptions hold, chronic mercury intoxication is likely to have been one of the top 20 hazards for population health in Zimbabwe in 2004 when comparing with more than 130 categories of diseases and injuries quantified in the WHO's GBD 2004 update. Improving data quality would allow more accurate estimates. However, the results highlight the need to reduce a burden which could be entirely avoided. C1 [Steckling, Nadine; Hornberg, Claudia] Univ Bielefeld, Sch Publ Hlth, Dept Environm & Hlth, D-33615 Bielefeld, Germany. [Steckling, Nadine; Bose-O'Reilly, Stephan] Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, WHO Collaborating Ctr Occupat Hlth, Workgrp Paediat Environm Epidemiol, D-80336 Munich, Germany. [Steckling, Nadine; Bose-O'Reilly, Stephan; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. [Pinheiro, Paulo] Univ Bielefeld, Fac Educ Sci, D-33615 Bielefeld, Germany. [Plass, Dietrich] Fed Environm Agcy, Sect Exposure Assessment & Environm Hlth Indicato, D-14195 Berlin, Germany. [Shoko, Dennis] Tailjet Consultancy Serv, Harare, Zimbabwe. [Drasch, Gustav] Univ Munich LMU, Dept Forens Toxicol, Inst Forens Med, D-80336 Munich, Germany. [Bernaudat, Ludovic] UN Ind Dev Org, Vienna Int Ctr, A-1400 Vienna, Austria. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. RP Steckling, N (reprint author), Univ Bielefeld, Sch Publ Hlth, Dept Environm & Hlth, Univ Str 25, D-33615 Bielefeld, Germany. EM nadine.steckling@uni-bielefeld.de FU GEF (Global Environment Facility); LMU; Deutsche Forschungsgemeinschaft; Bielefeld University FX Thanks are due to all the volunteers and colleagues who were involved in the UNIDO Global Mercury Project and the LMU project. Data were taken from a 2004 project organized by UNIDO as part of the Global Mercury Project, with funds from the GEF (Global Environment Facility) and a 2006 project funded by the LMU. Special thanks are due to Beate Lettmeier for assisting with data collection. Thanks are also due to Debbie Johnson and Saskia Untiet- Kepp for English language editing. This analysis received no funding. We acknowledge support of the publication fee by the Deutsche Forschungsgemeinschaft and the Open Access Publication Funds of Bielefeld University. NR 124 TC 7 Z9 8 U1 7 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD DEC 13 PY 2014 VL 13 AR 111 DI 10.1186/1476-069X-13-111 PG 20 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AY3MP UT WOS:000347488100001 PM 25495641 ER PT J AU Zhang, LY Li, K Sun, R Zhang, Y Ji, JF Huang, PG Yang, HY Tian, Y AF Zhang, Liyuan Li, Kun Sun, Rui Zhang, Yuan Ji, JianFeng Huang, Peigeng Yang, Hongying Tian, Ye TI Minocycline ameliorates cognitive impairment induced by whole-brain irradiation: an animal study SO RADIATION ONCOLOGY LA English DT Article DE Whole-brain irradiation; Cognitive deficit; Minocycline; Newborn neuron; Apoptosis; Neurogenesis ID MORRIS WATER MAZE; NEURAL STEM-CELLS; HIPPOCAMPAL NEUROGENESIS; DENTATE GYRUS; CRANIAL IRRADIATION; ADULT NEUROGENESIS; X-IRRADIATION; MICE; RAT; LITHIUM AB Background: It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Methods: Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Results: Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation. Conclusions: Minocycline significantly inhibits WBI-induced neuron apoptosis, leading to less newborn neurons loss shortly after irradiation. In the long run, minocycline improves the cognitive performance of rats post WBI. The results indicate a potential clinical implication of minocycline as an effective adjunct in radiotherapy for brain tumor patients. C1 [Zhang, Liyuan; Li, Kun; Sun, Rui; Zhang, Yuan; Ji, JianFeng; Tian, Ye] Soochow Univ, Affiliated Hosp 2, Dept Radiotherapy & Oncol, Suzhou 215004, Jiangsu, Peoples R China. [Zhang, Liyuan; Li, Kun; Sun, Rui; Zhang, Yuan; Ji, JianFeng; Tian, Ye] Soochow Univ, Affiliated Hosp 2, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215004, Jiangsu, Peoples R China. [Zhang, Liyuan; Yang, Hongying; Tian, Ye] Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiat Med, Suzhou 215123, Jiangsu, Peoples R China. [Li, Kun] Taishan Med Univ, Affiliated Hosp, Dept Med Oncol, Tai An 271000, Shandong, Peoples R China. [Huang, Peigeng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Hongying] Soochow Univ, Sch Radiat Med & Protect, Coll Med, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Jiangsu, Peoples R China. RP Yang, HY (reprint author), Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiat Med, Suzhou 215123, Jiangsu, Peoples R China. EM yanghongying@suda.edu.cn; dryetian@hotmail.com FU National Natural Science Foundation of China [81172128, 81102077, 81372411, 81472804]; Jiangsu Provincial Special Program of Clinical Medical Science [BL2014040]; Jiangsu Province's Key Medical Department; Priority Academic Program Development of Jiangsu Higher Education Institutions (PARD) FX This research was supported by the National Natural Science Foundation of China grants (81172128, 81102077, 81372411, 81472804), Jiangsu Provincial Special Program of Clinical Medical Science (BL2014040), Jiangsu Province's Key Medical Department in 2011 and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PARD). NR 36 TC 8 Z9 8 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-717X J9 RADIAT ONCOL JI Radiat. Oncol. PD DEC 12 PY 2014 VL 9 AR 281 DI 10.1186/s13014-014-0281-8 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CA9XZ UT WOS:000349280100001 PM 25498371 ER PT J AU Dempsey, PP Businger, AC Whaley, LE Gagne, JJ Linder, JA AF Dempsey, Patrick P. Businger, Alexandra C. Whaley, Lauren E. Gagne, Joshua J. Linder, Jeffrey A. TI Primary care clinicians? perceptions about antibiotic prescribing for acute bronchitis: a qualitative study SO BMC FAMILY PRACTICE LA English DT Article DE Bronchitis; Respiratory tract infections; Anti-bacterial agents; Primary health care; Qualitative research ID RESPIRATORY-TRACT INFECTIONS; PATIENT SATISFACTION; PHYSICAL-EXAMINATION; PRACTICE GUIDELINES; EXPECTATIONS; ADULTS; TRIAL; PRINCIPLES AB Background: Clinicians prescribe antibiotics to over 65% of adults with acute bronchitis despite guidelines stating that antibiotics are not indicated. Methods: To identify and understand primary care clinician perceptions about antibiotic prescribing for acute bronchitis, we conducted semi-structured interviews with 13 primary care clinicians in Boston, Massachusetts and used thematic content analysis. Results: All the participants agreed with guidelines that antibiotics are not indicated for acute bronchitis and felt that clinicians other than themselves were responsible for overprescribing. Barriers to guideline adherence included 6 themes: (1) perceived patient demand, which was the main barrier, although some clinicians perceived a recent decrease; (2) lack of accountability for antibiotic prescribing; (3) saving time and money; (4) other clinicians? misconceptions about acute bronchitis; (5) diagnostic uncertainty; and (6) clinician dissatisfaction in failing to meet patient expectations. Strategies to decrease inappropriate antibiotic prescribing included 5 themes: (1) patient educational materials; (2) quality reporting; (3) clinical decision support; (4) use of an over-the-counter prescription pad; and (5) pre-visit triage and education by nurses to prevent visits. Conclusions: Clinicians continued to cite patient demand as the main reason for antibiotic prescribing for acute bronchitis, though some clinicians perceived a recent decrease. Clinicians felt that other clinicians were responsible for inappropriate antibiotic prescribing and that better pre-visit triage by nurses could prevent visits and change patients? expectations. C1 [Dempsey, Patrick P.; Businger, Alexandra C.; Linder, Jeffrey A.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA. [Whaley, Lauren E.] Massachusetts Dept Publ Hlth, Bur Infect Dis, Boston, MA USA. [Gagne, Joshua J.] Dana Farber Canc Inst, Survey & Data Management Core, Boston, MA 02115 USA. [Linder, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA. EM jlinder@partners.org FU Agency for Healthcare Research and Quality [R18 HS018419] FX This project was funded by the Agency for Healthcare Research and Quality (R18 HS018419). NR 44 TC 8 Z9 8 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2296 J9 BMC FAM PRACT JI BMC Fam. Pract. PD DEC 12 PY 2014 VL 15 AR UNSP 194 DI 10.1186/s12875-014-0194-5 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AZ3DZ UT WOS:000348109200001 PM 25495918 ER PT J AU Veena, MS Wilken, R Zheng, JY Gholkar, A Venkatesan, N Vira, D Ahmed, S Basak, SK Dalgard, CL Ravichandran, S Batra, RK Kasahara, N Elashoff, D Fishbein, MC Whitelegge, JP Torres, JZ Wang, MB Srivatsan, ES AF Veena, Mysore S. Wilken, Reason Zheng, Jun-Ying Gholkar, Ankur Venkatesan, Natarajan Vira, Darshni Ahmed, Sameer Basak, Saroj K. Dalgard, Clifton L. Ravichandran, Sandhiya Batra, Raj K. Kasahara, Noriyuki Elashoff, David Fishbein, Michael C. Whitelegge, Julian P. Torres, Jorge Z. Wang, Marilene B. Srivatsan, Eri S. TI p16 Protein and Gigaxonin Are Associated with the Ubiquitination of NF kappa B in Cisplatin-induced Senescence of Cancer Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cancer Stem Cells; Cellular Senescence; Chemoresistance; Head and Neck Cancer; Ubiquitination; Cisplatin; Gigaxonin; NFB; p16 Suppressor Gene ID CURCUMIN SUPPRESSES GROWTH; RANDOMIZED PHASE-II; TRANSCRIPTION FACTOR; NECK-CANCER; OROPHARYNGEAL CANCER; HUMAN-PAPILLOMAVIRUS; INDUCTION CHEMOTHERAPY; INDEPENDENT PATHWAY; HUMAN HEAD; IN-VITRO AB Background: Molecular mechanism of p16-mediated cellular senescence in cisplatin-treated cells is not known. Results: Cisplatin treatment leads to p16 nuclear transport and association with gigaxonin for the ubiquitination of NFB. Conclusion: A protein associated with neural diseases is involved in cisplatin-mediated cellular senescence. Significance: Nuclear expression of p16 and gigaxonin is a useful marker of cancer cell chemosensitivity. The molecular mechanism of p16-mediated senescence in cisplatin-treated cancer cells is not fully understood. Here we show that cisplatin treatment of head and neck cancer cells results in nuclear transport of p16 leading to a molecular modification of NFB. Chromatin immunoprecipitation assays show that this modification is associated with the inhibition of NFB interacting with its DNA binding sequences, leading to decreased expression of NFB-transcribed proteins. LCMS proteomic analysis of LAP-TAP-purified proteins from HeLa cells containing a tetracycline-inducible GFP-S peptide-NFB expression system identified gigaxonin, an ubiquitin E3 ligase adaptor, as an NFB-interacting protein. Immunoblotting and siRNA studies confirmed the NFB-gigaxonin interaction and the dependence of this binding on p16-NFB binding. Using gel shift assays, we have confirmed p16-NFB and gigaxonin-NFB interactions. Furthermore, we have observed increased NFB ubiquitination with cisplatin treatment that is abolished in the absence of p16 and gigaxonin expression. Analysis of 103 primary tumors has shown that increased nuclear p16 expression correlates with enhanced survival of head and neck cancer patients (p < 0.0000542), indicating the importance of nuclear p16 expression in prognosis. Finally, p16 expression is associated with reduced cytokine expression and the presence of human papilloma virus in chemoradiation-sensitive basaloid tumors. However, the absence of p16 expression is associated with enhanced cytokine expression and the absence of human papilloma virus in aggressive tumors. These results clearly demonstrate that nuclear p16 and gigaxonin play an important role in chemosensitivity of head and neck cancers through ubiquitination of NF kappa B. C1 [Veena, Mysore S.; Wilken, Reason; Zheng, Jun-Ying; Venkatesan, Natarajan; Vira, Darshni; Basak, Saroj K.; Ravichandran, Sandhiya; Wang, Marilene B.; Srivatsan, Eri S.] UCLA, David Geffen Sch Med, VAGLAHS, Dept Surg, Los Angeles, CA 90073 USA. [Gholkar, Ankur; Torres, Jorge Z.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Vira, Darshni; Ahmed, Sameer; Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. [Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Genet, Bethesda, MD 20814 USA. [Batra, Raj K.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90073 USA. [Batra, Raj K.; Kasahara, Noriyuki; Elashoff, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Fishbein, Michael C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Whitelegge, Julian P.] UCLA, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Batra, Raj K.; Torres, Jorge Z.; Wang, Marilene B.; Srivatsan, Eri S.] UCLA, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Srivatsan, ES (reprint author), UCLA, David Geffen Sch Med, VAGLAHS, Dept Surg, Bldg 304,Rm E2-218,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM esrivats@ucla.edu FU National Institutes of Health [R21 CA116826-01]; Veterans Affairs, Washington, D. C.; Veterans Affairs Greater Los Angeles Healthcare System; West Los Angeles Surgical Education Research Center; UCLA Academic Senate grant FX This work was supported, in whole or in part, by National Institutes of Health Grant R21 CA116826-01 (to M. W.). This work was also supported by a merit grant from Veterans Affairs, Washington, D. C. (to E. S. S.), by funds from Veterans Affairs Greater Los Angeles Healthcare System, West Los Angeles Surgical Education Research Center, and by a UCLA Academic Senate grant (to M. W.). NR 59 TC 6 Z9 7 U1 0 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2014 VL 289 IS 50 BP 34921 EP 34937 DI 10.1074/jbc.M114.568543 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW4OP UT WOS:000346260800042 PM 25331947 ER PT J AU Haggerty, TJ Dunn, IS Rose, LB Newton, EE Pandolfi, F Kurnick, JT AF Haggerty, Timothy J. Dunn, Ian S. Rose, Lenora B. Newton, Estelle E. Pandolfi, Franco Kurnick, James T. TI Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells SO PLOS ONE LA English DT Article ID PHASE-II TRIAL; HSP90 INHIBITORS; METASTATIC MELANOMA; ANTITUMOR-ACTIVITY; PANCREATIC-CANCER; BRAF INHIBITION; DOWN-MODULATION; B-RAF; IMMUNOTHERAPY; CHAPERONE AB In an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90) share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer. C1 [Haggerty, Timothy J.; Dunn, Ian S.; Rose, Lenora B.; Newton, Estelle E.; Kurnick, James T.] CytoCure LLC, Beverly, MA USA. [Haggerty, Timothy J.; Kurnick, James T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Pandolfi, Franco] Catholic Univ, Dept Internal Med, Rome, Italy. RP Pandolfi, F (reprint author), Catholic Univ, Dept Internal Med, Rome, Italy. EM pandolfi@rm.unicatt.it FU National Institutes of Health [CA-165553]; International Cancer Research Scholarship FX The studies were supported in part by a grant from the National Institutes of Health, CA-165553 (TJH, ISD, EEN, LBR, JTK), and by an International Cancer Research Scholarship to JTK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 4 Z9 4 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2014 VL 9 IS 12 AR e114506 DI 10.1371/journal.pone.0114506 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6JI UT WOS:000346375400032 PM 25503774 ER PT J AU King, LY Johnson, KB Zheng, H Wei, L Gudewicz, T Hoshida, Y Corey, KE Ajayi, T Ufere, N Baumert, TF Chan, AT Tanabe, KK Fuchs, BC Chung, RT AF King, Lindsay Y. Johnson, Kara B. Zheng, Hui Wei, Lan Gudewicz, Thomas Hoshida, Yujin Corey, Kathleen E. Ajayi, Tokunbo Ufere, Nneka Baumert, Thomas F. Chan, Andrew T. Tanabe, Kenneth K. Fuchs, Bryan C. Chung, Raymond T. TI Host Genetics Predict Clinical Deterioration in HCV-Related Cirrhosis SO PLOS ONE LA English DT Article ID CHRONIC HEPATITIS-C; THAN-G POLYMORPHISM; GROWTH-FACTOR GENE; HEPATOCELLULAR-CARCINOMA; FUNCTIONAL POLYMORPHISM; RISK; VIRUS; ENTRY; PROGRESSION; EXPRESSION AB Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31-6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0-1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95% CI 0.96-3.35) for 2 unfavorable genotypes and 4.03 (95% CI 2.13-7.62) for unfavorable genotypes for all three loci (P-trend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression. C1 [King, Lindsay Y.; Johnson, Kara B.; Corey, Kathleen E.; Chan, Andrew T.; Chung, Raymond T.] Massachusetts Gen Hosp, Ctr Liver, Gastrointestinal Div, Boston, MA 02114 USA. [King, Lindsay Y.; Johnson, Kara B.; Corey, Kathleen E.; Ufere, Nneka; Chan, Andrew T.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wei, Lan; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gudewicz, Thomas] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [King, Lindsay Y.; Johnson, Kara B.; Zheng, Hui; Wei, Lan; Gudewicz, Thomas; Corey, Kathleen E.; Ufere, Nneka; Baumert, Thomas F.; Chan, Andrew T.; Tanabe, Kenneth K.; Fuchs, Bryan C.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Hoshida, Yujin] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Ajayi, Tokunbo] North Shore Med Ctr, Dept Med, Salem, MA USA. [Baumert, Thomas F.] Univ Strasbourg, INSERM, U1110, Strasbourg, France. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Ctr Liver, Gastrointestinal Div, Boston, MA 02114 USA. EM rtchung@partners.org FU National Institutes of Health [DK078772, T32DK007191, DK098311]; National Cancer Institute [CA140861] FX This study was funded by the National Institutes of Health DK078772 (RC), National Cancer Institute CA140861 (BF), National Institutes of Health T32DK007191 (LK and KJ), National Institutes of Health DK098311 (AC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 4 Z9 4 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2014 VL 9 IS 12 AR e114747 DI 10.1371/journal.pone.0114747 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6JI UT WOS:000346375400049 PM 25504078 ER PT J AU Martinez, KG Franco-Chaves, JA Milad, MR Quirk, GJ AF Martinez, Karen G. Franco-Chaves, Jose A. Milad, Mohammed R. Quirk, Gregory J. TI Ethnic Differences in Physiological Responses to Fear Conditioned Stimuli SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; EXTINCTION; CONTEXT; RECOMMENDATIONS; METAANALYSIS; MECHANISMS; CULTURE; HUMANS; SEX AB The idea that emotional expression varies with ethnicity is based largely on questionnaires and behavioral observations rather than physiological measures. We therefore compared the skin conductance responses (SCR) of Hispanic (Puerto Rican) and White non-Hispanic subjects in a fear conditioning and fear extinction task. Subjects were recruited from two sites: San Juan, Puerto Rico (PR), and Boston, Massachusetts (MA), using identical methods. A total of 78 healthy subjects (39 from PR, 39 from MA) were divided by sex and matched for age and educational level. Females from the two sites did not differ in their SCRs during any experimental phase of fear conditioning (habituation, conditioning, or extinction). In contrast, PR males responded significantly to the conditioned stimulus than MA males or PR females. Subtracting ethnic differences observed during the habituation phase (prior to conditioning) eliminated differences from subsequent phases, suggesting that PR males are elevated in their response to novelty rather than fear learning. Our findings suggest that, in addition to sex differences, there are ethnic differences in physiological responses to novel stimuli at least in males, which could be relevant for the assessment and treatment of anxiety disorders. C1 [Martinez, Karen G.; Franco-Chaves, Jose A.; Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA. [Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Martinez, KG (reprint author), Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA. EM Karen.martinez4@upr.edu FU National Center for Research Resources [U54 RR026139]; National Institute on Minority Health and Health Disparities [8U54MD 007587-03]; HISPANICS-IN-RESEARCH CAPABILITY: SoHP & SoM PARTNERSHIP (HiREC) [S21MD001830] FX The project described was supported by award number U54 RR026139 from the National Center for Research Resources, award number 8U54MD 007587-03 from the National Institute on Minority Health and Health Disparities and the HISPANICS-IN-RESEARCH CAPABILITY: SoHP & SoM PARTNERSHIP (HiREC) Endowment Program award number: S21MD001830 (kgm). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 2 Z9 2 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2014 VL 9 IS 12 AR e114977 DI 10.1371/journal.pone.0114977 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW6JI UT WOS:000346375400064 PM 25501365 ER PT J AU Gutchess, A AF Gutchess, Angela TI Recognizing the risks of brain stimulation Response SO SCIENCE LA English DT Letter ID TRANSCRANIAL MAGNETIC STIMULATION; SAFETY C1 [Gutchess, Angela] Brandeis Univ, Ctr Complex Syst, Dept Psychol & Volen Natl, Waltham, MA 02453 USA. [Gutchess, Angela] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Gutchess, A (reprint author), Brandeis Univ, Ctr Complex Syst, Dept Psychol & Volen Natl, Waltham, MA 02453 USA. EM gutchess@brandeis.edu NR 8 TC 0 Z9 0 U1 2 U2 6 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 DEC 12 PY 2014 VL 346 IS 6215 BP 1307 EP 1307 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW3MA UT WOS:000346189600031 PM 25504708 ER PT J AU Mansour, MR Abraham, BJ Anders, L Berezovskaya, A Gutierrez, A Durbin, AD Etchin, J Lawton, L Sallan, SE Silverman, LB Loh, ML Hunger, SP Sanda, T Young, RA Look, AT AF Mansour, Marc R. Abraham, Brian J. Anders, Lars Berezovskaya, Alla Gutierrez, Alejandro Durbin, Adam D. Etchin, Julia Lawton, Lee Sallan, Stephen E. Silverman, Lewis B. Loh, Mignon L. Hunger, Stephen P. Sanda, Takaomi Young, Richard A. Look, A. Thomas TI An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element SO SCIENCE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MONOALLELIC EXPRESSION; TRANSCRIPTION FACTORS; SELECTIVE-INHIBITION; CELL IDENTITY; TAL1 COMPLEX; GENES; DISRUPTION; DISEASE; LINEAGE AB In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB binds to this new site and recruits its H3K27 acetylase-binding partner CBP, as well as core components of a major leukemogenic transcriptional complex that contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super-enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a general role for MYB in super-enhancer initiation. Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells. C1 [Mansour, Marc R.; Berezovskaya, Alla; Gutierrez, Alejandro; Durbin, Adam D.; Etchin, Julia; Sallan, Stephen E.; Silverman, Lewis B.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Mansour, Marc R.] UCL, UCL Canc Inst, Dept Haematol, London WC1E 6BT, England. [Abraham, Brian J.; Anders, Lars; Lawton, Lee; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Gutierrez, Alejandro; Sallan, Stephen E.; Silverman, Lewis B.; Look, A. Thomas] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Loh, Mignon L.] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA. [Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Hunger, Stephen P.] Childrens Hosp Colorado, Aurora, CO 80045 USA. [Sanda, Takaomi] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore. [Sanda, Takaomi] Yong Loo Lin Sch Med, Dept Med, Singapore 117599, Singapore. [Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. EM young@wi.mit.edu; thomas_look@dfci.harvard.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU Claudia Adams Barr Innovative Basic Science Research Program; Kay Kendall Leukaemia Trust; Leukaemia and Lymphoma Research, UK; National Cancer Institute, NIH [CA167124]; Department of Defense [CA120215]; William Lawrence and Blanche Hughes Foundation; National Research Foundation (NRF), Prime Minister's Office, Singapore under its NRF Fellowship Program [NRF-NRFF2013-02]; NIH [1R01CA176746-01, 5P01CA109901-08, 5P01CA68484, CA98543, CA114766, CA98413, CA30969, CA29139] FX We thank J. Gilbert for helpful editorial comments on the manuscript, J. Reddy for sharing data, and F. Alt and F. Meng for helpful advice on the design of the CRISPR experiments. We would like to dedicate this paper to the memory of Michael Fayngersh. We gratefully acknowledge the children with T-ALL and their families for the samples analyzed in these studies. M.R.M. was supported by the Claudia Adams Barr Innovative Basic Science Research Program, the Kay Kendall Leukaemia Trust, and a Bennett Fellowship from Leukaemia and Lymphoma Research, UK. A.G. is a Research Fellow of the Gabrielle's Angel Foundation for Cancer Research, a Clinical Investigator of the Damon Runyon Cancer Research Foundation, and is supported by grants National Cancer Institute, NIH, CA167124, Department of Defense, CA120215 and an award from the William Lawrence and Blanche Hughes Foundation. T.S. is supported by a grant from the National Research Foundation (NRF), Prime Minister's Office, Singapore under its NRF Fellowship Program (award no. NRF-NRFF2013-02). This work was funded by NIH grants 1R01CA176746-01 and 5P01CA109901-08 (A.T.L.), and 5P01CA68484 (S.E.S. and A.T.L.). Children's Oncology Group cell banking and sample distribution were supported by grants CA98543, CA114766, CA98413, CA30969, and CA29139 from the NIH. S.P.H. is the Ergen Family Chair in Pediatric Cancer. R.A.Y. is a founder and member of the Board of Directors of Syros Pharmaceuticals, a company developing therapies that target gene regulatory elements including super-enhancers. NR 24 TC 120 Z9 123 U1 5 U2 25 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 DEC 12 PY 2014 VL 346 IS 6215 BP 1373 EP 1377 DI 10.1126/science.1259037 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW3MA UT WOS:000346189600053 PM 25394790 ER PT J AU Craft, D Bangert, M Long, T Papp, D Unkelbach, J AF Craft, David Bangert, Mark Long, Troy Papp, David Unkelbach, Jan TI Shared data for intensity modulated radiation therapy (IMRT) optimization research: the CORT dataset SO GIGASCIENCE LA English DT Article DE IMRT; Optimization; Radiation therapy; Beam angle optimization; VMAT; Treatment plan optimization ID DIRECT APERTURE OPTIMIZATION; BEAM ANGLE; ARC THERAPY; PENCIL BEAM; GENERATION; RADIOTHERAPY; NUMBER; PLANS AB Background: We provide common datasets (which we call the CORT dataset: common optimization for radiation therapy) that researchers can use when developing and contrasting radiation treatment planning optimization algorithms. The datasets allow researchers to make one-to-one comparisons of algorithms in order to solve various instances of the radiation therapy treatment planning problem in intensity modulated radiation therapy (IMRT), including beam angle optimization, volumetric modulated arc therapy and direct aperture optimization. Results: We provide datasets for a prostate case, a liver case, a head and neck case, and a standard IMRT phantom. We provide the dose-influence matrix from a variety of beam/couch angle pairs for each dataset. The dose-influence matrix is the main entity needed to perform optimizations: it contains the dose to each patient voxel from each pencil beam. In addition, the original Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) scan, as well as the DICOM structure file, are provided for each case. Conclusions: Here we present an open dataset - the first of its kind - to the radiation oncology community, which will allow researchers to compare methods for optimizing radiation dose delivery. C1 [Craft, David; Papp, David; Unkelbach, Jan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Bangert, Mark] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Long, Troy] Univ Michigan, Ann Arbor, MI 48109 USA. RP Craft, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM dcraft@mgh.harvard.edu NR 31 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND EI 2047-217X J9 GIGASCIENCE JI GigaScience PD DEC 12 PY 2014 VL 3 AR 37 DI 10.1186/2047-217X-3-37 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX4HI UT WOS:000365659600001 PM 25678961 ER PT J AU Korn, LL Hubbeling, HG Porrett, PM Yang, Q Barnett, LG Laufer, TM AF Korn, Lisa L. Hubbeling, Harper G. Porrett, Paige M. Yang, Qi Barnett, Lisa G. Laufer, Terri M. TI Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent SO CELL REPORTS LA English DT Article ID THYMIC EMIGRANTS; ULCERATIVE-COLITIS; COMMENSAL BACTERIA; COLONIC-MUCOSA; GENERATION; IL-2; INDUCTION; METABOLITES; EXPRESSION; EPITHELIUM AB Regulatory T cells (Tregs) are CD4(+) T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4(+) T cells, Tregs require antigenspecific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. However, the requirement for MHCII in Treg homeostasis in tissues such as intestinal lamina propria (LP) is unknown. We examined LP Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs (iTregs). Thymically generated Tregs entered the LP of weanlings and proliferated independently of MHCII to fill the compartment. The adult LP was a closed niche; new thymic Tregs were excluded, and Tregs in parabiotic pairs were LP resident. The isolated LP niche was interleukin-2 (IL-2) independent but dependent on commensal bacteria. Thus, an LP Treg niche can be filled, isolated, and maintained independently of antigen signals and iTregs. This niche may represent a tissue-specific mechanism for maintaining immune tolerance. C1 [Korn, Lisa L.; Hubbeling, Harper G.; Barnett, Lisa G.; Laufer, Terri M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Porrett, Paige M.] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Yang, Qi] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Laufer, TM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu FU Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine [P30DK050306]; Training Program in Rheumatic Disease [5T32AR007442-25] FX The authors would like to thank Yasmine Belkaid, Nicolas Bouladoux, Tim Hand, and Sean Spencer for helpful discussions, Amy Wagers for technical advice, and Chris Hunter and Helen Simkins for critical reading of the manuscript. This work was initiated with support from pilot grant from the Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine (P30DK050306). L. L. K. was supported by the Training Program in Rheumatic Disease (5T32AR007442-25). NR 35 TC 3 Z9 3 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 11 PY 2014 VL 9 IS 5 BP 1567 EP 1573 DI 10.1016/j.celrep.2014.11.006 PG 7 WC Cell Biology SC Cell Biology GA AX3PR UT WOS:000346851900001 PM 25482559 ER PT J AU Cai, CM He, HH Gao, S Chen, S Yu, ZY Gao, YF Chen, SY Chen, MW Zhang, J Ahmed, M Wang, Y Metzger, E Schule, R Liu, XS Brown, M Balk, SP AF Cai, Changmeng He, Housheng Hansen Gao, Shuai Chen, Sen Yu, Ziyang Gao, Yanfei Chen, Shaoyong Chen, Mei Wei Zhang, Jesse Ahmed, Musaddeque Wang, Yang Metzger, Eric Schuele, Roland Liu, X. Shirley Brown, Myles Balk, Steven P. TI Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity SO CELL REPORTS LA English DT Article ID METASTATIC PROSTATE-CANCER; INCREASED SURVIVAL; GENE-EXPRESSION; LSD1; METHYLATION; ENHANCERS; CHROMATIN; FOXA1; PHOSPHORYLATION; CHEMOTHERAPY AB Lysine-Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4) but has a coactivator function on some genes through mechanisms that are unclear. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR-regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show that LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and that it has a distinct AR-linked coactivator function mediated by demethylation of other substrates. C1 [Cai, Changmeng; Gao, Shuai; Chen, Sen; Yu, Ziyang; Gao, Yanfei; Chen, Shaoyong; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Cai, Changmeng; He, Housheng Hansen; Gao, Shuai; Chen, Sen; Yu, Ziyang; Gao, Yanfei; Chen, Shaoyong; Chen, Mei Wei; Zhang, Jesse; Brown, Myles; Balk, Steven P.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [He, Housheng Hansen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [He, Housheng Hansen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [He, Housheng Hansen; Chen, Mei Wei; Zhang, Jesse; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng Hansen; Ahmed, Musaddeque] Princess Margaret Canc Ctr, Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada. [He, Housheng Hansen] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. [Wang, Yang] Tianjin Med Univ, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Dept Biochem & Mol Biol, Tianjin Key Lab Med Epigenet, Tianjin 300070, Peoples R China. [Metzger, Eric; Schuele, Roland] Univ Freiburg, Klinikum Univ Freiburg, Urolog Klin & Zentrale Klin Forsch, D-79106 Freiburg, Germany. [Wang, Yang; Metzger, Eric; Schuele, Roland] DKTK, D-79106 Freiburg, Germany. [Liu, X. Shirley; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. RP Cai, CM (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. EM ccai1@bidmc.harvard.edu; hansenhe@uhnresearch.ca OI Brown, Myles/0000-0002-8213-1658; Cai, Changmeng/0000-0002-8701-2586 FU NIH [K99 CA166507, K99 CA172948-01, R01 GM099409, P01 CA163227]; SPORE in Prostate Cancer [P50 CA090381]; DOD [W81XWH-11-1-0295, W81XWH-131-0266, W81XWH-10-1-0557, W81XWH-13-PCRP-PTA, W81XWH-12-PCRP-PTA, W81XWH-13-PCRP-EHDA]; DF/HCC Mazzone Impact Award; Prostate Cancer Foundation FX Supported by grants from NIH (K99 CA166507 to C.C., K99 CA172948-01 to H.H.H., R01 GM099409 to X.S.L., P01 CA163227, and SPORE in Prostate Cancer P50 CA090381), and DOD (W81XWH-11-1-0295 and W81XWH-131-0266 to S.P.B., W81XWH-10-1-0557 to H.H.H., W81XWH-13-PCRP-PTA to Y.G., W81XWH-12-PCRP-PTA and W81XWH-13-PCRP-EHDA to Z.Y.), a DF/HCC Mazzone Impact Award, and by Awards from the Prostate Cancer Foundation. NR 33 TC 23 Z9 23 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 11 PY 2014 VL 9 IS 5 BP 1618 EP 1627 DI 10.1016/j.celrep.2014.11.008 PG 10 WC Cell Biology SC Cell Biology GA AX3PR UT WOS:000346851900007 PM 25482560 ER PT J AU Chow, NA Jasenosky, LD Goldfeld, AE AF Chow, Nancy A. Jasenosky, Luke D. Goldfeld, Anne E. TI A Distal Locus Element Mediates IFN-gamma Priming of Lipopolysaccharide- Stimulated TNF Gene Expression SO CELL REPORTS LA English DT Article ID TUMOR-NECROSIS-FACTOR; CREB-BINDING-PROTEIN; FACTOR-ALPHA; INTERFERON-GAMMA; TRANSCRIPTION FACTORS; MONOCYTIC CELLS; IRF FAMILY; CHROMATIN; PROMOTER; ACTIVATION AB Interferon gamma (IFN-gamma) priming sensitizes monocytes and macrophages to lipopolysaccharide (LPS) stimulation, resulting in augmented expression of a set of genes including TNF. Here, we demonstrate that IFN-gamma priming of LPS-stimulated TNF transcription requires a distal TNF/LT locus element 8 kb upstream of the TNF transcription start site (hHS-8). IFN-gamma stimulation leads to increased DNase I accessibility of hHS-8 and its recruitment of interferon regulatory factor 1 (IRF1), and subsequent LPS stimulation enhances H3K27 acetylation and induces enhancer RNA synthesis at hHS-8. Ablation of IRF1 or targeting the hHS-8 IRF1 binding site in vivo with Cas9 linked to the KRAB repressive domain abolishes IFN-gamma priming, but does not affect LPS induction of the gene. Thus, IFN-gamma poises a distal enhancer in the TNF/LT locus by chromatin remodeling and IRF1 recruitment, which then drives enhanced TNF gene expression in response to a secondary toll-like receptor (TLR) stimulus. C1 [Chow, Nancy A.; Jasenosky, Luke D.; Goldfeld, Anne E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, 200 Longwood Ave, Boston, MA 02115 USA. EM anne.goldfeld@childrens.harvard.edu FU GlaxoSmithKline; NIH/NIGMS [GM076685] FX We are indebted to Laurens Kruidenier and David Tough for stimulating discussions and experimental suggestions. We thank Alla Tsytsykova and Shahin Ranjbar for critical experimental advice and discussions. We also thank James Falvo for helpful discussions. This work was supported by grants from GlaxoSmithKline and the NIH/NIGMS (GM076685) to A.E.G. NR 41 TC 5 Z9 5 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 11 PY 2014 VL 9 IS 5 BP 1718 EP 1728 DI 10.1016/j.celrep.2014.11.011 PG 11 WC Cell Biology SC Cell Biology GA AX3PR UT WOS:000346851900017 PM 25482561 ER PT J AU Sung, VMH Tsai, CL AF Sung, Vicky M-H Tsai, Chia-Lun TI ADP-Ribosylargininyl reaction of cholix toxin is mediated through diffusible intermediates SO BMC BIOCHEMISTRY LA English DT Article DE Cholix toxin; ADP-ribosylation; Auto-ADP-ribosylation; Arginine ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; PSEUDOMONAS-AERUGINOSA EXOS; SITE-DIRECTED MUTAGENESIS; DIPHTHERIA-TOXIN; CRYSTAL-STRUCTURE; VIBRIO-CHOLERAE; POLY(ADP-RIBOSE) POLYMERASE; RIBOSYLTRANSFERASE ACTIVITY; RIBOSYLATING TOXINS; ESCHERICHIA-COLI AB Background: Cholix toxin is an ADP-ribosyltransferase found in non-O1/non-O139 strains of Vibrio cholera. The catalytic fragment of cholix toxin was characterized as a diphthamide dependent ADP-ribosyltransferase. Results: Our studies on the enzymatic activity of cholix toxin catalytic fragment show that the transfer of ADP-ribose to toxin takes place by a predominantly intramolecular mechanism and results in the preferential alkylation of arginine residues proximal to the NAD(+) binding pocket. Multiple arginine residues, located near the catalytic site and at distal sites, can be the ADP-ribose acceptor in the auto-reaction. Kinetic studies of a model enzyme, M8, showed that a diffusible intermediate preferentially reacted with arginine residues in proximity to the NAD(+) binding pocket. ADP-ribosylarginine activity of cholix toxin catalytic fragment could also modify exogenous substrates. Auto-ADP-ribosylation of cholix toxin appears to have negatively regulatory effect on ADP-ribosylation of exogenous substrate. However, at the presence of both endogenous and exogenous substrates, ADP-ribosylation of exogenous substrates occurred more efficiently than that of endogenous substrates. Conclusions: We discovered an ADP-ribosylargininyl activity of cholix toxin catalytic fragment from our studies in auto-ADP-ribosylation, which is mediated through diffusible intermediates. The lifetime of the hypothetical intermediate exceeds recorded and predicted lifetimes for the cognate oxocarbenium ion. Therefore, a diffusible strained form of NAD(+) intermediate was proposed to react with arginine residues in a proximity dependent manner. C1 [Sung, Vicky M-H; Tsai, Chia-Lun] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sung, Vicky M-H] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Sung, VMH (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM mvsung@gmail.com FU Massachusetts General Hospital FX We thank Drs. Chi-Wang Lin and Jesse Chen for assistance with circular dichroism spectra analysis; Dr. Stephen H. Leppla (NIH) for providing diphthamide synthesis deficient CHO cell lines; Naifang Lu for providing the catalytic fragment of cholix toxin; Drs. Mikako Tsuchiya and Harumi Osago for mass spectrometry analysis for orn peptide detection; Dr. Brian Seed for critical review, suggestions and language editing this manuscript. This research is supported by Massachusetts General Hospital. NR 49 TC 2 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2091 J9 BMC BIOCHEM JI BMC Boichem. PD DEC 11 PY 2014 VL 15 AR 26 DI 10.1186/s12858-014-0026-1 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW7LQ UT WOS:000346446000002 PM 25494717 ER PT J AU Koven, S AF Koven, Suzanne TI The Disease of the Little Paper SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Koven, Suzanne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koven, Suzanne] Harvard Univ, Sch Med, Boston, MA USA. RP Koven, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2251 EP 2253 DI 10.1056/NEJMp1411685 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800005 PM 25494267 ER PT J AU Trivedi, AN Nsa, W Hausmann, LRM Lee, JS Ma, A Bratzler, DW Mor, MK Baus, K Larbi, F Fine, MJ AF Trivedi, Amal N. Nsa, Wato Hausmann, Leslie R. M. Lee, Jonathan S. Ma, Allen Bratzler, Dale W. Mor, Maria K. Baus, Kristie Larbi, Fiona Fine, Michael J. TI Quality and Equity of Care in US Hospitals SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TO-BALLOON TIME; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; OF-CARE; ETHNIC DISPARITIES; RACIAL DISPARITIES; BLACK PATIENTS; PERFORMANCE; RACE; VACCINATION AB BACKGROUND Nearly every U.S. hospital publicly reports its performance on quality measures for patients who are hospitalized for acute myocardial infarction, heart failure, or pneumonia. Because performance rates are not reported according to race or ethnic group, it is unclear whether improvements in equity of care have accompanied aggregate improvements in health care quality over time. METHODS We assessed performance rates for quality measures covering three conditions (six measures for acute myocardial infarction, four for heart failure, and seven for pneumonia). These rates, adjusted for patient-and hospital-level covariates, were compared among non-Hispanic white, non-Hispanic black, and Hispanic patients who received care between 2005 and 2010 in acute care hospitals throughout the United States. RESULTS Adjusted performance rates for the 17 quality measures improved by 3.4 to 57.6 percentage points between 2005 and 2010 for white, black, and Hispanic adults (P<0.001 for all comparisons). In 2005, as compared with adjusted performance rates for white patients, adjusted performance rates were more than 5 percentage points lower for black patients on 3 measures (range of differences, 12.3 to 14.2) and for Hispanic patients on 6 measures (5.6 to 14.5). Gaps decreased significantly on all 9 of these measures between 2005 and 2010, with adjusted changes for differences between white patients and black patients ranging from -8.5 to -11.8 percentage points and from -6.2 to -15.1 percentage points for differences between white patients and Hispanic patients. Decreasing differences according to race or ethnic group were attributable to more equitable care for white patients and minority patients treated in the same hospital, as well as to greater performance improvements among hospitals that disproportionately serve minority patients. CONCLUSIONS Improved performance on quality measures for white, black, and Hispanic adults hospitalized for acute myocardial infarction, heart failure, or pneumonia was accompanied by increased racial and ethnic equity in performance rates both within and among U.S. hospitals. C1 [Trivedi, Amal N.] Brown Univ, Sch Publ Hlth, Providence Vet Affairs VA Med Ctr, Providence, RI 02903 USA. [Trivedi, Amal N.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02903 USA. [Nsa, Wato; Ma, Allen] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma City, OK 73190 USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Oklahoma City, OK 73190 USA. [Hausmann, Leslie R. M.; Mor, Maria K.; Fine, Michael J.] VA Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hausmann, Leslie R. M.; Lee, Jonathan S.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Baus, Kristie; Larbi, Fiona] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Trivedi, AN (reprint author), Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, 121 S Main St,6th Fl, Providence, RI 02903 USA. EM amal_trivedi@brown.edu FU Centers for Medicare and Medicaid Services; Veterans Affairs Health Services Research and Development Career Development Program FX Funded by the Centers for Medicare and Medicaid Services and the Veterans Affairs Health Services Research and Development Career Development Program. NR 39 TC 11 Z9 11 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2298 EP 2308 DI 10.1056/NEJMoa1405003 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800010 PM 25494269 ER PT J AU Kraut, JA Madias, NE AF Kraut, Jeffrey A. Madias, Nicolaos E. TI DISORDERS OF FLUIDS AND ELECTROLYTES Lactic Acidosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CRITICALLY-ILL PATIENTS; VENOUS OXYGEN-SATURATION; SEPTIC SHOCK; METABOLIC-ACIDOSIS; LACTATE CLEARANCE; MICROCIRCULATORY ALTERATIONS; SEVERE SEPSIS; ANION GAP; HOSPITAL MORTALITY; CONTROLLED-TRIAL C1 [Kraut, Jeffrey A.] Univ Calif Los Angeles, Med Serv, Membrane Biol Lab, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, Res Serv, Membrane Biol Lab, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Nephrol, Los Angeles, CA 90095 USA. [Kraut, Jeffrey A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Madias, Nicolaos E.] St Elizabeths Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Madias, Nicolaos E.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu; nicolaos.madias@steward.org NR 61 TC 61 Z9 62 U1 9 U2 34 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2309 EP 2319 DI 10.1056/NEJMra1309483 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800011 PM 25494270 ER PT J AU Iyasere, CA Simmons, LH Fintelmann, FJ Dighe, AS AF Iyasere, Christiana A. Simmons, Leigh H. Fintelmann, Florian J. Dighe, Anand S. TI Case 38-2014: An 87-Year-Old Man with Sore Throat, Hoarseness, Fatigue, and Dyspnea SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CREATINE-KINASE LEVELS; VENA-CAVA SYNDROME; SUBCLINICAL HYPOTHYROIDISM; THYROXINE; MYOPATHY; OVERT C1 [Iyasere, Christiana A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Simmons, Leigh H.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Fintelmann, Florian J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Iyasere, Christiana A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Simmons, Leigh H.] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. [Fintelmann, Florian J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Dighe, Anand S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Iyasere, CA (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 16 TC 4 Z9 4 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 11 PY 2014 VL 371 IS 24 BP 2321 EP 2327 DI 10.1056/NEJMcpc1410935 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AW1KQ UT WOS:000346048800013 PM 25494272 ER PT J AU Cisterna, BA Cardozo, C Saez, JC AF Cisterna, Bruno A. Cardozo, Christopher Saez, Juan C. TI Neuronal involvement in muscular atrophy SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE acetylcholine; hemichannels; connexins; trophic factors; electrical activity ID SPINAL-CORD-INJURY; CILIARY NEUROTROPHIC FACTOR; RAT SKELETAL-MUSCLE; FUNCTIONAL ELECTRICAL-STIMULATION; CHOLINERGIC SYNAPTIC VESICLES; RECEPTOR GENE-EXPRESSION; CONNEXIN-43 HEMICHANNELS MEDIATE; PHOSPHATE ADENINE-NUCLEOTIDES; MYOGENIC REGULATORY FACTORS; IN-SITU HYBRIDIZATION AB The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels (HCs) formed by connexins (Cxs) and other none selective channels, including P2X(7) receptors (P2X(7)Rs), and transient receptor potential, sub family V, member 2 (TRPV2) channels was demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically reduced in denervated muscles deficient in Cxs 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned non selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATR neurotrophic factors (i.e., brain-derived neurotrophic factor (BDNF)), agrin/LDL receptor-related protein 4 (Lrp4)/muscle-specific receptor kinase (MuSK) and acetylcholine (Ach) are among the possible signals for repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression. C1 [Cisterna, Bruno A.; Saez, Juan C.] Pontificia Univ Catolica Chile, Dept Fisiol, Santiago 8331150, Chile. [Cardozo, Christopher] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. [Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Cardozo, Christopher] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Saez, Juan C.] Univ Valparaiso, Ctr Interdisciplinario Neurociencias Valparaiso, Valparaiso, Chile. RP Cisterna, BA (reprint author), Pontificia Univ Catolica Chile, Dept Fisiol, Alameda 340, Santiago 8331150, Chile. EM bcisterna@uc.cl FU FONDECYT [1111033]; millennium institute; CONICYT; Department of Veterans Affairs Rehabilitation Research and Development Service [B9212C]; James J. Peters VA Medical Center FX This work was partially funded by FONDECYT grants 1111033 (to Juan C. Saez), millennium institute (to Juan C. Saez), and Bruno A. Cisterna acknowledge the support of a CONICYT fellowship, and the Department of Veterans Affairs Rehabilitation Research and Development Service (B9212C) and the James J. Peters VA Medical Center. NR 182 TC 6 Z9 6 U1 1 U2 18 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD DEC 10 PY 2014 VL 8 AR 405 DI 10.3389/fncel.2014.00405 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AX9QE UT WOS:000347236200001 PM 25540609 ER PT J AU Hayes, J Jackson, JL McNutt, GM Hertz, BJ Ryan, JJ Pawlikowski, SA AF Hayes, John Jackson, Jeffrey L. McNutt, Gail M. Hertz, Brian J. Ryan, Jeffrey J. Pawlikowski, Scott A. TI Association Between Physician Time-Unlimited vs Time-Limited Internal Medicine Board Certification and Ambulatory Patient Care Quality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-CARE; HEALTH-CARE; PREVENTION; METAANALYSIS; MAINTENANCE; OUTCOMES; DISEASE; SCORES AB IMPORTANCE American Board of Internal Medicine (ABIM) initiatives encourage internists with time-unlimited certificates to recertify. However, there are limited data evaluating differences in performance between internists with time-limited or time-unlimited board certification. OBJECTIVE To determine whether there are differences in primary care quality between physicians holding time-limited or time-unlimited certification. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of performance data from 1 year (2012-2013) at 4 Veterans Affairs (VA) medical centers. Participants were internists with time-limited (n = 71) or time-unlimited (n = 34) ABIM certification providing primary care to 68 213 patients. Median physician panel size was 610 patients (range, 19-1316), with no differences between groups (P = .90). MAIN OUTCOMES AND MEASURES Ten primary care performance measures: colorectal screening rates; diabetes with glycated hemoglobin (HbA(1c) level) less than 9.0%; diabetes with blood pressure less than 140/90 mmHg; diabetes with low-density lipoprotein cholesterol (LDL-C) level less than 100 mg/dL; hypertension with blood pressure less than 140/90 mmHg; thiazide diuretics used in multidrug hypertensive regimen; atherosclerotic coronary artery disease and LDL-C level less than 100 mg/dL; post-myocardial infarction use of aspirin; post-myocardial infarction use of beta-blockers; congestive heart failure (CHF) with use of angiotensin-converting enzyme (ACE) inhibitor. RESULTS After adjustment for practice site, panel size, years since certification, and clustering by physician, there were no differences in outcomes for patients cared for by internists with time-limited or time-unlimited certification for any performance measure: colorectal screening (odds ratio [OR], 0.95 [95% CI, 0.89-1.01]); diabetes with HbA1c level less than 9.0% (OR, 0.96 [95% CI, 0.74-1.2]); blood pressure control (OR, 0.99 [95% CI, 0.69-1.4]); LDL-C level less than 100 mg/dL (OR, 1.1 [95% CI, 0.79-1.5]); hypertension with blood pressure less than 140/90 mmHg (OR, 1.0 [95% CI, 0.92-1.2]); thiazide use (OR, 1.0 [95% CI, 0.8-1.3]); atherosclerotic coronary artery disease with LDL-C level less than 100 mg/dL (OR, 1.1 [95% CI, 0.75-1.7]); post-myocardial infarction use of aspirin (OR, 0.98 [95% CI, 0.58-1.68]) or beta-blockers (OR, 1.0 [95% CI, 0.57-1.9]); CHF with use of ACE inhibitor (OR, 0.98 [95% CI, 0.61-1.6]). CONCLUSIONS AND RELEVANCE Among internists providing primary care at 4 VA medical centers, there were no significant differences between those with time-limited ABIM certification and those with time-unlimited ABIM certification on 10 primary care performance measures. Additional research to examine the difference in patient outcomes among holders of time-limited and time-unlimited certificates in non-VA and nonacademic settings and the association with other ABIM goals may help clarify the potential benefit of Maintenance of Certification participation. Copyright 2014 American Medical Association. All rights reserved. C1 [Hayes, John] Clement J Zablocki VA Med Ctr, Milwaukee, WI 53295 USA. [Jackson, Jeffrey L.] Clement J Zablocki VA Med Ctr, GIM Sect, Milwaukee, WI 53295 USA. [McNutt, Gail M.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Hertz, Brian J.; Pawlikowski, Scott A.] Hines VA Med Ctr, Chicago, IL USA. [Ryan, Jeffrey J.] Jesse Brown VA Med Ctr, Chicago, IL USA. RP Hayes, J (reprint author), Clement J Zablocki VA Med Ctr, 5000 W Natl Ave, Milwaukee, WI 53295 USA. EM john.hayes3@va.gov NR 28 TC 13 Z9 13 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 10 PY 2014 VL 312 IS 22 BP 2358 EP 2363 DI 10.1001/jama.2014.13992 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YB UT WOS:000346345700010 PM 25490326 ER PT J AU Patel, MS Volpp, KG Small, DS Hill, AS Even-Shoshan, O Rosenbaum, L Ross, RN Bellini, L Zhu, JS Silber, JH AF Patel, Mitesh S. Volpp, Kevin G. Small, Dylan S. Hill, Alexander S. Even-Shoshan, Orit Rosenbaum, Lisa Ross, Richard N. Bellini, Lisa Zhu, Jingsan Silber, Jeffrey H. TI Association of the 2011 ACGME Resident Duty Hour Reforms With Mortality and Readmissions Among Hospitalized Medicare Patients SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; ADMINISTRATIVE DATA; COMORBIDITY MEASURES; INTERNAL-MEDICINE; BENEFICIARIES; ICD-9-CM; CONSEQUENCES; INFORMATION; EDUCATION AB IMPORTANCE Patient outcomes associated with the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour reforms have not been evaluated at a national level. OBJECTIVE To evaluate the association of the 2011 ACGME duty hour reforms with mortality and readmissions. DESIGN, SETTING, AND PARTICIPANTS Observational study of Medicare patient admissions (6 384 273 admissions from 2 790 356 patients) to short-term, acute care, nonfederal hospitals (n = 3104) with principal medical diagnoses of acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure or a Diagnosis Related Group classification of general, orthopedic, or vascular surgery. Of the hospitals, 96 (3.1%) were very major teaching, 138 (4.4%) major teaching, 442 (14.2%) minor teaching, 443 (14.3%) very minor teaching, and 1985 (64.0%) nonteaching. EXPOSURE Resident-to-bed ratio as a continuous measure of hospital teaching intensity. MAIN OUTCOMES AND MEASURES Change in 30-day all-location mortality and 30-day all-cause readmission, comparing patients in more intensive relative to less intensive teaching hospitals before (July 1, 2009-June 30, 2011) and after (July 1, 2011-June 30, 2012) duty hour reforms, adjusting for patient comorbidities, time trends, and hospital site. RESULTS In the 2 years before duty hour reforms, there were 4 325 854 admissions with 288 422 deaths and 602 380 readmissions. In the first year after the reforms, accounting for teaching hospital intensity, there were 2 058 419 admissions with 133 547 deaths and 272 938 readmissions. There were no significant postreform differences in mortality accounting for teaching hospital intensity for combined medical conditions (odds ratio [OR], 1.00; 95% CI, 0.96-1.03), combined surgical categories (OR, 0.99; 95% CI, 0.94-1.04), or any of the individual medical conditions or surgical categories. There were no significant postreform differences in readmissions for combined medical conditions (OR, 1.00; 95% CI, 0.97-1.02) or combined surgical categories (OR, 1.00; 95% CI, 0.98-1.03). For the medical condition of stroke, there were higher odds of readmissions in the postreform period (OR, 1.06; 95% CI, 1.001-1.13). However, this finding was not supported by sensitivity analyses and there were no significant postreform differences for readmissions for any other individual medical condition or surgical category. CONCLUSIONS AND RELEVANCE Among Medicare beneficiaries, there were no significant differences in the change in 30-day mortality rates or 30-day all-cause readmission rates for those hospitalized in more intensive relative to less intensive teaching hospitals in the year after implementation of the 2011 ACGME duty hour reforms compared with those hospitalized in the 2 years before implementation. Copyright 2014 American Medical Association. All rights reserved. C1 [Patel, Mitesh S.; Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Patel, Mitesh S.; Volpp, Kevin G.; Bellini, Lisa; Zhu, Jingsan] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.; Silber, Jeffrey H.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Patel, Mitesh S.; Volpp, Kevin G.; Small, Dylan S.; Zhu, Jingsan] Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Hill, Alexander S.; Even-Shoshan, Orit; Ross, Richard N.; Silber, Jeffrey H.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Even-Shoshan, Orit; Silber, Jeffrey H.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Rosenbaum, Lisa] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Silber, Jeffrey H.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. RP Patel, MS (reprint author), Univ Penn, 423 Guardian Dr,12th Floor,Blockley Hall, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu FU National Heart, Lung, and Blood Institute [RO1-HLO94593]; Department of Veteran Affairs; Robert Wood Johnson Foundation FX This project was funded in part through National Heart, Lung, and Blood Institute grant RO1-HLO94593. Dr Patel was supported by the Department of Veteran Affairs and the Robert Wood Johnson Foundation. NR 46 TC 29 Z9 29 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 10 PY 2014 VL 312 IS 22 BP 2364 EP 2373 DI 10.1001/jama.2014.15273 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YB UT WOS:000346345700011 PM 25490327 ER PT J AU Rajaram, R Chung, JW Jones, AT Cohen, ME Dahlke, AR Ko, CY Tarpley, JL Lewis, FR Hoyt, DB Bilimoria, KY AF Rajaram, Ravi Chung, Jeanette W. Jones, Andrew T. Cohen, Mark E. Dahlke, Allison R. Ko, Clifford Y. Tarpley, John L. Lewis, Frank R. Hoyt, David B. Bilimoria, Karl Y. TI Association of the 2011 ACGME Resident Duty Hour Reform With General Surgery Patient Outcomes and With Resident Examination Performance SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SURGICAL QUALITY; WORK HOURS; RESTRICTIONS; MORTALITY; EDUCATION; INTERNS; CARE; REGULATIONS; MEDICINE; FAILURES AB IMPORTANCE In 2011, the Accreditation Council for Graduate Medical Education (ACGME) restricted resident duty hour requirements beyond those established in 2003, leading to concerns about the effects on patient care and resident training. OBJECTIVE To determine if the 2011 ACGME duty hour reform was associated with a change in general surgery patient outcomes or in resident examination performance. DESIGN, SETTING, AND PARTICIPANTS Quasi-experimental study of general surgery patient outcomes 2 years before (academic years 2009-2010) and after (academic years 2012-2013) the 2011 duty hour reform. Teaching and nonteaching hospitals were compared using a difference-in-differences approach adjusted for procedural mix, patient comorbidities, and time trends. Teaching hospitals were defined based on the proportion of cases at which residents were present intraoperatively. Patients were those undergoing surgery at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). General surgery resident performance on the annual in-training, written board, and oral board examinations was assessed for this same period. EXPOSURES National implementation of revised resident duty hour requirements on July 1, 2011, in all ACGME accredited residency programs. MAIN OUTCOMES AND MEASURES Primary outcome was a composite of death or serious morbidity; secondary outcomes were other postoperative complications and resident examination performance. RESULTS In the main analysis, 204 641 patients were identified from 23 teaching (n = 102 525) and 31 nonteaching (n = 102 116) hospitals. The unadjusted rate of death or serious morbidity improved during the study period in both teaching (11.6%[95% CI, 11.3%-12.0%] to 9.4%[95% CI, 9.1%-9.8%], P < .001) and nonteaching hospitals (8.7%[95% CI, 8.3%-9.0%] to 7.1% [95% CI, 6.8%-7.5%], P < .001). In adjusted analyses, the 2011 ACGME duty hour reform was not associated with a significant change in death or serious morbidity in either postreform year 1 (OR, 1.12; 95% CI, 0.98-1.28) or postreform year 2 (OR, 1.00; 95% CI, 0.86-1.17) or when both postreform years were combined (OR, 1.06; 95% CI, 0.93-1.20). There was no association between duty hour reform and any other postoperative adverse outcome. Mean (SD) in-training examination scores did not significantly change from 2010 to 2013 for first-year residents (499.7 [85.2] to 500.5 [84.2], P = .99), for residents from other postgraduate years, or for first-time examinees taking the written or oral board examinations during this period. CONCLUSIONS AND RELEVANCE Implementation of the 2011 ACGME duty hour reform was not associated with a change in general surgery patient outcomes or differences in resident examination performance. The implications of these findings should be considered when evaluating the merit of the 2011 ACGME duty hour reform and revising related policies in the future. Copyright 2014 American Medical Association. All rights reserved. C1 [Rajaram, Ravi; Cohen, Mark E.; Ko, Clifford Y.; Hoyt, David B.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Rajaram, Ravi; Chung, Jeanette W.; Dahlke, Allison R.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, SOQIC, Chicago, IL 60611 USA. [Rajaram, Ravi; Chung, Jeanette W.; Dahlke, Allison R.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Inst Publ Hlth & Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [Jones, Andrew T.; Lewis, Frank R.] Amer Board Surg, Philadelphia, PA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Tarpley, John L.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Dept Surg, SOQIC, 633 N St Clair St,20th Floor, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu FU Agency for Healthcare Research and Quality [T32HS000078]; American College of Surgeons Clinical Scholars in Residence Program; Merck FX Dr Rajaramis supported by grant T32HS000078 from the Agency for Healthcare Research and Quality, the American College of Surgeons Clinical Scholars in Residence Program, and an unrestricted educational grant from Merck. NR 38 TC 40 Z9 40 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 10 PY 2014 VL 312 IS 22 BP 2374 EP 2384 DI 10.1001/jama.2014.15277 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW5YB UT WOS:000346345700012 PM 25490328 ER PT J AU Wayne, PM Gow, BJ Costa, MD Peng, CK Lipsitz, LA Hausdorff, JM Davis, RB Walsh, JN Lough, M Novak, V Yeh, GY Ahn, AC Macklin, EA Manor, B AF Wayne, Peter M. Gow, Brian J. Costa, Madalena D. Peng, C. -K. Lipsitz, Lewis A. Hausdorff, Jeffrey M. Davis, Roger B. Walsh, Jacquelyn N. Lough, Matthew Novak, Vera Yeh, Gloria Y. Ahn, Andrew C. Macklin, Eric A. Manor, Brad TI Complexity-Based Measures Inform Effects of Tai Chi Training on Standing Postural Control: Cross-Sectional and Randomized Trial Studies SO PLOS ONE LA English DT Article ID OLDER-ADULTS; BALANCE CONTROL; PHYSIOLOGICAL COMPLEXITY; CEREBRAL CONCUSSION; CHALLENGES INHERENT; MULTISCALE ENTROPY; STABILITY LIMITS; OPEN-LOOP; FALLS; EXERCISE AB Background: Diminished control of standing balance, traditionally indicated by greater postural sway magnitude and speed, is associated with falls in older adults. Tai Chi (TC) is a multisystem intervention that reduces fall risk, yet its impact on sway measures vary considerably. We hypothesized that TC improves the integrated function of multiple control systems influencing balance, quantifiable by the multi-scale "complexity'' of postural sway fluctuations. Objectives: To evaluate both traditional and complexity-based measures of sway to characterize the short- and potential long-term effects of TC training on postural control and the relationships between sway measures and physical function in healthy older adults. Methods: A cross-sectional comparison of standing postural sway in healthy TC-nalve and TC-expert (24.5 +/- 12 yrs experience) adults. TC-nalve participants then completed a 6-month, two-arm, wait-list randomized clinical trial of TC training.Postural sway was assessed before and after the training during standing on a force-plate with eyes-open (EO) and eyes-closed (EC). Anterior-posterior (AP) and medio-lateral (ML) sway speed, magnitude, and complexity (quantified by multiscale entropy) were calculated. Single- legged standing time and Timed-Up-and- Go tests characterized physical function. Results: At baseline, compared to TC-nalve adults (n=60, age 64.5 +/- 7.5 yrs), TC-experts (n=27, age 62.8 +/- 7.5 yrs) exhibited greater complexity of sway in the AP EC (P=0.023), ML EO (P, 0.001), and ML EC (P, 0.001) conditions. Traditional measures of sway speed and magnitude were not significantly lower among TC-experts. Intention-to-treat analyses indicated no significant effects of short-term TC training; however, increases in AP EC and ML EC complexity amongst those randomized to TC were positively correlated with practice hours (P=0.044, P=0.018). Long- and short-term TC training were positively associated with physical function. Conclusion: Multiscale entropy offers a complementary approach to traditional COP measures for characterizing sway during quiet standing, and may be more sensitive to the effects of TC in healthy adults. C1 [Wayne, Peter M.; Gow, Brian J.; Walsh, Jacquelyn N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Osher Ctr Integrat Med, Boston, MA 02115 USA. [Costa, Madalena D.; Peng, C. -K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Interdisciplinary Med & Biotechnol, Boston, MA 02115 USA. [Costa, Madalena D.; Peng, C. -K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Margret & HA Rey Inst Nonlinear Dynam Med, Boston, MA 02115 USA. [Peng, C. -K.] Natl Cent Univ, Ctr Dynam Biomarkers & Translat Med, Chungli 32054, Taiwan. [Lipsitz, Lewis A.; Novak, Vera; Manor, Brad] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gerontol, Boston, MA 02115 USA. [Lipsitz, Lewis A.; Lough, Matthew] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA. [Hausdorff, Jeffrey M.] Tel Aviv Med Ctr & Sch Med, Dept Neurol, Movement Disorders Unit, Tel Aviv, Israel. [Hausdorff, Jeffrey M.] Tel Aviv Univ, Dept Phys Therapy, IL-69978 Tel Aviv, Israel. [Hausdorff, Jeffrey M.] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. [Davis, Roger B.; Yeh, Gloria Y.; Ahn, Andrew C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Novak, Vera] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Ahn, Andrew C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02115 USA. RP Wayne, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Osher Ctr Integrat Med, Boston, MA 02115 USA. EM pwayne@partners.org FU National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) [R21 AT005501-01A1]; Harvard Clinical and Translational Science Center, from the National Center for Research Resourses (NCRR) [UL1 RR025758]; National Institute on Aging (NIA) [R37-AG25037]; NIH-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5R21-DK-084463-02]; National Institutes of Health (NIH)-National Institute on Aging (NIA) [1R01-AG-0287601-A2]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Institutes of Health Award) [8UL1TR000170-05]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (Harvard University); Irving and Edyth S. Usen and Family Chair in Geriatric Medicine at Hebrew SeniorLife FX This publication was made possible by grant number R21 AT005501-01A1 from the National Center for Complementary and Alternative Medicine (NCCAM: http://nccam.nih.gov/) at the National Institutes of Health (NIH: http://www.nih.gov/), and from grant number UL1 RR025758 supporting the Harvard Clinical and Translational Science Center, from the National Center for Research Resourses (NCRR: http://www.nih.gov/about/almanac/organization/NCRR.htm). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, NCRR, or the NIH. Dr. Lipsitz was supported by grant R37-AG25037 from the National Institute on Aging (NIA: http://www.nia. nih.gov/) and the Irving and Edyth S. Usen and Family Chair in Geriatric Medicine at Hebrew SeniorLife. Dr. Novak has received grants from the NIH-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK: http://www.niddk.nih. gov/) (5R21-DK-084463-02) and the National Institutes of Health (NIH)-National Institute on Aging (NIA: http://www.nia.nih.gov/) (1R01-AG-0287601-A2) unrelated to this study. The work in the SAFE lab was conducted with support from Harvard Catalyst (http://catalyst.harvard.edu/) vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 10 Z9 10 U1 3 U2 25 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 10 PY 2014 VL 9 IS 12 AR e114731 DI 10.1371/journal.pone.0114731 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW9YP UT WOS:000346611400072 PM 25494333 ER PT J AU Liu, Y Asnani, A Zou, L Bentley, VL Yu, M Wang, Y Dellaire, G Sarkar, KS Dai, M Chen, HH Sosnovik, DE Shin, JT Haber, DA Berman, JN Chao, W Peterson, RT AF Liu, Yan Asnani, Aarti Zou, Lin Bentley, Victoria L. Yu, Min Wang, You Dellaire, Graham Sarkar, Kumar S. Dai, Matthew Chen, Howard H. Sosnovik, David E. Shin, Jordan T. Haber, Daniel A. Berman, Jason N. Chao, Wei Peterson, Randall T. TI Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IN-VIVO; ZEBRAFISH; CANCER; CARDIOTOXICITY; CELLS; DEXRAZOXANE; CARDIOPROTECTION; INHIBITION; HEART; CONTRACTILITY AB Doxorubicin is a highly effective anticancer chemotherapy agent, but its use is limited by its cardiotoxicity. To develop a drug that prevents this toxicity, we established a doxorubicin-induced cardiomyopathy model in zebrafish that recapitulates the cardiomyocyte apoptosis and contractility decline observed in patients. Using this model, we screened 3000 compounds and found that visnagin (VIS) and diphenylurea (DPU) rescue the cardiac performance and circulatory defects caused by doxorubicin in zebrafish. VIS and DPU reduced doxorubicin-induced apoptosis in cultured cardiomyocytes and in vivo in zebrafish and mouse hearts. VIS treatment improved cardiac contractility in doxorubicin-treated mice. Further, VIS and DPU did not reduce the chemotherapeutic efficacy of doxorubicin in several cultured tumor lines or in zebrafish and mouse xenograft models. Using affinity chromatography, we found that VIS binds to mitochondrial malate dehydrogenase (MDH2), a key enzyme in the tricarboxylic acid cycle. As with VIS, treatment with the MDH2 inhibitors mebendazole, thyroxine, and iodine prevented doxorubicin cardiotoxicity, as did treatment with malate itself, suggesting that modulation of MDH2 activity is responsible for VIS' cardioprotective effects. Thus, VIS and DPU are potent cardioprotective compounds, and MDH2 is a previously undescribed, druggable target for doxorubicin-induced cardiomyopathy. C1 [Liu, Yan; Asnani, Aarti; Wang, You; Sarkar, Kumar S.; Dai, Matthew; Chen, Howard H.; Sosnovik, David E.; Shin, Jordan T.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Liu, Yan; Asnani, Aarti; Zou, Lin; Yu, Min; Wang, You; Sarkar, Kumar S.; Dai, Matthew; Chen, Howard H.; Sosnovik, David E.; Shin, Jordan T.; Haber, Daniel A.; Chao, Wei; Peterson, Randall T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Liu, Yan; Asnani, Aarti; Wang, You; Sarkar, Kumar S.; Peterson, Randall T.] Broad Inst, Cambridge, MA 02142 USA. [Zou, Lin; Chao, Wei] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Bentley, Victoria L.; Dellaire, Graham] Dalhousie Univ, Dept Pathol, Halifax, NS B3H 4R2, Canada. [Yu, Min; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Dellaire, Graham] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 4R2, Canada. [Chen, Howard H.; Sosnovik, David E.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Haber, Daniel A.] Dalhousie Univ, Howard Hughes Med Inst, Halifax, NS B3H 4R2, Canada. [Berman, Jason N.] Dalhousie Univ, Dept Pediat, Halifax, NS B3H 4R2, Canada. [Berman, Jason N.] Izaak Walton Killam Hlth Ctr, Dept Pediat, Halifax, NS B3K 6R8, Canada. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM rtpeterson@mgh.harvard.edu OI Dellaire, Graham/0000-0002-3466-6316 FU National Heart, Lung, and Blood Institute [T32HL007208]; John S. LaDue Memorial Fellowship; American Heart Association [IRG14600006]; Charles and Ann Sanders MGH Research Scholar Award; Howard Hughes Medical Institute; Beatrice Hunter Cancer Research Institute; Canadian Imperial Bank of Commerce; Nova Scotia Health Research Foundation; Natural Sciences and Engineering Research Council Collaborative Health Research Project; CIHR; Cancer Care Nova Scotia, The Terry Fox Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research (CIHR) FX Y.L. and A.A. are supported by training grant T32HL007208 from the National Heart, Lung, and Blood Institute. A.A. is supported by a John S. LaDue Memorial Fellowship. This work was supported by an Innovative Research Grant from the American Heart Association (IRG14600006 to R.T.P.) and by the Charles and Ann Sanders MGH Research Scholar Award (to R.T.P.). D.A.H. and M.Y. are supported by the Howard Hughes Medical Institute. V.L.B. is supported by a trainee award from the Beatrice Hunter Cancer Research Institute, with funds provided by the Canadian Imperial Bank of Commerce and Cancer Care Nova Scotia as part of The Terry Fox Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research (CIHR), and a trainee award from the Nova Scotia Health Research Foundation. Zebrafish xenograft studies were funded by a CIHR and Natural Sciences and Engineering Research Council Collaborative Health Research Project awarded to G.D. and J.N.B. NR 43 TC 11 Z9 11 U1 0 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 10 PY 2014 VL 6 IS 266 AR 266ra170 DI 10.1126/scitranslmed.3010189 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AW3NJ UT WOS:000346193300002 PM 25504881 ER PT J AU Greenfield, E Griner, E AF Greenfield, Edward Griner, Erin CA Reproducibility Project Canc Biol TI Registered report: Widespread potential for growth factor-driven resistance to anticancer kinase inhibitors SO ELIFE LA English DT Article ID LUNG-CANCER; M14 MELANOMA; CELL-LINES; MDA-MB-435; EGFR; RAF; MET AB The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from 'Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors' by Wilson and colleagues, published in Nature in 2012 (Wilson et al., 2012). The experiments that will be replicated are those reported in Figure 2B and C. In these experiments, Wilson and colleagues show that sensitivity to receptor tyrosine kinase (RTK) inhibitors can be bypassed by various ligands through reactivation of downstream signaling pathways (Figure 2A; Wilson et al., 2012), and that blocking the receptors for these bypassing ligands abrogates their ability to block sensitivity to the original RTK inhibitor (Figure 2C; Wilson et al., 2012). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. C1 [Greenfield, Edward] Dana Farber Canc Inst, Monoclonal Antibody Core Facil, Boston, MA 02115 USA. [Griner, Erin] Univ Virginia, Charlottesville, VA USA. RP Greenfield, E (reprint author), Dana Farber Canc Inst, Monoclonal Antibody Core Facil, Boston, MA 02115 USA. OI Errington, Timothy/0000-0002-4959-5143 FU Laura and John Arnold Foundation; American Type Culture Collection (ATCC) FX Laura and John Arnold Foundation Reproducibility Project: Cancer Biology; American Type Culture Collection (ATCC) Reproducibility Project: Cancer Biology; The Reproducibility Project: Cancer Biology is funded by the Laura and John Arnold Foundation, provided to the Center for Open Science in collaboration with Science Exchange. The funders had no role in study design or the decision to submit the work for publication. NR 23 TC 0 Z9 0 U1 1 U2 3 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD DEC 10 PY 2014 VL 3 AR e04037 DI 10.7554/eLife.04037 PG 17 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AW3FD UT WOS:000346170600005 ER PT J AU Beerman, I Rossi, DJ AF Beerman, Isabel Rossi, Derrick J. TI Epigenetic regulation of hematopoietic stem cell aging SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Aging; HSC; Hematopoietic stem cells; Epigenetics; Methylation; miRNA ID ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL CAPACITY; DNA METHYLATION DYNAMICS; LONG NONCODING RNAS; MYELODYSPLASTIC SYNDROMES; TUMOR-SUPPRESSOR; PROGENITOR CELLS; HISTONE MODIFICATIONS; IN-VIVO; DIFFERENTIATION AB Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks - DNA methylation and histone modifications - but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging. (C) 2014 Elsevier Inc. All rights reserved. C1 [Beerman, Isabel; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Beerman, Isabel; Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Beerman, Isabel; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA 02116 USA. RP Beerman, I (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM isabel.beerman@childrens.harvard.edu FU National Institutes of Health [RO1HL107630, R00AG029760, UO1DK072473-01]; Leona M. and Harry B. Helmsley Charitable Trust [2012PG-T1D007]; New York Stem Cell Foundation [RI04]; Harvard Stem Cell Institute [DP-0132-13-01]; Joint Program in Transfusion Medicine fellowship [5T32HL066987-12] FX Special thanks to Morag Stewart, Paula Gutierrez-Martinez, Wataru Ebina, and Brian Garrison for their thoughtful comments and conversation about this manuscript. Our research is supported by grants from the National Institutes of Health (RO1HL107630, R00AG029760, and UO1DK072473-01) as well as grants from The Leona M. and Harry B. Helmsley Charitable Trust (2012PG-T1D007), The New York Stem Cell Foundation (RI04), and The Harvard Stem Cell Institute (DP-0132-13-01). IB also received funding from a Joint Program in Transfusion Medicine fellowship (5T32HL066987-12). DJR is New York Stem Cell Foundation, Robertson Investigator. NR 117 TC 11 Z9 11 U1 1 U2 31 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD DEC 10 PY 2014 VL 329 IS 2 BP 192 EP 199 DI 10.1016/j.yexcr.2014.09.013 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JH UT WOS:000346113400002 PM 25261778 ER PT J AU Blayney, DW McNiff, K Eisenberg, PD Gilmore, T Jacobsen, PB Jacobson, JO Kadlubek, PJ Neuss, MN Simone, J AF Blayney, Douglas W. McNiff, Kristen Eisenberg, Peter D. Gilmore, Terry Jacobsen, Paul B. Jacobson, Joseph O. Kadlubek, Pamela J. Neuss, Michael N. Simone, Joseph TI Development and Future of the American Society of Clinical Oncology's Quality Oncology Practice Initiative SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOP 5 LIST; CANCER CARE; UNITED-STATES; IMPROVEMENT C1 [Blayney, Douglas W.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [McNiff, Kristen; Gilmore, Terry; Kadlubek, Pamela J.] Amer Soc Clin Oncol, Alexandria, VA USA. [Eisenberg, Peter D.] Marin Specialty Care, Greenbrae, CA USA. [Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Jacobson, Joseph O.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Simone, Joseph] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Med Ctr, Nashville, TN 37235 USA. Simone Consulting, Dunwoody, GA USA. RP Blayney, DW (reprint author), Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. NR 31 TC 5 Z9 5 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2014 VL 32 IS 35 BP 3907 EP 3913 DI 10.1200/JCO.2014.56.8899 PG 7 WC Oncology SC Oncology GA AU9IK UT WOS:000345905100002 PM 25225418 ER PT J AU Tevaarwerk, AJ Wang, ML Zhao, FM Fetting, JH Cella, D Wagner, LI Martino, S Ingle, JN Sparano, JA Solin, LJ Wood, WC Robert, NJ AF Tevaarwerk, Amye J. Wang, Molin Zhao, Fengmin Fetting, John H. Cella, David Wagner, Lynne I. Martino, Silvana Ingle, James N. Sparano, Joseph A. Solin, Lawrence J. Wood, William C. Robert, Nicholas J. TI Phase III Comparison of Tamoxifen Versus Tamoxifen Plus Ovarian Function Suppression in Premenopausal Women With Node-Negative, Hormone Receptor-Positive Breast Cancer (E-3193, INT-0142): A Trial of the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED-TRIAL; ADJUVANT TREATMENT; RESEARCH-ASSOCIATION; LEUPRORELIN ACETATE; CMF CHEMOTHERAPY; ZOLEDRONIC ACID; FOLLOW-UP; GOSERELIN; CYCLOPHOSPHAMIDE AB Purpose The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS. Patients and Methods Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring <= 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration. Results In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up. Conclusion When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen. (C) 2014 by American Society of Clinical Oncology C1 [Tevaarwerk, Amye J.] Univ Wisconsin, Madison, WI 53705 USA. [Wang, Molin] Harvard Univ, Cambridge, MA 02138 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fetting, John H.] Johns Hopkins Univ, Baltimore, MD USA. [Cella, David; Wagner, Lynne I.] Northwestern Univ, Chicago, IL 60611 USA. [Martino, Silvana] Angeles Clin & Res Inst, Santa Monica, CA USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Sparano, Joseph A.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Solin, Lawrence J.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Wood, William C.] Emory Univ, Atlanta, GA 30322 USA. [Robert, Nicholas J.] Virginia Canc Specialists, Fairfax, VA USA. RP Tevaarwerk, AJ (reprint author), Univ Wisconsin, 1111 Highland Ave,WIMR 6037, Madison, WI 53705 USA. EM at4@medicine.wisc.edu FU National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services [CA23318, CA66636, CA21115, CA21076, CA16116, CA17145, CA14958, CA32102, CA25224]; Clinical and Translational Science Award program through the NIH National Center for Advancing Translational Sciences [UL1TR000427] FX Supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA21076, CA16116, CA17145, CA14958, CA32102, and CA25224 from the National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services, and by Grant No. UL1TR000427 from the Clinical and Translational Science Award program through the NIH National Center for Advancing Translational Sciences (A.J.T.). NR 40 TC 31 Z9 34 U1 1 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2014 VL 32 IS 35 BP 3948 EP U237 DI 10.1200/JCO.2014.55.6993 PG 15 WC Oncology SC Oncology GA AU9IK UT WOS:000345905100010 PM 25349302 ER PT J AU Burstein, HJ Cirrincione, CT Barry, WT Chew, HK Tolaney, SM Lake, DE Ma, C Blackwell, KL Winer, EP Hudis, CA AF Burstein, Harold J. Cirrincione, Constance T. Barry, William T. Chew, Helen K. Tolaney, Sara M. Lake, Diana E. Ma, Cynthia Blackwell, Kimberly L. Winer, Eric P. Hudis, Clifford A. TI Endocrine Therapy With or Without Inhibition of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib for Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer-CALGB 40302 (Alliance) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ESTROGEN-RECEPTOR; TYROSINE KINASES; MCF-7 CELLS; TAMOXIFEN; RESISTANCE; ANASTROZOLE; PATHWAYS; REGIMENS; GW572016; SAFETY AB Purpose CALGB 40302 sought to determine whether lapatinib would improve progression-free survival (PFS) among women with hormone receptor-positive metastatic breast cancer treated with fulvestrant. Patients and Methods Eligible women had estrogen receptor-positive and/or progesterone receptor-positive tumors, regardless of human epidermal growth factor receptor 2 (HER2) status, and prior aromatase inhibitor treatment. Patients received fulvestrant 500 mg intramuscularly on day 1, followed by 250 mg on days 15 and 28 and every 4 weeks thereafter, and either lapatinib 1,500 mg or placebo daily. The study planned to accrue 324 patients and was powered for a 50% improvement in PFS with lapatinib from 5 to 7.5 months. Results At the third planned interim analysis, the futility boundary was crossed, and the data and safety monitoring board recommend study closure, having accrued 295 patients. At the final analysis, there was no difference in PFS (hazard ratio [HR] of placebo to lapatinib, 1.04; 95% CI, 0.82 to 1.33; P = .37); median PFS was 4.7 months for fulvestrant plus lapatinib versus 3.8 months for fulvestrant plus placebo. There was no difference in overall survival (OS) (HR, 0.91; 95% CI, 0.68 to 1.21; P = .25). For HER2-normal tumors, median PFS did not differ by treatment arm (4.1 v 3.8 months). For HER2-positive tumors, lapatinib was associated with longer median PFS (5.9 v 3.3 months), but the differential treatment effect by HER2 status was not significant (P = .53). The most frequent toxicities were diarrhea, fatigue, and rash associated with lapatinib. Conclusion Adding lapatinib to fulvestrant does not improve PFS or OS in advanced ER-positive breast cancer and is more toxic. (C) 2014 by American Society of Clinical Oncology C1 [Burstein, Harold J.; Barry, William T.; Tolaney, Sara M.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Cirrincione, Constance T.] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Blackwell, Kimberly L.] Duke Univ, Med Ctr, Durham, NC USA. [Chew, Helen K.] Univ Calif Davis, Davis, CA 95616 USA. [Lake, Diana E.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ma, Cynthia] Washington Univ, Sch Med, St Louis, MO USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM hburstein@partners.org FU National Cancer Institute [CA31946, CA33601, CA32102, CA46441] FX Supported in part by National Cancer Institute Grants No. CA31946 to the Alliance for Clinical Trials in Oncology, No. CA33601 to the Alliance Statistics and Data Center, and No. CA32102 and CA46441 to the Southwest Oncology Group. NR 32 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2014 VL 32 IS 35 BP 3959 EP U247 DI 10.1200/JCO.2014.56.7941 PG 10 WC Oncology SC Oncology GA AU9IK UT WOS:000345905100011 PM 25348000 ER PT J AU Hagedorn, EJ Durand, EM Fast, EM Zon, LI AF Hagedorn, Elliott J. Durand, Ellen M. Fast, Eva M. Zon, Leonard I. TI Getting more for your marrow: Boosting hematopoietic stem cell numbers with PGE(2) SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Hematopoietic stem cells; Ex Vivo expansion; Umbilical cord blood transplantation; Self-renewal; Engraftment; Prostaglandin E-2 ID PROGENITOR CELLS; CORD-BLOOD; PROSTAGLANDIN E-2; EP4 RECEPTOR; EXPANSION; TRANSPLANTATION; PROLIFERATION; EXPRESSION; BIOLOGY; RECONSTITUTION AB Throughout the lifetime of an individual, hematopoietic stem cells (HSCs) self-renew and differentiate into lineages that include erythrocytes, platelets and all immune cells. HSC transplantation offers a potentially curative treatment for a number of hematopoietic and non-hematopoietic malignancies as well as immune and genetic disorders. Limited availability of immune-matched donors reduces the viable options for many patients in need of HSC transplantation, particularly those of diverse racial and ethnic backgrounds. Due to rapid availability and less stringent immune-matching requirements, umbilical cord blood (UCB) has emerged as a valuable source of transplantable HSCs. A single UCB unit contains a suboptimal number of HSCs for treating larger children or adults and there has thus been great clinical interest in expanding UCB HSCs ex vivo for use in transplantation. In this review we discuss the latest research and future avenues for the therapeutic use of small lipid mediator dmPGE(2) to expand HSC numbers for transplantation. Originally identified in a chemical screen in zebrafish, dmPGE2 has now advanced to a phase II clinical trial as a therapy for patients with leukemia and lymphoma who are undergoing UCB transplantation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zon, LI (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NIH [R01 HL04880, 5P30 DK49216, R24 DK092760, 5U01 HL10001-05] FX This work was supported by NIH Grants R01 HL04880, 5P30 DK49216, R24 DK092760 and 5U01 HL10001-05. In addition, L.I.Z. is a Howard Hughes Medical Institute Investigator. E.J.H. is a Howard Hughes Medical Institute Fellow of The Helen Hay Whitney Foundation. NR 39 TC 14 Z9 14 U1 1 U2 9 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD DEC 10 PY 2014 VL 329 IS 2 BP 220 EP 226 DI 10.1016/j.yexcr.2014.07.030 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JH UT WOS:000346113400006 PM 25094063 ER PT J AU Jones, CN Moore, M Dimisko, L Alexander, A Ibrahim, A Hassell, BA Warren, HS Tompkins, RG Fagan, SP Irimia, D AF Jones, Caroline N. Moore, Molly Dimisko, Laurie Alexander, Andrew Ibrahim, Amir Hassell, Bryan A. Warren, H. Shaw Tompkins, Ronald G. Fagan, Shawn P. Irimia, Daniel TI Spontaneous Neutrophil Migration Patterns during Sepsis after Major Burns SO PLOS ONE LA English DT Article ID CLINICAL MICROBIOLOGY; MICROFLUIDIC CHANNELS; CHEMICAL GRADIENTS; SEPTIC PATIENTS; INJURY; CHEMOTAXIS; INTERLEUKIN-6; EXPRESSION; PROCALCITONIN; INFLAMMATION AB Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns. C1 [Jones, Caroline N.; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Jones, Caroline N.; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Warren, H. Shaw; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Caroline N.; Dimisko, Laurie; Hassell, Bryan A.; Irimia, Daniel] BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA USA. [Jones, Caroline N.; Ibrahim, Amir; Warren, H. Shaw; Irimia, Daniel] Shriners Hosp Children, Boston, MA USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Irimia, D (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM dirimia@mgh.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU Kidder Burn Critical Care Fellowship; National Institutes of Health [GM007035, GM092804, EB002503] FX MM was the recipient of the Kidder Burn Critical Care Fellowship. CNJ has been supported by an institutional training grant from the National Institutes of Health: GM007035. This research has been supported through research grants from the National Institutes of Health GM092804 and EB002503. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 10 Z9 10 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 9 PY 2014 VL 9 IS 12 AR e114509 DI 10.1371/journal.pone.0114509 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY3YM UT WOS:000347515300044 PM 25489947 ER PT J AU Dong, F Irshad, H Oh, EY Lerwill, MF Brachtel, EF Jones, NC Knoblauch, NW Montaser-Kouhsari, L Johnson, NB Rao, LKF Faulkner-Jones, B Wilbur, DC Schnitt, SJ Beck, AH AF Dong, Fei Irshad, Humayun Oh, Eun-Yeong Lerwill, Melinda F. Brachtel, Elena F. Jones, Nicholas C. Knoblauch, Nicholas W. Montaser-Kouhsari, Laleh Johnson, Nicole B. Rao, Luigi K. F. Faulkner-Jones, Beverly Wilbur, David C. Schnitt, Stuart J. Beck, Andrew H. TI Computational Pathology to Discriminate Benign from Malignant Intraductal Proliferations of the Breast SO PLOS ONE LA English DT Article ID CARCINOMA IN-SITU; NUCLEAR MORPHOMETRIC FEATURES; WHOLE-SLIDE IMAGES; DUCTAL HYPERPLASIA; PROGNOSTIC VALUE; CANCER; EXPRESSION; LESIONS; TISSUE; INTEROBSERVER AB The categorization of intraductal proliferative lesions of the breast based on routine light microscopic examination of histopathologic sections is in many cases challenging, even for experienced pathologists. The development of computational tools to aid pathologists in the characterization of these lesions would have great diagnostic and clinical value. As a first step to address this issue, we evaluated the ability of computational image analysis to accurately classify DCIS and UDH and to stratify nuclear grade within DCIS. Using 116 breast biopsies diagnosed as DCIS or UDH from the Massachusetts General Hospital (MGH), we developed a computational method to extract 392 features corresponding to the mean and standard deviation in nuclear size and shape, intensity, and texture across 8 color channels. We used L1-regularized logistic regression to build classification models to discriminate DCIS from UDH. The top-performing model contained 22 active features and achieved an AUC of 0.95 in cross-validation on the MGH data-set. We applied this model to an external validation set of 51 breast biopsies diagnosed as DCIS or UDH from the Beth Israel Deaconess Medical Center, and the model achieved an AUC of 0.86. The top-performing model contained active features from all color-spaces and from the three classes of features (morphology, intensity, and texture), suggesting the value of each for prediction. We built models to stratify grade within DCIS and obtained strong performance for stratifying low nuclear grade vs. high nuclear grade DCIS (AUC=0.98 in cross-validation) with only moderate performance for discriminating low nuclear grade vs. intermediate nuclear grade and intermediate nuclear grade vs. high nuclear grade DCIS (AUC=0.83 and 0.69, respectively). These data show that computational pathology models can robustly discriminate benign from malignant intraductal proliferative lesions of the breast and may aid pathologists in the diagnosis and classification of these lesions. C1 [Dong, Fei; Lerwill, Melinda F.; Brachtel, Elena F.; Jones, Nicholas C.; Rao, Luigi K. F.; Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dong, Fei] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Irshad, Humayun; Oh, Eun-Yeong; Knoblauch, Nicholas W.; Montaser-Kouhsari, Laleh; Johnson, Nicole B.; Faulkner-Jones, Beverly; Schnitt, Stuart J.; Beck, Andrew H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Beck, AH (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. EM abeck2@bidmc.harvard.edu FU National Library of Medicine of the National Institutes of Health [K22LM011931] FX The research reported in this publication was supported in part by the National Library of Medicine of the National Institutes of Health under Award Number K22LM011931. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 4 Z9 4 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 9 PY 2014 VL 9 IS 12 AR UNSP e114885 DI 10.1371/journal.pone.0114885 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY3YM UT WOS:000347515300091 PM 25490766 ER PT J AU Litvinova, L Atochin, D Vasilenko, M Fattakhov, N Zatolokin, P Vaysbeyn, I Kirienkova, E AF Litvinova, Larisa Atochin, Dmitriy Vasilenko, Mariia Fattakhov, Nikolai Zatolokin, Pavel Vaysbeyn, Igor Kirienkova, Elena TI Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome SO DIABETOLOGY & METABOLIC SYNDROME LA English DT Article DE Metabolic syndrome; Adipose tissue; Inflammation; Obesity; Adipokine; Gene expression ID C-REACTIVE PROTEIN; ENDOTHELIAL GROWTH-FACTOR; INTIMA-MEDIA THICKNESS; NF-KAPPA-B; INSULIN-RESISTANCE; OBESE SUBJECTS; FAT THICKNESS; WEIGHT-LOSS; ADIPOKINES; ASSOCIATION AB Background: The purpose of this research was to study the gene expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), nuclear factor kappa B (NF-kappa B), vascular endothelial growth factor A (VEGF-A) and adiponectin (AdipoQ) genes in the visceral (omental, mesenteric) and subcutaneous adipose tissue depots in metabolic syndrome (MS). We studied 23 women with MS, with a mean age of 50.7 +/- 4.5 years and mean body mass index (BMI) of 45.6 +/- 9.8 kg/m(2). The control group included 10 women, with a mean age of 40.6 +/- 8.7 years and normal BMI (22.3 +/- 3.7 kg/m(2)). The gene expression levels in the omental (OAT), mesenteric (MAT) and subcutaneous (SAT) adipose tissues were assessed by quantitative real-time PCR. Findings: Increased gene expression levels of IL-6 and TNF-alpha were detected in MAT in patients with MS, compared with the control group (p < 0.05 and p < 0.005, respectively). Significant positive correlations were observed between IL-6 mRNA expression levels in OAT and the content of CD14 + cells in the peripheral blood (r = 0.55, p < 0.05), as well as between NF-kappa B and VEGF-A mRNA levels in OAT (r = 0.43, p < 0.05) in patients with MS. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group (p < 0.05). In addition, there were inverse correlations between AdipoQ gene levels in MAT and serum CRP levels (r = -0.63, p < 0.05), as well as between AdipoQ gene levels in MAT and serum IL-6 levels (r = -0.46, p < 0.05). Conclusion: These data demonstrate that proinflammatory gene expression of MAT in women with MS was increased compared with the control group. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group. C1 [Litvinova, Larisa; Atochin, Dmitriy; Vasilenko, Mariia; Fattakhov, Nikolai; Kirienkova, Elena] Immanuel Kant Balt Fed Univ, Kaliningrad, Russia. [Atochin, Dmitriy] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Zatolokin, Pavel] Kaliningrad Reg Hosp, Dept Reconstruct & Endoscop Surg, Kaliningrad, Russia. [Vaysbeyn, Igor] Kaliningrad Reg Hosp, Dept Gen Surg, Kaliningrad, Russia. RP Litvinova, L (reprint author), Immanuel Kant Balt Fed Univ, Innovat Pk,Bldg 3,Botkina St, Kaliningrad, Russia. EM larisalitvinova@yandex.ru; atochin@cvrc.mgh.harvard.edu RI Atochin, Dmitriy/Q-3150-2016; Василенко, Мария/E-4926-2017 OI Василенко, Мария/0000-0002-4989-045X FU Federal Targeted Program Scientific and Pedagogical Personnel of Innovative Russia; President of Russian Federation for young scientists and postgraduates [SP-454.2013]; [14.A18.21.1518] FX This study was supported by the Federal Targeted Program Scientific and Pedagogical Personnel of Innovative Russia in 2009-2013, the State contract 14.A18.21.1518 and a Scholarship of the President of Russian Federation for young scientists and postgraduates, number SP-454.2013. NR 59 TC 7 Z9 8 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-5996 J9 DIABETOL METAB SYNDR JI Diabetol. Metab. Syndr. PD DEC 9 PY 2014 VL 6 AR 137 DI 10.1186/1758-5996-6-137 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX3ZO UT WOS:000346874300001 PM 25516772 ER PT J AU Jarzabek, MA Amberger-Murphy, V Callanan, JJ Gao, C Zagozdzon, AM Shiels, L Wang, J Ligon, KL Rich, BE Dicker, P Gallagher, WM Prehn, JHM Byrne, AT AF Jarzabek, M. A. Amberger-Murphy, V. Callanan, J. J. Gao, C. Zagozdzon, A. M. Shiels, L. Wang, J. Ligon, K. L. Rich, B. E. Dicker, P. Gallagher, W. M. Prehn, J. H. M. Byrne, A. T. TI Interrogation of gossypol therapy in glioblastoma implementing cell line and patient-derived tumour models SO BRITISH JOURNAL OF CANCER LA English DT Article DE GBM; gossypol; TMZ; angiogenesis; apoptosis; invasion ID CENTRAL-NERVOUS-SYSTEM; HUMAN PROSTATE-CANCER; GLIOMA STEM-CELLS; IN-VIVO; LACTATE-DEHYDROGENASE; MALIGNANT GLIOMA; BRAIN-TUMORS; SENSITIZES GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; BCL-2 OVEREXPRESSION AB Background: Glioblastoma (GBM), being a highly vascularised and locally invasive tumour, is an attractive target for antiangiogenic and anti-invasive therapies. The GBM/endothelial cell response to gossypol/temozolomide (TMZ) treatment was investigated with a particular aim to assess treatment effects on cancer hallmarks. Methods: Cell viability, endothelial tube formation and GBM tumour cell invasion were variously assessed following combined treatment in vitro. The U87MG-luc2 subcutaneous xenograft model was used to investigate therapeutic response in vivo. Viable tumour response to treatment was interrogated using immunohistochemistry. Combined treatment protocols were also tested in primary GBM patient-derived cultures. Results: An endothelial/GBM cell viability inhibitory effect, as well as an anti-angiogenic and anti-invasive response, to combined treatment have been demonstrated in vitro. A significantly greater anti-proliferative (P = 0.020, P = 0.030), anti-angiogenic (P = 0.040, P<0.0001) and pro-apoptotic (P = 0.0083, P = 0.0149) response was observed when combined treatment was compared with single gossypol/TMZ treatment response, respectively. GBM cell line and patient-specific response to gossypol/TMZ treatment was observed. Conclusions: Our results indicate that response to a combined gossypol/TMZ treatment is related to inhibition of tumour-associated angiogenesis, invasion and proliferation and warrants further investigation as a novel targeted GBM treatment strategy. C1 [Jarzabek, M. A.; Shiels, L.; Prehn, J. H. M.; Byrne, A. T.] Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Dublin 2, Ireland. [Jarzabek, M. A.; Shiels, L.; Prehn, J. H. M.; Byrne, A. T.] Royal Coll Surgeons Ireland, Ctr Syst Med, Dublin 2, Ireland. [Amberger-Murphy, V.] Dublin City Univ, Mol Therapeut Canc Ireland, Dublin 9, Ireland. [Amberger-Murphy, V.] All Ireland Cooperat Oncol Res Grp, Dublin 2, Ireland. [Callanan, J. J.] Univ Coll Dublin, UCD Sch Vet Med, Dublin 4, Ireland. [Callanan, J. J.] Ross Sch Vet Med, Basseterre, St Kitts & Nevi. [Gao, C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Zagozdzon, A. M.; Gallagher, W. M.; Byrne, A. T.] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland. [Wang, J.] Univ Bergen, Dept Biomed, Bergen, Norway. [Ligon, K. L.; Rich, B. E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dicker, P.] Royal Coll Surgeons Ireland, PHS Dept Epidemiol & Publ Hlth Med, Dublin 2, Ireland. RP Byrne, AT (reprint author), Royal Coll Surgeons Ireland, Dept Physiol & Med Phys, Dublin 2, Ireland. EM annettebyrne@rcsi.ie RI Prehn, Jochen/A-3928-2010 OI Prehn, Jochen/0000-0003-3479-7794 FU Higher Education Authority Program in Research in Third Level Institution Cycle 4 (National Biophotonics Imaging Platform Ireland); FP7 AngioTox Industry Academic Pathways and Partnerships initiative; Science Foundation Ireland in the context of the Molecular Therapeutics for Cancer Ireland Strategic Research Cluster; [08/IN.1/B1949]; [13/IA/1881] FX We kindly acknowledge Professor Rolf Bjerkvig for providing GBM patient-derived spheroids. Funding is acknowledged from the Higher Education Authority Program in Research in Third Level Institution Cycle 4 (National Biophotonics Imaging Platform Ireland), FP7 AngioTox Industry Academic Pathways and Partnerships initiative (www. angiotox. com) and Science Foundation Ireland in the context of the Molecular Therapeutics for Cancer Ireland Strategic Research Cluster to ATB and WMG and Investigator Awards 08/IN.1/B1949 and 13/IA/1881 to JHMP. NR 69 TC 3 Z9 3 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2014 VL 111 IS 12 BP 2275 EP 2286 DI 10.1038/bjc.2014.529 PG 12 WC Oncology SC Oncology GA AW4JJ UT WOS:000346247000012 PM 25375271 ER PT J AU Wheeler, SE Clark, AM Taylor, DP Young, CL Pillai, VC Stolz, DB Venkataramanan, R Lauffenburger, D Griffith, L Wells, A AF Wheeler, S. E. Clark, A. M. Taylor, D. P. Young, C. L. Pillai, V. C. Stolz, D. B. Venkataramanan, R. Lauffenburger, D. Griffith, L. Wells, A. TI Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system SO BRITISH JOURNAL OF CANCER LA English DT Article DE bioreactor; 3D culture systems; mammary carcinoma; liver; hepatocytes ID EPITHELIAL-MESENCHYMAL TRANSITION; BALANCED PROLIFERATION; CULTURE MODELS; TUMOR DORMANCY; E-CADHERIN; PROGRESSION; THERAPY; TISSUE; MORPHOGENESIS; CHEMOTHERAPY AB Background: Metastatic outgrowth in breast cancer can occur years after a seeming cure. Existing model systems of dormancy are limited as they do not recapitulate human metastatic dormancy without exogenous manipulations and are unable to query early events of micrometastases. Methods: Here, we describe a human ex vivo hepatic microphysiologic system. The system is established with fresh human hepatocytes and non-parenchymal cells (NPCs) creating a microenvironment into which breast cancer cells (MCF7 and MDA-MB-231) are added. Results: The hepatic tissue maintains function through 15 days as verified by liver-specific protein production and drug metabolism assays. The NPCs form an integral part of the hepatic niche, demonstrated within the system through their participation in differential signalling cascades and cancer cell outcomes. Breast cancer cells intercalate into the hepatic niche without interfering with hepatocyte function. Examination of cancer cells demonstrated that a significant subset enter a quiescent state of dormancy as shown by lack of cell cycling (EdU(-) or Ki67(-)). The presence of NPCs altered the cancer cell fraction entering quiescence, and lead to differential cytokine profiles in the microenvironment effluent. Conclusions: These findings establish the liver microphysiologic system as a relevant model for the study of breast cancer metastases and entry into dormancy. C1 [Wheeler, S. E.; Clark, A. M.; Taylor, D. P.; Stolz, D. B.; Venkataramanan, R.; Wells, A.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. [Taylor, D. P.; Wells, A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Young, C. L.; Lauffenburger, D.; Griffith, L.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Pillai, V. C.; Venkataramanan, R.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Stolz, D. B.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA USA. [Stolz, D. B.; Wells, A.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Stolz, D. B.; Wells, A.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Wells, A.] VA Pittsburgh Healthcare Syst, Pittsburgh VA Med Ctr, Pittsburgh, PA USA. RP Wells, A (reprint author), Univ Pittsburgh, Dept Pathol, S711 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15260 USA. EM wellsa@upmc.edu OI Clark, Amanda/0000-0003-1590-2560; Wells, Alan/0000-0002-1637-8150 FU NIH [1UH2TR000496-01]; VA Merit Award; DARPA [BAA-11-73, W911NF-12-2-0039] FX The authors thank other members of their laboratories for thoughtful discussions. The work described herein is being funded by grants from the NIH (1UH2TR000496-01), a VA Merit Award, and DARPA (BAA-11-73 Microphysiological Systems: W911NF-12-2-0039). NR 45 TC 11 Z9 11 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 9 PY 2014 VL 111 IS 12 BP 2342 EP 2350 DI 10.1038/bjc.2014.533 PG 9 WC Oncology SC Oncology GA AW4JJ UT WOS:000346247000018 PM 25314052 ER PT J AU Amato, AA Sivakumar, K Goyal, N David, WS Salajegheh, M Praestgaard, J Lach-Trifilieff, E Trendelenburg, AU Laurent, D Glass, DJ Roubenoff, R Tseng, BS Greenberg, SA AF Amato, Anthony A. Sivakumar, Kumaraswamy Goyal, Namita David, William S. Salajegheh, Mohammad Praestgaard, Jens Lach-Trifilieff, Estelle Trendelenburg, Anne-Ulrike Laurent, Didier Glass, David J. Roubenoff, Ronenn Tseng, Brian S. Greenberg, Steven A. TI Treatment of sporadic inclusion body myositis with bimagrumab SO NEUROLOGY LA English DT Article ID CYTOSOLIC 5'-NUCLEOTIDASE 1A; RANDOMIZED PILOT TRIAL; DOUBLE-BLIND; MUSCLE; HYPERTROPHY; PLACEBO; PATHWAY; DIFFERENTIATION; MYOSTATIN; THERAPY AB Objective:To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial.Methods:We measured transforming growth factor signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n = 11) or placebo (n = 3). The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks. Lean body mass, strength, and function were secondary outcomes. Twelve of the patients (10 bimagrumab, 2 placebo) participated in a subsequent 16-week observation phase.Results:Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied (p = 0.003). Eight weeks after dosing, the bimagrumab-treated patients increased thigh muscle volume (right leg +6.5% compared with placebo, p = 0.024; left leg +7.6%, p = 0.009) and lean body mass (+5.7% compared with placebo, p = 0.014). Subsequently, bimagrumab-treated patients had improved 6-minute walking distance, which peaked at 16 weeks (+14.6%, p = 0.008) compared with placebo. There were no serious adverse events; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions.Conclusions:Transforming growth factor superfamily signaling, at least through ActRII, is implicated in the pathophysiology of sIBM. Inhibition of ActRII increased muscle mass and function in this pilot trial, offering a potential novel treatment of sIBM.Classification of evidence:This study provides Class I evidence that for patients with inclusion body myositis, bimagrumab increases thigh muscle volume at 8 weeks. C1 [Amato, Anthony A.; Salajegheh, Mohammad; Greenberg, Steven A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amato, Anthony A.; Salajegheh, Mohammad; Greenberg, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Greenberg, Steven A.] Boston Childrens Hosp, Boston, MA USA. [Greenberg, Steven A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sivakumar, Kumaraswamy] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Goyal, Namita; David, William S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lach-Trifilieff, Estelle; Trendelenburg, Anne-Ulrike; Laurent, Didier; Glass, David J.; Roubenoff, Ronenn; Tseng, Brian S.] Novartis Inst Biomed Res, Cambridge, MA USA. [Lach-Trifilieff, Estelle; Trendelenburg, Anne-Ulrike; Laurent, Didier; Glass, David J.; Roubenoff, Ronenn; Tseng, Brian S.] Novartis Inst Biomed Res, Basel, Switzerland. [Praestgaard, Jens] Novartis Pharmaceut, E Hanover, NJ USA. RP Greenberg, SA (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM brian.tseng@novartis.com; sagreenberg@partners.org FU Novartis Institutes for Biomedical Research; Boston Children's Hospital; Brigham and Women's Hospital, Harvard Medical School; Novartis FX Supported by Novartis Institutes for Biomedical Research, Boston Children's Hospital, and Brigham and Women's Hospital, Harvard Medical School. Role of the funding source: The study was designed and the data were analyzed by the sponsor, Novartis, in collaboration with the principal investigator (S.A.G.). Novartis participated in the interpretation of data, review, and approval of the report. An initial draft of the report was prepared by R.R. and S.A.G. All authors participated in interpretation of the data, contributed substantially to report drafts, and agreed to submit the report for publication. All authors had full access to the data and vouch for accuracy and completeness of the data and analyses. NR 24 TC 36 Z9 36 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 9 PY 2014 VL 83 IS 24 BP 2239 EP 2246 DI 10.1212/WNL.0000000000001070 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AW1SK UT WOS:000346070000013 PM 25381300 ER PT J AU Bonaca, MP Scirica, BM Braunwald, E Wiviott, SD O'Donoghue, ML Murphy, SA Morrow, DA AF Bonaca, Marc P. Scirica, Benjamin M. Braunwald, Eugene Wiviott, Stephen D. O'Donoghue, Michelle L. Murphy, Sabina A. Morrow, David A. TI Coronary Stent Thrombosis With Vorapaxar Versus Placebo Results From the TRA 2 degrees P-TIMI 50 Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE antiplatelet therapy; atherothrombosis; DES; PAR-1; stent; thienopyridine ID DRUG-ELUTING STENTS; DUAL-ANTIPLATELET THERAPY; RANDOMIZED CLINICAL-TRIALS; SECONDARY PREVENTION; EVENTS; INTERVENTION; IMPLANTATION; METAANALYSIS; MULTICENTER; PREDICTORS AB BACKGROUND Vorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease. OBJECTIVES The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stable patients with a history of coronary stenting. METHODS TRA2 degrees P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a multinational, randomized, double-blind, placebocontrolled trial of vorapaxar in stable patients with prior myocardial infarction, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria. RESULTS A total of 26,449 patients were randomized, with 14,042 (53%) having a history of a coronary stent implantation before randomization, and an additional 449 patients receiving a coronary stent during the trial (total 14,491). During follow-up (median 2.5 years), there were 152 definite ST events, with the majority (92%) occurring late or very late. Vorapaxar reduced ARC definite ST (1.1% vs. 1.4%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.51 to 0.98; p = 0.037). The reduction was consistent, regardless of time from percutaneous coronary intervention, history of diabetes, use of drug-eluting stents, and use of dual antiplatelet therapy (DAPT) at randomization. Vorapaxar increased GUSTO moderate/severe bleeding (HR: 1.57, 95% CI: 1.26 to 1.94; p < 0.001). CONCLUSIONS The rate of ARC definite ST in stable patients, the majority of whom were receiving DAPT, was approximately 1.4% at 3 years. In stable patients with coronary stenting receiving standard antiplatelet therapy, vorapaxar administered for long-term secondary prevention significantly reduced ARC definite ST, including very late ST. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU Merck Co. FX This study was supported by a grant from Merck & Co. The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi-Sankyo Co. Ltd., Eli Lilly and Company, GlaxoSmithKline, Integrated Therapeutics, Merck & Co., Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi, Sanofi-Synthelabo, Siemens Medical Solutions, and Singulex. Dr. Bonaca has received consulting fees from Roche Diagnostics, Merck & Co., AstraZeneca, and Bayer. Dr. Scirica has received research grants via the TIMI Study and Brigham and Women's Hospital from AstraZeneca, BristolMyers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson & Johnson, Bayer Healthcare, Gilead, Eisai, and Merck & Co.; and consulting fees from AstraZeneca, GE Healthcare, Gilead, Lexicon, Arena, Eisai, St. Jude's Medical, Forest Pharmaceuticals, Bristol-Myers Squibb, Boston ClinicalResearch Institute, Covance, University of Calgary, and Elsevier PracticeUpdate Cardiology. Dr. Braunwald has received research grants (institutional) from Daiichi- Sankyo, Duke University, AstraZeneca, Merck & Co., and GlaxoSmithKline; has received fees for lectures from Daiichi- Sankyo, Menarini International, and Medscape; has received fees as a consultant for The Medicines Company and Sanofi; and has been an unpaid consultant and has given unpaid lectures for Merck & Co. Dr. Wiviott has received research grants from Merck & Co., AstraZeneca, and Eisai; and has been a consultant for Eli Lilly and Company, AstraZeneca, Johnson & Johnson, St. Jude Medical, ICON, and Bristol-Myers Squibb. Dr. O'Donoghue has received research grants from GlaxoSmithKline, AstraZeneca, and Eisai; and has been a consultant with Aegerion. Dr. Morrow has received research grant support from Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Critical Diagnostics, CV Therapeutics, Daiichi- Sankyo Co. Ltd., Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Merck and Co., Novartis Pharmaceuticals, Roche Diagnostics, Sanofi, and Singulex; and has received consulting fees from Abbott Laboratories, BG Medicine, Daiichi- Sankyo, Eli Lilly and Company, Gilead, Instrumentation Laboratory, Johnson & Johnson, Konica Minolta, Merck & Co., Novartis, Roche Diagnostics, and Servier. Ms. Murphy has reported that she has no relationships relevant to the contents of this paper to disclose. NR 18 TC 18 Z9 18 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 9 PY 2014 VL 64 IS 22 BP 2309 EP 2317 DI 10.1016/j.jacc.2014.09.037 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW0ED UT WOS:000345962200002 PM 25465416 ER PT J AU Bonaca, MP Scirica, BM Braunwald, E Wiviott, SD Goto, S Nilsen, DW Bonarjee, V Murphy, SA Morrow, DA AF Bonaca, Marc P. Scirica, Benjamin M. Braunwald, Eugene Wiviott, Stephen D. Goto, Shinya Nilsen, Dennis W. Bonarjee, Vernon Murphy, Sabina A. Morrow, David A. TI New Ischemic Stroke and Outcomes With Vorapaxar Versus Placebo Results From the TRA 2 degrees P-TIMI 50 Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE antiplatelet therapy; intracranial hemorrhage; PAR-1; platelet aggregation inhibitors; secondary prevention; thrombin receptor ID RECENT LACUNAR STROKE; SECONDARY PREVENTION; CLOPIDOGREL; ASPIRIN; DISEASE; ATTACK; EVENTS; RISK; ASSOCIATION; UPDATE AB BACKGROUND Vorapaxar, a novel antiplatelet therapy, reduces thrombotic events in patients with a history of myocardial infarction (MI) or peripheral artery disease (PAD); however, because of an increased risk of intracranial hemorrhage, it is contraindicated in patients with a history of stroke. OBJECTIVES The aim of this study was to investigate the incidence of new ischemic stroke and subsequent death or intracerebral hemorrhage in patients with MI or PAD and no cerebrovascular disease (CVD) treated with vorapaxar. METHODS The TRA 2 degrees P-TIMI 50 (Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis In Myocardial Infarction 50) was a randomized, double-blind, place-bocontrolled trial of vorapaxar 2.5 mg daily in 26,449 patients with atherosclerosis, stratified by qualifying disease (MI, PAD, or CVD). A total of 20,170 patients with MI/ PAD, but no CVD, were enrolled. RESULTS In patients with MI/ PAD and no prior stroke or transient ischemic attack, vorapaxar reduced first ischemic stroke (hazard ratio [ HR]: 0.57, 95% confidence interval [ CI]: 0.43 to 0.75; p < 0.001). The risk of hemorrhagic conversion after stroke (HR: 1.19, 95% CI: 0.49 to 2.91; p = 0.70) or death (HR: 1.09, 95% CI: 0.57 to 2.07; p = 0.79) during follow-up was not significantly increased with vorapaxar in patients who had a new ischemic stroke (n = 204). Although hemorrhagic stroke was increased (HR: 2.79, 95% CI: 1.00 to 7.73; p = 0.049), overall stroke was significantly reduced (HR: 0.67, 95% CI: 0.52 to 0.87; p = 0.002). CONCLUSIONS Vorapaxar reduces ischemic stroke in patients with MI or PAD and no known CVD. There does not appear to be a significant increase in the risk of hemorrhagic conversion or death in patients who experienced a first ischemic stroke on vorapaxar. Although primary hemorrhagic stroke is increased, vorapaxar reduces the total incidence of stroke. C1 [Bonaca, Marc P.; Scirica, Benjamin M.; Braunwald, Eugene; Wiviott, Stephen D.; Murphy, Sabina A.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Bonaca, Marc P.; Scirica, Benjamin M.; Braunwald, Eugene; Wiviott, Stephen D.; Murphy, Sabina A.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Goto, Shinya] Tokai Univ, Sch Med, Inst Med Sci, Dept Med Cardiol, Isehara, Kanagawa 25911, Japan. [Nilsen, Dennis W.; Bonarjee, Vernon] Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway. [Nilsen, Dennis W.; Bonarjee, Vernon] Univ Bergen, Fac Med & Dent, Dept Clin Sci, Bergen, Norway. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU Merck Co. FX This study was supported by a grant from Merck & Co. The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi-Sankyo Co. Ltd., Eli Lilly and Company, GlaxoSmithKline, Integrated Therapeutics, Merck & Co., Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi, Sanofi-Synthelabo, Siemens Medical Solutions, and Singulex. Dr. Bonaca was supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute; and has received consulting fees from Roche Diagnostics, Merck & Co., AstraZeneca, and Bayer. Dr. Scirica has received research grants via the TIMI Study and Brigham and Women's Hospital from AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson & Johnson, Bayer Healthcare, Gilead, Eisai, and Merck & Co.; and consulting fees from AstraZeneca, GE Healthcare, Gilead, Lexicon, Arena, Eisai, St. Jude's Medical, Forest Pharmaceuticals, Bristol-Myers Squibb, Boston Clinical Research Institute, Covance, University of Calgary, and Elsevier Practice Update Cardiology. Dr. Braunwald has received research grants (institutional) from Daiichi-Sankyo, Duke University, AstraZeneca, Merck & Co., and GlaxoSmithKline; has received fees for lectures from Daiichi-Sankyo, Menarini International, and Medscape; has received fees as a consultant for The Medicines Company and Sanofi; and has been an unpaid consultant and has given unpaid lectures for Merck & Co. Dr. Wiviott has received research grants from Merck & Co., AstraZeneca, and Eisai; and has been a consultant for Eli Lilly and Company, AstraZeneca, Johnson & Johnson, Arena, St. Jude Medical, Icon Medical Imaging, and Bristol-Myers Squibb. Dr. Goto has received honoraria from Eisai, Sanofi, Otsuka, Bayer, Novartis, AstraZeneca, Asteras, Pfizer, Medtronics-Japan, Tanabe-Mitsubishi, Takeda, DaiichiSankyo, Mochida, and MSD; and has received research grants from Sanofi, Boehringer Ingelheim, Otsuka, and Daiichi-Sankyo. Dr. Morrow has received research grant support from Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, Critical Diagnostics, CV Therapeutics, Daiichi-Sankyo Co. Ltd., Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Novartis Pharmaceuticals, Roche Diagnostics, Sanofi, and Singulex; and has received consulting fees from Abbott Laboratories, BG Medicine, Daiichi-Sankyo, Eli Lilly and Company, Gilead, Instrumentation Laboratory, Johnson & Johnson, Konica Minolta, Merck & Co., Novartis, Roche Diagnostics, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 21 TC 17 Z9 18 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 9 PY 2014 VL 64 IS 22 BP 2318 EP 2326 DI 10.1016/j.jacc.2014.07.997 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW0ED UT WOS:000345962200003 PM 25465417 ER PT J AU Lopez-Pelaez, M Lamont, DJ Peggie, M Shpiro, N Gray, NS Cohen, P AF Lopez-Pelaez, Marta Lamont, Douglas J. Peggie, Mark Shpiro, Natalia Gray, Nathanael S. Cohen, Philip TI Protein kinase IKK beta-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IKK beta; interferon beta; IRF5; plasmacytoid dendritic cell; TLR7 ID INTERFERON REGULATORY FACTOR; PLASMACYTOID DENDRITIC CELLS; VIRAL-INFECTION; IN-VIVO; INHIBITORS; INDUCTION; ACTIVATION; GENE; TOLL-LIKE-RECEPTOR-7; LOCALIZATION AB The siRNA knockdown of IFN Regulatory Factor 5 (IRF5) in the human plasmacytoid dendritic cell line Gen2.2 prevented IFN alpha production induced by compound CL097, a ligand for Toll-like receptor 7 (TLR7). CL097 also stimulated the phosphorylation of IRF5 at Ser462 and stimulated the nuclear translocation of wild-type IRF5, but not the IRF5[Ser462Ala] mutant. The CL097-stimulated phosphorylation of IRF5 at Ser462 and its nuclear translocation was prevented by the pharmacological inhibition of protein kinase IKK beta or the siRNA knockdown of IKK beta or its "upstream" activator, the protein kinase TAK1. Similar results were obtained in a murine macrophage cell line stimulated with the TLR7 agonist compound R848 or the nucleotide oligomerization domain 1 (NOD1) agonist KF-1B. IKK beta phosphorylated IRF5 at Ser462 in vitro and induced the dimerization of wild-type IRF5 but not the IRF5[S462A] mutant. These findings demonstrate that IKK beta activates two "master" transcription factors of the innate immune system, IRF5 and NF-kappa B. C1 [Lopez-Pelaez, Marta; Peggie, Mark; Shpiro, Natalia; Cohen, Philip] Univ Dundee, Prot Phosphorylat & Ubiquitylat Unit, MRC, Dundee DD1 5EH, Scotland. [Lamont, Douglas J.] Univ Dundee, Coll Life Sci, Dundee DD1 5EH, Scotland. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Cohen, P (reprint author), Univ Dundee, Prot Phosphorylat & Ubiquitylat Unit, MRC, Dundee DD1 5EH, Scotland. EM p.cohen@dundee.ac.uk FU Wellcome Trust [WT100294]; UK Medical Research Council; AstraZeneca; Boehringer Ingelheim; GlaxoSmithKline; Janssen Pharmaceutica; Merck-Serono; Pfizer FX The Gen2.2 cells were generously provided by Joel Plumas and Laurence Chaperot (French Blood Bank). The research was supported by the Wellcome Trust (WT100294), the UK Medical Research Council, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen Pharmaceutica, Merck-Serono, and Pfizer. NR 35 TC 15 Z9 15 U1 2 U2 7 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 DEC 9 PY 2014 VL 111 IS 49 BP 17432 EP 17437 DI 10.1073/pnas.1418399111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NR UT WOS:000345921500031 PM 25326418 ER PT J AU Sok, D van Gils, MJ Pauthner, M Julien, JP Saye-Francisco, KL Hsueh, J Briney, B Lee, JH Le, KM Lee, PS Hua, YZ Seaman, MS Moore, JP Ward, AB Wilson, IA Sanders, RW Burton, DR AF Sok, Devin van Gils, Marit J. Pauthner, Matthias Julien, Jean-Philippe Saye-Francisco, Karen L. Hsueh, Jessica Briney, Bryan Lee, Jeong Hyun Le, Khoa M. Lee, Peter S. Hua, Yuanzi Seaman, Michael S. Moore, John P. Ward, Andrew B. Wilson, Ian A. Sanders, Rogier W. Burton, Dennis R. TI Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV; broadly neutralizing antibodies; BG505 SOSIP; B cell; vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; BROADLY NEUTRALIZING ANTIBODIES; N-GLYCAN RECOGNITION; CONFORMATIONAL EPITOPE; BINDING-SITE; ENV TRIMERS; CD4 BINDING; B-CELLS; TYPE-1 AB Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 mu g/mL. Overall, our results highlight the utility of BG505 SOSIP. 664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family. C1 [Sok, Devin; Pauthner, Matthias; Saye-Francisco, Karen L.; Hsueh, Jessica; Briney, Bryan; Le, Khoa M.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Sok, Devin; Pauthner, Matthias; Julien, Jean-Philippe; Saye-Francisco, Karen L.; Hsueh, Jessica; Briney, Bryan; Lee, Jeong Hyun; Le, Khoa M.; Hua, Yuanzi; Ward, Andrew B.; Wilson, Ian A.; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Sok, Devin; Pauthner, Matthias; Julien, Jean-Philippe; Saye-Francisco, Karen L.; Hsueh, Jessica; Briney, Bryan; Lee, Jeong Hyun; Le, Khoa M.; Hua, Yuanzi; Ward, Andrew B.; Wilson, Ian A.; Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Julien, Jean-Philippe; Lee, Jeong Hyun; Lee, Peter S.; Hua, Yuanzi; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Sok, Devin] Int AIDS Vaccine Initiat, New York, NY 10038 USA. [van Gils, Marit J.; Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, Lab Expt Virol,Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Julien, Jean-Philippe] Univ Toronto, Hosp Sick Children, Res Inst, Program Mol Struct & Funct, Toronto, ON M5G 0A4, Canada. [Julien, Jean-Philippe] Univ Toronto, Dept Biochem, Toronto, ON M5G 0A4, Canada. [Julien, Jean-Philippe] Univ Toronto, Dept Immunol, Toronto, ON M5G 0A4, Canada. [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Moore, John P.; Sanders, Rogier W.] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. [Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02142 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02142 USA. RP Sanders, RW (reprint author), Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, Lab Expt Virol,Dept Med Microbiol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM rws2002@med.cornell.edu; burton@scripps.edu RI Ward, Andrew/F-9203-2014; OI Ward, Andrew/0000-0001-7153-3769; Hsueh, Jessica/0000-0002-4070-5270 FU International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium [SFP1849]; National Institutes of Health (NIH) [R01 AI033292, R01 AI84817, R37 AI36082]; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant [UM1AI100663]; HIV Vaccine Research and Design Program [P01 AI82362]; NIH Interdisciplinary Training Program in Immunology [5T32AI007606-10]; Dutch Aids Fonds [2012041, 2009012, 2011032]; European Molecular Biology Organization Application Short-Term Fellowship [260-2013]; Netherlands Organization for Scientific Research; European Research Council [ERC-StG-2011-280829-SHEV]; Canadian Institutes of Health Research fellowship; Bill and Melinda Gates Foundation [38619]; Ministry of Foreign Affairs of Denmark; Irish Aid; Ministry of Finance of Japan; Ministry of Foreign Affairs of the Netherlands; Norwegian Agency for Development Cooperation; United Kingdom Department for International Development; US Agency for International Development (USAID); American people through USAID; Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery FX This work was supported by the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium SFP1849 (D.R.B.); National Institutes of Health (NIH) Grants R01 AI033292 (to D.R.B.), R01 AI84817 (to I.A.W.), and R37 AI36082 (to J.P.M.); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1AI100663 (to D.R.B., I.A.W., and A.B.W.); and HIV Vaccine Research and Design Program Grant P01 AI82362 (to J.P.M., I.A.W., and A.B.W.). Funding also was provided by the NIH Interdisciplinary Training Program in Immunology 5T32AI007606-10 (D.S.); Dutch Aids Fonds Grant 2012041 and a European Molecular Biology Organization Application Short-Term Fellowship 260-2013 (to M.J.v.G.); Dutch Aids Fonds Grants 2009012 and 2011032 (to R.W.S.); a Vidi grant from the Netherlands Organization for Scientific Research (to R.W.S.); Starting Investigator Grant ERC-StG-2011-280829-SHEV from the European Research Council (to R.W.S.); and a Canadian Institutes of Health Research fellowship (to J.-P.J.). A portion of the neutralization experiments was done by the M.S. group (Beth Israel Deaconess Medical Center, Harvard Medical School), and that work was funded by Bill and Melinda Gates Foundation Grant 38619. The work of the IAVI is made possible by generous support from many donors, including the Bill and Melinda Gates Foundation; the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of Japan; the Ministry of Foreign Affairs of the Netherlands; the Norwegian Agency for Development Cooperation; the United Kingdom Department for International Development, and the US Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org. This study was made possible by the generous support of the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery and the American people through USAID. NR 45 TC 72 Z9 72 U1 1 U2 15 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 DEC 9 PY 2014 VL 111 IS 49 BP 17624 EP 17629 DI 10.1073/pnas.1415789111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9NR UT WOS:000345921500063 PM 25422458 ER PT J AU Olsen, LR Campos, B Winther, O Sgroi, DC Karger, BL Brusic, V AF Olsen, Lars Ronn Campos, Benito Winther, Ole Sgroi, Dennis C. Karger, Barry L. Brusic, Vladimir TI Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas SO BMC MEDICAL GENOMICS LA English DT Article ID HUMAN BREAST-CANCER; EPITHELIAL OVARIAN-CANCER; SET ENRICHMENT ANALYSIS; PHOSPHOGLYCERATE KINASE; EXPRESSION PROFILES; IMMUNE SURVEILLANCE; SUPPRESSOR-CELLS; CLINICAL-TRIALS; TESTIS ANTIGEN; BETA-CATENIN AB Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic. Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature of transcriptional and translation regulatory mechanisms and the disparities between genomic and proteomic data from the same samples. In this study, we have examined tumor antigens as potential biomarkers for breast cancer using genomics and proteomics data from previously reported laser capture microdissected ER+ tumor samples. Results: We applied proteogenomic analyses to study the genetic aberrations of 32 tumor antigens determined in the proteomic data. We found that tumor antigens that are aberrantly expressed at the genetic level and expressed at the protein level, are likely involved in perturbing pathways directly linked to the hallmarks of cancer. The results found by proteogenomic analysis of the 32 tumor antigens studied here, capture largely the same pathway irregularities as those elucidated from large-scale screening of genomics analyses, where several thousands of genes are often found to be perturbed. Conclusion: Tumor antigens are a group of proteins recognized by the cells of the immune system. Specifically, they are recognized in tumor cells where they are present in larger than usual amounts, or are physiochemically altered to a degree at which they no longer resemble native human proteins. This proteogenomic analysis of 32 tumor antigens suggests that tumor antigens have the potential to be highly specific biomarkers for different cancers. C1 [Olsen, Lars Ronn; Winther, Ole] Univ Copenhagen, Dept Biol, Bioinformat Ctr, Copenhagen, Denmark. [Olsen, Lars Ronn] Univ Copenhagen, Biotech Res & Innovat Ctr, Copenhagen, Denmark. [Olsen, Lars Ronn; Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Campos, Benito] Univ Heidelberg Hosp, Dept Neurosurg, Div Expt Neurosurg, Heidelberg, Germany. [Winther, Ole] Tech Univ Denmark, Cognit Syst, DTU Compute, DK-2800 Lyngby, Denmark. [Sgroi, Dennis C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Karger, Barry L.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Brusic, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Brusic, Vladimir] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA. [Brusic, Vladimir] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan. RP Brusic, V (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, 44 Binney St, Boston, MA 02115 USA. EM vladimir.brusic@nu.edu.kz OI Olsen, Lars Ronn/0000-0002-6725-7850 FU Novo Nordisk Foundation; Susan G. Komen Breast Cancer Foundation; NIH [RO1GM15847, R01CA112021]; NCI; Avon Foundation FX This work was supported by the Novo Nordisk Foundation (LRO and OW), the Susan G. Komen Breast Cancer Foundation (BLK and DCS), NIH grant RO1GM15847 (BLK), NIH grant R01CA112021 (DCS), the NCI SPORE in breast cancer at Massachusetts General Hospital (DCS) and the Avon Foundation (DCS). Publication charges for this work was funded by a Novo Nordisk Foundation grant to OW. NR 117 TC 4 Z9 4 U1 1 U2 2 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 DEC 8 PY 2014 VL 7 SU 3 AR S2 DI 10.1186/1755-8794-7-S3-S2 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA CH4DF UT WOS:000353981300002 PM 25521819 ER PT J AU Lee, SJ Ritchie, CS Yaffe, K Cenzer, IS Barnes, DE AF Lee, Sei J. Ritchie, Christine S. Yaffe, Kristine Cenzer, Irena Stijacic Barnes, Deborah E. TI A Clinical Index to Predict Progression from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease SO PLOS ONE LA English DT Article ID OLDER-ADULTS; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RISK; RECOMMENDATIONS; CLASSIFICATION; VALIDATION; BIOMARKERS; CONVERSION AB Background: Mild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment. Objective: To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings. Design and Participants: 382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study. Main Predictors Measures: Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales. Main Outcome Measure: Progression to probable Alzheimer's disease. Key Results: Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68-0.75). Fourteen percent of subjects with low risk scores (0-2 points, n=124) converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3-8 points, n=223) and 91% of those with high risk scores (9-16 points, n=35). Conclusions: An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression. C1 [Lee, Sei J.; Ritchie, Christine S.; Cenzer, Irena Stijacic] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Lee, Sei J.; Ritchie, Christine S.; Yaffe, Kristine; Cenzer, Irena Stijacic; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ritchie, Christine S.] Jewish Home San Francisco, San Francisco, CA USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. EM sei.lee@ucsf.edu FU S.D. Bechtel, Jr. Foundation; National Institutes of Health [K24-AG031155, R01-DK69406, R01-AG26720]; Veterans Health Administration FX SJL was supported by the S.D. Bechtel, Jr. Foundation (http://sdbjrfoundation.org/). KY was supported for this study by the National Institutes of Health (K24-AG031155, R01-DK69406 and R01-AG26720) and the Veterans Health Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 4 Z9 4 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 8 PY 2014 VL 9 IS 12 AR e113535 DI 10.1371/journal.pone.0113535 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MX UT WOS:000346907600021 PM 25486250 ER PT J AU Umeh, CC Peerez, A Augustine, EF Dhall, R Dewey, RB Mari, Z Simon, DK Wills, AMA Christine, CW Schneider, JS Suchowersky, O AF Umeh, Chizoba C. Perez, Adriana Augustine, Erika F. Dhall, Rohit Dewey, Richard B., Jr. Mari, Zoltan Simon, David K. Wills, Anne-Marie A. Christine, Chadwick W. Schneider, Jay S. Suchowersky, Oksana TI No Sex Differences in Use of Dopaminergic Medication in Early Parkinson Disease in the US and Canada - Baseline Findings of a Multicenter Trial SO PLOS ONE LA English DT Article ID POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; GENDER-DIFFERENCES; LEVODOPA; DISPARITIES; DYSKINESIA; STROKE AB Background: Sex differences in Parkinson disease clinical features have been reported, but few studies have examined sex influences on use of dopaminergic medication in early Parkinson disease. The objective of this study was to test if there are differences in the type of dopaminergic medication used and levodopa equivalent daily dose between men and women with early Parkinson disease enrolled in a large multicenter study of Creatine as a potential disease modifying therapy - the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease Long-Term Study-1. Methods: Baseline data of 1,741 participants from 45 participating sites were analyzed. Participants from the United States and Canada were enrolled within five years of Parkinson Disease diagnosis. Two outcome variables were studied: type of dopaminergic medication used and levodopa equivalent daily dose at baseline in the Long-Term Study-1. Chi-square statistic and linear regression models were used for statistical analysis. Results: There were no statistically significant differences in the frequency of use of different types of dopaminergic medications at baseline between men and women with Parkinson Disease. A small but statistically significant difference was observed in the median unadjusted levodopa equivalent daily dose at baseline between women (300 mg) and men (325 mg), but this was not observed after controlling for disease duration (years since Parkinson disease diagnosis), disease severity (Unified Parkinson's Disease Rating Scale Motor and Activities of Daily Living Scores), and body weight. Conclusions: In this large multicenter study, we did not observe sex differences in the type and dose of dopaminergic medications used in early Parkinson Disease. Further research is needed to evaluate the influence of male or female sex on use of dopaminergic medication in mid-and late-stage Parkinson Disease. C1 [Umeh, Chizoba C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Perez, Adriana] Univ Texas Austin, Sch Publ Hlth, Dept Biostat, Austin, TX 78712 USA. [Augustine, Erika F.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Dhall, Rohit] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. [Dewey, Richard B., Jr.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Mari, Zoltan] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Simon, David K.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Simon, David K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wills, Anne-Marie A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Christine, Chadwick W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Schneider, Jay S.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Suchowersky, Oksana] Univ Alberta, Dept Med Neurol, Edmonton, AB, Canada. [Suchowersky, Oksana] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada. [Suchowersky, Oksana] Univ Alberta, Dept Pediat, Edmonton, AB, Canada. RP Umeh, CC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM cumeh@partners.org FU NIH [U01NS043128] FX Dr. Adriana Perez received financial support from NIH grant U01NS043128. NIH had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 2 Z9 2 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 8 PY 2014 VL 9 IS 12 AR e112287 DI 10.1371/journal.pone.0112287 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MX UT WOS:000346907600009 PM 25486269 ER PT J AU Sun, J Zhang, GL Li, SY Ivanov, AR Fenyo, D Lisacek, F Murthy, SK Karger, BL Brusic, V AF Sun, Jing Zhang, Guang Lan Li, Siyang Ivanov, Alexander R. Fenyo, David Lisacek, Frederique Murthy, Shashi K. Karger, Barry L. Brusic, Vladimir TI Pathway analysis and transcriptomics improve protein identification by shotgun proteomics from samples comprising small number of cells - a benchmarking study SO BMC GENOMICS LA English DT Article ID CIRCULATING TUMOR-CELLS; MASS-SPECTROMETRY; CANCER-CELLS; RESOURCE UNIPROT; SINGLE-CELL; DATABASE; SPECTRA; LINE AB Background: Proteomics research is enabled with the high-throughput technologies, but our ability to identify expressed proteome is limited in small samples. The coverage and consistency of proteome expression are critical problems in proteomics. Here, we propose pathway analysis and combination of microproteomics and transcriptomics analyses to improve mass-spectrometry protein identification from small size samples. Results: Multiple proteomics runs using MCF-7 cell line detected 4,957 expressed proteins. About 80% of expressed proteins were present in MCF-7 transcripts data; highly expressed transcripts are more likely to have expressed proteins. Approximately 1,000 proteins were detected in each run of the small sample proteomics. These proteins were mapped to gene symbols and compared with gene sets representing canonical pathways, more than 4,000 genes were extracted from the enriched gene sets. The identified canonical pathways were largely overlapping between individual runs. Of identified pathways 182 were shared between three individual small sample runs. Conclusions: Current technologies enable us to directly 10% of expressed proteomes from small sample comprising as few as 50 cells. We used knowledge-based approaches to elucidate the missing proteome that can be verified by targeted proteomics. This knowledge-based approach includes pathway analysis and combination of gene expression and protein expression data for target prioritization. Genes present in both the enriched gene sets (canonical pathways collection) and in small sample proteomics data correspond to approximately 50% of expressed proteomes in larger sample proteomics data. In addition, 90% of targets from canonical pathways were estimated to be expressed. The comparison of proteomics and transcriptomics data, suggests that highly expressed transcripts have high probability of protein expression. However, approximately 10% of expressed proteins could not be matched with the expressed transcripts. C1 [Sun, Jing; Zhang, Guang Lan; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Zhang, Guang Lan; Brusic, Vladimir] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA. [Li, Siyang; Ivanov, Alexander R.; Karger, Barry L.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Fenyo, David] NYU, Med Ctr, Ctr Hlth Informat & Bioinformat, Lab Computat Prote, New York, NY 10016 USA. [Lisacek, Frederique] CMU, Swiss Inst Bioinformat, Proteome Informat Grp, Geneva, Switzerland. [Murthy, Shashi K.] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. [Brusic, Vladimir] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. EM Vladimir.brusic@nu.edu.kz OI LISACEK, Frederique/0000-0002-0948-4537; Fenyo, David/0000-0001-5049-3825 FU Vladimir Brusic FX The cost of this publication was funded by Vladimir Brusic. NR 43 TC 1 Z9 1 U1 4 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 8 PY 2014 VL 15 SU 9 AR S1 DI 10.1186/1471-2164-15-S9-S1 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AW3DQ UT WOS:000346166300002 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI DisABLing Kidney Cancers Caused by Fumarate Hydratase Mutations SO CANCER CELL LA English DT Editorial Material ID RENAL-CELL CARCINOMA; PHENOTYPE AB Reprogramming of cellular metabolism by oncogenic mutations probably creates specific vulnerabilities that could be exploited therapeutically. In this issue of Cancer Cell, Sourbier and colleagues show that kidney cancers lacking fumarate hydratase display increased sensitivity to agents that interfere with their ability to cope with reactive oxygen species. C1 [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM william_kaelin@dfci.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 8 PY 2014 VL 26 IS 6 BP 779 EP 780 DI 10.1016/j.ccell.2014.11.022 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JN UT WOS:000346114000005 PM 25490441 ER PT J AU Landau, DA Clement, K Ziller, MJ Boyle, P Fan, J Gu, HC Stevenson, K Sougnez, C Wang, L Li, SQ Kotliar, D Zhang, W Ghandi, M Garraway, L Fernandes, SM Livak, KJ Gabriel, S Gnirke, A Lander, ES Brown, JR Neuberg, D Kharchenko, PV Hacohen, N Getz, G Meissner, A Wu, CJ AF Landau, Dan A. Clement, Kendell Ziller, Michael J. Boyle, Patrick Fan, Jean Gu, Hongcang Stevenson, Kristen Sougnez, Carrie Wang, Lili Li, Shuqang Kotliar, Dylan Zhang, Wandi Ghandi, Mahmoud Garraway, Levi Fernandes, Stacey M. Livak, Kenneth J. Gabriel, Stacey Gnirke, Andreas Lander, Eric S. Brown, Jennifer R. Neuberg, Donna Kharchenko, Peter V. Hacohen, Nir Getz, Gad Meissner, Alexander Wu, Catherine J. TI Locally Disordered Methylation Forms the Basis of Intratumor Methylome Variation in Chronic Lymphocytic Leukemia SO CANCER CELL LA English DT Article ID DNA METHYLATION; GENE-EXPRESSION; EPIGENETIC MEMORY; STEM-CELLS; RNA-SEQ; CANCER; GENOME; HYPOMETHYLATION; PROFILE; IDENTIFICATION AB Intratumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLLs). Compared with 26 normal B cell samples, CLLs consistently displayed higher intrasample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to that of genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories. C1 [Landau, Dan A.; Wang, Lili; Garraway, Levi; Fernandes, Stacey M.; Brown, Jennifer R.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Landau, Dan A.; Clement, Kendell; Ziller, Michael J.; Boyle, Patrick; Gu, Hongcang; Sougnez, Carrie; Ghandi, Mahmoud; Garraway, Levi; Gabriel, Stacey; Gnirke, Andreas; Lander, Eric S.; Hacohen, Nir; Getz, Gad; Meissner, Alexander] Broad Inst, Cambridge, MA 02139 USA. [Clement, Kendell; Ziller, Michael J.; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Clement, Kendell; Ziller, Michael J.; Meissner, Alexander] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Fan, Jean; Kharchenko, Peter V.] Harvard Univ, Sch Med, Ctr Informat Biol, Boston, MA 02115 USA. [Stevenson, Kristen; Neuberg, Donna] Dana Farber Canc Inst, Deptt Biostatist & Computat Biol, Boston, MA 02115 USA. [Li, Shuqang; Livak, Kenneth J.] Fluidigm, San Francisco, CA 94080 USA. [Brown, Jennifer R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kharchenko, Peter V.; Wu, Catherine J.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Meissner, A (reprint author), Broad Inst, Cambridge, MA 02139 USA. EM alexander_meissner@harvard.edu; cwu@partners.org OI Fan, Jean/0000-0002-0212-5451; Ghandi, Mahmoud/0000-0003-1897-2265 FU American Cancer Society (ACS); NIH Big Data to Knowledge initiative [BD2K, 1K01ES025431-01]; National Science Foundation [DGE1144152]; NIH [U01ES017155, R01DA036898]; Blavatnik Family Foundation; American Association for Cancer Research; National Heart, Lung, and Blood Institute [1R01HL103532-01]; National Cancer Institute [1R01CA15501001A1] FX We thank all members of the Broad Institute's Biological Samples, Genetic Analysis, and Genome Sequencing Platforms, who made this work possible (NHGRI-U54HG003067). We thank Rahul Satija, Angela Brooks, Scott Carter and Brad Bernstein for their Valuable input and insights. We thank John Daley, Suzan Lazo-Kallanian, Jonna Grimsby, and Niall Lennon for their assistance in the single-cell RNA-seq. We thank Adam Kiezun for his guidance regarding germline SNP detection and Michael Lawrence for the replication time data. D.A.L. is supported by a Postdoctoral Fellowship from the American Cancer Society (ACS) and by the NIH Big Data to Knowledge initiative (BD2K, 1K01ES025431-01). K.C. is supported by the National Science Foundation Graduate Research Fellowship under Grant No. 112237. L.W. is supported by a Lymphoma Research Foundation Postdoctoral Fellowship. J.F. is supported by the National Science Foundation Graduate Research Fellowship (DGE1144152). J.R.B. is a Scholar in Clinical Research of the Leukemia & Lymphoma Society (LLS) and is supported by a LLS Translational Research Program award as well as an ACS Research Scholar Grant and the Melton and Rosenbach Funds. A.M. is a New York Stem Cell Foundation Robertson Investigator and received support from NIH grants U01ES017155 and 1R01DA036898. C.J.W. is a Scholar of LLS and the recipient of a Quest for Cures Award from LLS. She acknowledges support from the Blavatnik Family Foundation, the American Association for Cancer Research (Stand Up to Cancer Innovative Research Grant), the National Heart, Lung, and Blood Institute (1R01HL103532-01), and the National Cancer Institute (1R01CA15501001A1). K.J.L. and S.L. are employees of Fluidigm Corporation. NR 52 TC 57 Z9 58 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 8 PY 2014 VL 26 IS 6 BP 813 EP 825 DI 10.1016/j.ccell.2014.10.012 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JN UT WOS:000346114000011 PM 25490447 ER PT J AU Deshpande, AJ Deshpande, A Sinha, AU Chen, L Chang, J Cihan, A Fazio, M Chen, CW Zhu, N Koche, R Dzhekieva, L Ibanez, G Dias, S Banka, D Krivtsov, A Luo, M Roeder, RG Bradner, JE Bernt, KM Armstrong, SA AF Deshpande, Aniruddha J. Deshpande, Anagha Sinha, Amit U. Chen, Liying Chang, Jenny Cihan, Ali Fazio, Maurizio Chen, Chun-wei Zhu, Nan Koche, Richard Dzhekieva, Liuda Ibanez, Gloria Dias, Stuart Banka, Deepti Krivtsov, Andrei Luo, Minkui Roeder, Robert G. Bradner, James E. Bernt, Kathrin M. Armstrong, Scott A. TI AF10 Regulates Progressive H3K79 Methylation and HOX Gene Expression in Diverse AML Subtypes SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; METHYLTRANSFERASE ACTIVITY; CHROMATIN MODIFICATIONS; STEM-CELLS; ADULT AML; DOT1L; EZH2; FUSION; INHIBITION; PROTEIN AB Homeotic (HOX) genes are dysregulated in multiple malignancies, including several AML subtypes. We demonstrate that H3K79 dimethylation (H3K79me2) is converted to monomethylation (H3K79me1) at HOX loci as hematopoietic cells mature, thus coinciding with a decrease in HOX gene expression. We show that H3K79 methyltransferase activity as well as H3K79me1-to-H3K79me2 conversion is regulated by the DOT1L cofactor AF10. AF10 inactivation reverses leukemia-associated epigenetic profiles, precludes abnormal HOXA gene expression, and impairs the transforming ability of MLL-AF9, MLL-AF6, and NUP98-NSD1 fusions-mechanistically distinct HOX-activating oncogenes. Furthermore, NUP98-NSD1-transformed cells are sensitive to small-molecule inhibition of DOT1L. Our findings demonstrate that pharmacological inhibition of the DOT1L/JAF10 complex may provide therapeutic benefits in an array of malignancies with abnormal HOXA gene expression. C1 [Deshpande, Aniruddha J.; Chen, Liying; Dias, Stuart; Banka, Deepti; Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Dzhekieva, Liuda; Luo, Minkui] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bernt, Kathrin M.] Univ Colorado, Dept Pediat, Aurora, CO 80045 USA. [Cihan, Ali; Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA. [Deshpande, Aniruddha J.; Deshpande, Anagha; Sinha, Amit U.; Chang, Jenny; Fazio, Maurizio; Chen, Chun-wei; Zhu, Nan; Koche, Richard; Krivtsov, Andrei; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA. [Deshpande, Aniruddha J.; Deshpande, Anagha; Sinha, Amit U.; Chang, Jenny; Fazio, Maurizio; Chen, Chun-wei; Zhu, Nan; Koche, Richard; Krivtsov, Andrei; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. RP Armstrong, SA (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM armstros@mskcc.org RI Bernt, Kathrin/L-1826-2016; OI Bernt, Kathrin/0000-0002-5400-0482; Krivtsov, Andrei/0000-0002-5511-1686 FU American Cancer Society; Leukemia and Lymphoma Society; Gabrielle's Angel Foundation; NCI [CA105423, CA140575, CA176745] FX We acknowledge Ronald Hendrickson, Yuko Fujiwara, and Stuart Orkin for valuable assistance with MS analysis and knockout mouse generation. This work was supported by the American Cancer Society; by the Leukemia and Lymphoma Society; by Gabrielle's Angel Foundation and by NCI Grants CA105423, CA140575, and CA176745 (to S.A.A.); and by the NCI K99 Award (to A.J.D.). S.A.A. is a consultant for Epizyme Inc. The protein complex purification work and the MS studies were supported by LLS SCOR Grant 7132-08 (to R.G.R.) and by NCI Cancer Center Support Grant P30 CA08748 (to M.S.K.C.C.). NR 39 TC 29 Z9 30 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 8 PY 2014 VL 26 IS 6 BP 896 EP 908 DI 10.1016/j.ccell.2014.10.009 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JN UT WOS:000346114000017 PM 25464900 ER PT J AU Christensen, CL Kwiatkowski, N Abrahanm, BJ Carretero, J Al-Shahrour, F Zhang, TH Chipumuro, E Herter-Sprie, GS Akbay, EA Altabef, A Zhang, JM Shimamura, T Capelletti, M Reibel, JB Cavanaugh, JD Gao, P Liu, Y Michaelsen, SR Poulsen, HS Aref, AR Barbie, DA Bradner, JE George, RE Gray, NS Young, RA Won, KK AF Christensen, Camilla L. Kwiatkowski, Nicholas Abrahanm, Brian J. Carretero, Julian Al-Shahrour, Fatima Zhang, Tinghu Chipumuro, Edmond Herter-Sprie, Grit S. Akbay, Esra A. Altabef, Abigail Zhang, Jianming Shimamura, Takeshi Capelletti, Marzia Reibel, Jakob B. Cavanaugh, Jillian D. Gao, Peng Liu, Yan Michaelsen, Signe R. Poulsen, Hans S. Aref, Amir R. Barbie, David A. Bradner, James E. George, Rani E. Gray, Nathanael S. Young, Richard A. Won, Kwok-Kin TI Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor SO CANCER CELL LA English DT Article ID CONDITIONAL MOUSE MODEL; NEUROENDOCRINE DIFFERENTIATION; SUPER-ENHANCERS; GENE-EXPRESSION; SELECTIVE-INHIBITION; TUMOR-CELLS; AMPLIFICATION; MYC; CARCINOMA; GENOME AB Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that THZ1 represents a prototype drug for tailored SCLC therapy. C1 [Christensen, Camilla L.; Herter-Sprie, Grit S.; Akbay, Esra A.; Altabef, Abigail; Capelletti, Marzia; Reibel, Jakob B.; Cavanaugh, Jillian D.; Gao, Peng; Liu, Yan; Aref, Amir R.; Barbie, David A.; Bradner, James E.; Won, Kwok-Kin] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kwiatkowski, Nicholas; Abrahanm, Brian J.; Young, Richard A.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Carretero, Julian] Univ Valencia, Fac Farm, Dept Fisiol, E-46010 Valencia, Spain. [Al-Shahrour, Fatima] Spanish Natl Canc Res Ctr, Translat Bioinformat Unit, Clin Res Programme, Madrid 28029, Spain. [Zhang, Tinghu; Zhang, Jianming; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Chipumuro, Edmond; George, Rani E.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Chipumuro, Edmond; George, Rani E.] Childrens Hosp, Boston, MA 02115 USA. [Shimamura, Takeshi] Loyola Univ Chicago, Dept Mol Pharmacol & Therapeut, Oncol Res Inst, Stritch Sch Med, Maywood, IL 60153 USA. [Michaelsen, Signe R.; Poulsen, Hans S.] Univ Copenhagen Hosp, Dept Radiat Biol, Finsen Ctr, DK-2100 Copenhagen, Denmark. [Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Gray, Nathanael S.; Won, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. RP Young, RA (reprint author), MIT, Whitehead Inst Biomed Res, 77 Massachusetts Ave, Cambridge, MA 02142 USA. EM young@wi.mit.edu; kwong1@partners.org RI Carretero, Julian/N-5214-2014; Young, Richard/F-6495-2012 OI Carretero, Julian/0000-0001-7269-8506; Young, Richard/0000-0001-8855-8647 FU Danish Cancer Society [R56-A3106-12-S2]; Deutsche Forschungsgemeinschaft [HE6897/1-1]; National Institutes of Health [CA122794, CA140594, CA163896, CA166480, CA154303, CA120964, R01 CA179483-01A1]; Thoracic Foundation; Susan Spooner Foundation; MIT-DFCI Bridge grant FX This work was supported by a Post-Doctoral Fellowship (R56-A3106-12-S2) from the Danish Cancer Society (C.L.C.), Deutsche Forschungsgemeinschaft (HE6897/1-1) (G.S.H.-S.), National Institutes of Health grants CA122794, CA140594, CA163896, CA166480, CA154303, and CA120964 (K.-K.W.), grant R01 CA179483-01A1 (N.S.G.), the Thoracic Foundation (K.-K.W.), the Susan Spooner Foundation (K.-K.W.), and an MIT-DFCI Bridge grant (K.-K.W., N.S.G., and RAY.). R.A.Y., N.S.G., and J.E.B. are founders and equity holders in Syros, which has licensed the CDK7 intellectual property from the DanaFarber Cancer Institute. N.K., T.Z., and N.S.G. are inventors on a patent application covering THZ1. NR 42 TC 43 Z9 43 U1 8 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 8 PY 2014 VL 26 IS 6 BP 909 EP 922 DI 10.1016/j.ccell.2014.10.019 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AW2JN UT WOS:000346114000018 PM 25490451 ER PT J AU Tardif, JC Ballantyne, CM Barter, P Dasseux, JL Fayad, ZA Guertin, MC Kastelein, JJP Keyserling, C Klepp, H Koenig, W L'Allier, PL Lesperance, J Luscher, TF Paolini, JF Tawakol, A Waters, DD AF Tardif, Jean-Claude Ballantyne, Christie M. Barter, Philip Dasseux, Jean-Louis Fayad, Zahi A. Guertin, Marie-Claude Kastelein, John J. P. Keyserling, Constance Klepp, Heather Koenig, Wolfgang L'Allier, Philippe L. Lesperance, Jacques Luescher, Thomas F. Paolini, John F. Tawakol, Ahmed Waters, David D. CA Can Hdl Infusions Significantly TI Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Atherosclerosis; Coronary disease; High-density lipoproteins; Clinical trial ID ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; INTERVENTION TRIAL; STATIN THERAPY; HIGH-RISK; CHOLESTEROL; PROGRESSION; PROBUCOL; ANGIOPLASTY; INHIBITOR AB Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL:http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001 & rank=2; Trial registration number: NCT01201837. C1 [Tardif, Jean-Claude; Guertin, Marie-Claude; L'Allier, Philippe L.; Lesperance, Jacques] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Tardif, Jean-Claude; Guertin, Marie-Claude; L'Allier, Philippe L.; Lesperance, Jacques] Univ Montreal, MHICC, Montreal, PQ H1T 1C8, Canada. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Barter, Philip] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Dasseux, Jean-Louis; Keyserling, Constance; Klepp, Heather; Paolini, John F.] Cerenis Therapeut Holding, Labege, France. [Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Luescher, Thomas F.] Univ Zurich Hosp, Univ Heart Ctr, CH-8091 Zurich, Switzerland. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Waters, David D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Tardif, JC (reprint author), Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM jean-claude.tardif@icm-mhi.org OI Brilakis, Emmanouil/0000-0001-9416-9701 NR 25 TC 64 Z9 65 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD DEC 7 PY 2014 VL 35 IS 46 BP 3277 EP 3286 DI 10.1093/eurheartj/ehu171 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW6WN UT WOS:000346406300016 PM 24780501 ER PT J AU Verburg, JM Seco, J AF Verburg, Joost M. Seco, Joao TI Proton range verification through prompt gamma-ray spectroscopy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE proton therapy; range verification; prompt gamma-ray detection ID CROSS-SECTIONS; TREATMENT SITE; THERAPY; EMISSION; DISTRIBUTIONS; NUCLEI; CARBON; PET; RADIOTHERAPY; BOMBARDMENT AB We present an experimental study of a novel method to verify the range of proton therapy beams. Differential cross sections were measured for 15 prompt gamma-ray lines from proton-nuclear interactions with C-12 and O-16 at proton energies up to 150 MeV. These cross sections were used to model discrete prompt gamma-ray emissions along proton pencil-beams. By fitting detected prompt gamma-ray counts to these models, we simultaneously determined the beam range and the oxygen and carbon concentration of the irradiated matter. The performance of the method was assessed in two phantoms with different elemental concentrations, using a small scale prototype detector. Based on five pencil-beams with different ranges delivering 5 x 108 protons and without prior knowledge of the elemental composition at the measurement point, the absolute range was determined with a standard deviation of 1.0-1.4 mm. Relative range shifts at the same dose level were detected with a standard deviation of 0.3-0.5 mm. The determined oxygen and carbon concentrations also agreed well with the actual values. These results show that quantitative prompt gamma-ray measurements enable knowledge of nuclear reaction cross sections to be used for precise proton range verification in the presence of tissue with an unknown composition. C1 [Verburg, Joost M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Verburg, Joost M.; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Verburg, Joost M.] Eindhoven Univ Technol, Sch Med Phys & Engn, NL-5600 MB Eindhoven, Netherlands. RP Verburg, JM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM jverburg@fas.harvard.edu FU Federal Share of program [C06-CA059267] FX The authors would like to thank M Testa PhD, for the helpful discussions and for his assistance with the experiments. We would like to thank E Cascio for designing the electronic circuit for beam monitoring and T Ruggieri for machining parts for the experimental setup. Also, thanks to B Clasie PhD, B Brett and J Flanz PhD, for their help with the cyclotron operations. This work was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. NR 30 TC 33 Z9 33 U1 1 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 7 PY 2014 VL 59 IS 23 BP 7089 EP 7106 DI 10.1088/0031-9155/59/23/7089 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AT9NN UT WOS:000345254000004 PM 25365362 ER PT J AU Edmund, JM Kjer, HM Van Leemput, K Hansen, RH Andersen, JAL Andreasen, D AF Edmund, Jens M. Kjer, Hans M. Van Leemput, Koen Hansen, Rasmus H. Andersen, Jon A. L. Andreasen, Daniel TI A voxel-based investigation for MRI-only radiotherapy of the brain using ultra short echo times SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE radiotherapy; MRI; imaging; MRI-only; pseudo CT; radiation therapy; substitute CT ID MAGNETIC-RESONANCE; ATTENUATION-CORRECTION; COMPUTED-TOMOGRAPHY; IMAGE REGISTRATION; RADIATION-THERAPY; QUALITY-ASSURANCE; ION RADIOTHERAPY; CT; PROSTATE; SEQUENCES AB Radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, so-called MRI-only RT, would remove the systematic registration error between MR and computed tomography (CT), and provide co-registered MRI for assessment of treatment response and adaptive RT. Electron densities, however, need to be assigned to the MRI images for dose calculation and patient setup based on digitally reconstructed radiographs (DRRs). Here, we investigate the geometric and dosimetric performance for a number of popular voxel-based methods to generate a so-called pseudo CT (pCT). Five patients receiving cranial irradiation, each containing a co-registered MRI and CT scan, were included. An ultra short echo time MRI sequence for bone visualization was used. Six methods were investigated for three popular types of voxel-based approaches; (1) threshold-based segmentation, (2) Bayesian segmentation and (3) statistical regression. Each approach contained two methods. Approach 1 used bulk density assignment of MRI voxels into air, soft tissue and bone based on logical masks and the transverse relaxation time T-2 of the bone. Approach 2 used similar bulk density assignments with Bayesian statistics including or excluding additional spatial information. Approach 3 used a statistical regression correlating MRI voxels with their corresponding CT voxels. A similar photon and proton treatment plan was generated for a target positioned between the nasal cavity and the brainstem for all patients. The CT agreement with the pCT of each method was quantified and compared with the other methods geometrically and dosimetrically using both a number of reported metrics and introducing some novel metrics. The best geometrical agreement with CT was obtained with the statistical regression methods which performed significantly better than the threshold and Bayesian segmentation methods (excluding spatial information). All methods agreed significantly better with CT than a reference water MRI comparison. The mean dosimetric deviation for photons and protons compared to the CT was about 2% and highest in the gradient dose region of the brainstem. Both the threshold based method and the statistical regression methods showed the highest dosimetrical agreement. Generation of pCTs using statistical regression seems to be the most promising candidate for MRI-only RT of the brain. Further, the total amount of different tissues needs to be taken into account for dosimetric considerations regardless of their correct geometrical position. C1 [Edmund, Jens M.; Andersen, Jon A. L.; Andreasen, Daniel] Copenhagen Univ Hosp, Dept Oncol, Radiotherapy Res Unit, Herlev, Denmark. [Kjer, Hans M.; Van Leemput, Koen; Andreasen, Daniel] Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark. [Van Leemput, Koen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Hansen, Rasmus H.] Copenhagen Univ Hosp, Dept Radiol, Herlev, Denmark. RP Edmund, JM (reprint author), Copenhagen Univ Hosp, Dept Oncol, Radiotherapy Res Unit, Herlev, Denmark. EM jens.edmund@regionh.dk RI Van Leemput, Koen/A-9197-2009; OI Van Leemput, Koen/0000-0001-6466-5309; Edmund, Jens Morgenthaler/0000-0001-5831-6209 FU Varian Medical Systems, Inc. FX This work was supported by a research grant from Varian Medical Systems, Inc. NR 54 TC 14 Z9 14 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD DEC 7 PY 2014 VL 59 IS 23 BP 7501 EP 7519 DI 10.1088/0031-9155/59/23/7501 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AT9NN UT WOS:000345254000026 PM 25393873 ER PT J AU Advani, AS Stein, AS Kantarjian, HM Shustov, AR DeAngelo, DJ Ananthakrishnan, R Liau, K Vandendries, E Stock, W AF Advani, Anjali S. Stein, Anthony S. Kantarjian, Hagop M. Shustov, Andrei R. DeAngelo, Daniel J. Ananthakrishnan, Revathi Liau, Katherine Vandendries, Erik Stock, Wendy TI A Phase II Study of Weekly Inotuzumab Ozogamicin (InO) in Adult Patients with CD22-Positive Acute Lymphoblastic Leukemia (ALL) in Second or Later Salvage SO BLOOD LA English DT Meeting Abstract C1 [Advani, Anjali S.] Cleveland Clin, Cleveland, OH 44106 USA. [Stein, Anthony S.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shustov, Andrei R.] Univ Washington, Seattle, WA 98195 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ananthakrishnan, Revathi; Liau, Katherine; Vandendries, Erik] Pfizer Inc, Cambridge, MA USA. [Stock, Wendy] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707062 ER PT J AU Aftab, BT Anderson, DJ Le Moigne, R Djakovic, S Dhimolea, E Murnane, M King, E Rice, J Wong, S Kumar, B Valle, E Menon, MK von Soly, SK Wang, JH Yao, B Soriano, F Kampmann, M Alcost-Alvear, D Chesi, M Bergsagel, L Yakes, FM Zhou, HJ Wustrow, D Martin, TG Wolf, JL Mitsiades, CS Rolfe, M AF Aftab, Blake T. Anderson, Daniel J. Le Moigne, Ronan Djakovic, Stevan Dhimolea, Eugen Murnane, Megan King, Emily Rice, Julie Wong, Steve Kumar, Brajesh Valle, Eduardo Menon, Mary-Kamala von Soly, Szerenke Kiss Wang, Jinhai Yao, Bing Soriano, Ferdie Kampmann, Martin Alcost-Alvear, Diego Chesi, Marta Bergsagel, Leif Yakes, F. Michael Zhou, Han-Jie Wustrow, David Martin, Thomas G. Wolf, Jeffrey L. Mitsiades, Constantine S. Rolfe, Mark TI Pre-Clinical Activity of the Novel, First-in-Class p97 Inhibitor, CB-5083, in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Aftab, Blake T.; Murnane, Megan; Kampmann, Martin; Alcost-Alvear, Diego; Martin, Thomas G.; Wolf, Jeffrey L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Anderson, Daniel J.; Le Moigne, Ronan; Djakovic, Stevan; Rice, Julie; Wong, Steve; Kumar, Brajesh; Valle, Eduardo; Menon, Mary-Kamala; von Soly, Szerenke Kiss; Wang, Jinhai; Yao, Bing; Soriano, Ferdie; Yakes, F. Michael; Zhou, Han-Jie; Wustrow, David; Rolfe, Mark] Cleave Biosci, Burlingame, CA USA. [Dhimolea, Eugen; King, Emily; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chesi, Marta; Bergsagel, Leif] Mayo Clin Scottsdale, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700049 ER PT J AU An, G Jiang, H Acharya, C Zhong, MY Cai, T Yang, G Song, ZL Theilhaber, J Adrian, F Tai, YT Anderson, KC AF An, Gang Jiang, Hua Acharya, Chirag Zhong, Mike Y. Cai, Ti Yang, Guang Song, Zhili Theilhaber, Joachim Adrian, Francisco Tai, Yu-Tzu Anderson, Kenneth C. TI SAR 650984, a Therapeutic Anti-CD38 Monoclonal Antibody, Blocks CD38-CD31 Interaction in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [An, Gang; Jiang, Hua; Acharya, Chirag; Zhong, Mike Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cai, Ti; Yang, Guang; Song, Zhili; Theilhaber, Joachim; Adrian, Francisco] Sanofi Oncol, Cambridge, MA USA. [Tai, Yu-Tzu] Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Tai, Yu-Tzu] LeBow Inst Myeloma Therapeut, Boston, MA USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704074 ER PT J AU Barnes, JA Redd, RA Jacobsen, ED Fisher, DC Freedman, AS Hochberg, EP Takvorian, T Neuberg, D Abramson, JS AF Barnes, Jeffrey A. Redd, Robert Allyn Jacobsen, Eric D. Fisher, David C. Freedman, Arnold S. Hochberg, Ephraim P. Takvorian, Tak Neuberg, Donna Abramson, Jeremy S. TI Panobinostat in Combination with Rituximab in Heavily Pretreated Diffuse Large B-Cell Lymphoma: Results of a Phase II Study SO BLOOD LA English DT Meeting Abstract C1 [Barnes, Jeffrey A.; Hochberg, Ephraim P.; Takvorian, Tak; Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Redd, Robert Allyn; Jacobsen, Eric D.; Fisher, David C.; Freedman, Arnold S.; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706020 ER PT J AU Beltran, BE Castro, D Chavez, JC Sotomayor, EM Castillo, JJ AF Beltran, Brady E. Castro, Denisse Chavez, Julio C. Sotomayor, Eduardo M. Castillo, Jorge J. TI The Prognostic Value of the Neutrophil to Lymphocyte Ratio in 209 Patients with Peripheral T-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Beltran, Brady E.; Castro, Denisse] Hosp Nacl Edgardo Rebagliati Martins, Lima, Peru. [Chavez, Julio C.; Sotomayor, Eduardo M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708181 ER PT J AU Castillo, JJ Olszewski, AJ Kanan, S Meid, K Hunter, Z Treon, SP AF Castillo, Jorge J. Olszewski, Adam J. Kanan, Sandra Meid, Kirsten Hunter, Zachary Treon, Steven P. TI Incidence and Survival Outcomes of Secondary Malignancies Among Survivors of Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract C1 [Castillo, Jorge J.; Kanan, Sandra; Meid, Kirsten; Hunter, Zachary; Treon, Steven P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Olszewski, Adam J.] Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704066 ER PT J AU Chapuy, B Roemer, MGM Tan, YX Stewart, C Zhang, LY Dunford, AJ Jordanova, ES Feuerhake, F Illerhaus, G Gusenleitner, D Linden, E Sun, HH Aono, M Freeman, GJ Golub, TR Getz, G Rodig, SJ de Jong, D Monti, S Shipp, MA AF Chapuy, Bjoern Roemer, Margaretha G. M. Tan, Yuxiang Stewart, Chip Zhang, Liye Dunford, Andrew J. Jordanova, Ekaterina S. Feuerhake, Friedrich Illerhaus, Gerald Gusenleitner, Daniel Linden, Erica Sun, Heather H. Aono, Miyuki Freeman, Gordon J. Golub, Todd R. Getz, Gad Rodig, Scott J. de Jong, Daphne Monti, Stefano Shipp, Margaret A. TI Actionable Genetic Features of Primary Testicular and Primary Central Nervous System Lymphomas SO BLOOD LA English DT Meeting Abstract C1 [Chapuy, Bjoern; Roemer, Margaretha G. M.; Aono, Miyuki; Freeman, Gordon J.; Golub, Todd R.; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roemer, Margaretha G. M.; Jordanova, Ekaterina S.; de Jong, Daphne] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Tan, Yuxiang; Zhang, Liye; Gusenleitner, Daniel; Monti, Stefano] Boston Univ, Sch Med, Boston, MA 02118 USA. [Stewart, Chip; Dunford, Andrew J.; Golub, Todd R.] Broad Inst, Cambridge, MA USA. [Feuerhake, Friedrich] Hannover Med Sch, Hannover, Germany. [Illerhaus, Gerald] Univ Hosp Freiburg, Freiburg, Germany. [Linden, Erica] MGH North Shore Canc Ctr, Danvers, MA USA. [Sun, Heather H.; Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Getz, Gad] Broad Inst Harvard & MIT, Cambridge, MA USA. [Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704021 ER PT J AU Chen, YB Shuli, L Andrew, LA Connolly, C Del Rio, C Valles, B Curtis, M Ballen, KK Cutler, CS Dey, BR El-Jawahri, A Fathi, AT Ho, VT Joyce, A McAfee, SL Rudek, MA Rajkhowa, T Verselis, S Antin, JH Spitzer, TR Levis, M Soiffer, RJ AF Chen, Yi-Bin Shuli, Li Andrew, Lane A. Connolly, Christine Del Rio, Candice Valles, Betsy Curtis, Morgan Ballen, Karen K. Cutler, Corey S. Dey, Bimalangshu R. El-Jawahri, Areej Fathi, Amir T. Ho, Vincent T. Joyce, Amy McAfee, Steven L. Rudek, Michelle A. Rajkhowa, Trivikram Verselis, Sigitas Antin, Joseph H. Spitzer, Thomas R. Levis, Mark Soiffer, Robert J. TI Phase I Trial of Maintenance Sorafenib after Allogeneic Hematopoietic Stem Cell Transplantation for Patients with FLT3-ITD AML SO BLOOD LA English DT Meeting Abstract C1 [Chen, Yi-Bin; Ballen, Karen K.; Dey, Bimalangshu R.; McAfee, Steven L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Shuli, Li; Andrew, Lane A.; Cutler, Corey S.; Ho, Vincent T.; Joyce, Amy; Verselis, Sigitas; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Connolly, Christine; Del Rio, Candice; Valles, Betsy; Curtis, Morgan; Fathi, Amir T.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [El-Jawahri, Areej] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rudek, Michelle A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Rajkhowa, Trivikram] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Levis, Mark] Johns Hopkins Univ, Kimmel Canc Ctr, Baltimore, MD USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700218 ER PT J AU Ciurea, SO Zhang, MJ Bacigalupo, A Bashey, A Appelbaum, FR Antin, JH Chen, JF Devine, SM Fowler, DH Nakamura, R Perales, MA Pingali, SR Porter, DL Ringden, O Rocha, V Vij, R Weisdorf, DJ Champlin, RE Fuchs, EJ Eapen, M AF Ciurea, Stefan O. Zhang, Mei-Jie Bacigalupo, Andrea Bashey, Asad Appelbaum, Frederick R. Antin, Joseph H. Chen, Junfang Devine, Steven M. Fowler, Daniel H. Nakamura, Ryotaro Perales, Miguel-Angel Pingali, Sai Ravi Porter, David L. Ringden, Olle Rocha, Vanderson Vij, Ravi Weisdorf, Daniel J. Champlin, Richard E. Fuchs, Ephraim J. Eapen, Mary TI Survival after T-Cell Replete Haplo-Identical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor Transplant for Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Ciurea, Stefan O.; Pingali, Sai Ravi; Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhang, Mei-Jie; Chen, Junfang; Eapen, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Bacigalupo, Andrea] IRCCS AOU San Martino IST, Genoa, Italy. [Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Devine, Steven M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Fowler, Daniel H.] NCI, Bethesda, MD 20892 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA USA. [Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Porter, David L.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ringden, Olle] Karolinska Univ Hosp Huddinge, Stockholm, Sweden. [Rocha, Vanderson] Churchill Hosp, Oxford OX3 7LJ, England. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Fuchs, Ephraim J.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708145 ER PT J AU Cleynen, A Szalat, R Samur, MK Rashid, N Parmigiani, G Munshi, NC Avet-Loiseau, H AF Cleynen, Alice Szalat, Raphael Samur, Mehmet Kemal Rashid, Naim Parmigiani, Giovanni Munshi, Nikhil C. Avet-Loiseau, Herve TI Frequent Igh Fusion Transcripts with Clinical Impact in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Cleynen, Alice; Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cleynen, Alice; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Szalat, Raphael] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Szalat, Raphael] Hop St Louis, Paris, France. [Samur, Mehmet Kemal; Rashid, Naim] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Avet-Loiseau, Herve] Univ Hosp Toulouse, Toulouse, France. [Avet-Loiseau, Herve] CHU Rangueil, F-31054 Toulouse, France. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705057 ER PT J AU Corbacioglu, S Carreras, E Mohty, M Pagliuca, A Ballabio, M Hume, RL Bandiera, V Finetto, G Richardson, PG AF Corbacioglu, Selim Carreras, Enric Mohty, Mohamad Pagliuca, Antonio Ballabio, Maria Hume, Robin L. Bandiera, Valeria Finetto, Giorgia Richardson, Paul G. TI Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease: An Update from the International Compassionate Use Program in 710 Patients SO BLOOD LA English DT Meeting Abstract C1 [Corbacioglu, Selim] Univ Regensburg, Childrens Hosp Regensburg, D-93053 Regensburg, Germany. [Carreras, Enric] Hosp Clin Barcelona, Barcelona, Spain. [Mohty, Mohamad] Hosp St Antoine, Paris, France. [Pagliuca, Antonio] Kings Coll Hosp NHS Fdn Trust, London, England. [Ballabio, Maria; Bandiera, Valeria; Finetto, Giorgia] Gentium SpA, Villa Guardia, Italy. [Hume, Robin L.] Jazz Pharmaceut Inc, Palo Alto, CA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700214 ER PT J AU Cottini, F Hideshima, T Suzuki, R Richardson, PG Anderson, KC Tonon, G AF Cottini, Francesca Hideshima, Teru Suzuki, Rikio Richardson, Paul G. Anderson, Kenneth C. Tonon, Giovanni TI Synthetic Lethal Approaches to Exploit Replicative Stress in Aggressive Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Cottini, Francesca; Hideshima, Teru; Suzuki, Rikio; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706184 ER PT J AU Danis, E Yamauchi, T Echanique, K Haladyna, J Xie, HF Zhu, N Riedel, S Bernt, KM Orkin, SH Armstrong, SA Neff, T AF Danis, Etienne Yamauchi, Taylor Echanique, Kristen Haladyna, Jessica Xie, Huafeng Zhu, Nan Riedel, Simone Bernt, Kathrin M. Orkin, Stuart H. Armstrong, Scott A. Neff, Tobias TI Context Dependent Role of Polycomb Repressive Complex 2 in Acute Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Danis, Etienne; Yamauchi, Taylor; Echanique, Kristen; Haladyna, Jessica; Riedel, Simone; Bernt, Kathrin M.; Neff, Tobias] Childrens Hosp Colorado, Aurora, CO USA. [Xie, Huafeng; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Zhu, Nan; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705024 ER PT J AU Das, DS Tian, Z Ray, A Ravillah, D Song, Y Richardson, PG Oronsky, B Scicinski, J Chauhan, D Anderson, KC AF Das, Deepika Sharma Tian, Ze Ray, Arghya Ravillah, Durgadevi Song, Yan Richardson, Paul G. Oronsky, Bryan Scicinski, Jan Chauhan, Dharminder Anderson, Kenneth C. TI Anti-Myeloma Activity of a Novel Free Radical Inducer Rrx-001 SO BLOOD LA English DT Meeting Abstract C1 [Das, Deepika Sharma; Tian, Ze; Ray, Arghya; Ravillah, Durgadevi; Song, Yan; Richardson, Paul G.; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Das, Deepika Sharma; Tian, Ze; Ray, Arghya; Ravillah, Durgadevi; Song, Yan; Richardson, Paul G.; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Oronsky, Bryan; Scicinski, Jan] RadioRx Inc, Mountain View, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706148 ER PT J AU Davids, MS Kim, HT Costello, CL Avigan, D Chen, YB Armand, P Alyea, EP Hedlund, J McSweeney, PA Liguori, R Ritz, J Ball, ED Bashey, A Soiffer, RJ AF Davids, Matthew S. Kim, Haesook T. Costello, Caitlin L. Avigan, David Chen, Yi-Bin Armand, Philippe Alyea, Edwin P. Hedlund, Jacquelyn McSweeney, Peter A. Liguori, Rebecca Ritz, Jerome Ball, Edward D. Bashey, Asad Soiffer, Robert J. TI A Multicenter Phase I Study of CTLA-4 Blockade with Ipilimumab for Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation SO BLOOD LA English DT Meeting Abstract C1 [Davids, Matthew S.; Kim, Haesook T.; Armand, Philippe; Alyea, Edwin P.; Liguori, Rebecca; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Costello, Caitlin L.; Ball, Edward D.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hedlund, Jacquelyn] New England Canc Specialisits, Scarborough, ME USA. [McSweeney, Peter A.] Rocky Mt Canc Ctr, Denver, CO USA. [Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707213 ER PT J AU Davids, MS Deng, J Ryan, J Fernandes, SM Brown, JR Letai, AG AF Davids, Matthew S. Deng, Jing Ryan, Jeremy Fernandes, Stacey M. Brown, Jennifer R. Letai, Anthony G. TI Mitochondrial Apoptotic Priming Is Associated with Clinical Response to the Bcl-2 Antagonist ABT-199 in Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Davids, Matthew S.; Deng, Jing; Ryan, Jeremy; Fernandes, Stacey M.; Brown, Jennifer R.; Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701094 ER PT J AU Deveau, A Forrester, AM Coombs, AJ Wagner, GS Grabher, C Chute, I Leger, D Lewis, S Mingay, M Hirst, M Look, AT Berman, JN AF Deveau, Adam Forrester, Alexander Michael Coombs, Andrew J. Wagner, Gretchen S. Grabher, Clemens Chute, Ian Leger, Daniel Lewis, Stephen Mingay, Matthew Hirst, Martin Look, A. Thomas Berman, Jason N. TI Preclinical Determination of the Efficacy of Epigenetic Therapy in High Risk Myeloid Disease Using the Zebrafish Model SO BLOOD LA English DT Meeting Abstract C1 [Deveau, Adam; Coombs, Andrew J.; Wagner, Gretchen S.] Dalhousie Univ, Halifax, NS, Canada. [Forrester, Alexander Michael] McMaster Univ, Hamilton, ON, Canada. [Grabher, Clemens] Karlsruhe Inst Technol, D-76021 Karlsruhe, Germany. [Chute, Ian; Leger, Daniel] Atlantic Canc Res Inst, Moncton, NB, Canada. [Lewis, Stephen] Univ Moncton, Moncton, NB E1A 3E9, Canada. [Mingay, Matthew; Hirst, Martin] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Hirst, Martin] BC Canc Agcy, Vancouver, BC, Canada. [Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berman, Jason N.] Dalhousie Univ, IWK Hlth Ctr, Halifax, NS, Canada. RI Hirst, Martin/B-7684-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700006 ER PT J AU Dhimolea, E King, E Sheffer, M Hu, YG Sarkar, S Murnane, M Bariteau, MA Aftab, BT Mitsiades, CS AF Dhimolea, Eugen King, Emily Sheffer, Michal Hu, Yiguo Sarkar, Subhashis Murnane, Megan Bariteau, Megan A. Aftab, Blake T. Mitsiades, Constantine S. TI Functional Mapping of Multiple Myeloma Kinome Using a Small Molecule Inhibitor Library SO BLOOD LA English DT Meeting Abstract C1 [Dhimolea, Eugen; King, Emily; Sheffer, Michal; Hu, Yiguo; Sarkar, Subhashis; Bariteau, Megan A.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Murnane, Megan; Aftab, Blake T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702035 ER PT J AU Dohner, H Seymour, JF Butrym, A Wierzbowska, A Selleslag, D Lang, JH Cavenagh, JD Kumar, R Schuh, AC Candoni, A Recher, C Sandhu, I del Castillo, TB Al-Ali, HK Martinelli, G Falantes, J Stone, RM Minden, MD McIntyre, H Songer, S Lucy, LM Beach, CL Dombret, H AF Doehner, Hartmut Seymour, John F. Butrym, Aleksandra Wierzbowska, Agnieszka Selleslag, Dominik Lang, Jun Ho Cavenagh, James D. Kumar, Rajat Schuh, Andre C. Candoni, Anna Recher, Christian Sandhu, Irwindeep Bernal del Castillo, Teresa Al-Ali, Haifa Kathrin Martinelli, Giovanni Falantes, Jose Stone, Richard M. Minden, Mark D. McIntyre, Heidi Songer, Stephen Lucy, Lela M. Beach, C. L. Dombret, Herve TI Overall Survival in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with > 30% Bone Marrow Blasts Treated with Azacitidine By Cytogenetic Risk Status: Results of the AZA-AML-001 Study SO BLOOD LA English DT Meeting Abstract C1 [Doehner, Hartmut] Univ Ulm Klinikum, Ulm, Germany. [Seymour, John F.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Butrym, Aleksandra] Wroclaw Med Univ, Wroclaw, Poland. [Wierzbowska, Agnieszka] Med Univ Lodz, Lodz, Poland. [Selleslag, Dominik] AZ Sint Jan Brugge Oostende, Brugge, Belgium. [Lang, Jun Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Cavenagh, James D.] St Bartholomews Hosp, London, England. [Kumar, Rajat] CancerCare Manitoba, Winnipeg, MB, Canada. [Schuh, Andre C.; Minden, Mark D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Candoni, Anna] Azienda Osped Univ S Maria della Misericordia Udi, Udine, Italy. [Recher, Christian] Inst Univ Canc Toulouse Oncopole, Toulouse, France. [Sandhu, Irwindeep] Univ Alberta, Edmonton, AB, Canada. [Bernal del Castillo, Teresa] Univ Oviedo, Hosp Cent Asturias, E-33080 Oviedo, Spain. [Al-Ali, Haifa Kathrin] Univ Hosp Leipzig, Leipzig, Germany. [Martinelli, Giovanni] Inst Hematol & Med Oncol L&A Seragnoli, Bologna, Italy. [Falantes, Jose] Hosp Univ Virgen del Rocio, Inst BioMed Sevilla, Seville, Spain. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McIntyre, Heidi; Songer, Stephen; Lucy, Lela M.; Beach, C. L.] Gelgene Corp, Summit, NJ USA. [Dombret, Herve] Hop St Louis, Paris 10, France. RI Wierzbowska, Agnieszka/S-9449-2016 NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705065 ER PT J AU Donato, J Campigotto, F Coletti, E Neuberg, D Weber, G Zwicker, JI AF Donato, Jessica Campigotto, Federico Coletti, Erika Neuberg, Donna Weber, Griffin Zwicker, Jeffrey I. TI Risk of Intracranial Hemorrhage Associated with Enoxaparin Administration in Patients with Brain Metastasis SO BLOOD LA English DT Meeting Abstract C1 [Donato, Jessica; Coletti, Erika; Weber, Griffin; Zwicker, Jeffrey I.] Harvard Univ, Sch Med, Boston, MA USA. [Campigotto, Federico] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700180 ER PT J AU Dunleavy, K Fanale, M LaCasce, A Noy, A Caimi, P Parekh, S Hayslip, JW Jagadeesh, D Lord, RS Lechowicz, MJ Gaur, R Lucas, A Staudt, LM Steinberg, SM Kahl, B Friedberg, JW Little, RF Bartlett, NL Wilson, WH AF Dunleavy, Kieron Fanale, Michelle LaCasce, Ann Noy, Ariela Caimi, Paolo Parekh, Samir Hayslip, John W. Jagadeesh, Deepa Lord, Raymond S. Lechowicz, Mary J. Gaur, Rakesh Lucas, Andrea Staudt, Louis M. Steinberg, Seth M. Kahl, Brad Friedberg, Jonathan W. Little, Richard F. Bartlett, Nancy L. Wilson, Wyndham H. TI Preliminary Report of a Multicenter Prospective Phase II Study of DA-EPOCH-R in MYC-Rearranged Aggressive B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Dunleavy, Kieron; Lucas, Andrea; Staudt, Louis M.; Steinberg, Seth M.; Little, Richard F.; Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. [Fanale, Michelle] Univ Texas, Houston, TX USA. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Noy, Ariela] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Caimi, Paolo] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Parekh, Samir] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Hayslip, John W.] Univ Kentucky, Lexington, KY USA. [Jagadeesh, Deepa] Cleveland Clin, Cleveland, OH 44106 USA. [Lord, Raymond S.] West Michigan Canc Ctr, Kalamazoo, MI USA. [Lechowicz, Mary J.] Emory Univ, Sch Med, Atlanta, GA USA. [Gaur, Rakesh] Kansas City CCOP, Kansas City, KS USA. [Kahl, Brad] UW Carbone Canc Ctr, Madison, WI USA. [Friedberg, Jonathan W.] Univ Rochester, Rochester, NY USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 3 U2 10 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707201 ER PT J AU Fathi, AT Chen, R Trippett, TM O'Brien, MM DeAngelo, DJ Shah, BD Cooper, TM Foran, JM Hale, GA Pressey, J Silverman, LB Tibes, R Kim, S Albertson, TM Sandalic, L Zhao, BT Borate, U AF Fathi, Amir T. Chen, Robert Trippett, Tanya M. O'Brien, Maureen M. DeAngelo, Daniel J. Shah, Bijal D. Cooper, Todd M. Foran, James M. Hale, Gregory A. Pressey, Joseph Silverman, Lewis B. Tibes, Raoul Kim, Stella Albertson, Tina M. Sandalic, Larissa Zhao, Baiteng Borate, Uma TI Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Acute Leukemia and Highly Aggressive Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Chen, Robert] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Trippett, Tanya M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [O'Brien, Maureen M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shah, Bijal D.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Cooper, Todd M.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA. [Foran, James M.] Mayo Clin, Jacksonville, FL 32224 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Pressey, Joseph] Univ Alabama Birmingham, Childrens Hosp Alabama, Birmingham, AL USA. [Silverman, Lewis B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Tibes, Raoul] Mayo Clin Arizona, Scottsdale, AZ USA. [Kim, Stella] Cizik Eye Clin, Houston, TX USA. [Albertson, Tina M.; Sandalic, Larissa; Zhao, Baiteng] Seattle Genet Inc, Bothell, WA USA. [Borate, Uma] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700139 ER PT J AU Freytes, CO Callander, NS Goodman, SA Luo, SH Toro, JJ Carson, KR AF Freytes, Cesar O. Callander, Natalie S. Goodman, Stacey A. Luo, Suhong Toro, Juan J. Carson, Kenneth R. TI The Veterans Health Administration Provides Equal Access to Autologous Hematopoietic Stem Cell Transplantation for Patients with Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Freytes, Cesar O.; Toro, Juan J.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Freytes, Cesar O.; Toro, Juan J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Callander, Natalie S.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Callander, Natalie S.] Univ Wisconsin, Madison, WI USA. [Goodman, Stacey A.] Nashville VA Med Ctr, Nashville, TN USA. [Goodman, Stacey A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Luo, Suhong; Carson, Kenneth R.] St Louis VA Med Ctr, Res Serv, St Louis, MO USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706152 ER PT J AU Fulciniti, M Bhasin, M Samur, MK Bandi, RL Rashid, N Jaime, R Lin, C Anderson, KC Parmigiani, G Bradner, JE Munshi, NC AF Fulciniti, Mariateresa Bhasin, Manoj Samur, Mehmet Kemal Bandi, Rajya Lakshmi Rashid, Naim Jaime, Reyes Lin, Charles Anderson, Kenneth C. Parmigiani, Giovanni Bradner, James E. Munshi, Nikhil C. TI Functional and Clinical Relevance of Splicing Factor SRSF1 in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract C1 [Fulciniti, Mariateresa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bhasin, Manoj] Beth Israel, Boston, MA USA. [Samur, Mehmet Kemal; Bandi, Rajya Lakshmi; Jaime, Reyes; Lin, Charles; Parmigiani, Giovanni; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rashid, Naim] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708006 ER PT J AU Fulciniti, M Bandi, RL Amodio, N Cagnetta, A Senapedis, W Baloglu, E Anderson, KC Munshi, NC AF Fulciniti, Mariateresa Bandi, Rajya Lakshmi Amodio, Nicola Cagnetta, Antonia Senapedis, William Baloglu, Erkan Anderson, Kenneth C. Munshi, Nikhil C. TI Cytoskeleton Regulator PAK4 Plays a Role in Growth and Survival of Myeloma with a Potential Therapeutic Intervention Using PAK4 Allosteric Modulators (PAMs) SO BLOOD LA English DT Meeting Abstract C1 [Fulciniti, Mariateresa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bandi, Rajya Lakshmi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Amodio, Nicola] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Cagnetta, Antonia; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Cagnetta, Antonia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Senapedis, William] Karyopharm Therapeut, Boston, MA USA. [Baloglu, Erkan] Karyopharm Therapeut Inc, Newton, MA USA. [Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700017 ER PT J AU Garbati, MR Rathbun, RK Yates, JE Yang, WJ Bagby, GC AF Garbati, Michael R. Rathbun, R. K. Yates, Jane E. Yang, Wenjin Bagby, Grover C. TI ALDH1A1 Dysfunction in FA-Deficient Macrophages Contributes to Aberrant Activation of the Innate Immune Response SO BLOOD LA English DT Meeting Abstract C1 [Garbati, Michael R.; Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. [Rathbun, R. K.; Yates, Jane E.; Bagby, Grover C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Yang, Wenjin] Aldea Pharmaceut, Redwood City, CA USA. [Bagby, Grover C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707171 ER PT J AU Garcia-Manero, G Fenaux, P Al-Kali, A Baer, MR Sekeres, MA Roboz, GJ Gaidano, G Scott, BL Greenberg, PL Platzbecker, U Steensma, DP Kambhampati, S Kreuzer, KA Godley, LA Collins, R Atallah, E Wilhelm, F Wilhelm, IE Azarnia, N Maniar, M Silverman, LR AF Garcia-Manero, Guillermo Fenaux, Pierre Al-Kali, Aref Baer, Maria R. Sekeres, Mikkael A. Roboz, Gail J. Gaidano, Gianluca Scott, Bart L. Greenberg, Peter L. Platzbecker, Uwe Steensma, David P. Kambhampati, Suman Kreuzer, Karl-Anton Godley, Lucy A. Collins, Robert Atallah, Ehab Wilhelm, Francois Wilhelm, Isabelle E. Azarnia, Nozar Maniar, Manoj Silverman, Lewis R. TI Overall Survival and Subgroup Analysis from a Randomized Phase III Study of Intravenous Rigosertib Versus Best Supportive Care (BSC) in Patients (pts) with Higher-Risk Myelodysplastic Syndrome (HR-MDS) after Failure of Hypomethylating Agents (HMAs) SO BLOOD LA English DT Meeting Abstract C1 [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fenaux, Pierre] Univ Paris 07, Hop St Louis, Paris, France. [Al-Kali, Aref] Mayo Clin, Rochester, MN USA. [Baer, Maria R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Roboz, Gail J.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Gaidano, Gianluca] Amedeo Avogadro Univ Eastern Piedmont, Novara, Italy. [Scott, Bart L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Greenberg, Peter L.] Stanford Univ, Stanford, CA 94305 USA. [Platzbecker, Uwe] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kambhampati, Suman] Univ Kansas, Ctr Canc, Kansas City, KS USA. [Kreuzer, Karl-Anton] Univ Cologne, D-50931 Cologne, Germany. [Godley, Lucy A.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Collins, Robert] Univ Texas Southwestern, Dallas, TX USA. [Atallah, Ehab] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wilhelm, Francois; Wilhelm, Isabelle E.; Azarnia, Nozar; Maniar, Manoj] Onconova Therapeut Inc, Newtown, PA USA. [Silverman, Lewis R.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700138 ER PT J AU Gardie, B Couve, S Ladroue, C Laine, E Mahtouk, K Guegan, J Gad, S Le Jeune, H Lecomte, B Pages, JC Benusiglio, P Bressac-de Paillerets, B Feunteun, J Dessen, P Hermouet, S Tchertanov, L Mole, DR Kaelin, WG Ratcliffe, PJ Richard, S AF Gardie, Betty Couve, Sophie Ladroue, Charline Laine, Elodie Mahtouk, Karene Guegan, Justine Gad, Sophie Le Jeune, Helene Lecomte, Bernard Pages, Jean-Christophe Benusiglio, Patrick Bressac-de Paillerets, Brigitte Feunteun, Jean Dessen, Philippe Hermouet, Sylvie Tchertanov, Luba Mole, David R. Kaelin, William G. Ratcliffe, Peter J. Richard, Stephane TI A Comprehensive Study of the VHL-R200W Chuvash Polycythemia Mutation Reveals a Gradual Dysregulation of the Hypoxia Pathway in Oncogenesis SO BLOOD LA English DT Meeting Abstract C1 [Gardie, Betty; Couve, Sophie; Ladroue, Charline; Mahtouk, Karene; Gad, Sophie; Le Jeune, Helene; Richard, Stephane] Ecole Prat Hautes Etud, Villejuif, France. [Gardie, Betty; Hermouet, Sylvie] CRCNA, UMR INSERM U892, CNRS 6299, Nantes, France. [Gardie, Betty; Couve, Sophie; Ladroue, Charline; Mahtouk, Karene; Gad, Sophie; Le Jeune, Helene; Richard, Stephane] Gustave Roussy Canc Campus, INSERM U753, Villejuif, France. [Laine, Elodie; Tchertanov, Luba] LBPA, Cachan, France. [Guegan, Justine; Dessen, Philippe] Gustave Roussy Canc Campus, Plate Forme Genom, Villejuif, France. [Pages, Jean-Christophe] Univ Tours, Tours, France. [Benusiglio, Patrick] Gustave Roussy Canc Campus, Dept Med Oncol, Villejuif, France. [Benusiglio, Patrick; Richard, Stephane] Ctr Expert Natl Canc Rares INCa PREDIR, Le Kremlin Bicetre, France. [Benusiglio, Patrick; Richard, Stephane] Reseau Natl INCa Malad VHL & Predisposit Canc Rei, Le Kremlin Bicetre, France. [Bressac-de Paillerets, Brigitte] Gustave Roussy Canc Campus, Serv Genet, Villejuif, France. [Feunteun, Jean] Gustave Roussy Canc Campus, Lab Stabil Genet & Oncogenese, Villejuif, France. [Tchertanov, Luba] CNRS ENS Cachan, Cachan, France. [Mole, David R.] Univ Oxford, Oxford, England. [Kaelin, William G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ratcliffe, Peter J.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705020 ER PT J AU Gavillet, M Martinod, K Wagner, DD Williams, DA AF Gavillet, Mathilde Martinod, Kimberly Wagner, Denisa D. Williams, David A. TI The Role of Rac and Pak in Neutrophil Histone Hypercitrullination and Neutrophil Extracellular Traps Formation SO BLOOD LA English DT Meeting Abstract C1 [Gavillet, Mathilde; Wagner, Denisa D.; Williams, David A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Martinod, Kimberly] Harvard Univ, Sch Med, Div Med Sci, Grad Program Immunol, Boston, MA USA. [Martinod, Kimberly; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wagner, Denisa D.; Williams, David A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706174 ER PT J AU Ghamari, A Jaensch, E Giadone, R Akie, TE Xu, J Bauer, D Orkin, SH Cantor, AB AF Ghamari, Alireza Jaensch, Elizabeth Giadone, Richard Akie, Thomas E. Xu, Jian Bauer, Daniel Orkin, Stuart H. Cantor, Alan B. TI An SCF-FBXW7 Ubiquitin Ligase Mediated Feedback Loop Facilitates GATA Factor Switching and Reinforces Commitment to Terminal Erythroid Maturation SO BLOOD LA English DT Meeting Abstract C1 [Ghamari, Alireza; Jaensch, Elizabeth; Giadone, Richard; Akie, Thomas E.; Xu, Jian; Bauer, Daniel; Orkin, Stuart H.; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707107 ER PT J AU Ghobrial, IM AF Ghobrial, Irene M. TI Molecular Modification of the Microenvironment by the Tumor Clone SO BLOOD LA English DT Meeting Abstract C1 [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707012 ER PT J AU Ghobrial, IM Laubach, JP Shain, KH Baz, R Boswell, EN Henrick, PM Azab, AK Hanlon, C Chuma, S Leblebjian, H Noonan, K MacNabb, MH Warren, D Armand, P Paba-Prada, CE Munshi, NC Schlossman, RL Anderson, KC Richardson, PG AF Ghobrial, Irene M. Laubach, Jacob P. Shain, Kenneth H. Baz, Rachid Boswell, Erica N. Henrick, Patrick M. Azab, Abdel Kareem Hanlon, Courtney Chuma, Stacey Leblebjian, Houry Noonan, Kimberly MacNabb, Megan H. Warren, Diane Armand, Philippe Paba-Prada, Claudia E. Munshi, Nikhil C. Schlossman, Robert L. Anderson, Kenneth C. Richardson, Paul G. TI Phase I/II Trial of Plerixafor and Bortezomib As a Chemosensitization Strategy in Relapsed or Relapsed/Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Ghobrial, Irene M.; Laubach, Jacob P.; Henrick, Patrick M.; Azab, Abdel Kareem; Hanlon, Courtney; Chuma, Stacey; Noonan, Kimberly; MacNabb, Megan H.; Warren, Diane; Paba-Prada, Claudia E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shain, Kenneth H.; Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Boswell, Erica N.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Leblebjian, Houry; Armand, Philippe; Schlossman, Robert L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700051 ER PT J AU Gkotzamanidou, M Shammas, M Sanchez, JM Ding, L Minvielle, S Magrangeas, F Avet-Loiseau, H Anderson, KC Munshi, NC AF Gkotzamanidou, Maria Shammas, Masood Martin Sanchez, Jesus Ding, Lai Minvielle, Stephane Magrangeas, Florence Avet-Loiseau, Herve Anderson, Kenneth C. Munshi, Nikhil C. TI HDAC8 Mediates Homologous Recombination and Cytoskeleton Integrity in Myeloma with Potential Impact on Cell Growth and Survival SO BLOOD LA English DT Meeting Abstract C1 [Gkotzamanidou, Maria; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Gkotzamanidou, Maria; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Shammas, Masood; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Shammas, Masood] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Martin Sanchez, Jesus] Hosp Univ Virgen del Rocio, Seville, Spain. [Ding, Lai] Harvard Neurodiscovery Ctr, Boston, MA USA. [Minvielle, Stephane; Magrangeas, Florence] CNRS 6299, Ctr Rech Cancerol Nantes Angers UMR Inserm 892, Nantes, France. [Avet-Loiseau, Herve] Univ Hosp Toulouse, Toulouse, France. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702163 ER PT J AU Glavey, S Naba, A Manier, S Gambella, M Rocci, A Sacco, A Asara, JM Moschetta, M Reagan, MR Mishima, Y Kawano, Y Roccaro, AM Palumbo, A Hynes, RO Ghobrial, IM AF Glavey, Siobhan Naba, Alexandra Manier, Salomon Gambella, Manuela Rocci, Alberto Sacco, Antonio Asara, John M. Moschetta, Michele Reagan, Michaela R. Mishima, Yuji Kawano, Yawara Roccaro, Aldo M. Palumbo, Antonio Hynes, Richard O. Ghobrial, Irene M. TI Proteomic Characterization of the Multiple Myeloma Bone Marrow Extracellular Matrix SO BLOOD LA English DT Meeting Abstract C1 [Glavey, Siobhan; Manier, Salomon; Sacco, Antonio; Moschetta, Michele; Reagan, Michaela R.; Mishima, Yuji; Kawano, Yawara; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Naba, Alexandra; Hynes, Richard O.] MIT, Howard Hughes Med Inst, Koch Inst, Cambridge, MA USA. [Gambella, Manuela] Univ Turin, Turin, Italy. [Rocci, Alberto] Dept Haematol, Manchester, Lancs, England. [Asara, John M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Palumbo, Antonio] Univ Turin, Div Hematol, Myeloma Unit, Turin, Italy. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704012 ER PT J AU Godbersen, C Paiva, C Berger, AJ Brown, JR Danilov, AV AF Godbersen, Claire Paiva, Cody Berger, Allison J. Brown, Jennifer R. Danilov, Alexey V. TI Targeting Nedd8 Activating Enzyme Induces DNA Damage and Cell Cycle Arrest and Sensitizes Chronic Lymphocytic Leukemia (CLL) B-Cells to Alkylating Agents SO BLOOD LA English DT Meeting Abstract C1 [Godbersen, Claire; Danilov, Alexey V.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Paiva, Cody] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Berger, Allison J.] Takeda Pharmaceut Co Ltd, Cambridge, MA USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707028 ER PT J AU Graw, JA Rosales, IA Liu, YM Sabbisetti, VS Riley, FE Rechester, O Bloch, KD Warren, HS Bonventre, JV Zapol, WM AF Graw, Jan A. Rosales, Ivy A. Liu, Yumin Sabbisetti, Venkata S. Riley, Frank E. Rechester, Osher Bloch, Kenneth D. Warren, H. Shaw Bonventre, Joseph V. Zapol, Warren M. TI Haptoglobin Therapy Prevents Kidney Injury in Stored Blood Resuscitation of Murine Hemorrhagic Shock SO BLOOD LA English DT Meeting Abstract C1 [Graw, Jan A.; Rosales, Ivy A.; Riley, Frank E.; Rechester, Osher; Bloch, Kenneth D.; Warren, H. Shaw; Zapol, Warren M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Graw, Jan A.; Rosales, Ivy A.; Riley, Frank E.; Rechester, Osher; Bloch, Kenneth D.; Warren, H. Shaw; Zapol, Warren M.] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Yumin; Sabbisetti, Venkata S.; Bonventre, Joseph V.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708091 ER PT J AU Jain, S Alam, M Rajabi, H Stroopinsky, D Yin, L Rosenblatt, J Palmer, KA Douglas, M Pyzer, AR Luptakova, K Arnason, J Joyce, R Bar-Natan, M Somaiya, P Clark, RA Kupper, TS Kufe, D Avigan, D AF Jain, Salvia Alam, Maroof Rajabi, Hasan Stroopinsky, Dina Yin, Li Rosenblatt, Jacalyn Palmer, Kristen A. Douglas, Maxwell Pyzer, Athalia Rachel Luptakova, Katarina Arnason, Jon Joyce, Robin Bar-Natan, Michal Somaiya, Poorvi Clark, Rachael A. Kupper, Thomas S. Kufe, Donald Avigan, David TI MUC1 As a Potential Therapeutic Target in Cutaneous T-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract C1 [Jain, Salvia; Stroopinsky, Dina; Rosenblatt, Jacalyn; Palmer, Kristen A.; Douglas, Maxwell; Pyzer, Athalia Rachel; Luptakova, Katarina; Arnason, Jon; Bar-Natan, Michal; Somaiya, Poorvi; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Alam, Maroof; Rajabi, Hasan; Yin, Li; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Joyce, Robin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Clark, Rachael A.; Kupper, Thomas S.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707211 ER PT J AU Joshi, I Jena, N Yoshida, T Paraskevopoulou, L Zhang, ZH Liu, ZY Korber, S Krause, DS Shapiro, IM Weaver, DT Pachter, JA Paietta, EM Van Etten, RA Georgopoulos, K AF Joshi, Ila Jena, Nilamani Yoshida, Toshimi Paraskevopoulou, Leto Zhang, Zhihong Liu, Zhong-Ying Korber, Shane Krause, Daniela S. Shapiro, Irina M. Weaver, David T. Pachter, Jonathan A. Paietta, Elisabeth M. Van Etten, Richard A. Georgopoulos, Katia TI Focal Adhesion Kinase Inhibitors Reverse the Stromal Adhesion Phenotype of Ikaros-Mutant B-ALL, Induce Apopotosis, and Synergize with ABL1 Tyrosine Kinase Inhibitors: A New Paradigm for Pathogenesis and Therapy of High-Risk B-ALL SO BLOOD LA English DT Meeting Abstract C1 [Joshi, Ila; Yoshida, Toshimi; Paraskevopoulou, Leto; Zhang, Zhihong; Georgopoulos, Katia] Massachusetts Gen Hosp, Charlestown, MA USA. [Jena, Nilamani; Liu, Zhong-Ying; Korber, Shane; Van Etten, Richard A.] Univ Calif Irvine, Irvine, CA USA. [Krause, Daniela S.] Georg Speyer Haus, Frankfurt, Germany. [Shapiro, Irina M.; Weaver, David T.; Pachter, Jonathan A.] Verastem Inc, Cambridge, MA USA. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707081 ER PT J AU Joung, JK AF Joung, J. Keith TI Genome and Epigenome Editing: A Revolution in Science and Medicine SO BLOOD LA English DT Meeting Abstract C1 [Joung, J. Keith] Massachusetts Gen Hosp, Charlestown, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 5 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700078 ER PT J AU Kanan, S Meid, K Treon, SP Castillo, JJ AF Kanan, Sandra Meid, Kirsten Treon, Steven P. Castillo, Jorge J. TI Clinical Characteristics of Rituximab Intolerance in Patients with Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract C1 [Kanan, Sandra; Meid, Kirsten; Treon, Steven P.; Castillo, Jorge J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700035 ER PT J AU Kassim, AA Payne, AB Rodeghier, M Macklin, EA Strunk, RC DeBaun, MR AF Kassim, Adetola A. Payne, Amanda B. Rodeghier, Mark Macklin, Eric A. Strunk, Robert C. DeBaun, Michael R. TI Forced Expiratory Volume in 1 Second Is Associated with Earlier Death in Sickle Cell Anemia SO BLOOD LA English DT Meeting Abstract C1 [Kassim, Adetola A.; DeBaun, Michael R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Payne, Amanda B.] Ctr Dis Control & Prevent, Nashville, TN USA. [Rodeghier, Mark] Rodeghier Consultants, Chicago, IL USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Strunk, Robert C.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702032 ER PT J AU Kekre, N Mak, K Binder, M Branvall, E Ishii, K Stopsack, K Cutler, CS AF Kekre, Natasha Mak, Kimberley Binder, Moritz Branvall, Elsa Ishii, Kazusa Stopsack, Konrad Cutler, Corey S. TI Meta-Analysis of HLA-Mismatched Compared to HLA-Matched Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract C1 [Kekre, Natasha; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mak, Kimberley] Harvard Radiat Oncol Program, Boston, MA USA. [Binder, Moritz; Stopsack, Konrad] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Branvall, Elsa] Karolinska Univ Hosp, Stockholm, Sweden. [Ishii, Kazusa] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708130 ER PT J AU Kelly, KM Ladas, EJ Cole, P Silverman, LB Stevenson, KE Orjuela, M AF Kelly, Kara M. Ladas, Elena J. Cole, Peter Silverman, Lewis B. Stevenson, Kristen E. Orjuela, Manuela TI Dietary Intake of Zinc and Severity of Infection during Prophase/Induction in Children with Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Kelly, Kara M.; Ladas, Elena J.; Orjuela, Manuela] Columbia Univ, Med Ctr, New York, NY USA. [Cole, Peter] Montefiore Med Ctr, Bronx, NY 10467 USA. [Silverman, Lewis B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Stevenson, Kristen E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 10 Z9 10 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707024 ER PT J AU Kelly, KR Chanan-Khan, A Heffner, LT Somlo, G Siegel, DS Zimmerman, T Karnad, A Munshi, NC Jagannath, S Greenberg, AL Lonial, S Roy, V Ailawadhi, S Barmaki-Rad, F Chavan, S Patel, P Wartenberg-Demand, A Thomas, H Anderson, KC AF Kelly, Kevin R. Chanan-Khan, Asher Heffner, Leonard T. Somlo, George Siegel, David S. Zimmerman, Todd Karnad, Anand Munshi, Nikhil C. Jagannath, Sundar Greenberg, Allen L. Lonial, Sagar Roy, Vivek Ailawadhi, Sikander Barmaki-Rad, Farima Chavan, Shailesh Patel, Pankaj Wartenberg-Demand, Andrea Haeder, Thomas Anderson, Kenneth C. TI Indatuximab Ravtansine (BT062) in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma: Clinical Activity in Patients Already Exposed to Lenalidomide and Bortezomib SO BLOOD LA English DT Meeting Abstract C1 [Kelly, Kevin R.] Univ So Calif, Los Angeles, CA USA. [Chanan-Khan, Asher; Roy, Vivek; Ailawadhi, Sikander] Mayo Clin, Jacksonville, FL 32224 USA. [Heffner, Leonard T.; Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Somlo, George] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Siegel, David S.] Hackensack Univ Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Zimmerman, Todd] Univ Chicago Med, Chicago, IL USA. [Karnad, Anand] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Jagannath, Sundar] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Greenberg, Allen L.] Mem Canc Inst, Pembroke Pines, FL USA. [Barmaki-Rad, Farima; Wartenberg-Demand, Andrea; Haeder, Thomas] Biotest AG, Dreieich, Germany. [Chavan, Shailesh; Patel, Pankaj] Biotest Pharmaceut Corp, Boca Raton, FL USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704099 ER PT J AU Komrokji, RS Garcia-Manero, G Ades, L Laadem, A Vo, B Prebet, T Stamatoullas, A Boyd, T Delaunay, J Steensma, DP Sekeres, MA Beyne-Rauzy, O Zou, J Attie, K Sherman, ML Fenaux, P List, AF AF Komrokji, Rami S. Garcia-Manero, Guillermo Ades, Lionel Laadem, Abderrahmane Vo, Bond Prebet, Thomas Stamatoullas, Aspasia Boyd, Thomas Delaunay, Jacques Steensma, David P. Sekeres, Mikkael A. Beyne-Rauzy, Odile Zou, Jun Attie, Kenneth Sherman, Matthew L. Fenaux, Pierre List, Alan F. TI An Open-Label, Phase 2, Dose-Finding Study of Sotatercept (ACE-011) in Patients with Low or Intermediate-1 (Int-1)-Risk Myelodysplastic Syndromes (MDS) or Non-Proliferative Chronic Myelomonocytic Leukemia (CMML) and Anemia Requiring Transfusion SO BLOOD LA English DT Meeting Abstract C1 [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ades, Lionel] Hop St Louis, Paris, France. [Laadem, Abderrahmane; Vo, Bond; Zou, Jun] Celgene Corp, Summit, NJ USA. [Prebet, Thomas] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Stamatoullas, Aspasia] Ctr Henri Becquerel, F-76038 Rouen, France. [Boyd, Thomas] North Star Lodge Canc Ctr, Yakima, WA USA. [Delaunay, Jacques] Hop Hotel Dieu, CHU Nantes, Nantes, France. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Beyne-Rauzy, Odile] CHU Purpan, Toulouse, France. [Attie, Kenneth; Sherman, Matthew L.] Acceleron Pharma, Cambridge, MA USA. [Fenaux, Pierre] Univ Paris 07, Hop St Louis, Paris, France. [List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700134 ER PT J AU Konantz, M Grzywna, S Pereboom, TC Carroll, KJ Esain, V Kanz, L North, TE Lengerke, C AF Konantz, Martina Grzywna, Sarah Pereboom, Tamara C. Carroll, Kelli J. Esain, Virginie Kanz, Lothar North, Trista E. Lengerke, Claudia TI Multiple Roles for the Zebrafish Homologue of the Murine Evi1 Gene during Primitive Myelopoiesis and HSC Development SO BLOOD LA English DT Meeting Abstract C1 [Konantz, Martina; Pereboom, Tamara C.; Lengerke, Claudia] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Grzywna, Sarah; Kanz, Lothar; Lengerke, Claudia] Univ Tubingen Hosp, Tubingen, Germany. [Carroll, Kelli J.; Esain, Virginie; North, Trista E.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700185 ER PT J AU Kopolovic, I Ostro, J Cserti, C Dzik, WS Tsubota, H Keir, A Messner, HA denHollander, N Lin, YL Callum, J AF Kopolovic, Ilana Ostro, Jackie Cserti, Christine Dzik, Walter Sunny Tsubota, Hidacki Keir, Amy Messner, Hans A. denHollander, Neal Lin, Yulia Callum, Jeannie TI Product Attributes and Donor Factors in Reported Cases of Transfusion-Associated Graft Versus Host Disease: A Systematic Review SO BLOOD LA English DT Meeting Abstract C1 [Kopolovic, Ilana; Ostro, Jackie] Univ Toronto, Toronto, ON, Canada. [Ostro, Jackie; Tsubota, Hidacki; Lin, Yulia; Callum, Jeannie] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Cserti, Christine; denHollander, Neal] Univ Hlth Network, Toronto, ON, Canada. [Dzik, Walter Sunny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keir, Amy] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Messner, Hans A.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [denHollander, Neal] Canadian Blood Serv, Toronto, ON, Canada. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702144 ER PT J AU Koreth, J Kim, HT Jones, KT Reynolds, CG Chammas, MJ Dusenbury, K Whangbo, J Nikiforow, S Alyea, EP Armand, P Cutler, CS Ho, VT Chen, YB Avigan, D Antin, JH Ritz, J Soiffer, RJ AF Koreth, John Kim, Haesook T. Jones, Kyle T. Reynolds, Carol G. Chammas, Marie J. Dusenbury, Katherine Whangbo, Jennifer Nikiforow, Sarah Alyea, Edwin P. Armand, Philippe Cutler, Corey S. Ho, Vincent T. Chen, Yi-Bin Avigan, David Antin, Joseph H. Ritz, Jerome Soiffer, Robert J. TI Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-Vs.-Host Disease: Phase 2 and Long Term Efficacy, Safety and Immune Correlates SO BLOOD LA English DT Meeting Abstract C1 [Koreth, John; Reynolds, Carol G.; Chammas, Marie J.; Ho, Vincent T.; Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Haesook T.; Jones, Kyle T.; Dusenbury, Katherine; Nikiforow, Sarah; Alyea, Edwin P.; Armand, Philippe; Cutler, Corey S.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Whangbo, Jennifer] Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707108 ER PT J AU Kumar, S Gkotzamanidou, M Pal, J Lu, RQ Nanjappa, P Shi, JL Shammas, M Munshi, NC AF Kumar, Subodh Gkotzamanidou, Maria Pal, Jagannath Lu, Renquan Nanjappa, Puru Shi, Jialan Shammas, Masood Munshi, Nikhil C. TI Elevated APE1 Mediates Dysregulation of Homologous Recombination in Myeloma: Mechanisms and Translational Significance SO BLOOD LA English DT Meeting Abstract C1 [Kumar, Subodh; Pal, Jagannath; Lu, Renquan; Nanjappa, Puru; Shammas, Masood; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Kumar, Subodh; Pal, Jagannath; Lu, Renquan; Nanjappa, Puru; Shammas, Masood; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Shi, Jialan; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708168 ER PT J AU LaCasce, A Bociek, RG Matous, J Sawas, A Caimi, P Ansell, SM Islas-Ohlmayer, M Cheung, E Agura, E Behler, C Crosswell, H Vose, JM Josephson, N Advani, R AF LaCasce, Ann Bociek, R. Gregory Matous, Jeffrey Sawas, Ahmed Caimi, Paolo Ansell, Stephen M. Islas-Ohlmayer, Miguel Cheung, Eric Agura, Edward Behler, Caroline Crosswell, Howland Vose, Julie M. Josephson, Neil Advani, Ranjana TI Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy SO BLOOD LA English DT Meeting Abstract C1 [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bociek, R. Gregory; Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Matous, Jeffrey] Colorado Blood Canc Inst, Denver, CO USA. [Sawas, Ahmed] Columbia Univ, Med Ctr, New York, NY USA. [Caimi, Paolo] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ansell, Stephen M.] Mayo Clin, Rochester, MN USA. [Islas-Ohlmayer, Miguel] Jewish Hosp Mercy Hlth, Cincinnati, OH USA. [Cheung, Eric] Oncol Inst Hope & Innovat, Whittier, CA USA. [Agura, Edward] Charles A Sammons Canc Ctr, Dallas, TX USA. [Behler, Caroline] Pacific Hematol Oncol Associates, San Francisco, CA USA. [Crosswell, Howland] St Francis Hosp, Greenville, SC USA. [Josephson, Neil] Seattle Genet Inc, Bothell, WA USA. [Advani, Ranjana] Stanford Canc Ctr, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708087 ER PT J AU Lai, HY Morse, SJ Luty, SB Garbati, MR Edmiston, JB Bagby, GC Druker, BJ Fleischman, AG AF Lai, Hew Yeng Morse, Sarah J. Luty, Samuel B. Garbati, Michael R. Edmiston, J. Blair Bagby, Grover C. Druker, Brian J. Fleischman, Angela G. TI Exaggerated Response to Toll-like Receptor Agonist Contributes to Excessive TNF Production in Myeloproliferative Neoplasm SO BLOOD LA English DT Meeting Abstract C1 [Lai, Hew Yeng; Morse, Sarah J.; Fleischman, Angela G.] Univ Calif Irvine, Irvine, CA USA. [Luty, Samuel B.; Edmiston, J. Blair; Bagby, Grover C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Garbati, Michael R.] Portland VA Med Ctr, Portland, OR USA. [Druker, Brian J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702116 ER PT J AU Lesokhin, AM Ansell, SM Armand, P Scott, EC Halwani, A Gutierrez, M Millenson, MM Cohen, AD Schuster, SJ Lebovic, D Dhodapkar, MV Avigan, D Chapuy, B Ligon, AH Rodig, SJ Cattry, D Zhu, LL Grosso, JF Kim, SY Shipp, MA Borrello, I Timmerman, J AF Lesokhin, Alexander M. Ansell, Stephen M. Armand, Philippe Scott, Emma C. Halwani, Ahmad Gutierrez, Martin Millenson, Michael M. Cohen, Adam D. Schuster, Stephen J. Lebovic, Daniel Dhodapkar, Madhav V. Avigan, David Chapuy, Bjoern Ligon, Azra H. Rodig, Scott J. Cattry, Deepika Zhu, Lili Grosso, Joseph F. Kim, Su Young Shipp, Margaret A. Borrello, Ivan Timmerman, John TI Preliminary Results of a Phase I Study of Nivolumab (BMS-936558) in Patients with Relapsed or Refractory Lymphoid Malignancies SO BLOOD LA English DT Meeting Abstract C1 [Lesokhin, Alexander M.; Cattry, Deepika] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ansell, Stephen M.] Mayo Clin, Rochester, MN USA. [Armand, Philippe; Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Scott, Emma C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Halwani, Ahmad] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Gutierrez, Martin] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cohen, Adam D.; Schuster, Stephen J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Lebovic, Daniel] Univ Michigan, Ann Arbor, MI 48109 USA. [Dhodapkar, Madhav V.] Yale Canc Ctr, New Haven, CT USA. [Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ligon, Azra H.; Rodig, Scott J.] Brigham & Womens Hosp, Clin Cytogenet Lab, Boston, MA 02115 USA. [Zhu, Lili; Grosso, Joseph F.; Kim, Su Young] Bristol Myers Squibb Co, Princeton, NJ USA. [Borrello, Ivan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Borrello, Ivan] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Timmerman, John] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 2 U2 8 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706112 ER PT J AU Levine, JE Braun, TM Harris, AC Holler, E Taylor, A Miller, HK Magenau, JM Weisdorf, DJ Ho, VT Bolanos-Meade, J Alousi, AM Ferrara, JLM AF Levine, John E. Braun, Thomas M. Harris, Andrew C. Holler, Ernst Taylor, Austin Miller, Holly K. Magenau, John M. Weisdorf, Daniel J. Ho, Vincent T. Bolanos-Meade, Javier Alousi, Amin M. Ferrara, James L. M. TI A Biomarker Algorithm Defines Onset Grades of Acute Graft-Vs-Host Disease with Distinct Non-Relapse Mortality SO BLOOD LA English DT Meeting Abstract C1 [Levine, John E.; Braun, Thomas M.; Harris, Andrew C.; Taylor, Austin; Miller, Holly K.; Magenau, John M.; Ferrara, James L. M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Holler, Ernst] Univ Hosp Regensburg, Regensburg, Germany. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolanos-Meade, Javier] Johns Hopkins Univ, Baltimore, MD USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700090 ER PT J AU Li, LS Wu, SC Kopp, N Montero, J Ryan, J Chapuy, B Van der Zwet, JC Layer, J Weigert, O Christie, AL Christodoulou, AN Liu, HY Yoda, A Hofmann, F Baffert, F Vangrevelinghe, E Gaul, C Radimerski, T Letai, AG Weinstock, DM AF Li, Loretta S. Wu, Shuo-Chieh Kopp, Nadja Montero, Joan Ryan, Jeremy Chapuy, Bjoern Van der Zwet, Jordy C. Layer, Jacob Weigert, Oliver Christie, Amanda L. Christodoulou, Alexandra N. Liu, Huiyun Yoda, Akinori Hofmann, Francesco Baffert, Fabienne Vangrevelinghe, Eric Gaul, Christoph Radimerski, Thomas Letai, Anthony G. Weinstock, David M. TI Type II JAK2 Inhibitor NVP-CHZ868 Is Active in Vivo Against JAK2-Dependent B-Cell Acute Lymphoblastic Leukemias (B-ALLs) SO BLOOD LA English DT Meeting Abstract C1 [Li, Loretta S.; Wu, Shuo-Chieh; Kopp, Nadja; Montero, Joan; Ryan, Jeremy; Chapuy, Bjoern; Van der Zwet, Jordy C.; Layer, Jacob; Christie, Amanda L.; Christodoulou, Alexandra N.; Liu, Huiyun; Yoda, Akinori; Letai, Anthony G.; Weinstock, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weigert, Oliver] Helmholtz Ctr, Munich, Germany. [Weigert, Oliver] LMU, Univ Hosp Munich, Munich, Germany. [Hofmann, Francesco; Baffert, Fabienne; Vangrevelinghe, Eric; Gaul, Christoph; Radimerski, Thomas] Novartis Inst Biomed Res, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701083 ER PT J AU Li, Y Esain, V Teng, L Xu, J Frost, I Kwan, W Yzaguirre, AD Maijenberg, MW Orkin, SH Tan, K North, TE Speck, NA AF Li, Yan Esain, Virginie Teng, Li Xu, Jian Frost, Isaura Kwan, Wanda Yzaguirre, Amanda D. Maijenberg, Marijke W. Orkin, Stuart H. Tan, Kai North, Trista E. Speck, Nancy A. TI Inflammatory Signaling Regulates Embryonic Hematopoietic Stem and Lymphoid Progenitor Cell Formation SO BLOOD LA English DT Meeting Abstract C1 [Li, Yan; Yzaguirre, Amanda D.; Maijenberg, Marijke W.; Speck, Nancy A.] Univ Penn, Philadelphia, PA 19104 USA. [Esain, Virginie; Frost, Isaura; Kwan, Wanda; North, Trista E.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Teng, Li; Tan, Kai] Univ Iowa, Iowa City, IA USA. [Xu, Jian] Boston Childrens Hosp, Boston, MA USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705058 ER PT J AU Luskin, MR Lee, JW Fernandez, HF Lazarus, HM Rowe, JM Tallman, MS Paietta, EM Litzow, M Abdel-Wahab, O Patel, JP Levine, RL Sun, ZX Luger, SM AF Luskin, Marlise R. Lee, Ju-Whei Fernandez, Hugo F. Lazarus, Hillard M. Rowe, Jacob M. Tallman, Martin S. Paietta, Elisabeth M. Litzow, Mark Abdel-Wahab, Omar Patel, Jay P. Levine, Ross L. Sun, Zhuoxin Luger, Selina M. TI Results of the ECOG E1900 Trial in Younger Adults with AML Using an Event Free Survival Endpoint Are Concordant with Results Based on Overall Survival: Potential for a Surrogate Endpoint to Facilitate Rapid Approval of Therapies in AML SO BLOOD LA English DT Meeting Abstract C1 [Luskin, Marlise R.; Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Lee, Ju-Whei; Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fernandez, Hugo F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Tallman, Martin S.; Abdel-Wahab, Omar; Patel, Jay P.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Litzow, Mark] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706175 ER PT J AU MacMillan, ML Robin, M Harris, AC Defor, TE Martin, PJ Alousi, A Ho, VT Bolanos-Meade, J Ferrara, JLM Jones, RJ Arora, M Blazar, BR Holtan, SG Jacobsohn, D Pasquini, MC Socie, G Antin, JH Levine, JE Weisdorf, DJ AF MacMillan, Margaret L. Robin, Marie Harris, Andrew C. Defor, Todd E. Martin, Paul J. Alousi, Amin Ho, Vincent T. Bolanos-Meade, Javier Ferrara, James L. M. Jones, Richard J. Arora, Mukta Blazar, Bruce R. Holtan, Shernan G. Jacobsohn, David Pasquini, Marcelo C. Socie, Gerard Antin, Joseph H. Levine, John E. Weisdorf, Daniel J. TI A Refined Clinical Risk Score at Onset of Treatment for Acute Gvhd That Predicts Response to Initial Therapy, Survival and Transplant-Related Mortality SO BLOOD LA English DT Meeting Abstract C1 [MacMillan, Margaret L.; Defor, Todd E.; Arora, Mukta; Blazar, Bruce R.; Holtan, Shernan G.; Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Robin, Marie] St Louis Hosp, Paris, France. [Harris, Andrew C.; Ferrara, James L. M.; Levine, John E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Alousi, Amin] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Alousi, Amin; Ho, Vincent T.; Bolanos-Meade, Javier; Ferrara, James L. M.; Jones, Richard J.; Jacobsohn, David; Pasquini, Marcelo C.; Antin, Joseph H.; Levine, John E.; Weisdorf, Daniel J.] BMT CTN GVHD Study Comm, Milwaukee, WI USA. [Ho, Vincent T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolanos-Meade, Javier] Johns Hopkins Univ, Baltimore, MD USA. [Jones, Richard J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pasquini, Marcelo C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Socie, Gerard] Hop St Louis, Paris, France. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707010 ER PT J AU Majerus, EM Ataga, KI Vichinsky, E Eaton, CA Mazanet, R Nathan, DG Field, JJ AF Majerus, Elaine M. Ataga, Kenneth I. Vichinsky, Elliott Eaton, Cheryl A. Mazanet, Rosemary Nathan, David G. Field, Joshua J. TI NKTT120 Reduces iNKT Cells without Dose Limiting Toxicity in Stable Adult Sickle Cell Patients in a Phase 1 Trial SO BLOOD LA English DT Meeting Abstract C1 [Majerus, Elaine M.] Washington Univ, St Louis, MO USA. [Ataga, Kenneth I.] Univ N Carolina, Chapel Hill, NC USA. [Vichinsky, Elliott] UCSF Benioff Childrens Hosp Oakland, Oakland, CA USA. [Eaton, Cheryl A.; Mazanet, Rosemary] NKT Therapeut, Waltham, MA USA. [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Field, Joshua J.] BloodCtr Wisconsin, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703113 ER PT J AU Marshall, AL Li, A Drucker, A Dzik, WS AF Marshall, Ariela L. Li, Ang Drucker, Adrienne Dzik, Walter Sunny TI Aminocaproic Acid Use in Patients with Hematologic Malignancy: A Case Series SO BLOOD LA English DT Meeting Abstract C1 [Marshall, Ariela L.; Li, Ang; Drucker, Adrienne; Dzik, Walter Sunny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marshall, Ariela L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707042 ER PT J AU Meister, M Spencer, JA Wu, J Zhao, C Stefania, L Ferraro, F Lo Celso, C Scadden, DT Van Etten, RA Lin, C Krause, DS AF Meister, Melanie Spencer, Joel A. Wu, Juwell Zhao, Cher Stefania, Lymperi Ferraro, Francesca Lo Celso, Cristina Scadden, David T. Van Etten, Richard A. Lin, Charles Krause, Daniela S. TI The Microanatomy of the Leukemic Stem Cell Niche in Murine Chronic Myelogenous Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Meister, Melanie; Krause, Daniela S.] Georg Speyer Haus, Frankfurt, Germany. [Spencer, Joel A.; Wu, Juwell; Zhao, Cher; Stefania, Lymperi; Ferraro, Francesca; Lin, Charles] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lo Celso, Cristina] Univ London Imperial Coll Sci Technol & Med, London, England. [Scadden, David T.] Harvard Stem Cell Inst, Boston, MA USA. [Van Etten, Richard A.] Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700186 ER PT J AU Montillo, M O'Brien, S Tedeschi, A Hillmen, P Dearden, C Gill, D Brown, JR Barrientos, JC Mulligan, S Furman, RR Cymbalista, F Plascencia, C Chang, S Hsu, E James, DF Byrd, JC AF Montillo, Marco O'Brien, Susan Tedeschi, Alessandra Hillmen, Peter Dearden, Claire Gill, Devinder Brown, Jennifer R. Barrientos, Jaqueline C. Mulligan, Stephen Furman, Richard R. Cymbalista, Florence Plascencia, Clara Chang, Stephen Hsu, Emily James, Danelle F. Byrd, John C. TI Autoimmune Hemolytic Anemia and Immune Mediated Thrombocytopenia in the Phase III RESONATE (TM) Study of Ibrutinib Vs Ofatumumab in Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Including a Case Report SO BLOOD LA English DT Meeting Abstract C1 [Montillo, Marco; Tedeschi, Alessandra] Osped Niguarda Ca Granda, Milan, Italy. [O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [Dearden, Claire] Royal Marsden Hosp, London SW3 6JJ, England. [Gill, Devinder] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barrientos, Jaqueline C.] North Shore LIJ Canc Inst, Lake Success, NY USA. [Mulligan, Stephen] Royal N Shore Hosp, Sydney, NSW, Australia. [Furman, Richard R.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Cymbalista, Florence] Hop Avicenne, Paris, France. [Plascencia, Clara; Chang, Stephen; Hsu, Emily; James, Danelle F.] Pharmacyclics Inc, Sunnyvale, CA USA. [Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705173 ER PT J AU Munshi, NC Minvielle, S Tai, YT Fulciniti, M Richardson, PG Attal, M Moreau, P Magrangeas, F Anderson, KC Faham, M Avet-Loiseau, H AF Munshi, Nikhil C. Minvielle, Stephane Tai, Yu-Tzu Fulciniti, Mariateresa Richardson, Paul G. Attal, Michel Moreau, Philippe Magrangeas, Florence Anderson, Kenneth C. Faham, Malek Avet-Loiseau, Herve TI Deep Sequencing of Immunoglobulin Loci Reveals Evolution of IgH Clone in Multiple Myeloma Patients over the Course of Treatment SO BLOOD LA English DT Meeting Abstract C1 [Munshi, Nikhil C.; Tai, Yu-Tzu; Fulciniti, Mariateresa; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, Roxbury, MA USA. [Minvielle, Stephane; Moreau, Philippe; Magrangeas, Florence] Ctr Rech Cancerol Nantes Angers UMR Inserm 892CNR, F-44007 Nantes, France. [Minvielle, Stephane; Moreau, Philippe; Magrangeas, Florence] IRT UN, F-44007 Nantes, France. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Attal, Michel; Avet-Loiseau, Herve] CHU Rangueil, Unite Genom Myelome, F-31054 Toulouse, France. [Faham, Malek] Sequenta Inc, San Francisco, CA USA. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706124 ER PT J AU Murphy, EJ Neuberg, D Rai, KR Rassenti, L Emson, C Li, K Kay, NE Wierda, WG Hayes, GM Brown, JR Byrd, JC McConnel, C Barrientos, JC Redd, RA Turner, S Busch, R Greaves, A Hellerstein, M Chiorazzi, N Kipps, TJ AF Murphy, Elizabeth J. Neuberg, Donna Rai, Kanti R. Rassenti, Laura Emson, Claire Li, Kelvin Kay, Neil E. Wierda, William G. Hayes, Gregory M. Brown, Jennifer R. Byrd, John C. McConnel, Coline Barrientos, Jacqueline C. Redd, Robert Allyn Turner, Scott Busch, Robert Greaves, Andrew Hellerstein, Marc Chiorazzi, Nicholas Kipps, Thomas J. TI Kinetic Measurement of Leukemia-Cell Proliferation Rate By Deuterium Labeling Predicts Time to Initial Treatment of Patients with Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract C1 [Murphy, Elizabeth J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Neuberg, Donna; Brown, Jennifer R.; Redd, Robert Allyn] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rai, Kanti R.] Hofstra North Shore Long Isl Jewish Sch Med, Hempstead, NY USA. [Rassenti, Laura; Greaves, Andrew; Kipps, Thomas J.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Emson, Claire; Li, Kelvin; McConnel, Coline; Turner, Scott; Hellerstein, Marc] KineMed Inc, Emeryville, CA USA. [Kay, Neil E.] Mayo Clin, Rochester, MN USA. [Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hayes, Gregory M.] Igenica Inc, Burlingame, CA USA. [Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Barrientos, Jacqueline C.] North Shore LIJ Canc Inst, Lake Success, NY USA. [Busch, Robert] Univ Roehampton, London, England. [Chiorazzi, Nicholas] North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. NR 0 TC 1 Z9 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706126 ER PT J AU Nand, S Diaz, MO Marinier, DE Walshauser, MA Rosenfeld, AB Michaelis, LC Stiff, PJ Gai, XW AF Nand, Sucha Diaz, Manuel O. Marinier, David E. Walshauser, Mark A. Rosenfeld, Amy B. Michaelis, Laura C. Stiff, Patrick J. Gai, Xiaowu TI Germ-Line and Somatic Mutations in Familial Myeloproliferative Neoplasms (MPNs). a Pilot Study SO BLOOD LA English DT Meeting Abstract C1 [Nand, Sucha; Rosenfeld, Amy B.; Stiff, Patrick J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Diaz, Manuel O.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Marinier, David E.] Gundersen Hlth, La Crosse, WI USA. [Walshauser, Mark A.] Canc Care Specialists Illinois, Swansea, IL USA. [Michaelis, Laura C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gai, Xiaowu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704100 ER PT J AU Newell, LF Rathbun, RK Garbati, MR Dao, KHT Holtan, SG Cook, RJ Meyers, G Bagby, GC AF Newell, Laura F. Rathbun, R. K. Garbati, Michael R. Dao, Kim-Hien T. Holtan, Shernan G. Cook, Rachel J. Meyers, Gabrielle Bagby, Grover C. TI The Contribution of Toll-like Receptor (TLR) Pathway Hyper-Reactivity to Clonal Selection in Secondary MDS and AML SO BLOOD LA English DT Meeting Abstract C1 [Newell, Laura F.; Rathbun, R. K.; Cook, Rachel J.; Meyers, Gabrielle; Bagby, Grover C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Garbati, Michael R.; Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. [Dao, Kim-Hien T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Holtan, Shernan G.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708115 ER PT J AU Obeng, EA McConkey, ME Campagna, D Schneider, RK Chen, MC Schmidt, PJ Mullally, A Fleming, MD Ebert, BL AF Obeng, Esther A. McConkey, Marie E. Campagna, Dean Schneider, Rebekka K. Chen, Michelle C. Schmidt, Paul J. Mullally, Ann Fleming, Mark D. Ebert, Benjamin L. TI Mutant Splicing Factor 3b Subunit 1 (SF3B1) Causes Dysregulated Erythropoiesis and a Stem Cell Disadvantage SO BLOOD LA English DT Meeting Abstract C1 [Obeng, Esther A.; McConkey, Marie E.; Schneider, Rebekka K.; Chen, Michelle C.; Mullally, Ann; Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Obeng, Esther A.; Ebert, Benjamin L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Obeng, Esther A.; Campagna, Dean; Schmidt, Paul J.; Fleming, Mark D.] Boston Childrens Hosp, Boston, MA USA. [Mullally, Ann] Broad Inst, Cambridge, MA USA. [Mullally, Ann] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708125 ER PT J AU Parnes, A Mitchell, C Rachel, W Campigotto, F Lashley, L Brunswick, C Neuberg, D Lin, JC AF Parnes, Aric Mitchell, Christine Rachel, Wentz Campigotto, Federico Lashley, Latoya Brunswick, Cathee Neuberg, Donna Lin, Judith C. TI The Effects of Hemophilia on Socialization SO BLOOD LA English DT Meeting Abstract C1 [Parnes, Aric; Mitchell, Christine; Rachel, Wentz; Lashley, Latoya; Brunswick, Cathee; Lin, Judith C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Campigotto, Federico] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707087 ER PT J AU Plesner, T Arkenau, HT Lokhorst, HM Gimsing, P Krejcik, J Lemech, C Minnema, MC Lassen, U Laubach, JP Ahmadi, T Yeh, H Guckert, ME Feng, HB Brun, NC Lisby, S Basse, L Palumbo, A Richardson, PG AF Plesner, Torben Arkenau, Hendrik-Tobias Lokhorst, Henk M. Gimsing, Peter Krejcik, Jakub Lemech, Charlotte Minnema, Monique C. Lassen, Ulrik Laubach, Jacob P. Ahmadi, Tahamtan Yeh, Howard Guckert, Mary E. Feng, Huaibao Brun, Nikolai Constantin Lisby, Steen Basse, Linda Palumbo, Antonio Richardson, Paul G. TI Safety and Efficacy of Daratumumab with Lenalidomide and Dexamethasone in Relapsed or Relapsed, Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Plesner, Torben; Krejcik, Jakub] Vejle Hosp, Velje, Denmark. [Arkenau, Hendrik-Tobias] Sarah Cannon Res Insitute, London, England. [Lokhorst, Henk M.; Minnema, Monique C.] UMC Utrecht, Utrecht, Netherlands. [Gimsing, Peter] Univ Copenhagen, Copenhagen, Denmark. [Lemech, Charlotte] Sarah Cannon Res Inst, London, England. [Lassen, Ulrik] Rigshosp, DK-2100 Copenhagen, Denmark. [Laubach, Jacob P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ahmadi, Tahamtan; Guckert, Mary E.] Janssen, Spring House, PA USA. [Yeh, Howard; Feng, Huaibao] Janssen Res & Dev, Raritan, NJ USA. [Brun, Nikolai Constantin; Basse, Linda] Genmab AS, Copenhagen, Denmark. [Lisby, Steen] Genmab, Copenhagen, Denmark. [Palumbo, Antonio] Univ Turin, Myeloma Unit, Div Hematol, Turin, Italy. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706117 ER PT J AU Politikos, I Kim, HT Nikiforow, S Li, LQ Ballen, KK Antin, JH Ritz, J Cutler, CS Boussiotis, VA AF Politikos, Ioannis Kim, Haesook T. Nikiforow, Sarah Li, Lequn Ballen, Karen K. Antin, Joseph H. Ritz, Jerome Cutler, Corey S. Boussiotis, Vassiliki A. TI Prognostic Value of TREC, IL-7 and SCF Levels on Clinical Outcomes after Double Umbilical Cord Blood Transplantation in Adults SO BLOOD LA English DT Meeting Abstract C1 [Politikos, Ioannis; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Kim, Haesook T.; Antin, Joseph H.; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nikiforow, Sarah; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242700131 ER PT J AU Prabhu, VV Ishizawa, J Zhao, D Allen, JE Batchelor, TT Chi, AS Andreeff, M El-Deiry, WS AF Prabhu, Varun Vijay Ishizawa, Jo Zhao, Dan Allen, Joshua E. Batchelor, Tracy T. Chi, Andrew S. Andreeff, Michael El-Deiry, Wafik S. TI ONC201 Depletes Cancer Stem Cells in Refractory Cancer Patient Samples SO BLOOD LA English DT Meeting Abstract C1 [Prabhu, Varun Vijay; El-Deiry, Wafik S.] Penn State Hershey Canc Inst, Hershey, PA USA. [Ishizawa, Jo; Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhao, Dan; Batchelor, Tracy T.; Chi, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Allen, Joshua E.] Oncoceutics Inc, Hummelstown, PA USA. NR 0 TC 1 Z9 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704169 ER PT J AU Rand, KA Song, C Hwang, AE Huff, CA Bernal-Mizrachi, L Tomasson, MH Ailawadhi, S Van Den Berg, DJ Sheng, X Graff, JJ Conti, DV Zimmerman, T Peters, E Singhal, S Bock, CH Pawlish, K Colditz, GA Sheng, X Stram, A Strom, SS Rybicki, B Kittles, R Terebelo, H Stanford, J Goodman, PJ Berndt, SI Carpten, J Hennis, AJ Chu, LS Casey, G Driver, WR Klein, EA Leske, MC John, E Murphy, AB Neslund-Dudas, C Stevens, VL Pettaway, C Zheng, W Wu, SY Witte, J Zheng, SL Xu, JF Munshi, NC Hsing, A Ingles, S Mehta, J Signorello, LB Chanock, SJ Nemesure, B Mohrbacher, AM Janakiraman, N Blot, WJ Henderson, BE Kolonel, LN Anderson, KC Chiu, BCH Zonder, J Orlowski, RZ Lonial, S Stram, DO Haiman, C Cozen, W AF Rand, Kristin A. Song, Chi Hwang, Amie E. Huff, Carol A. Bernal-Mizrachi, Leon Tomasson, Michael H. Ailawadhi, Sikander Van Den Berg, David J. Sheng, Xin Graff, John J. Conti, David V. Zimmerman, Todd Peters, Edward Singhal, Seema Bock, Cathryn H. Pawlish, Karen Colditz, Graham A. Sheng, Xin Stram, Alexander Strom, Sara S. Rybicki, Benjamin Kittles, Rick Terebelo, Howard Stanford, Janet Goodman, Phyllis J. Berndt, Sonja I. Carpten, John Hennis, Anselm Jm Chu, Lisa Casey, Graham Driver, W. R. Klein, Eric A. Leske, M. Christina John, Esther Murphy, Adam Bryant Neslund-Dudas, Christine Stevens, Victoria L. Pettaway, Curtis Zheng, Wei Wu, Suh-Yuh Witte, John Zheng, Siqun Lilly Xu, Jianfeng Munshi, Nikhil C. Hsing, Ann Ingles, Sue Mehta, Jayesh Signorello, Lisa B. Chanock, Stephen Jacob Nemesure, Barbara Mohrbacher, Ann M. Janakiraman, Nalini Blot, William J. Henderson, Brian E. Kolonel, Laurence N. Anderson, Kenneth C. Chiu, Brian C-H Zonder, Jeffrey Orlowski, Robert Z. Lonial, Sagar Stram, Daniel O. Haiman, Christopher Cozen, Wendy TI Genetic Susceptibility Markers of Multiple Myeloma in African-Americans SO BLOOD LA English DT Meeting Abstract C1 [Rand, Kristin A.; Hwang, Amie E.; Conti, David V.; Mohrbacher, Ann M.; Henderson, Brian E.; Haiman, Christopher] Univ So Calif, USC Keck Sch Med, Los Angeles, CA USA. [Song, Chi; Sheng, Xin; Sheng, Xin; Ingles, Sue; Stram, Daniel O.; Cozen, Wendy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hwang, Amie E.; Van Den Berg, David J.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. [Huff, Carol A.] Johns Hopkins Univ, Baltimore, MD USA. [Bernal-Mizrachi, Leon] Emory Univ, Sch Med, Atlanta, GA USA. [Tomasson, Michael H.; Colditz, Graham A.] Washington Univ, Sch Med, St Louis, MO USA. [Ailawadhi, Sikander] Mayo Clin, Jacksonville, FL 32224 USA. [Graff, John J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Zimmerman, Todd] Univ Chicago Med, Chicago, IL USA. [Peters, Edward] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Singhal, Seema] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Bock, Cathryn H.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Pawlish, Karen] New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. [Stram, Alexander; Casey, Graham; Witte, John] Univ So Calif, Keck Sch Med, Norris Comprehens Ctr, Los Angeles, CA 90033 USA. [Pettaway, Curtis; Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rybicki, Benjamin; Murphy, Adam Bryant; Janakiraman, Nalini] Henry Ford Hosp, Detroit, MI 48202 USA. [Kittles, Rick] Univ Arizona, Tucson, AZ USA. [Terebelo, Howard] Providence Canc Inst, Southfield, MI USA. [Stanford, Janet; Goodman, Phyllis J.] Univ Washington, Seattle, WA 98195 USA. [Berndt, Sonja I.] NCI, NIH, Bethesda, MD 20892 USA. [Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA. [Hennis, Anselm Jm] Univ W Indies, Bridgetown, Barbados. [Chu, Lisa; John, Esther; Hsing, Ann] Canc Prevent Inst Calif, Fremont, CA USA. [Driver, W. R.; Stevens, Victoria L.] Amer Canc Soc, Atlanta, GA 30329 USA. Cleveland Clin, Cleveland, OH 44106 USA. [Leske, M. Christina] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Murphy, Adam Bryant; Mehta, Jayesh] Northwestern Univ, Chicago, IL 60611 USA. [Neslund-Dudas, Christine] Henry Ford Hlth Syst, Detroit, MI USA. [Zheng, Wei] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Wu, Suh-Yuh; Nemesure, Barbara] SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zheng, Siqun Lilly] Wake Forest Sch Med, Winston Salem, NC USA. [Xu, Jianfeng] Wake Forest Sch Med, Salem Winston, NC USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chanock, Stephen Jacob] NCI, NIH, US Dept Human Hlth Serv, Rockville, MD USA. [Blot, William J.] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. [Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Chiu, Brian C-H] Univ Chicago, Chicago, IL 60637 USA. [Zonder, Jeffrey] Karmanos Canc Inst, Detroit, MI USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702025 ER PT J AU Rashid, N Minvielle, S Magrangeas, F Samur, MK Clynen, A Sperling, A Tai, YT Fulciniti, M Richardson, PG Attal, M Moreau, P Anderson, KC Parmigiani, G Avet-Loiseau, H Munshi, NC AF Rashid, Naim Minvielle, Stephane Magrangeas, Florence Samur, Mehmet Kemal Clynen, Alice Sperling, Adam Tai, Yu-Tzu Fulciniti, Mariateresa Richardson, Paul G. Attal, Michel Moreau, Philippe Anderson, Kenneth C. Parmigiani, Giovanni Avet-Loiseau, Herve Munshi, Nikhil C. TI Alternative Splicing Is a Frequent Event and Impacts Clinical Outcome in Myeloma: A Large RNA-Seq Data Analysis of Newly-Diagnosed Myeloma Patients SO BLOOD LA English DT Meeting Abstract C1 [Rashid, Naim; Samur, Mehmet Kemal; Clynen, Alice; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Minvielle, Stephane; Magrangeas, Florence] CNRS 6299, UMR 892, INSERM, Ctr Rech Cancerol Nantes Angers, Nantes, France. [Sperling, Adam; Tai, Yu-Tzu; Fulciniti, Mariateresa; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Paul G.; Munshi, Nikhil C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Attal, Michel] CHU Purpan, Toulouse, France. [Moreau, Philippe] CHU Nantes, F-44035 Nantes 01, France. [Avet-Loiseau, Herve] CHU Rangueil, F-31054 Toulouse, France. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704211 ER PT J AU Rhee, C Manzo, V Shea, T Desjardins, C van der Auwera, G Young, S Riley, AM DeAngelo, DJ Baden, LR Gee, J Meyerson, M Klompas, M Yokoe, D Weiser, L Pedamallu, CS Bhatt, AS AF Rhee, Chanu Manzo, Veronica Shea, Terrance Desjardins, Christopher van der Auwera, Geraldine Young, Sarah Riley, Ann Marie DeAngelo, Daniel J. Baden, Lindsey R. Gee, Jay Meyerson, Matthew Klompas, Michael Yokoe, Deborah Weiser, Linda Pedamallu, Chandra Sekhar Bhatt, Ami S. TI Bacillus Cereus: A Leukemia-Specific, Neuroinvasive Pathogen? SO BLOOD LA English DT Meeting Abstract C1 [Rhee, Chanu] Harvard Univ, Sch Med, Boston, MA USA. [Manzo, Veronica; Bhatt, Ami S.] Stanford Univ, Stanford, CA 94305 USA. [Shea, Terrance; Desjardins, Christopher; van der Auwera, Geraldine; Young, Sarah; Pedamallu, Chandra Sekhar] Broad Inst, Cambridge, MA USA. [Riley, Ann Marie] Boston Childrens Hosp, Boston, MA USA. [DeAngelo, Daniel J.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baden, Lindsey R.; Klompas, Michael; Yokoe, Deborah; Weiser, Linda] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gee, Jay] Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707200 ER PT J AU Rosenblat, T Heaney, ML Jurcic, JG Raza, A Mears, JG Santos, R Carrillo, D Shum, D Gonzales, J Zikaras, K Santos, M Zhang, R Ibanezs, G Hogdal, L Crombie, J Djaballah, H Scandura, JM Letai, AG Frattini, MG AF Rosenblat, Todd Heaney, Mark L. Jurcic, Joseph G. Raza, Azra Mears, John G. Santos, Ruth Carrillo, Diana Shum, David Gonzales, Jacquelyn Zikaras, Kevin Santos, Martin Zhang, Rong Ibanezs, Glorymar Hogdal, Leah Crombie, Jennifer Djaballah, Hakim Scandura, Joseph M. Letai, Anthony G. Frattini, Mark G. TI A Phase I Trial of a Pharmacodynamically-Conceived Decitabine and Thioguanine Combination in Patients with Advanced Myeloid Malignancies SO BLOOD LA English DT Meeting Abstract C1 [Rosenblat, Todd; Heaney, Mark L.; Jurcic, Joseph G.; Raza, Azra; Mears, John G.; Santos, Ruth; Carrillo, Diana; Gonzales, Jacquelyn; Zikaras, Kevin; Santos, Martin; Zhang, Rong; Frattini, Mark G.] Columbia Univ, Med Ctr, New York, NY USA. [Shum, David; Ibanezs, Glorymar; Djaballah, Hakim] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hogdal, Leah] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Crombie, Jennifer] Brigham & Womens Hosp, Boston, MA 02115 USA. [Scandura, Joseph M.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708105 ER PT J AU Roti, G Qi, J Su, A Varca, A Aster, JC Bradner, JE Stegmaier, K AF Roti, Giovanni Qi, Jun Su, Angela Varca, Antony Aster, Jon C. Bradner, James E. Stegmaier, Kimberly TI Selectively Targeting Mutated NOTCH1 with a Folate-Thapsigargin Derivative SO BLOOD LA English DT Meeting Abstract C1 [Roti, Giovanni; Qi, Jun; Su, Angela; Varca, Antony; Bradner, James E.; Stegmaier, Kimberly] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Aster, Jon C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bradner, James E.; Stegmaier, Kimberly] Broad Inst MIT & Harvard, Cambridge, MA USA. [Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706021 ER PT J AU Schram, AM Mullally, A Fogerty, AE Massarotti, E Berliner, N AF Schram, Alison M. Mullally, Ann Fogerty, Annemarie E. Massarotti, Elena Berliner, Nancy TI Hemophagocytic Lymphohistiocytosis: The Partners Healthcare Experience over the Past 8 Years SO BLOOD LA English DT Meeting Abstract C1 [Schram, Alison M.; Massarotti, Elena; Berliner, Nancy] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mullally, Ann; Berliner, Nancy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mullally, Ann] Broad Inst, Cambridge, MA USA. [Mullally, Ann] Harvard Univ, Sch Med, Boston, MA USA. [Fogerty, Annemarie E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242708063 ER PT J AU Schram, AM Mullally, A Campigotto, F Fogerty, AE Massarotti, E Neuberg, DS Berliner, N AF Schram, Alison M. Mullally, Ann Campigotto, Federico Fogerty, Annemarie E. Massarotti, Elena Neuberg, Donna S. Berliner, Nancy TI Marked Hyperferritinemia Does Not Predict for Hemophagocytic Lymphohistiocytosis (HLH) in the Adult Population SO BLOOD LA English DT Meeting Abstract C1 [Schram, Alison M.; Massarotti, Elena; Berliner, Nancy] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mullally, Ann; Campigotto, Federico; Neuberg, Donna S.; Berliner, Nancy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mullally, Ann] Broad Inst, Cambridge, MA USA. [Mullally, Ann] Harvard Univ, Sch Med, Boston, MA USA. [Fogerty, Annemarie E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704033 ER PT J AU Sekeres, MA Othus, M List, AF Odenike, O Stone, RM Gore, SD Litzow, MR Buckstein, R Velasco, MR Gaur, R Atallah, E Attar, E Appelbaum, FR Erba, HP AF Sekeres, Mikkael A. Othus, Megan List, Alan F. Odenike, Olatoyosi Stone, Richard M. Gore, Steven D. Litzow, Mark R. Buckstein, Rena Velasco, Mario R. Gaur, Rakesh Atallah, Ehab Attar, Eyal Appelbaum, Frederick R. Erba, Harry P. TI A Randomized Phase II Study of Azacitidine Combined with Lenalidomide or with Vorinostat Vs. Azacitidine Monotherapy in Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML): North American Intergroup Study SWOG S1117 SO BLOOD LA English DT Meeting Abstract C1 [Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Othus, Megan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Odenike, Olatoyosi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gore, Steven D.] Yale Univ, Sch Med, New Haven, CT USA. [Gore, Steven D.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Buckstein, Rena] Univ Toronto, Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Toronto, ON, Canada. [Velasco, Mario R.] Cent Illinois CCOP, Decatur, IL USA. [Gaur, Rakesh] Kansas City CCOP, Kansas City, KS USA. [Atallah, Ehab] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Attar, Eyal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Appelbaum, Frederick R.] Univ Washington, Seattle, WA 98195 USA. [Erba, Harry P.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707005 ER PT J AU Shammas, M Kumar, S Pal, J Nanjappa, P Samur, M Gkotzamanidou, M Shi, JL Munshi, NC AF Shammas, Masood Kumar, Subodh Pal, Jagannath Nanjappa, Puru Samur, Mehmat Gkotzamanidou, Maria Shi, Jialan Munshi, Nikhil C. TI Dysregulation of SHFM1, a Novel Target for Prevention of Genomic Instability in Myeloma, Is Associated with Epigenetic Changes at Specific CpG Sites SO BLOOD LA English DT Meeting Abstract C1 [Shammas, Masood; Kumar, Subodh; Pal, Jagannath; Nanjappa, Puru; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Shammas, Masood; Kumar, Subodh; Pal, Jagannath; Nanjappa, Puru; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Samur, Mehmat] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Shi, Jialan; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705035 ER PT J AU Shi, JL Lu, XG Thatte, HS AF Shi, Jialan Lu, Xiu-Gui Thatte, Hemant S. TI Extended Storage of Platelets in a Novel Organ Preservation Solution, Somah SO BLOOD LA English DT Meeting Abstract C1 [Shi, Jialan] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA USA. [Lu, Xiu-Gui; Thatte, Hemant S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, West Roxbury, MA USA. [Lu, Xiu-Gui; Thatte, Hemant S.] VA Boston Healthcare Syst, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703010 ER PT J AU Shinde, A Rhieu, BH Berhane, H Guinan, EC Parmar, K Wang, H Franicola, D Zhang, XC Li, S Dixon, TM Greenberger, JS AF Shinde, Ashwin Rhieu, Byung Han Berhane, Hebist Guinan, Eva C. Parmar, Kalindi Wang, Hong Franicola, Darcy Zhang, Xichen Li, Song Dixon, Tracy M. Greenberger, Joel S. TI Intraoral Mitochondrial-Targeted GS Nitroxide JP4-039 Ameliorates Radiation-Induced Mucositis in Orthotopic Tumor-Bearing Fanconi Anemia (FA) (Fancd2-/-) Mice SO BLOOD LA English DT Meeting Abstract C1 [Shinde, Ashwin; Rhieu, Byung Han; Zhang, Xichen; Li, Song] Univ Pittsburgh, Pittsburgh, PA USA. [Berhane, Hebist; Wang, Hong; Franicola, Darcy; Dixon, Tracy M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Parmar, Kalindi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Greenberger, Joel S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707153 ER PT J AU Shirai, CL Ley, JN White, BS Tibbitts, J Shao, J Ndonwi, M Kim, S Wadugu, B Okeyo-Owuor, T Graubert, TA Walter, MJ AF Shirai, Cara Lunn Ley, James N. White, Brian S. Tibbitts, Justin Shao, Jin Ndonwi, Matthew Kim, Sanghyun Wadugu, Brian Okeyo-Owuor, Theresa Graubert, Timothy A. Walter, Matthew J. TI Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing in Transgenic Mice SO BLOOD LA English DT Meeting Abstract C1 [Shirai, Cara Lunn; Ley, James N.; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Kim, Sanghyun; Wadugu, Brian; Walter, Matthew J.] Washington Univ, Sch Med, St Louis, MO USA. [White, Brian S.; Okeyo-Owuor, Theresa] Washington Univ, St Louis, MO USA. [Graubert, Timothy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706054 ER PT J AU Silverman, LR Fenaux, P Al-Kali, A Baer, MR Sekeres, MA Roboz, GJ Gaidano, G Scott, BL Greenberg, PL Platzbecker, U Steensma, DP Kambhampati, S Kreuzer, KA Godley, LA Collins, R Atallah, E Navada, SC Wilhelm, F Azarnia, N Garcia-Manero, G AF Silverman, Lewis R. Fenaux, Pierre Al-Kali, Aref Baer, Maria R. Sekeres, Mikkael A. Roboz, Gail J. Gaidano, Gianluca Scott, Bart L. Greenberg, Peter L. Platzbecker, Uwe Steensma, David P. Kambhampati, Suman Kreuzer, Karl-Anton Godley, Lucy A. Collins, Robert Atallah, Ehab Navada, Shyamala C. Wilhelm, Francois Azarnia, Nozar Garcia-Manero, Guillermo TI Relationship of Bone Marrow Blast (BMBL) Response to Overall Survival (OS) in Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS) Treated with Rigosertib after Failure of Hypomethylating Agents (HMAs) SO BLOOD LA English DT Meeting Abstract C1 [Silverman, Lewis R.; Navada, Shyamala C.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Fenaux, Pierre] Univ Paris 07, Hop St Louis, Paris, France. [Al-Kali, Aref] Mayo Clin, Rochester, MN USA. [Baer, Maria R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Roboz, Gail J.] Weill Cornell Med Coll, New York, NY USA. [Gaidano, Gianluca] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy. [Scott, Bart L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Greenberg, Peter L.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Platzbecker, Uwe] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kambhampati, Suman] Univ Kansas, Ctr Canc, Kansas City, KS USA. [Kreuzer, Karl-Anton] Univ Cologne, D-50931 Cologne, Germany. [Godley, Lucy A.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Collins, Robert] Univ Texas Southwestern, Dallas, TX USA. [Atallah, Ehab] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wilhelm, Francois; Azarnia, Nozar] Onconova Therapeut Inc, Newtown, PA USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703148 ER PT J AU Sivina, M Werner, L Rassenti, L Wierda, WG Keating, MJ O'Brien, S Neuberg, D Kipps, TJ Burger, JA AF Sivina, Mariela Werner, Lillian Rassenti, Laura Wierda, William G. Keating, Michael J. O'Brien, Susan Neuberg, Donna Kipps, Thomas J. Burger, Jan A. TI Dynamics Changes in CCL3 and CCL4 Plasma Chemokine Levels in Patients with Chronic Lymhocytic Leukemia (CLL) Managed with Observation SO BLOOD LA English DT Meeting Abstract C1 [Sivina, Mariela; Wierda, William G.; Keating, Michael J.; O'Brien, Susan; Burger, Jan A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rassenti, Laura; Kipps, Thomas J.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701003 ER PT J AU Song, Y Das, DS Ray, A Ravillah, D Munshi, NC Chauhan, D Anderson, KC AF Song, Yan Das, Deepika Sharma Ray, Arghya Ravillah, Durgadevi Munshi, Nikhil C. Chauhan, Dharminder Anderson, Kenneth C. TI Targeting Proteasome Ubiquitin Receptor RPN13/ADRM1 in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract C1 [Song, Yan; Das, Deepika Sharma; Ray, Arghya; Ravillah, Durgadevi; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Song, Yan; Das, Deepika Sharma; Ray, Arghya; Ravillah, Durgadevi; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242706230 ER PT J AU Spitzer, B Guryanova, OA Abdel-Wahab, O Kucine, N Adli, M Berman, JN Meshinchi, S Bernstein, B Pelossof, R Leslie, C Levine, RL AF Spitzer, Barbara Guryanova, Olga A. Abdel-Wahab, Omar Kucine, Nicole Adli, Mazhar Berman, Jason N. Meshinchi, Soheil Bernstein, Bradley Pelossof, Raphael Leslie, Christina Levine, Ross L. TI Characterizing Transcriptional and Epigenetic Signatures Induced By FLT3-ITD Activation SO BLOOD LA English DT Meeting Abstract C1 [Spitzer, Barbara; Guryanova, Olga A.; Abdel-Wahab, Omar; Pelossof, Raphael; Leslie, Christina; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kucine, Nicole] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Adli, Mazhar] Massachusetts Gen Hosp, Dept Pathol, Broad Inst Harvard & MIT, Howard Hughes Med Inst, Boston, MA 02114 USA. [Adli, Mazhar] Harvard Univ, Sch Med, Boston, MA USA. [Berman, Jason N.] Dalhousie Univ, IWK Hlth Ctr, Halifax, NS, Canada. [Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Bernstein, Bradley] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242705224 ER PT J AU Szalat, R Dreze, M Samur, MK Calkins, AS Parmigiani, G Avet-Loiseau, H Anderson, KC Fermand, JP Lazaro, JB Munshi, NC AF Szalat, Raphael Dreze, Matija Samur, Mehmet Kemal Calkins, Anne S. Parmigiani, Giovanni Avet-Loiseau, Herve Anderson, Kenneth C. Fermand, Jean-Paul Lazaro, Jean-Bernard Munshi, Nikhil C. TI Nucleotide Excision Repair (NER) Is Frequently Impaired and Affects Outcome in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract C1 [Szalat, Raphael; Samur, Mehmet Kemal; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dreze, Matija; Calkins, Anne S.; Parmigiani, Giovanni; Lazaro, Jean-Bernard] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avet-Loiseau, Herve] Univ Hosp, Unit Genom Myeloma, Toulouse, France. [Fermand, Jean-Paul] Hop St Louis, Paris, France. [Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702201 ER PT J AU Tai, YT Acharya, C An, G Zhong, MY Cea, M Cagnetta, A Jiang, H van Eenennaam, H van Elsas, A Munshi, NC Anderson, KC AF Tai, Yu-Tzu Acharya, Chirag An, Gang Zhong, Mike Y. Cea, Michele Cagnetta, Antonia Jiang, Hua van Eenennaam, Hans van Elsas, Andrea Munshi, Nikhil C. Anderson, Kenneth C. TI A Novel Anti-a Proliferation-Inducing Ligand Hapril.01A Monoclonal Antibody Targets Multiple Myeloma Cells in the Bone Marrow Microenvironment SO BLOOD LA English DT Meeting Abstract C1 [Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Acharya, Chirag; Zhong, Mike Y.; Cea, Michele; Cagnetta, Antonia; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Acharya, Chirag; Zhong, Mike Y.; Cea, Michele; Cagnetta, Antonia; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [An, Gang; Jiang, Hua] Dana Farber Canc Inst, Boston, MA 02115 USA. [van Eenennaam, Hans; van Elsas, Andrea] BioNovion, Oss, Netherlands. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242704020 ER PT J AU Tatetsu, H Wang, F Gao, C Ueno, S Tian, X Armant, M Federation, A Qi, J Bradner, JE Tenen, DG Chai, L AF Tatetsu, Hiro Wang, Fei Gao, Chong Ueno, Shikiko Tian, Xi Armant, Myriam Federation, Alex Qi, Jun Bradner, James E. Tenen, Daniel G. Chai, Li TI SALL4 Is a Key Factor in HDAC Inhibitor Mediated Ex Vivo Expansion of Human Peripheral Blood Mobilized Stem/Progenitor CD34+CD90+Cells SO BLOOD LA English DT Meeting Abstract C1 [Tatetsu, Hiro; Wang, Fei; Gao, Chong; Tian, Xi; Chai, Li] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ueno, Shikiko] Kumamoto Univ, Sch Med, Kumamoto 860, Japan. [Armant, Myriam] Ctr Human Cell Therapy, Boston, MA USA. [Federation, Alex; Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tenen, Daniel G.] Harvard Univ, Sch Med, Boston, MA USA. [Tenen, Daniel G.] Natl Univ Singapore, Singapore 117548, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702082 ER PT J AU Touzeau, C Ryan, J Moreau, P Chonghaile, TN Le Gouill, S Richardson, PG Anderson, KC Amiot, M Letai, AG AF Touzeau, Cyrille Ryan, Jeremy Moreau, Philippe Chonghaile, Triona Ni Le Gouill, Steven Richardson, Paul G. Anderson, Kenneth C. Amiot, Martine Letai, Anthony G. TI BH3 Profiling Identifies Bcl-2 Dependency in Multiple Myeloma and Predicts Sensitivity to BH3 Mimetics SO BLOOD LA English DT Meeting Abstract C1 [Touzeau, Cyrille; Ryan, Jeremy; Chonghaile, Triona Ni; Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moreau, Philippe] Univ Hosp Nantes, Nantes, France. [Le Gouill, Steven] CHU Nantes, F-44035 Nantes 01, France. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Amiot, Martine] CNRS 6299, Inserm 892, CRCNA, Nantes, France. RI Ni Chonghaile, Triona/L-9418-2015; richard, chrystelle/K-8595-2015 OI Ni Chonghaile, Triona/0000-0002-3041-4031; NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701161 ER PT J AU Vaughn, JE Storer, BE Armand, P Raimondi, R Gibson, CJ Rambaldi, A Ciceri, F Oneto, R Bruno, B Martin, PJ Sandmaier, BM Storb, RF Sorror, ML AF Vaughn, Jennifer E Storer, Barry E Armand, Philippe P Raimondi, Roberto R Gibson, Christopher J Rambaldi, Alessandro A Ciceri, Fabio C Oneto, Rosi R Bruno, Benedetto B Martin, Paul J Sandmaier, Brenda M Storb, Rainer F Sorror, Mohamed L TI Pre-Transplant Ferritin, Albumin and Platelet Count Add Prognostic Information to Comorbidities for Allogeneic Hematopoietic Cell Transplantation (HCT) Outcomes: A Multi-Center Discovery-Validation Study SO BLOOD LA English DT Meeting Abstract C1 [Vaughn, Jennifer E; Storer, Barry E; Martin, Paul J; Sandmaier, Brenda M; Storb, Rainer F; Sorror, Mohamed L] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Vaughn, Jennifer E; Martin, Paul J; Sandmaier, Brenda M; Sorror, Mohamed L] Univ Washington, Seattle, WA 98195 USA. [Storer, Barry E] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Armand, Philippe P; Gibson, Christopher J] Dana Farber Canc Inst, Boston, MA 02115 USA. [Raimondi, Roberto R] Osped San Bortolo, Vicenza, Italy. [Rambaldi, Alessandro A] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Ciceri, Fabio C] Ist Sci San Raffaele, I-20132 Milan, Italy. [Oneto, Rosi R] Osped San Martino Genova, Genoa, Italy. [Bruno, Benedetto B] Univ Turin, AOU San Giovanni Battista, Turin, Italy. [Storb, Rainer F] Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701142 ER PT J AU Verstovsek, S Talpaz, M Ritchie, EK Wadleigh, M Odenike, O Jamieson, C Stein, BL Tomonori, U Mesa, R AF Verstovsek, Srdan Talpaz, Moshe Ritchie, Ellen K. Wadleigh, Martha Odenike, Olatoyosi Jamieson, Catriona Stein, Brady L. Tomonori, Uno Mesa, Ruben TI A Phase 1/2, Open-Label, Dose-Escalation, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered NS-018 in Patients with Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (postPV MF), or Post-Essential Thrombocythemia Myelofibrosis (postET MF) SO BLOOD LA English DT Meeting Abstract C1 [Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Talpaz, Moshe] Univ Michigan, Ann Arbor, MI 48109 USA. [Ritchie, Ellen K.] Cornell Univ, New York, NY 10021 USA. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Odenike, Olatoyosi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Jamieson, Catriona] Univ Calif San Diego, La Jolla, CA 92093 USA. [Stein, Brady L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Tomonori, Uno] NS Phrama Inc, Paramus, NJ USA. [Mesa, Ruben] Mayo Clin, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701160 ER PT J AU Wang, M Nooka, AK Yee, AJ Thomas, SK O'Donnell, E Shah, J Weber, DM Kaufman, JL Lonial, S Avigan, D Raje, N AF Wang, Michael (Luhua) Nooka, Ajay K. Yee, Andrew J. Thomas, Sheeba K. O'Donnell, Elizabeth Shah, Jatin Weber, Donna M. Kaufman, Jonathan L. Lonial, Sagar Avigan, David Raje, Noopur TI Initial Results of a Phase 1/2a, Dose Escalation Study of PVX-410 Multi-Peptide Cancer Vaccine in Patients with Smoldering Multiple Myeloma (SMM) SO BLOOD LA English DT Meeting Abstract C1 [Wang, Michael (Luhua); Thomas, Sheeba K.; Shah, Jatin; Weber, Donna M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nooka, Ajay K.; Kaufman, Jonathan L.; Lonial, Sagar] Emory Univ, Atlanta, GA 30322 USA. [Yee, Andrew J.; O'Donnell, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242707017 ER PT J AU Xie, HF Peng, C Qi, J Cheloni, G Das, P Huang, JL Nguyen, M Li, SG Bradner, JE Orkin, SH AF Xie, Huafeng Peng, Cong Qi, Jun Cheloni, Giullia Das, Partha Huang, Jialiang Minh Nguyen Li, Shaoguang Bradner, James E. Orkin, Stuart H. TI Eradication of Chronic Myelogenous Leukemia By Inactivation of the Polycomb Group Protein EZH2 SO BLOOD LA English DT Meeting Abstract C1 [Xie, Huafeng; Huang, Jialiang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Peng, Cong] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Qi, Jun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cheloni, Giullia; Li, Shaoguang] Univ Massachusetts, Sch Med, Worcester, MA USA. [Das, Partha] Boston Childrens Hosp, Boston, MA USA. [Bradner, James E.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701007 ER PT J AU Xu, J Shao, Z Li, D Xie, HF Kim, W Huang, JL Pinello, L Glass, K Yuan, GC Orkin, SH AF Xu, Jian Shao, Zhen Li, Dan Xie, Huafeng Kim, Woojin Huang, Jialiang Pinello, Luca Glass, Kimberly Yuan, Guo-Cheng Orkin, Stuart H. TI Developmental Control of Polycomb Subunit Composition Mediates a Switch to Non-Canonical Functions during Hematopoiesis SO BLOOD LA English DT Meeting Abstract C1 [Xu, Jian; Shao, Zhen; Xie, Huafeng; Kim, Woojin; Huang, Jialiang; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Xu, Jian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Shao, Zhen] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Shanghai, Peoples R China. [Li, Dan] Harvard Univ, Boston, MA USA. [Pinello, Luca; Glass, Kimberly; Yuan, Guo-Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701076 ER PT J AU Yeh, AC Spitzer, TR Chen, YB McAfee, S Ballen, KK Attar, EC Fathi, AT Dey, BR AF Yeh, Albert C. Spitzer, Thomas R. Chen, Yi-Bin McAfee, Steven Ballen, Karen K. Attar, Eyal C. Fathi, Amir T. Dey, Bimalangshu R. TI Serum Uric Acid Levels during Allogeneic Hematopoeitic Cell Transplantation and Subsequent Graft Versus Host Disease SO BLOOD LA English DT Meeting Abstract C1 [Yeh, Albert C.; Spitzer, Thomas R.; McAfee, Steven; Attar, Eyal C.; Dey, Bimalangshu R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, Yi-Bin; Ballen, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242703118 ER PT J AU Yi, JS Federation, A Qi, J Dhe-Paganon, S Hadler, M Xu, X Varca, A St Pierre, R Armstrong, SA Bradner, JE AF Yi, Joanna S. Federation, Alex Qi, Jun Dhe-Paganon, Sirano Hadler, Michael Xu, Xiang Varca, Anthony St Pierre, Roodolph Armstrong, Scott A. Bradner, James E. TI Structure-Guided Design of DOT1L Methyltransferase Inhibitors By a Novel, Label Free Assay Platform SO BLOOD LA English DT Meeting Abstract C1 [Yi, Joanna S.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Federation, Alex; Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dhe-Paganon, Sirano; Varca, Anthony; St Pierre, Roodolph] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hadler, Michael; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Xu, Xiang] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701202 ER PT J AU Yoda, A Adelmant, G Tamburini, J Chapuy, B Shindoh, N Yoda, Y Weigert, O Kopp, N Wu, SC Kim, SS Liu, HY Tivey, T Christie, AL Elpek, KG Card, J Gritsman, K Gotlib, J Deininger, MW Makishima, H Turley, S Javidi-Sharifi, N Maciejewski, JP Rodig, SJ Tyner, JW Marto, JA Weinstock, DM Lane, AA AF Yoda, Akinori Adelmant, Guillaume Tamburini, Jerome Chapuy, Bjoern Shindoh, Nobuaki Yoda, Yuka Weigert, Oliver Kopp, Nadja Wu, Shuo-Chieh Kim, Sunhee S. Liu, Huiyun Tivey, Trevor Christie, Amanda L. Elpek, Kutlu G. Card, Joseph Gritsman, Kira Gotlib, Jason Deininger, Michael W. Makishima, Hideki Turley, Shannon Javidi-Sharifi, Nathalie Maciejewski, Jaroslaw P. Rodig, Scott J. Tyner, Jeffrey W. Marto, Jarrod A. Weinstock, David M. Lane, Andrew A. TI GNB1 Activating Mutations Promote Myeloid and Lymphoid Neoplasms Targetable By Combined PI3K/mTOR Inhibition SO BLOOD LA English DT Meeting Abstract C1 [Yoda, Akinori; Adelmant, Guillaume; Chapuy, Bjoern; Shindoh, Nobuaki; Yoda, Yuka; Weigert, Oliver; Kopp, Nadja; Wu, Shuo-Chieh; Kim, Sunhee S.; Liu, Huiyun; Tivey, Trevor; Christie, Amanda L.; Elpek, Kutlu G.; Card, Joseph; Turley, Shannon; Marto, Jarrod A.; Weinstock, David M.; Lane, Andrew A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tamburini, Jerome] Univ Paris 05, Paris, France. [Shindoh, Nobuaki] Astellas Pharma Inc, Tsukuba, Ibaraki, Japan. [Weigert, Oliver] Univ Hosp, Dept Internal Med 3, Munich, Germany. [Gritsman, Kira] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gotlib, Jason] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Deininger, Michael W.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA. [Makishima, Hideki; Maciejewski, Jaroslaw P.] Cleveland Clin, Cleveland, OH 44106 USA. [Javidi-Sharifi, Nathalie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702149 ER PT J AU Zhang, Y Zhang, Y Mishima, Y Moschetta, M Zhang, WJ Maiso, P Sacco, A Aljawai, Y Sahin, I Reagan, MR Ring, JE Tam, WF Xu, QL Pachte, JA Roccaro, AM Ghobrial, IM AF Zhang, Yu Zhang, Yong Mishima, Yuji Moschetta, Michele Zhang, Wenjing Maiso, Patricia Sacco, Antonio Aljawai, Yosra Sahin, Ilyas Reagan, Michaela R. Ring, Jennifer E. Tam, Winnie F. Xu, Qunli Pachte, Jonathan A. Roccaro, Aldo M. Ghobrial, Irene M. TI Proline-Rich Tyrosine Kinase (Pyk2) Promotes Tumor Progression in Multiple Myeloma (MM) and Represents a Novel Target for Therapy in MM SO BLOOD LA English DT Meeting Abstract C1 [Zhang, Yu; Mishima, Yuji; Moschetta, Michele; Zhang, Wenjing; Maiso, Patricia; Sacco, Antonio; Aljawai, Yosra; Sahin, Ilyas; Reagan, Michaela R.; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Yong] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ring, Jennifer E.; Tam, Winnie F.; Xu, Qunli; Pachte, Jonathan A.] Verastem Inc, Cambridge, MA USA. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242702113 ER PT J AU Zhou, L Wang, WH Zimmerman, G Myers, J Huang, YS Yu, VWC Huang, D Yu, SL Wang, YW Huang, XR Shim, J Yan, MH Lowe, J Xin, W Stanley, P Scadden, DT Huang, AY Siebel, CW AF Zhou, Lan Wang, Weihuan Zimmerman, Grant Myers, Jay Huang, Yuanshuai Yu, Vionnie W. C. Huang, Dan Yu, Shuiliang Wang, Yiwei Huang, Xiaoran Shim, Jeongsup Yan, Minhong Lowe, John Xin, Wei Stanley, Pamela Scadden, David T. Huang, Alex Y. Siebel, Christian W. TI Loss of Notch Receptor-Ligand Engagement Leads to Increased Hematopoietic Stem and Progenitor Cell Egress and Mobilization SO BLOOD LA English DT Meeting Abstract C1 [Zhou, Lan; Wang, Weihuan; Zimmerman, Grant; Myers, Jay; Huang, Yuanshuai; Huang, Dan; Yu, Shuiliang; Wang, Yiwei; Huang, Xiaoran; Xin, Wei; Huang, Alex Y.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Yu, Vionnie W. C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Yu, Vionnie W. C.] Harvard Stem Cell Inst, Boston, MA USA. [Shim, Jeongsup; Yan, Minhong; Lowe, John; Siebel, Christian W.] Genentech Inc, San Francisco, CA 94080 USA. [Stanley, Pamela] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Scadden, David T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KQ UT WOS:000349242701041 ER PT J AU Abel, GA Efficace, F Buckstein, R Tinsley, S Jurcic, JG Martins, Y Steensma, DP Watts, CD Raza, A List, AF Klaassen, RJ AF Abel, Gregory A. Efficace, Fabio Buckstein, Rena Tinsley, Sara Jurcic, Joseph G. Martins, Yolanda Steensma, David P. Watts, Corey D. Raza, Azra List, Alan F. Klaassen, Robert J. TI Preliminary International Validation of the Quality of Life in Myelodysplasia Scale (QUALMS) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Abel, Gregory A.; Martins, Yolanda; Steensma, David P.; Watts, Corey D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Efficace, Fabio] GIMEMA Fdn, Italian Grp Adult Hematol Dis GIMEMA, Rome, Italy. [Buckstein, Rena] Odette Canc Ctr, Toronto, ON, Canada. [Tinsley, Sara; List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Jurcic, Joseph G.; Raza, Azra] Columbia Univ, Med Ctr, New York, NY USA. [Klaassen, Robert J.] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. NR 0 TC 0 Z9 0 U1 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801103 ER PT J AU Abramson, JS Jacobsen, ED Redd, RA Takvorian, T Fisher, DC Brown, JR Schwartz, JH Weitzman, J Neuberg, D Barnes, JA Hochberg, EP AF Abramson, Jeremy S. Jacobsen, Eric D. Redd, Robert Allyn Takvorian, Tak Fisher, David C. Brown, Jennifer R. Schwartz, Joel H. Weitzman, James Neuberg, Donna Barnes, Jeffrey A. Hochberg, Ephraim P. TI Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphomas: Final Results from a Phase 1-2 Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Abramson, Jeremy S.; Takvorian, Tak; Barnes, Jeffrey A.; Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Jacobsen, Eric D.; Redd, Robert Allyn; Fisher, David C.; Brown, Jennifer R.; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schwartz, Joel H.; Weitzman, James] MGH North Shore Canc Ctr, Danvers, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808119 ER PT J AU Acharya, C An, G Zhong, MY Cea, M Cagnetta, A Jiang, H Tai, YT Anderson, KC AF Acharya, Chirag An, Gang Zhong, Mike Y. Cea, Michele Cagnetta, Antonia Jiang, Hua Tai, Yu-Tzu Anderson, Kenneth C. TI NF kappa B Signaling and Mcl-1 Are Critical in B Cell Maturation Antigen-Promoted Multiple Myeloma Cell Growth and Survival SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Acharya, Chirag; Zhong, Mike Y.; Cea, Michele; Cagnetta, Antonia; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Acharya, Chirag; Zhong, Mike Y.; Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [An, Gang; Jiang, Hua] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805015 ER PT J AU Adamia, S Toniolo, P Fathi, AT Galinsky, I Liu, SY Yen, K Kim, HK Zhu, DW Kim, S Wadleigh, M Steensma, DP Dagogo-Jack, I DeAngelo, DJ Griffin, JD Stone, RM AF Adamia, Sophia Toniolo, Patricia Fathi, Amir T. Galinsky, Ilene Liu, Suiyang Yen, Katharine Kim, Hyeryun Kim Zhu, Dongwei Kim, Straley Wadleigh, Martha Steensma, David P. Dagogo-Jack, Ibiayi DeAngelo, Daniel J. Griffin, James D. Stone, Richard M. TI IDH1 Splicing Alterations in Patients with AML and Their Relationship to Blood 2HG Levels SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Adamia, Sophia; Toniolo, Patricia; Galinsky, Ilene; Liu, Suiyang; Wadleigh, Martha; Steensma, David P.; Dagogo-Jack, Ibiayi; DeAngelo, Daniel J.; Griffin, James D.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Adamia, Sophia] HMS, Boston, MA USA. [Fathi, Amir T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yen, Katharine; Kim, Hyeryun Kim; Zhu, Dongwei; Kim, Straley] Agios Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502069 ER PT J AU Alho, AC Haesook, KT Reynolds, CG Chammas, MJ McDonough, S Lazo-Kallanian, S Daley, J Nikiforow, S Cutler, CS Koreth, J Ho, VT Armand, P Soiffer, RJ Antin, JH Ritz, J AF Alho, Ana Cristina Haesook, Kim T. Reynolds, Carol G. Chammas, Marie J. McDonough, Sean Lazo-Kallanian, Suzan Daley, John Nikiforow, Sarah Cutler, Corey S. Koreth, John Ho, Vincent T. Armand, Philippe Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome TI Homeostatic Reconstitution of CD4+Regulatory and Conventional T Cell Subsets in Adult Patients after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Alho, Ana Cristina; Reynolds, Carol G.; Chammas, Marie J.; McDonough, Sean; Lazo-Kallanian, Suzan; Daley, John; Nikiforow, Sarah; Koreth, John; Ho, Vincent T.; Armand, Philippe; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Alho, Ana Cristina] Univ Lisbon, Fac Med, P-1699 Lisbon, Portugal. [Haesook, Kim T.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Haesook, Kim T.; Cutler, Corey S.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504024 ER PT J AU Amrein, PC Kai, X Iuchi, Y Arnason, J Brown, JR Ballen, KK Attar, EC Fathi, AT Hochberg, EP Hwang, H Pillai, S AF Amrein, Philip C. Kai, Xin Iuchi, Yasuyuki Arnason, Jon Brown, Jennifer R. Ballen, Karen K. Attar, Eyal C. Fathi, Amir T. Hochberg, Ephraim P. Hwang, HyukJoo Pillai, Shiv TI Inhibition of Phosphorylation of ERK in CLL Cells Pre-Treatment Correlates Best with Response to Dasatinib, Fludarabine, and Rituximab for Patients with Relapsed CLL SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Amrein, Philip C.; Kai, Xin; Iuchi, Yasuyuki; Hwang, HyukJoo; Pillai, Shiv] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arnason, Jon] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen K.; Attar, Eyal C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504199 ER PT J AU Anagnostou, T Arvanitis, M Ziakas, PD Zacharioudakis, I Zervou, F Caliendo, A Mylonakis, EE AF Anagnostou, Theodora Arvanitis, Marios Ziakas, Panayiotis D. Zacharioudakis, Ioannis Zervou, Fainareti Caliendo, Angela Mylonakis, Eleftherios E. TI Polymerase Chain Reaction in the Diagnosis of Invasive Aspergillosis in Hematopoietic Stem Cell Transplant Recipients: A Meta-Analysis of Diagnostic Performance SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Anagnostou, Theodora] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Anagnostou, Theodora] Harvard Univ, Sch Med, Mt Auburn Hosp, Boston, MA USA. [Arvanitis, Marios] Boston Med Ctr, Boston, MA USA. [Ziakas, Panayiotis D.; Zacharioudakis, Ioannis] Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. [Zervou, Fainareti; Caliendo, Angela; Mylonakis, Eleftherios E.] Brown Univ, Rhode Isl Hosp, Providence, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503002 ER PT J AU Appelmann, I Scuoppo, C Thapar, V Ledezma, D Lujambio, A Lowe, SW Chicas, A AF Appelmann, Iris Scuoppo, Claudio Thapar, Vishal Ledezma, Daniela Lujambio, Amaia Lowe, Scott W. Chicas, Agustin TI Suppression of EZH2 Accelerates MYC-Driven Lymphomagenesis By Inhibition of Apoptosis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Appelmann, Iris; Lujambio, Amaia; Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Scuoppo, Claudio] Columbia Univ, New York, NY USA. [Thapar, Vishal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ledezma, Daniela] Univ Nacl Autonoma Mexico, Cuernavaca 62191, Morelos, Mexico. [Chicas, Agustin] H3 Biomed, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500165 ER PT J AU Armand, P Ansell, SM Lesokhin, AM Halwani, A Millenson, MM Schuster, SJ Timmerman, J Borrello, I Gutierrez, M Scott, EC Cattry, D Chapuy, B Ligon, AH Rodig, SJ Zhu, LL Grosso, JF Kim, SY Shipp, MA AF Armand, Philippe Ansell, Stephen M. Lesokhin, Alexander M. Halwani, Ahmad Millenson, Michael M. Schuster, Stephen J. Timmerman, John Borrello, Ivan Gutierrez, Martin Scott, Emma C. Cattry, Deepika Chapuy, Bjoern Ligon, Azra H. Rodig, Scott J. Zhu, Lili Grosso, Joseph F. Kim, Su Young Shipp, Margaret A. TI Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma - Preliminary Safety, Efficacy and Biomarker Results of a Phase I Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Armand, Philippe; Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ansell, Stephen M.] Mayo Clin, Rochester, MN USA. [Lesokhin, Alexander M.; Cattry, Deepika] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Halwani, Ahmad] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Schuster, Stephen J.] Perelman Ctr Adv Med, Philadelphia, PA USA. [Timmerman, John] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Borrello, Ivan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Borrello, Ivan] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Gutierrez, Martin] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Scott, Emma C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Ligon, Azra H.; Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zhu, Lili; Grosso, Joseph F.; Kim, Su Young] Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805057 ER PT J AU Asano, T Kim, HT Koreth, J Soiffer, RJ Meguri, Y Yoshioka, T Yagita, H Tanimoto, M Ritz, J Matsuoka, K AF Asano, Takeru Kim, Haesook T. Koreth, John Soiffer, Robert J. Meguri, Yusuke Yoshioka, Takanori Yagita, Hideo Tanimoto, Mitsune Ritz, Jerome Matsuoka, Ken-ichi TI Enhanced Expression of PD-1 Modulates CD4+Foxp3+Regulatory T Cell Homeostasis during Low-Dose IL-2 Therapy in Patients with Chronic Graft-Versus-Host Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Asano, Takeru; Meguri, Yusuke; Yoshioka, Takanori; Tanimoto, Mitsune; Matsuoka, Ken-ichi] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. [Kim, Haesook T.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Koreth, John; Soiffer, Robert J.; Ritz, Jerome; Matsuoka, Ken-ichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yagita, Hideo] Juntendo Univ, Grad Sch Med, Tokyo, Japan. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502068 ER PT J AU Avet-Loiseau, H Corre, J Maheo, S Zheng, JB Faham, M Richardson, PG Anderson, KC Attal, M Munshi, N AF Avet-Loiseau, Herve Corre, Jill Maheo, Sabrina Zheng, Jianbiao Faham, Malek Richardson, Paul G. Anderson, Kenneth C. Attal, Michel Munshi, Nikhil TI Identification Rate of Myeloma-Specific Clonotypes in Multiple Diagnostic Sample Types from Patients with Multiple Myeloma Using Next-Generation Sequencing Method SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Avet-Loiseau, Herve; Corre, Jill; Maheo, Sabrina; Attal, Michel] Univ Hosp Toulouse, Toulouse, France. [Zheng, Jianbiao; Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.; Munshi, Nikhil] Dana Farber Canc Inst, Boston, MA 02115 USA. RI corre, jill/Q-2460-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504210 ER PT J AU Bagby, GC AF Bagby, Grover C. TI The Role of Innate Immune Dysfunction in Inherited Bone Marrow Failure SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. NR 1 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802005 ER PT J AU Baljevic, M Dumitriu, B Lee, JW Paietta, E Racevskis, J Chen, C Stein, EM Gallagher, RE Rowe, JM Appelbaum, FR Powell, BL Larson, RA Young, NS Tallman, MS AF Baljevic, Muhamed Dumitriu, Bogdan Lee, Ju-Whei Paietta, Elisabeth Racevskis, Janis Chen, Christina Stein, Eytan M. Gallagher, Robert E. Rowe, Jacob M. Appelbaum, Frederick R. Powell, Bayard L. Larson, Richard A. Young, Neal S. Tallman, Martin S. TI Telomere Length Recovery Strongly Predicts Overall Survival in Acute Promyelocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Baljevic, Muhamed] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dumitriu, Bogdan; Chen, Christina; Young, Neal S.] NIH, Bethesda, MD 20892 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paietta, Elisabeth] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Racevskis, Janis] 4Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY USA. [Stein, Eytan M.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gallagher, Robert E.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804117 ER PT J AU Ballen, KK Li, SL Cutler, CS Chen, YB McAfee, SL Dey, BR Le, MT Winkfield, KM Avigan, D Rosenblatt, J Joyce, R Boussiotis, VA Ho, VT Armand, P Alyea, EP Koreth, J Soiffer, RJ Spitzer, TR Antin, JH Makar, R Kuter, DJ AF Ballen, Karen K. Li, Shuli Cutler, Corey S. Chen, Yi-Bin McAfee, Steven L. Dey, Bimalangshu R. Le, Maria Theresa Winkfield, Karen M. Avigan, David Rosenblatt, Jacalyn Joyce, Robin Boussiotis, Vassiliki A. Ho, Vincent T. Armand, Philippe Alyea, Edwin P. Koreth, John Soiffer, Robert J. Spitzer, Thomas R. Antin, Joseph H. Makar, Robert Kuter, David J. TI Delayed Platelet Engraftment after Umbilical Cord Blood Transplant: Relationship to Circulating Levels of Thrombopoietin SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ballen, Karen K.; Chen, Yi-Bin; McAfee, Steven L.; Dey, Bimalangshu R.; Winkfield, Karen M.; Spitzer, Thomas R.; Makar, Robert; Kuter, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Li, Shuli; Cutler, Corey S.; Ho, Vincent T.; Armand, Philippe; Alyea, Edwin P.; Soiffer, Robert J.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Le, Maria Theresa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rosenblatt, Jacalyn; Joyce, Robin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Boussiotis, Vassiliki A.] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02215 USA. [Koreth, John] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501126 ER PT J AU Bar-Natan, M Luptakova, K Douglas, M Stroopinsky, D Rajabi, H Pyzer, AR Palmer, KA Reagan, MR Somaiya, P Jain, S Arnason, J Ghobrial, IM Rosenblatt, J Anderson, KC Kufe, D Avigan, D AF Bar-Natan, Michal Luptakova, Katarina Douglas, Maxwell Stroopinsky, Dina Rajabi, Hasan Pyzer, Athalia Rachel Palmer, Kristen A. Reagan, Michaela R. Somaiya, Poorvi Jain, Salvia Arnason, Jon Ghobrial, Irene M. Rosenblatt, Jacalyn Anderson, Kenneth C. Kufe, Donald Avigan, David TI Bone Marrow Stroma Protects Myeloma Cells from Cytotoxic Damage Via Induction of the Oncoprotein MUC1 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bar-Natan, Michal; Luptakova, Katarina; Douglas, Maxwell; Stroopinsky, Dina; Pyzer, Athalia Rachel; Palmer, Kristen A.; Somaiya, Poorvi; Jain, Salvia; Arnason, Jon; Rosenblatt, Jacalyn; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rajabi, Hasan; Reagan, Michaela R.; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ghobrial, Irene M.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808067 ER PT J AU Bararia, D Heide, M Romashova, T Alessandro, P Wilson, BG Roberts, CWM Hiddemann, W Weinstock, DM Weigert, O AF Bararia, Deepak Heide, Michael Romashova, Tatiana Alessandro, Pastore Wilson, Boris G. Roberts, Charles W. M. Hiddemann, Wolfgang Weinstock, David M. Weigert, Oliver TI ARID1A Is Recurrently and Significantly Mutated in Follicular Lymphoma (FL) and Impairs DNA Repair Efficiency SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bararia, Deepak; Heide, Michael; Romashova, Tatiana; Alessandro, Pastore; Hiddemann, Wolfgang; Weigert, Oliver] Univ Hosp Munich, LMU, Munich, Germany. [Wilson, Boris G.] GlaxoSmithKline, Collegeville, PA USA. [Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Weinstock, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500070 ER PT J AU Barrientos, JC O'Brien, S Brown, JR Kay, NE Reddy, NM Coutre, S Tam, C Mulligan, S Jaeger, U Devereux, S Pocock, C Robak, T Schuster, SJ Schuh, A Gill, D Bloor, A Dearden, C Moreno, C Cull, G Hamblin, M Jones, JA Kierschniak, T Eckert, K Suzuki, S Hsu, E James, DF Byrd, JC Hillmen, P AF Barrientos, Jacqueline C. O'Brien, Susan Brown, Jennifer R. Kay, Neil E. Reddy, Nishitha M. Coutre, Steven Tam, Constantine Mulligan, Stephen Jaeger, Ulrich Devereux, Steve Pocock, Christopher Robak, Tadeusz Schuster, Stephen J. Schuh, Anna Gill, Devinder Bloor, Adrian Dearden, Claire Moreno, Carol Cull, Gavin Hamblin, Michael Jones, Jeffrey A. Kierschniak, Tanja Eckert, Karl Suzuki, Samuel Hsu, Emily James, Danelle F. Byrd, John C. Hillmen, Peter TI Hematologic and Immunologic Function and Patient Well-Being for the Phase III RESONATE (TM) Study of Ibrutinib Vs Ofatumumab in Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Barrientos, Jacqueline C.] North Shore LIJ Canc Inst, Lake Success, NY USA. [O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kay, Neil E.] Mayo Clin, Rochester, MN USA. [Reddy, Nishitha M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Coutre, Steven] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Tam, Constantine] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, Constantine] St Vincents Hosp, Melbourne, Vic, Australia. [Mulligan, Stephen] Royal N Shore Hosp, Sydney, NSW, Australia. [Jaeger, Ulrich] Med Univ Vienna, Vienna, Austria. [Devereux, Steve] Kings Coll Hosp London, NHS Fdn Trust, London, England. [Pocock, Christopher] East Kent Hosp, Canterbury, Kent, England. [Robak, Tadeusz] Med Univ Lodz, Copernicus Mem Hosp, Lodz, Poland. [Schuster, Stephen J.] Perelman Ctr Adv Med, Philadelphia, PA USA. [Schuh, Anna] Univ Oxford, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford, England. [Gill, Devinder] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Bloor, Adrian] Christie Clin, Manchester, Lancs, England. [Dearden, Claire] Royal Marsden Hosp, London SW3 6JJ, England. [Moreno, Carol] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Cull, Gavin] Sir Charles Gairdner Hosp, Perth, WA, Australia. [Hamblin, Michael] Colchester Gen Hosp, Colchester, Essex, England. [Jones, Jeffrey A.; Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Kierschniak, Tanja; Eckert, Karl; Suzuki, Samuel; Hsu, Emily; James, Danelle F.] Pharmacyclics Inc, Sunnyvale, CA USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. NR 0 TC 2 Z9 2 U1 0 U2 4 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505160 ER PT J AU Bejar, R Papaemmanuil, E Haferlach, T Garcia-Manero, G Maciejewski, JP Sekeres, MA Walter, MJ Graubert, TA Cazzola, M Malcovati, L Campbell, PJ Ogawa, S Boultwood, J Bowen, D Tauro, S Groves, MJ Fontenay, M Shih, LY Tuchler, H Stevenson, KE Neuberg, D Greenberg, PL Ebert, BL AF Bejar, Rafael Papaemmanuil, Elli Haferlach, Torsten Garcia-Manero, Guillermo Maciejewski, Jaroslaw P. Sekeres, Mikkael A. Walter, Matthew J. Graubert, Timothy A. Cazzola, Mario Malcovati, Luca Campbell, Peter J. Ogawa, Seishi Boultwood, Jacqueline Bowen, David Tauro, Sudhir Groves, Michael J. Fontenay, Michaela Shih, Lee-Yung Tuechler, Heinz Stevenson, Kristen E. Neuberg, Donna Greenberg, Peter L. Ebert, Benjamin L. TI TP53 Mutation Status Divides MDS Patients with Complex Karyotypes into Distinct Prognostic Risk Groups: Analysis of Combined Datasets from the International Working Group for MDS-Molecular Prognosis Committee SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bejar, Rafael] UCSD Moores Canc Ctr, La Jolla, CA USA. [Papaemmanuil, Elli; Campbell, Peter J.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Haferlach, Torsten] MLL Munich Leukemia Lab, Munich, Germany. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Walter, Matthew J.] Washington Univ, Sch Med, St Louis, MO USA. [Graubert, Timothy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cazzola, Mario; Malcovati, Luca] Fdn IRCCS Policlin San Matteo, Pavia, Italy. [Cazzola, Mario; Malcovati, Luca] Univ Pavia, I-27100 Pavia, Italy. [Ogawa, Seishi] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Boultwood, Jacqueline] John Radcliffe Hosp, NDCLS, LRF Mol Haematol Unit, Oxford OX3 9DU, England. [Bowen, David] Leeds Teaching Hosp, Leeds, W Yorkshire, England. [Tauro, Sudhir; Groves, Michael J.] Ninewells Hosp, Dundee DD1 9SY, Scotland. [Fontenay, Michaela] AP HP, Paris, France. [Shih, Lee-Yung] Chang Gung Mem Hosp, Taipei 10591, Taiwan. [Tuechler, Heinz] Ludwig Boltzmann Inst Leukemia Res, Vienna, Austria. [Stevenson, Kristen E.; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Greenberg, Peter L.] Stanford Univ, Stanford, CA 94305 USA. [Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803090 ER PT J AU Beltran, BE Chavez, JC Sotomayor, EM Castillo, JJ AF Beltran, Brady E. Chavez, Julio C. Sotomayor, Eduardo M. Castillo, Jorge J. TI Lymphopenia Is an Adverse Prognostic Factor in EBV-Positive Diffuse Large B-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Beltran, Brady E.] Hosp Nacl Edgardo Rebagliati Martins, Lima, Peru. [Chavez, Julio C.; Sotomayor, Eduardo M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802016 ER PT J AU Bendapudi, PK Li, A Hamdan, A Fry, AM Uhl, L Marques, M Kaufman, R Stowell, CP Sunny, W Makar, RS AF Bendapudi, Pavan K. Li, Ang Hamdan, Ayad Fry, Ashley Michelle Uhl, Lynne Marques, Marisa Kaufman, Richard Stowell, Christopher P. Sunny, Walter Makar, Robert S. TI Derivation and Prospective Validation of a Predictive Score for the Rapid Diagnosis of Thrombotic Thrombocytopenic Purpura: The Plasmic Score SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bendapudi, Pavan K.; Li, Ang; Stowell, Christopher P.; Sunny, Walter; Makar, Robert S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hamdan, Ayad] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fry, Ashley Michelle] Univ Alabama Hosp & Clin, Birmingham, AL USA. [Uhl, Lynne] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Marques, Marisa] Univ Alabama Birmingham, Birmingham, AL USA. [Kaufman, Richard] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502064 ER PT J AU Blaser, BW Li, B Tamplin, OJ Binder, V Prober, D Schier, A Vidal, M Zon, LI AF Blaser, Bradley Wayne Li, Brian Tamplin, Owen J. Binder, Vera Prober, David Schier, Alexander Vidal, Marc Zon, Leonard I. TI Identification of Secreted Factors with a Role in Hematopoietic Stem and Progenitor Cell Engraftment in the Developing Zebrafish SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Blaser, Bradley Wayne; Vidal, Marc] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Brian; Binder, Vera] Boston Childrens Hosp, Boston, MA USA. [Tamplin, Owen J.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA USA. [Prober, David] CALTECH, Pasadena, CA 91125 USA. [Schier, Alexander] Harvard Univ, Cambridge, MA 02138 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston Childrens Hosp, Boston, MA 02115 USA. RI Binder, Vera/N-2078-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806009 ER PT J AU Bolli, N Bignell, GR Ganly, P Papaemmanuil, E Avet-Loiseau, H Sperling, A Minvielle, S Campbell, PJ Munshi, NC AF Bolli, Niccolo Bignell, Graham R. Ganly, Peter Papaemmanuil, Elli Avet-Loiseau, Herve Sperling, Adam Minvielle, Stephane Campbell, Peter J. Munshi, Nikhil C. TI A Next Generation Sequencing-Based Approach to Detect Gene Mutations, Copy Number Changes and IGH Translocations in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Bolli, Niccolo] Univ Cambridge, Cambridge, England. [Bignell, Graham R.; Papaemmanuil, Elli; Campbell, Peter J.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Ganly, Peter] Christchurch Hosp, Christchurch, New Zealand. [Avet-Loiseau, Herve] Univ Hosp, Unit Genom Myeloma, Toulouse, France. [Avet-Loiseau, Herve] Univ Hosp Toulouse, Toulouse, France. [Sperling, Adam] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Minvielle, Stephane] Ctr Rech Cancerol Nantes Angers UMR Inserm 892 CN, Nantes, France. [Munshi, Nikhil C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Minvielle, Stephane/K-8251-2015 NR 0 TC 0 Z9 0 U1 0 U2 6 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804201 ER PT J AU Brendel, C Guda, S Renella, R Du, P Bauer, DE Canver, MC Kamran, SC Thornton, J de Boer, H Milsom, MD Orkin, SH Gregory, R Williams, DA AF Brendel, Christian Guda, Swaroopa Renella, Raffaele Du, Peng Bauer, Daniel E. Canver, Matthew C. Kamran, Sophia C. Thornton, James de Boer, Helen Milsom, Michael D. Orkin, Stuart H. Gregory, Richard Williams, David A. TI Optimization of Bcl11a Knockdown By miRNA Scaffold Embedded Shrnas Leading to Enhanced Induction of Fetal Hemoglobin in Erythroid Cells for the Treatment of Beta-Hemoglobinopathies SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brendel, Christian; Guda, Swaroopa; Renella, Raffaele; Bauer, Daniel E.; Canver, Matthew C.; Gregory, Richard] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Du, Peng; Thornton, James; de Boer, Helen; Williams, David A.] Boston Childrens Hosp, Boston, MA USA. [Kamran, Sophia C.] Harvard Univ, Sch Med, Boston, MA USA. [Milsom, Michael D.] German Canc Res Ctr, Heidelberg, Germany. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502179 ER PT J AU Brissot, E Ito, S Lu, K Cantilena, C Smith, BD Prince, G Sadrzadeh, H Fathi, AT Strickland, SA Hensel, NF Chinian, F Keyvanfar, K Battiwalla, M Muranski, P Hourigan, CS Barrett, J AF Brissot, Eolia Ito, Sawa Lu, Kit Cantilena, Carly Smith, B. Douglas Prince, Gabrielle Sadrzadeh, Hossein Fathi, Amir T. Strickland, Stephen A. Hensel, Nancy F. Chinian, Fariba Keyvanfar, Keyvan Battiwalla, Minoo Muranski, Pawel Hourigan, Christopher S. Barrett, John TI T Cell Exhaustion and Downregulation of Cytotoxic NK Cells - an Immune Escape Mechanism in Adult Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brissot, Eolia] NHLBI, NIH, Bethesda, MD 20892 USA. [Ito, Sawa; Lu, Kit; Keyvanfar, Keyvan; Battiwalla, Minoo; Muranski, Pawel; Hourigan, Christopher S.; Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Cantilena, Carly] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Smith, B. Douglas; Prince, Gabrielle] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Sadrzadeh, Hossein; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Strickland, Stephen A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Hensel, Nancy F.; Chinian, Fariba] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507203 ER PT J AU Brown, JR Fernandes, SM Kasar, S Hoang, K Moorhead, M Carlton, V Faham, M Miklos, DB Logan, AC AF Brown, Jennifer R. Fernandes, Stacey M. Kasar, Siddha Hoang, Kevin Moorhead, Martin Carlton, Victoria Faham, Malek Miklos, David B. Logan, Aaron C. TI Next-Generation Sequencing Reveals Clonal Evolution at the Immunoglobulin Loci in Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brown, Jennifer R.; Fernandes, Stacey M.; Kasar, Siddha; Hoang, Kevin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moorhead, Martin; Carlton, Victoria; Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Miklos, David B.] Stanford Univ, Stanford, CA 94305 USA. [Logan, Aaron C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501218 ER PT J AU Brown, JR Hillmen, P O'Brien, S Barrientos, JC Reddy, N Coutre, S Tam, C Mulligan, S Jaeger, U Barr, PM Furman, RR Kipps, TJ Cymbalista, F Thornton, P Caligaris-Cappio, F Delgado, J Montillo, M Devos, S Moreno, C Pagel, J Burger, JA Chung, D Lin, J Gau, L Chang, B McGreivy, J James, DF Byrd, JC AF Brown, Jennifer R. Hillmen, Peter O'Brien, Susan Barrientos, Jaqueline C. Reddy, Nishitha Coutre, Steven Tam, Constantine Mulligan, Stephen Jaeger, Ulrich Barr, Paul M. Furman, Richard R. Kipps, Thomas J. Cymbalista, Florence Thornton, Patrick Caligaris-Cappio, Federico Delgado, Julio Montillo, Marco Devos, Sven Moreno, Carol Pagel, John Burger, Jan A. Chung, Devon Lin, Jennifer Gau, Linda Chang, Betty McGreivy, Jesse James, Danelle F. Byrd, John C. TI Updated Efficacy Including Genetic and Clinical Subgroup Analysis and Overall Safety in the Phase 3 RESONATE (TM) Trial of Ibrutinib Versus Ofatumumab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [O'Brien, Susan; Burger, Jan A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Barrientos, Jaqueline C.] North Shore LIJ Sch Med, New Hyde Pk, NY USA. [Reddy, Nishitha] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Coutre, Steven] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Tam, Constantine] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, Constantine] St Vincents Hosp, Melbourne, Vic, Australia. [Mulligan, Stephen] Royal N Shore Hosp, Sydney, NSW, Australia. [Jaeger, Ulrich] Med Univ Vienna, Vienna, Austria. [Barr, Paul M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Furman, Richard R.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Kipps, Thomas J.] UCSD Moores Canc Ctr, San Diego, CA USA. [Cymbalista, Florence] Hop Avicenne, Paris, France. [Thornton, Patrick] Beaumont Hosp, Dublin 9, Ireland. [Caligaris-Cappio, Federico] Univ Vita Salute San Raffaele, Milan, Italy. [Delgado, Julio] Hosp Clin Barcelona, Barcelona, Spain. [Montillo, Marco] Osped Niguarda Ca Granda, Milan, Italy. [Devos, Sven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Moreno, Carol] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Pagel, John] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chung, Devon; Lin, Jennifer; Gau, Linda; Chang, Betty; McGreivy, Jesse; James, Danelle F.] Pharmacyclics Inc, Sunnyvale, CA USA. [Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. RI Delgado, Julio/D-4891-2013 OI Delgado, Julio/0000-0002-5157-4376 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806080 ER PT J AU Brown, JR Klinger, M Hervold, K Fernandes, SM Hoang, K Faham, M Oki, Y Wolf, JL Martinez-Lopez, J AF Brown, Jennifer R. Klinger, Mark Hervold, Kieran Fernandes, Stacey M. Hoang, Kevin Faham, Malek Oki, Yasuhiro Wolf, Jeffrey L. Martinez-Lopez, Joaquin TI Chronic Lymphocytic Leukemia Patients Harbor Very Low Frequency Stereotypic Immunoglobulin CDR3 Sequences SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brown, Jennifer R.; Fernandes, Stacey M.; Hoang, Kevin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Klinger, Mark; Hervold, Kieran; Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Oki, Yasuhiro] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wolf, Jeffrey L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Martinez-Lopez, Joaquin] Hosp 12 Octubre, E-28041 Madrid, Spain. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806012 ER PT J AU Brunner, AM Wander, SA Neuberg, D Sadrzadeh, H Ballen, KK Amrein, PC Attar, EC Chen, YB Perry, AM Burke, M Silver, R Adamia, S Yen, K Yang, H Straley, K Agresta, S Borger, DR Iafrate, AJ Stone, RM Fathi, AT AF Brunner, Andrew M. Wander, Seth A. Neuberg, Donna Sadrzadeh, Hossein Ballen, Karen K. Amrein, Philip C. Attar, Eyal C. Chen, Yi-Bin Perry, Ashley M. Burke, Meghan Silver, Regina Adamia, Sophia Yen, Katharine Yang, Hua Straley, Kimberly Agresta, Sam Borger, Darrell R. Iafrate, Anthony J. Stone, Richard M. Fathi, Amir T. TI Diagnostic Features and 2-Hydroxyglutarate (2-HG) Levels Among Acute Myeloid Leukemia (AML) Patients with and without Isocitrate Dehydrogenase (IDH) Mutations SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Brunner, Andrew M.; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Wander, Seth A.; Ballen, Karen K.; Amrein, Philip C.; Attar, Eyal C.; Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Neuberg, Donna; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sadrzadeh, Hossein] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Perry, Ashley M.; Burke, Meghan; Silver, Regina; Borger, Darrell R.; Iafrate, Anthony J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adamia, Sophia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yen, Katharine; Yang, Hua; Straley, Kimberly; Agresta, Sam] Agios Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 3 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803155 ER PT J AU Buonamici, S Perino, S Lim, KH Feala, J Obeng, EA Aicher, M Aird, D Bailey, S Berkenblit, A Chan, B Erik, C Corson, L Darman, R Fekkes, P Furman, RR Keaney, GF Kumar, P Kunii, K Lee, L Mackenzie, C Park, E Puyang, XL Selvaraj, A Thomas, M Wang, J Warmuth, M Yu, LH Zhu, P Mizui, Y Ebert, BL Smith, PG AF Buonamici, Silvia Perino, Samantha Lim, Kian Huat Feala, Jacob Obeng, Esther A. Aicher, Michelle Aird, Daniel Bailey, Suzanna Berkenblit, Anna Chan, Betty Erik, Corcoran Corson, Laura Darman, Rachel Fekkes, Peter Furman, Richard R. Keaney, Gregg F. Kumar, Pavan Kunii, Kaiko Lee, Linda Mackenzie, Crystal Park, Eunice Puyang, Xiaoling Selvaraj, Anand Thomas, Michael Wang, John Warmuth, Markus Yu, Lihua Zhu, Ping Mizui, Yoshiharu Ebert, Benjamin L. Smith, Peter G. TI Cancer-Associated Mutations in SF3B1 Exhibit Neomorphic Splicing Activity and Block Erythroid Differentiation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Buonamici, Silvia; Perino, Samantha; Lim, Kian Huat; Feala, Jacob; Aicher, Michelle; Aird, Daniel; Bailey, Suzanna; Berkenblit, Anna; Chan, Betty; Erik, Corcoran; Corson, Laura; Darman, Rachel; Fekkes, Peter; Keaney, Gregg F.; Kunii, Kaiko; Lee, Linda; Park, Eunice; Puyang, Xiaoling; Selvaraj, Anand; Thomas, Michael; Wang, John; Warmuth, Markus; Yu, Lihua; Zhu, Ping; Mizui, Yoshiharu; Smith, Peter G.] H3 Biomed, Cambridge, MA USA. [Obeng, Esther A.] Boston Childrens Hosp, Boston, MA USA. [Obeng, Esther A.; Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Obeng, Esther A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Furman, Richard R.] Weill Cornell Med Coll, New York, NY USA. [Kumar, Pavan; Mackenzie, Crystal] Eisai, Andover, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804015 ER PT J AU Burgess, MR Hwang, E Firestone, AJ Huang, TN Xu, J Zuber, J Bohin, N Wen, T Kogan, SC Haigis, KM Lowe, SW Shannon, K Li, Q AF Burgess, Michael R. Hwang, Eugene Firestone, Ari J. Huang, Tannie Xu, Jin Zuber, Johannes Bohin, Natacha Wen, Tiffany Kogan, Scott C. Haigis, Kevin M. Lowe, Scott W. Shannon, Kevin Li, Qing TI Preclinical Efficacy of MEK Inhibition in Nras Mutant Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Burgess, Michael R.; Hwang, Eugene; Huang, Tannie; Xu, Jin; Kogan, Scott C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Firestone, Ari J.; Shannon, Kevin] UCSF, San Francisco, CA USA. [Zuber, Johannes] Res Inst Mol Pathol IMP, Vienna, Austria. [Bohin, Natacha; Wen, Tiffany; Li, Qing] Univ Michigan, Ann Arbor, MI 48109 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502046 ER PT J AU Calimeri, T Caracciolo, D Amodio, N Samur, MK Leotta, M Fulciniti, M Rossi, M Minvielle, S Avet-Loiseau, H Tagliaferri, P Shammas, M Anderson, KC Tassone, P Munshi, NC AF Calimeri, Teresa Caracciolo, Daniele Amodio, Nicola Samur, Mehmet Kemal Leotta, Marzia Fulciniti, Mariateresa Rossi, Marco Minvielle, Stephane Avet-Loiseau, Herve Tagliaferri, Pierosandro Shammas, Masood Anderson, Kenneth C. Tassone, Pierfrancesco Munshi, Nikhil C. TI Targeting Aberrant Non-Homologous End Joining in Multiple Myeloma: Role of the Classical and Alternative Pathways in Genomic Instability SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Calimeri, Teresa; Caracciolo, Daniele; Amodio, Nicola; Leotta, Marzia; Rossi, Marco; Tagliaferri, Pierosandro] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Calimeri, Teresa] Tommaso Campanella Canc Ctr, Catanzaro, Italy. [Calimeri, Teresa; Fulciniti, Mariateresa; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Calimeri, Teresa; Fulciniti, Mariateresa; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Samur, Mehmet Kemal] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leotta, Marzia; Rossi, Marco; Tagliaferri, Pierosandro] T Campanella Canc Ctr, Catanzaro, Italy. [Minvielle, Stephane] Ctr Rech Cancerol Nantes Angers UMR Inserm 892 CN, Nantes, France. [Avet-Loiseau, Herve] Univ Hosp, Unit Genom Myeloma, Toulouse, France. [Shammas, Masood; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Shammas, Masood] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Tassone, Pierfrancesco] Univ Catanzaro, Catanzaro, Italy. [Tassone, Pierfrancesco] Temple Univ, Ctr Biotechnol, Coll Sci & Technol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA. RI Minvielle, Stephane/K-8251-2015 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807115 ER PT J AU Cameron, DR Lonial, S Mazumder, A Mortimer, J Bowser, AD Obholz, KL Anderson, KC AF Cameron, Davecia R. Lonial, Sagar Mazumder, Amitabha Mortimer, Jim Bowser, Andrew D. Obholz, Kevin L. Anderson, Kenneth C. TI Clinical Impact of an Internet-Based Tool to Provide Expert Guidance for Multiple Myeloma ( MM) from 2012 to 2014 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cameron, Davecia R.] Clin Care Opt, Miami, FL USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Mazumder, Amitabha] NYU, Ctr Canc, New York, NY USA. [Mortimer, Jim; Bowser, Andrew D.; Obholz, Kevin L.] Clin Care Opt LLC, Reston, VA USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501027 ER PT J AU Carey, A Edwards, D Eide, CA Traer, E Tyner, JW Bagby, GC Druker, BJ Agarwal, A AF Carey, Alyssa Edwards, David Eide, Christopher A. Traer, Elie Tyner, Jeffrey W. Bagby, Grover C. Druker, Brian J. Agarwal, Anupriya TI Targeted Suppression of Interleukin-1 Signaling Attenuates Leukemic Cellular Growth and Disease Progression in Primary Human Cells and Murine Models of Acute Myeloid leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Carey, Alyssa; Edwards, David; Eide, Christopher A.; Traer, Elie; Tyner, Jeffrey W.; Bagby, Grover C.; Druker, Brian J.; Agarwal, Anupriya] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Eide, Christopher A.; Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503028 ER PT J AU Cassaday, RD Stevenson, PA Gooley, TA Chauncey, T Pagel, J Till, BG Philip, M Orozco, JJ Bensinger, WI Holmberg, L Shustov, AR Green, DJ Smith, SD Libby, EN Maloney, DG Soma, LA Press, OW Gopal, AK AF Cassaday, Ryan D. Stevenson, Philip A. Gooley, Theodore A. Chauncey, Thomas Pagel, John Till, Brian G. Philip, Mary Orozco, Johnnie J. Bensinger, William I. Holmberg, Leona Shustov, Andrei R. Green, Damian J. Smith, Stephen D. Libby, Edward N. Maloney, David G. Soma, Lorinda A. Press, Oliver W. Gopal, Ajay K. TI Long Term Follow-up of High-Dose CD20-Targeted Radioimmunotherapy-Based Autologous Transplantation for Patients with Mantle Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cassaday, Ryan D.; Gooley, Theodore A.; Pagel, John; Till, Brian G.; Bensinger, William I.; Green, Damian J.; Smith, Stephen D.; Maloney, David G.; Press, Oliver W.; Gopal, Ajay K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cassaday, Ryan D.; Stevenson, Philip A.; Gooley, Theodore A.; Chauncey, Thomas; Pagel, John; Till, Brian G.; Philip, Mary; Orozco, Johnnie J.; Bensinger, William I.; Shustov, Andrei R.; Green, Damian J.; Smith, Stephen D.; Libby, Edward N.; Soma, Lorinda A.; Press, Oliver W.; Gopal, Ajay K.] Univ Washington, Seattle, WA 98195 USA. [Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Holmberg, Leona] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Maloney, David G.] Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808151 ER PT J AU Chaudhury, S HiJiya, N Hu, ZH Sparapani, R Kalaycio, ME Alyea, EP Popat, UR Saber, W AF Chaudhury, Sonali HiJiya, Nobuko Hu, Zhenhuan Sparapani, Rodney Kalaycio, Matt E. Alyea, Edwin P. Popat, Uday R. Saber, Wael TI Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Chaudhury, Sonali; HiJiya, Nobuko] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp, Chicago, IL 60611 USA. [Hu, Zhenhuan; Sparapani, Rodney; Saber, Wael] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Kalaycio, Matt E.] Cleveland Clin, Cleveland, OH 44106 USA. [Alyea, Edwin P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Popat, Uday R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805104 ER PT J AU Chung, J Bauer, DE Ghamari, A Nizzi, CP Deck, KM Kingsley, PD Yien, YY Huston, NC Chen, CY Wittig, JG Palis, J Orkin, SH Lodish, HF Eisenstein, RS Cantor, AB Paw, BH AF Chung, Jacky Bauer, Daniel E. Ghamari, Alireza Nizzi, Christopher P. Deck, Kathryn M. Kingsley, Paul D. Yien, Yvette Y. Huston, Nicholas C. Chen, Caiyong Wittig, Johannes G. Palis, James Orkin, Stuart H. Lodish, Harvey F. Eisenstein, Richard S. Cantor, Alan B. Paw, Barry H. TI Erythroid Cells Adapt to L-Leucine Scarcity By Reducing Hemoglobin Production Via the mTORC1/4E-BP Pathway SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Chung, Jacky; Yien, Yvette Y.; Huston, Nicholas C.; Chen, Caiyong; Wittig, Johannes G.; Paw, Barry H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Bauer, Daniel E.; Ghamari, Alireza; Orkin, Stuart H.; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Nizzi, Christopher P.; Deck, Kathryn M.; Eisenstein, Richard S.] Univ Wisconsin, Madison, WI USA. [Kingsley, Paul D.; Palis, James] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Lodish, Harvey F.] MIT, Whitehead Inst, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804102 ER PT J AU Cole, P Neuberg, DS Silverman, LB Stevenson, KE Vijayanathan, V Finkelstein, Y Sallan, SE Waber, D AF Cole, Peter Neuberg, Donna S. Silverman, Lewis B. Stevenson, Kristen E. Vijayanathan, Veena Finkelstein, Yaron Sallan, Stephen E. Waber, Deborah TI Polymorphisms in Genes Related to Oxidative Stress Are Associated with Inferior Cognitive Function after Therapy for Childhood ALL SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cole, Peter; Vijayanathan, Veena] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Neuberg, Donna S.; Silverman, Lewis B.; Stevenson, Kristen E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Finkelstein, Yaron] Dept Clin Pharmacol & Emergency Med, Toronto, ON, Canada. [Sallan, Stephen E.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Waber, Deborah] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801192 ER PT J AU Cortes, JE Kim, DW Pinilla-Ibarz, J Le Coutre, P Paquette, R Chuah, C Nicolini, FE Apperley, JF Khoury, HJ Talpaz, M DiPersio, JF DeAngelo, DJ Abruzzese, E Rea, D Baccarani, M Muller, MC Gambacorti-Passerini, C Lustgarten, S Rivera, VM Clackson, T Turner, CD Haluska, FG Guilhot, F Deininger, MW Hochhaus, A Hughes, TP Shah, NP Kantarjian, HM AF Cortes, Jorge E. Kim, Dong-Wook Pinilla-Ibarz, Javier Le Coutre, Philipp Paquette, Ronald Chuah, Charles Nicolini, Franck E. Apperley, Jane F. Khoury, H. Jean Talpaz, Moshe DiPersio, John F. DeAngelo, Daniel J. Abruzzese, Elisabetta Rea, Delphine Baccarani, Michele Mueller, Martin C. Gambacorti-Passerini, Carlo Lustgarten, Stephanie Rivera, Victor M. Clackson, Tim Turner, Christopher D. Haluska, Frank G. Guilhot, Francois Deininger, Michael W. Hochhaus, Andreas Hughes, Timothy P. Shah, Neil P. Kantarjian, Hagop M. TI Long-Term Follow-up of Ponatinib Efficacy and Safety in the Phase 2 PACE Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cortes, Jorge E.; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kim, Dong-Wook] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. [Pinilla-Ibarz, Javier] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Le Coutre, Philipp] Charite, D-13353 Berlin, Germany. [Paquette, Ronald] Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Chuah, Charles] Singapore Gen Hosp, Singapore, Singapore. [Chuah, Charles] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore. [Nicolini, Franck E.] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [Apperley, Jane F.] Univ London Imperial Coll Sci Technol & Med, Ctr Haematol, London, England. [Khoury, H. Jean] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Talpaz, Moshe] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [DiPersio, John F.] Washington Univ Sch Med, Div Oncol, St Louis, MO USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abruzzese, Elisabetta] Univ Roma Tor Vergata, S Eugenio Hosp, Rome, Italy. [Rea, Delphine] Hop St Louis, Paris, France. [Baccarani, Michele] S Orsola Malpighi Univ Hosp, Bologna, Italy. [Mueller, Martin C.] Univ Med Mannheim, Mannheim, Germany. [Gambacorti-Passerini, Carlo] Univ Milano Bicocca, Azienda Osped San Gerardo, Monza, Italy. [Lustgarten, Stephanie; Rivera, Victor M.; Clackson, Tim; Turner, Christopher D.; Haluska, Frank G.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Guilhot, Francois] Univ Hosp, Poitiers, France. [Deininger, Michael W.] Univ Utah Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA. [Hochhaus, Andreas] Jena Univ Hosp, Jena, Germany. [Hughes, Timothy P.] Inst Med & Vet Sci, Adelaide, SA 5000, Australia. [Shah, Neil P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 5 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804111 ER PT J AU Cottini, F Hideshima, T Buhrlage, S Gray, NS Richardson, PG Tonon, G Anderson, KC AF Cottini, Francesca Hideshima, Teru Buhrlage, Sara Gray, Nathanael S. Richardson, Paul G. Tonon, Giovanni Anderson, Kenneth C. TI Serine/Threonine Kinase STK4 Is a Novel Target in Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cottini, Francesca; Hideshima, Teru; Buhrlage, Sara; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803025 ER PT J AU Coutre, S O'Brien, S Byrd, JC Hillmen, P Brown, JR Dyer, MJS Mato, AR Miklos, DB Keating, M Zhou, C Fardis, M Styles, L Jaglowski, S AF Coutre, Steven O'Brien, Susan Byrd, John C. Hillmen, Peter Brown, Jennifer R. Dyer, Martin J. S. Mato, Anthony R. Miklos, David B. Keating, Michael Zhou, Cathy Fardis, Maria Styles, Lori Jaglowski, Samantha TI Safety and Efficacy of Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Who Have Undergone Prior Allogeneic Stem Cell Transplant SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Coutre, Steven; Miklos, David B.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [O'Brien, Susan; Keating, Michael] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dyer, Martin J. S.] Univ Leicester, Leicester, Leics, England. [Mato, Anthony R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Zhou, Cathy; Fardis, Maria; Styles, Lori] Pharmacyclics Inc, Sunnyvale, CA USA. [Jaglowski, Samantha] Ohio State Univ, Columbus, OH 43210 USA. RI Jaglowski, Samantha/E-3304-2011 NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504209 ER PT J AU Cutler, CS Shoemaker, D Westervelt, P Couriel, DR Vasu, S Isola, LM Karanes, C Newell, L Rezner, B Guerrettaz, L Robbins, D Medcalf, A Wolchko, S Ferraro, J Multani, PS AF Cutler, Corey S. Shoemaker, Daniel Westervelt, Peter Couriel, Daniel R. Vasu, Sumithra Isola, Luis M. Karanes, Chatchada Newell, Laura Rezner, Betsy Guerrettaz, Lisa Robbins, David Medcalf, Amanda Wolchko, Scott Ferraro, John Multani, Pratik S. TI Ex Vivo Pharmacologic Modulation in a Nutrient-Rich Medium to Accelerate Engraftment of Human Umbilical Cord Blood SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shoemaker, Daniel; Rezner, Betsy; Guerrettaz, Lisa; Robbins, David; Medcalf, Amanda; Wolchko, Scott; Ferraro, John; Multani, Pratik S.] Fate Therapeut Inc, San Diego, CA USA. [Westervelt, Peter] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Couriel, Daniel R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Vasu, Sumithra] Ohio State Univ, Columbus, OH 43210 USA. [Isola, Luis M.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Karanes, Chatchada] City Hope Natl Med Ctr, Duarte, CA USA. [Newell, Laura] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500128 ER PT J AU Das, DS Ravillah, D Ray, A Song, Y Richardson, PG Trikha, M Chauhan, D Anderson, KC AF Das, Deepika Sharma Ravillah, Durgadevi Ray, Arghya Song, Yan Richardson, Paul G. Trikha, Mohit Chauhan, Dharminder Anderson, Kenneth C. TI Synergistic Anti-Myeloma Activity of a Proteasome Inhibitor Marizomib and IMiD (R) Immunomodulatory Drug Pomalidomide SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Das, Deepika Sharma; Ravillah, Durgadevi; Ray, Arghya; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Das, Deepika Sharma; Ravillah, Durgadevi; Ray, Arghya; Song, Yan; Richardson, Paul G.; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Trikha, Mohit] Triphase Accelerator, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507200 ER PT J AU Devaraj, SGT Fiskus, W Shah, B Sharma, S Qi, J Sun, BH Saha, S Iyer, SP Zu, YL Bradner, J Bhalla, KN AF Devaraj, Santhana G. T. Fiskus, Warren Shah, Bhavin Sharma, Sunil Qi, Jun Sun, Baohua Saha, Saikat Iyer, Swaminathan Padmanabhan Zu, Youli Bradner, James Bhalla, Kapil N. TI Mechanistic Role of HEXIM1 Induction in BRD4-Antagonist Mediated Growth Inhibition, Differentiation and in Vivo Lethal Activity Against Human AML Blast Progenitor Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Devaraj, Santhana G. T.; Fiskus, Warren; Shah, Bhavin; Sun, Baohua; Saha, Saikat; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX USA. [Sharma, Sunil] Huntsman Canc Inst, Salt Lake City, UT USA. [Qi, Jun; Bradner, James] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Iyer, Swaminathan Padmanabhan] Methodist Canc Ctr, Houston, TX USA. [Zu, Youli] Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502114 ER PT J AU El-Jawahri, A Traeger, L Kuzmuk, K Eusebio, J Vandusen, H Shin, J Gallagher, E Greer, J Pirl, W Jackson, V Ballen, KK Spitzer, TR Graubert, TA McAfee, SL Dey, BR Chen, YB Temel, JS AF El-Jawahri, Areej Traeger, Lara Kuzmuk, Kailyn Eusebio, Justin Vandusen, Harry Shin, Jennifer Gallagher, Emily Greer, Joseph Pirl, William Jackson, Vicki Ballen, Karen K. Spitzer, Thomas R. Graubert, Timothy A. McAfee, Steven L. Dey, Bimalangshu R. Chen, Yi-Bin Temel, Jennifer S. TI Prognostic Understanding, Quality of Life, and Mood in Patients Undergoing Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [El-Jawahri, Areej] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Traeger, Lara; Kuzmuk, Kailyn; Eusebio, Justin; Vandusen, Harry; Shin, Jennifer; Gallagher, Emily; Greer, Joseph; Pirl, William; Jackson, Vicki; Spitzer, Thomas R.; Dey, Bimalangshu R.; Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ballen, Karen K.; Graubert, Timothy A.; McAfee, Steven L.; Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500036 ER PT J AU Emerson, RO Nikiforow, S Milano, F Sherwood, AM Papermaster, A Guthrie, KA Carlson, CS Warren, EH Ritz, J Robins, H Cutler, CS Delaney, C AF Emerson, Ryan O. Nikiforow, Sarah Milano, Filippo Sherwood, Anna M. Papermaster, Adrienne Guthrie, Katherine A. Carlson, Christopher S. Warren, Edus H. Ritz, Jerome Robins, Harlan Cutler, Corey S. Delaney, Colleen TI TCR Repertoire Diversity Assessed with Immunosequencing Is Associated with Patient Mortality Following Cord Blood Transplant SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Emerson, Ryan O.; Sherwood, Anna M.; Carlson, Christopher S.; Robins, Harlan] Adapt Biotechnol Corp, Seattle, WA USA. [Nikiforow, Sarah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Milano, Filippo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Papermaster, Adrienne; Guthrie, Katherine A.; Carlson, Christopher S.; Warren, Edus H.; Robins, Harlan; Delaney, Colleen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Warren, Edus H.] Univ Washington, Seattle, WA 98195 USA. [Ritz, Jerome; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804036 ER PT J AU Etchin, J Le, BT Kentsis, A Mansour, MR Berezovskaya, A Stone, RM Galinsky, I DeAngelo, DJ McCauley, D Kauffman, M Shacham, S Wang, JCY Kung, AL Look, AT AF Etchin, Julia Bonnie Thi Le Kentsis, Alex Mansour, Marc R. Berezovskaya, Alla Stone, Richard M. Galinsky, Ilene DeAngelo, Daniel J. McCauley, Dilara Kauffman, Michael Shacham, Sharon Wang, Jean C. Y. Kung, Andrew L. Look, A. Thomas TI Selective Inhibitor of Nuclear Export (SINE), Selinexor (KPT-330), Shows Remarkable Activity Against AML Leukemia-Initiating Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Etchin, Julia; Bonnie Thi Le; Mansour, Marc R.; Berezovskaya, Alla; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston, Boston, MA 02115 USA. [Kentsis, Alex] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Stone, Richard M.; Galinsky, Ilene] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McCauley, Dilara; Kauffman, Michael; Shacham, Sharon] Karyopharm Therapeut Inc, Newton, MA USA. [Wang, Jean C. Y.] Univ Hlth Network, Toronto, ON, Canada. [Kung, Andrew L.] Columbia Univ, Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807014 ER PT J AU Fan, FJ Vallet, S Sattler, M Tonon, G Bashari, MH Bakiri, L Goldschmidt, H Wagner, EF Jaeger, D Podar, K AF Fan, Fengjuan Vallet, Sonia Sattler, Martin Tonon, Giovanni Bashari, Muhammad Hasan Bakiri, Latifa Goldschmidt, Hartmut Wagner, Erwin F. Jaeger, Dirk Podar, Klaus TI The AP-1 Transcription Factor JunB Promotes Multiple Myeloma (MM) Cell Proliferation, Survival and Drug Resistance in the Bone Marrow Microenvironment SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Fan, Fengjuan; Vallet, Sonia; Bashari, Muhammad Hasan; Goldschmidt, Hartmut; Jaeger, Dirk; Podar, Klaus] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Sattler, Martin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. [Bakiri, Latifa; Wagner, Erwin F.] Spanish Natl Canc Res Ctr, Madrid, Spain. RI Bashari, Muhammad Hasan/H-7079-2016 OI Bashari, Muhammad Hasan/0000-0001-7298-0317 NR 0 TC 0 Z9 0 U1 0 U2 5 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501133 ER PT J AU Fathi, AT DeAngelo, DJ Stevenson, KE Kolitz, JE Asch, JD Amrein, PC Attar, EC Steensma, DP Wadleigh, M Connolly, C Galinsky, I Stone, RM Neuberg, DS Ballen, KK AF Fathi, Amir T. DeAngelo, Daniel J. Stevenson, Kristen E. Kolitz, Jonathan E. Asch, Julie D. Amrein, Philip C. Attar, Eyal C. Steensma, David P. Wadleigh, Martha Connolly, Christine Galinsky, Ilene Stone, Richard M. Neuberg, Donna S. Ballen, Karen K. TI Intensified Chemotherapy for Older Patients with Acute Lymphoblastic Leukemia (ALL): A Phase II Study from the Dana Farber Cancer Institute (DFCI) ALL Consortium SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Fathi, Amir T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [DeAngelo, Daniel J.; Stevenson, Kristen E.; Steensma, David P.; Wadleigh, Martha; Galinsky, Ilene; Stone, Richard M.; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kolitz, Jonathan E.] North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. [Asch, Julie D.] Intermt Blood & Marrow Transplant Acute Leukemia, Salt Lake City, UT USA. [Amrein, Philip C.; Attar, Eyal C.; Ballen, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Connolly, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505127 ER PT J AU Fathi, AT Wander, SA Blonquist, TM Ballen, KK Attar, EC McAfee, SL Chen, YB Graubert, TA Brunner, AM Joseph, C Perry, AM Burke, M Silver, R Ramos, AY Connolly, C Neuberg, DS Amrein, PC AF Fathi, Amir T. Wander, Seth A. Blonquist, Traci M. Ballen, Karen K. Attar, Eyal C. McAfee, Steven L. Chen, Yi-Bin Graubert, Timothy A. Brunner, Andrew M. Joseph, Christelle Perry, Ashley M. Burke, Meghan Silver, Regina Ramos, Aura Y. Connolly, Christine Neuberg, Donna S. Amrein, Philip C. TI A Phase I Study of the Aurora a Kinase Inhibitor Alisertib in Combination with 7+3 Induction Chemotherapy in Patients with Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Fathi, Amir T.; Brunner, Andrew M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wander, Seth A.; Ballen, Karen K.; Attar, Eyal C.; McAfee, Steven L.; Chen, Yi-Bin; Graubert, Timothy A.; Amrein, Philip C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Blonquist, Traci M.; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joseph, Christelle; Perry, Ashley M.; Burke, Meghan; Silver, Regina; Ramos, Aura Y.; Connolly, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805016 ER PT J AU Flinn, I Bartlett, NL Blum, KA Ardeshna, KM LaCasce, A Flowers, CR Shustov, AR Thress, K Zheng, F Skolnik, J Friedberg, JW AF Flinn, Ian Bartlett, Nancy L. Blum, Kristie A. Ardeshna, Kirit M. LaCasce, Ann Flowers, Christopher R. Shustov, Andrei R. Thress, Kenneth Zheng, Fred Skolnik, Jeffery Friedberg, Jonathan W. TI A Phase ll Trial to Evaluate the Efficacy of Fostamatinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Flinn, Ian] Tennessee Oncol PLLC, Nashville, TN USA. [Bartlett, Nancy L.] Washington Univ, St Louis, MO USA. [Blum, Kristie A.] Ohio State Univ, Columbus, OH 43210 USA. [Ardeshna, Kirit M.] Univ Coll London Hosp, London, England. [Ardeshna, Kirit M.] Sarah Cannon Res Inst UK, London, England. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flowers, Christopher R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Shustov, Andrei R.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Thress, Kenneth] Astra Zeneca, Waltham, MA USA. [Zheng, Fred; Skolnik, Jeffery] GlaxoSmithKline, Philadelphia, PA USA. [Friedberg, Jonathan W.] Univ Rochester, Rochester, NY USA. RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800220 ER PT J AU Flynn, RP Goodman, K Qi, J Jing, D Panoskaltsis-Mortari, A Yi, Z Dong, C Liu, XD MacDonald, KPA Hill, GR Serody, JS Murphy, WJ Luznik, L Maillard, I Koreth, J Cutler, CS Soiffer, RJ Antin, JH Ritz, J Melnick, AM Bradner, JE Blazar, BR AF Flynn, Ryan P. Goodman, Katelyn Qi, Jun Jing, Du Panoskaltsis-Mortari, Angela Yi, Zhang Dong, Chen Liu, Xindong MacDonald, Kelli P. A. Hill, Geoffrey R. Serody, Jonathan S. Murphy, William J. Luznik, Leo Maillard, Ivan Koreth, John Cutler, Corey S. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome Melnick, Ari M. Bradner, James E. Blazar, Bruce R. TI Targeting BCL6 and Germinal Centers (GCs) in Chronic Graft-Versus-Host Disease (cGVHD) Using Direct and Epigenomic Therapies SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Flynn, Ryan P.; Goodman, Katelyn; Jing, Du; Panoskaltsis-Mortari, Angela; Blazar, Bruce R.] Univ Minnesota, Minneapolis, MN USA. [Qi, Jun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yi, Zhang] Univ Michigan, Ann Arbor, MI 48109 USA. [Dong, Chen; Liu, Xindong] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [MacDonald, Kelli P. A.; Hill, Geoffrey R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Serody, Jonathan S.] Univ N Carolina, Chapel Hill, NC USA. [Murphy, William J.] Univ Calif Davis, Sacramento, CA 95817 USA. [Luznik, Leo] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Maillard, Ivan] Ctr Stem Cell Biol, Ann Arbor, MI USA. [Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Melnick, Ari M.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500221 ER PT J AU Friedrich, P Guerra-Garcia, P Stetson, AE Duncan, C Lehmann, LE AF Friedrich, Paola Guerra-Garcia, Pilar Stetson, Alyssa E. Duncan, Christine Lehmann, Leslie E. TI Young Female Donors Do Not Confer an Increased Risk of Graft-Versus-Host Disease in Pediatric Hematopoietic Stem Cell Transplant SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Friedrich, Paola; Stetson, Alyssa E.; Duncan, Christine; Lehmann, Leslie E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Guerra-Garcia, Pilar] Univ Hosp 12 Octubre, Madrid, Spain. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808062 ER PT J AU Ganzel, C Sun, ZX Gonen, M Patel, JP Abdel-Wahab, O Fernandez, HF Rowe, JM Tallman, MS Levine, RL Paietta, EM AF Ganzel, Chezi Sun, Zhuoxin Gonen, Mithat Patel, Jay P. Abdel-Wahab, Omar Fernandez, Hugo F. Rowe, Jacob M. Tallman, Martin S. Levine, Ross L. Paietta, Elisabeth M. TI Minimal Residual Disease Assessment By Flow Cytometry in AML Is an Independant Prognostic Factor Even after Adjusting for Cytogenetic/Molecular Abnormalities SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ganzel, Chezi] Mem Sloan Kettering, New York, NY USA. [Ganzel, Chezi; Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gonen, Mithat; Patel, Jay P.; Abdel-Wahab, Omar; Tallman, Martin S.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Fernandez, Hugo F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Rowe, Jacob M.] Rambam Hlth Care Campus, Haifa, Israel. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807123 ER PT J AU Geiselhart, A Walter, D Lier, A Thalheimer, FB Huntscha, S Brocks, D Bayindir, I Kaschutnig, P Mudder, K Sobotta, M Dick, T Holland-Letz, T Schmezer, P Schroder, T Lane, SW Essers, M Rieger, MA Williams, DA Trumpp, A Milsom, MD AF Geiselhart, Anja Walter, Dagmar Lier, Amelie Thalheimer, Frederic B. Huntscha, Sina Brocks, David Bayindir, Irem Kaschutnig, Paul Muedder, Katja Sobotta, Mirko Dick, Tobias Holland-Letz, Tim Schmezer, Peter Schroeder, Timm Lane, Steven W. Essers, Marieke Rieger, Michael A. Williams, David A. Trumpp, Andreas Milsom, Michael D. TI Altered HSC Metabolism in Response to Stress Leads to De Novo dna Damage and Cellular Attrition SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Geiselhart, Anja; Brocks, David; Bayindir, Irem; Kaschutnig, Paul; Muedder, Katja; Sobotta, Mirko; Dick, Tobias; Holland-Letz, Tim; Schmezer, Peter; Essers, Marieke; Trumpp, Andreas; Milsom, Michael D.] German Canc Res Ctr, Heidelberg, Germany. [Walter, Dagmar; Lier, Amelie; Huntscha, Sina; Trumpp, Andreas; Milsom, Michael D.] Heidelberg Inst Stem Cell Technol & Expt Med HI S, Heidelberg, Germany. [Thalheimer, Frederic B.; Rieger, Michael A.] Goethe Univ Hosp, Dept Hematol Oncol, Frankfurt, Germany. [Schroeder, Timm] Swiss Fed Inst Technol, Basel, Switzerland. [Lane, Steven W.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Williams, David A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800190 ER PT J AU Gerds, AT Dennison, B Latsko, J Houk, A Chisolm, S Huber, JM Stone, RM Maciejewski, JP Komrokji, RS Garcia-Manero, G Steensma, DP Sekeres, MA AF Gerds, Aaron T. Dennison, Betsy Latsko, Joan Houk, Alice Chisolm, Stephanie Huber, John M. Stone, Richard M. Maciejewski, Jaroslaw P. Komrokji, Rami S. Garcia-Manero, Guillermo Steensma, David P. Sekeres, Mikkael A. TI Doctor-Patient Communication and Perception of Treatment Discontinuation in Myelodysplastic Syndromes (MDS) Diverge at the Time of Disease Progression SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gerds, Aaron T.; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Dennison, Betsy] Clar Commun, Pompton Lakes, NJ USA. [Latsko, Joan; Houk, Alice; Chisolm, Stephanie; Huber, John M.] Aplast Anemia & MDS Int Fdn, Rockville, MD USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500151 ER PT J AU Gerds, AT Dennison, B Latsko, J Houk, A Chisolm, S Huber, JM Stone, RM Maciejewski, JP Komrokji, RS Garcia-Manero, G Steensma, DP Sekeres, MA AF Gerds, Aaron T. Dennison, Betsy Latsko, Joan Houk, Alice Chisolm, Stephanie Huber, John M. Stone, Richard M. Maciejewski, Jaroslaw P. Komrokji, Rami S. Garcia-Manero, Guillermo Steensma, David P. Sekeres, Mikkael A. TI Knowledge That the Myelodysplastic Syndromes (MDS) Are a Type of Cancer Does Not Influence Patient Perception of Treatment Discontinuation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gerds, Aaron T.; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Dennison, Betsy] Clar Commun, Pompton Lakes, NJ USA. [Latsko, Joan; Chisolm, Stephanie; Huber, John M.] Aplast Anemia & MDS Int Fdn, Rockville, MD USA. [Houk, Alice] AA&MDSIF, Rockville, MD USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806096 ER PT J AU Ghamari, A Jaensch, E Giadone, R Akie, TE Xu, J Bauer, D Orkin, SH Cantor, AB AF Ghamari, Alireza Jaensch, Elizabeth Giadone, Richard Akie, Thomas E. Xu, Jian Bauer, Daniel Orkin, Stuart H. Cantor, Alan B. TI An SCF-FBXW7 Ubiquitin Ligase Mediated Feedback Loop Facilitates GATA Factor Switching and Reinforces Commitment to Terminal Erythroid Maturation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghamari, Alireza; Jaensch, Elizabeth; Giadone, Richard; Akie, Thomas E.; Xu, Jian; Bauer, Daniel; Orkin, Stuart H.; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805150 ER PT J AU Ghobrial, IM Redd, RA Matous, J Armand, P Boswell, EN Chuma, S Noonan, K MacNabb, MH Banwait, R Hanlon, C Leblebjian, H Warren, D Castillo, JJ Laubach, JP Paba-Prada, CE Anderson, KC Richardson, PG Weller, EA Treon, SP AF Ghobrial, Irene M. Redd, Robert Allyn Matous, Jeffrey Armand, Philippe Boswell, Erica N. Chuma, Stacey Noonan, Kimberly MacNabb, Megan H. Banwait, Ranjit Hanlon, Courtney Leblebjian, Houry Warren, Diane Castillo, Jorge J. Laubach, Jacob P. Paba-Prada, Claudia E. Anderson, Kenneth C. Richardson, Paul G. Weller, Edie A. Treon, Steven P. TI Final Results of Phase I/II Trial of the Oral mTOR Inhibitor Everolimus (RAD001) in Combination with Bortezomib and Rituximab (RVR) in Relapsed or Refractory Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghobrial, Irene M.; Chuma, Stacey; Noonan, Kimberly; MacNabb, Megan H.; Hanlon, Courtney; Warren, Diane; Laubach, Jacob P.; Paba-Prada, Claudia E.; Weller, Edie A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Redd, Robert Allyn; Armand, Philippe; Banwait, Ranjit; Leblebjian, Houry; Treon, Steven P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. [Boswell, Erica N.; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505151 ER PT J AU Ghobrial, IM Perez, R Baz, R Richardson, PG Anderson, KC Sabbatini, P Dilea, C Cardarelli, PM Wade, M Xing, G Gutierrez, A Cohen, L Becker, PS AF Ghobrial, Irene M. Perez, Raymond Baz, Rachid Richardson, Paul G. Anderson, Kenneth C. Sabbatini, Peter Dilea, Clifford Cardarelli, Pina M. Wade, Mark Xing, Guan Gutierrez, Andres Cohen, Lewis Becker, Pamela S. TI Phase Ib Study of the Novel Anti-CXCR4 Antibody Ulocuplumab (BMS-936564) in Combination with Lenalidomide Plus Low-Dose Dexamethasone, or with Bortezomib plus Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Perez, Raymond] Univ Kansas, Fairway, KS USA. [Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Sabbatini, Peter; Cardarelli, Pina M.] Bristol Myers Squibb Co, Sunnyvale, CA USA. [Dilea, Clifford; Wade, Mark; Xing, Guan; Gutierrez, Andres] Bristol Myers Squibb Co, Princeton, NJ USA. [Cohen, Lewis] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Becker, Pamela S.] Univ Washington, Seattle, WA 98195 USA. RI Perez, Raymond/R-6159-2016 OI Perez, Raymond/0000-0002-7432-2411 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802095 ER PT J AU Gkotzamanidou, M Fulciniti, M Sanchez, JM Samur, MK Parmigiani, G Anderson, KC Munshi, NC AF Gkotzamanidou, Maria Fulciniti, Mariateresa Martin Sanchez, Jesus Samur, Mehmet Kemal Parmigiani, Giovanni Anderson, Kenneth C. Munshi, Nikhil C. TI LSD1 Impairs the Epithelial-Mesenchymal Transition (EMT) and Osteoclastogenesis Potency in Multiple Myeloma and Synergistically Induces Cytotoxicity with HDAC Inhibitors SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gkotzamanidou, Maria; Fulciniti, Mariateresa; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Gkotzamanidou, Maria; Fulciniti, Mariateresa; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Martin Sanchez, Jesus] Univ Seville, CSIC, Inst Biomed Sevilla IBIS, Hosp Univ Virgen del Rocio, Seville, Spain. [Samur, Mehmet Kemal] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503017 ER PT J AU Gkotzamanidou, M Shammas, M Souliotis, VL Song, WH Pal, J Nanjappa, P Rashid, N Anderson, KC Dimopoulos, MA Bradner, J Munshi, NC AF Gkotzamanidou, Maria Shammas, Masood Souliotis, Vassilis L. Song, Weihua Pal, Jagannath Nanjappa, Puru Rashid, Naim Anderson, Kenneth C. Dimopoulos, Meletios A. Bradner, James Munshi, Nikhil C. TI Ongoing Spontaneous DNA Damage and the Role of Aberrant Epigenome in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Gkotzamanidou, Maria; Song, Weihua; Pal, Jagannath; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Gkotzamanidou, Maria; Song, Weihua; Pal, Jagannath; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Shammas, Masood; Nanjappa, Puru; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Shammas, Masood; Nanjappa, Puru; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Souliotis, Vassilis L.] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, Athens, Greece. [Rashid, Naim; Bradner, James] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806098 ER PT J AU Glavey, S Reagan, M Manier, S Moschetta, M Kawano, Y Sacco, A Roccaro, AM Robbins, M Ghobrial, IM AF Glavey, Siobhan Reagan, Michaela Manier, Salomon Moschetta, Michele Kawano, Yawara Sacco, Antonio Roccaro, Aldo M. Robbins, Michael Ghobrial, Irene M. TI Dissecting the Mechanisms of Activity of SLAMF7 and the Targeting Antibody Elotuzumab in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Glavey, Siobhan; Reagan, Michaela; Manier, Salomon; Moschetta, Michele; Kawano, Yawara; Sacco, Antonio; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Robbins, Michael] Bristol Myers Squibb Co, Princeton, NJ USA. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801152 ER PT J AU Haddad, A Kantar, R Tamim, H Jamali, FR Taher, A AF Haddad, Anthony Kantar, Rami Tamim, Hani Jamali, Faek R. Taher, Ali TI Venous Thromboembolism and Preoperative Steroid Use, a Retrospective Cohort Study from the ACS-NSQIP Database: Are Surgical Patients at Risk? SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Haddad, Anthony; Tamim, Hani] Amer Univ Beirut, Dept Internal Med, Med Ctr, Beirut, Lebanon. [Kantar, Rami] Massachusetts Gen Hosp, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Jamali, Faek R.] Amer Univ Beirut, Dept Surg, Med Ctr, Beirut, Lebanon. [Taher, Ali] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804162 ER PT J AU Hansen, E Quivoron, C Straley, K Lemieux, RM Popovici-Muller, J Sadrzadeh, H Fathi, AT Gliser, C David, M Saada, V Micol, JB Bernard, O Dorsch, M Yang, H Su, M Agresta, S de Botton, S Penard-Lacronique, V Yen, K AF Hansen, Erica Quivoron, Cyril Straley, Kim Lemieux, Rene M. Popovici-Muller, Janeta Sadrzadeh, Hossein Fathi, Amir T. Gliser, Camelia David, Muriel Saada, Veronique Micol, Jean-Baptiste Bernard, Olivier Dorsch, Marion Yang, Hua Su, Michael Agresta, Sam de Botton, Stephane Penard-Lacronique, Virginie Yen, Katharine TI AG-120, an Oral, Selective, First-in-Class, Potent Inhibitor of Mutant IDH1, Reduces Intracellular 2HG and Induces Cellular Differentiation in TF-1 R132H Cells and Primary Human IDH1 Mutant AML Patient Samples Treated Ex Vivo SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Hansen, Erica; Straley, Kim; Lemieux, Rene M.; Popovici-Muller, Janeta; Gliser, Camelia; Dorsch, Marion; Yang, Hua; Su, Michael; Agresta, Sam; Yen, Katharine] Agios Pharmaceut, Cambridge, MA USA. [Quivoron, Cyril; David, Muriel; Saada, Veronique; Micol, Jean-Baptiste; Bernard, Olivier; de Botton, Stephane; Penard-Lacronique, Virginie] INSERM, Villejuif, France. [Quivoron, Cyril; David, Muriel; Saada, Veronique; Bernard, Olivier; de Botton, Stephane; Penard-Lacronique, Virginie] Inst Rech Integree Cancerol Villejuif Gustave Rou, Villejuif, France. [Quivoron, Cyril; David, Muriel; Saada, Veronique; Bernard, Olivier; de Botton, Stephane; Penard-Lacronique, Virginie] Univ Paris 11, Orsay, France. [Sadrzadeh, Hossein; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Micol, Jean-Baptiste; Penard-Lacronique, Virginie] Gustave Roussy, Serv Hematol Clin, Villejuif, France. RI David, Muriel/F-9592-2012 OI David, Muriel/0000-0003-1392-2701 NR 0 TC 2 Z9 2 U1 0 U2 8 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500090 ER PT J AU Hari, PN Shain, KH Voorhees, PM Gabrail, N Abidi, MH Zonder, J Boccia, RV Richardson, PG Neuman, LL Dixon, SJ Prada, CP AF Hari, Parameswaran N. Shain, Kenneth H. Voorhees, Peter M. Gabrail, Nashat Abidi, Muneer H. Zonder, Jeffrey Boccia, Ralph V. Richardson, Paul G. Neuman, Linda L. Dixon, Sandra J. Prada, Claudia Paba TI Oprozomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma: Initial Results from the Dose Escalation Portion of a Phase 1b/2, Multicenter, Open-Label Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Hari, Parameswaran N.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Shain, Kenneth H.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Voorhees, Peter M.] Univ N Carolina, Chapel Hill, NC USA. [Gabrail, Nashat] Gabrail Canc Ctr, Canton, OH USA. [Abidi, Muneer H.; Zonder, Jeffrey] Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. [Boccia, Ralph V.] Ctr Canc & Blood Disorders, Bethesda, MD USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Neuman, Linda L.] Onyx Pharmaceut Inc, Redwood City, CA USA. [Dixon, Sandra J.] Onyx Pharmaceut Inc, San Francisco, CA USA. [Prada, Claudia Paba] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503200 ER PT J AU Harris, M Neuberg, DS Zheng, JB Faham, M Sallan, SE Silverman, LB AF Harris, Marian Neuberg, Donna S. Zheng, Jianbiao Faham, Malek Sallan, Stephen E. Silverman, Lewis B. TI Minimal Residual Disease Detection Using High-Throughput Sequencing Predicts Clinical Outcome in Patients with Pediatric B-Lineage Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Harris, Marian; Sallan, Stephen E.; Silverman, Lewis B.] Boston Childrens Hosp, Boston, MA USA. [Neuberg, Donna S.; Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zheng, Jianbiao; Faham, Malek] Sequenta Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505046 ER PT J AU Herrera, AF Kim, HT Faham, M Sun, H Sohani, AR Alyea, EP Chen, YB Cutler, CS Ho, VT Koreth, J Nikiforow, S Ritz, J Rodig, SJ Soiffer, RJ Antin, JH Armand, P AF Herrera, Alex F. Kim, Haesook T. Faham, Malek Sun, Heather Sohani, Aliyah R. Alyea, Edwin P. Chen, Yi-Bin Cutler, Corey S. Ho, Vincent T. Koreth, John Nikiforow, Sarah Ritz, Jerome Rodig, Scott J. Soiffer, Robert J. Antin, Joseph H. Armand, Philippe TI Sequencing-Based Detection of Minimal Residual Disease Is Associated with Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Lymphoid Malignancies SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Herrera, Alex F.; Kim, Haesook T.; Alyea, Edwin P.; Cutler, Corey S.; Ho, Vincent T.; Nikiforow, Sarah; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Sun, Heather] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sohani, Aliyah R.] Maasachusetts Gen Hosp, Boston, MA USA. [Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Koreth, John; Ritz, Jerome; Soiffer, Robert J.; Armand, Philippe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505177 ER PT J AU Hosoba, S Flowers, CR Wu, CJ Wrammert, JR Waller, EK AF Hosoba, Sakura Flowers, Christopher R. Wu, Catherine J. Wrammert, Jens R. Waller, Edmund K. TI Rituximab Administration before Allogeneic HSCT Is Associated with Accelerated T Cell Reconstitution after Transplantation: Kinetic Evidence for a Graft-Versus-Leukemia Effect SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Hosoba, Sakura; Flowers, Christopher R.; Wrammert, Jens R.; Waller, Edmund K.] Emory Univ, Atlanta, GA 30322 USA. [Hosoba, Sakura] Shiga Univ Med Sci, Otsu, Shiga 52021, Japan. [Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504177 ER PT J AU Huang, XG Di Liberto, M Chiron, D Niesvizky, R Schinzel, AC Hahn, WC Chen-Kiang, S AF Huang, Xiangao Di Liberto, Maurizio Chiron, David Niesvizky, Ruben Schinzel, Anna C. Hahn, William C. Chen-Kiang, Selina TI Sensitizing shRNA Screen for Molecular Targets in CDK4/CDK6-Based Combination Therapy in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Huang, Xiangao; Di Liberto, Maurizio; Chiron, David; Chen-Kiang, Selina] Weill Cornell Med Coll, New York, NY USA. [Niesvizky, Ruben] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. [Schinzel, Anna C.; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501085 ER PT J AU Inamoto, Y Martin, PJ Flowers, ME Urbano-Ispizua, A Wang, T Hemmer, MT Cutler, CS Couriel, DR Alousi, AM Arora, M Spellman, SR AF Inamoto, Yoshihiro Martin, Paul J. Flowers, Mary E. Urbano-Ispizua, Alvaro Wang, Tao Hemmer, Michael T. Cutler, Corey S. Couriel, Daniel R. Alousi, Amin M. Arora, Mukta Spellman, Stephen R. TI Comparison of Tacrolimus Versus Cyclosporine with Methotrexate for Immunosuppression after Allogeneic Hematopoietic Cell Transplantation for Severe Aplastic Anemia: A CIBMTR Analysis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Inamoto, Yoshihiro] Natl Canc Ctr, Tokyo, Japan. [Inamoto, Yoshihiro; Martin, Paul J.; Flowers, Mary E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Urbano-Ispizua, Alvaro] Hosp Clin Barcelona, Barcelona, Spain. [Wang, Tao; Hemmer, Michael T.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Couriel, Daniel R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503166 ER PT J AU Jabbour, E Sasaki, K Sekeres, MA Komrokji, RS Steensma, DP DeZern, AE Gail, RJ Daver, NG Pemmaraju, N Kadia, T DiNardo, CD Wang, XM Nogueras-Gonzalez, G Borthakur, G Estrov, Z Kantarjian, HM Garcia-Manero, G AF Jabbour, Elias Sasaki, Koji Sekeres, Mikkael A. Komrokji, Rami S. Steensma, David P. DeZern, Amy E. Gail, Roboz J. Daver, Naval G. Pemmaraju, Naveen Kadia, Tapan DiNardo, Courtney D. Wang, Xuemei Nogueras-Gonzalez, Graciela Borthakur, Gautam Estrov, Zeev Kantarjian, Hagop M. Garcia-Manero, Guillermo TI Long-Term Outcome of Patients with Myelodysplastic Syndromes (MDS) Treated with Hypomethylating Agents (HMA): A Report on Behalf of the MDS Clinical Research Consortium SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jabbour, Elias; Sasaki, Koji; Daver, Naval G.; Pemmaraju, Naveen; Kadia, Tapan; DiNardo, Courtney D.; Wang, Xuemei; Nogueras-Gonzalez, Graciela; Borthakur, Gautam; Estrov, Zeev; Kantarjian, Hagop M.; Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeZern, Amy E.] Johns Hopkins Univ, Baltimore, MD USA. [Gail, Roboz J.] Weill Cornell Phys, New York, NY USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505034 ER PT J AU Jakubikova, J Kastritis, E Cholujova, D Hideshima, T Flores, LM Leiba, M Laubach, JP Munshi, NC Richardson, P Dorfman, DM Anderson, KC AF Jakubikova, Jana Kastritis, Efstathios Cholujova, Danka Hideshima, Teru Flores, Ludmila M. Leiba, Merav Laubach, Jacob P. Munshi, Nikhil C. Richardson, Paul Dorfman, David M. Anderson, Kenneth C. TI Evaluation of Immune Profile in Patients with Multiple Myeloma Using Cytof Technology SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jakubikova, Jana; Hideshima, Teru; Flores, Ludmila M.; Laubach, Jacob P.; Munshi, Nikhil C.; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kastritis, Efstathios] Univ Athens, Sch Med, Athens 11528, Greece. [Cholujova, Danka] Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia. [Leiba, Merav] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Dorfman, David M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807206 ER PT J AU Jakubikova, J Cholujova, D Hideshima, T Laubach, JP Munshi, NC Treon, SP Richardson, P Kastritis, E Dorfman, DM Anderson, KC AF Jakubikova, Jana Cholujova, Danka Hideshima, Teru Laubach, Jacob P. Munshi, Nikhil C. Treon, Steven P. Richardson, Paul Kastritis, Efstathios Dorfman, David M. Anderson, Kenneth C. TI Inter and Intra-Clonal Heterogeneity in Multiple Myeloma and Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jakubikova, Jana; Hideshima, Teru; Laubach, Jacob P.; Munshi, Nikhil C.; Treon, Steven P.; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cholujova, Danka] Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia. [Kastritis, Efstathios] Univ Athens, Sch Med, Athens 11528, Greece. [Dorfman, David M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805099 ER PT J AU Jakubikova, J Cholujova, D Groen, RW Joo, J Kong, SY Hideshima, T Suzuki, R Sedlak, J Mitsiades, CS Dorfman, DM Laubach, JP Munshi, NC Richardson, PG Anderson, K AF Jakubikova, Jana Cholujova, Danka Groen, Richard W. Joo, Jungnam Kong, Sun-Young Hideshima, Teru Suzuki, Rikio Sedlak, Jan Mitsiades, Constantine S. Dorfman, David M. Laubach, Jacob P. Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth TI Mimicking Myeloma Niche Ex Vivo SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jakubikova, Jana; Groen, Richard W.; Hideshima, Teru; Suzuki, Rikio; Mitsiades, Constantine S.; Laubach, Jacob P.; Munshi, Nikhil C.; Richardson, Paul G.; Anderson, Kenneth] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cholujova, Danka; Sedlak, Jan] Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia. [Joo, Jungnam; Kong, Sun-Young] Natl Canc Ctr, Goyang, South Korea. [Dorfman, David M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802151 ER PT J AU Jazieh, KA Stetson, AE Duncan, C Lehmann, LE AF Jazieh, Khalid Abdulrahman Stetson, Alyssa E. Duncan, Christine Lehmann, Leslie E. TI No Effect of Birth Order on Relapse, Graft-Versus-Host Disease or Transplant Related Mortality in Matched Sibling Donor Bone Marrow Transplant in Pediatric Patients with Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jazieh, Khalid Abdulrahman] Alfaisal Univ, Riyadh, Saudi Arabia. [Stetson, Alyssa E.; Duncan, Christine; Lehmann, Leslie E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lehmann, Leslie E.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503195 ER PT J AU Jiang, H An, G Acharya, C Zhong, MY Cai, T Song, ZL Yang, G Adrian, F Munshi, NC Tai, YT Anderson, KC AF Jiang, Hua An, Gang Acharya, Chirag Zhong, Mike Y. Cai, Ti Song, Zhili Yang, Guang Adrian, Francisco Munshi, Nikhil C. Tai, Yu-Tzu Anderson, Kenneth C. TI SAR650984 (SAR) Directly Promotes Homotypic Adhesion-Related Multiple Myeloma (MM) Cell Death and SAR-Induced Anti-MM Activities Are Enhanced By Pomalidomide, More Potently Than Lenalidomide SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Jiang, Hua; An, Gang; Zhong, Mike Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Acharya, Chirag; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Acharya, Chirag; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506087 ER PT J AU Kaelin, WG AF Kaelin, William G. TI IDH Mutations, 2-Oxoglutarate-dependent Dioxygenases, and Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kaelin, William G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805200 ER PT J AU Karreth, F Reschke, M Chapuy, B Shipp, MA Chiarle, R Pandolfi, PP AF Karreth, Florian Reschke, Markus Chapuy, Bjoern Shipp, Margaret A. Chiarle, Roberto Pandolfi, Pier Paolo TI The BRAF Pseudogene Is a Proto-Oncogenic Competitive Endogenous RNA SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Karreth, Florian] Weill Cornell Med Coll, New York, NY USA. [Karreth, Florian; Reschke, Markus; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chiarle, Roberto] Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501127 ER PT J AU Kasar, S Tiao, G Improgo, R Kiezun, A Sougnez, C Bahl, S Fernandes, SM Vartanov, AR Hoang, K Gabriel, S Landau, DA Wu, CJ Lander, E Kim, HT Getz, G Brown, JR AF Kasar, Siddha Tiao, Grace Improgo, Reina Kiezun, Adam Sougnez, Carrie Bahl, Samira Fernandes, Stacey M. Vartanov, Alexander R. Hoang, Kevin Gabriel, Stacey Landau, Dan A. Wu, Catherine J. Lander, Eric Kim, Haesook T. Getz, Gad Brown, Jennifer R. TI Whole Genome Sequencing of Indolent CLL Reveals Novel Structural Rearrangements SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kasar, Siddha; Improgo, Reina; Fernandes, Stacey M.; Vartanov, Alexander R.; Hoang, Kevin; Landau, Dan A.; Wu, Catherine J.; Kim, Haesook T.; Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kasar, Siddha; Improgo, Reina; Wu, Catherine J.; Brown, Jennifer R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Tiao, Grace; Kiezun, Adam; Sougnez, Carrie; Bahl, Samira; Gabriel, Stacey; Landau, Dan A.; Lander, Eric; Getz, Gad] Broad Inst Harvard & MIT, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802181 ER PT J AU Kawano, Y Sahin, I Moschetta, M Wang, JH Manier, S Glavey, S Mishima, Y Kokubun, K Tsukamoto, S Sacco, A Anderson, KC Roccaro, AM Gray, NS Ghobrial, IM AF Kawano, Yawara Sahin, Ilyas Moschetta, Michele Wang, Jinhua Manier, Salomon Glavey, Siobhan Mishima, Yuji Kokubun, Katsutoshi Tsukamoto, Shokichi Sacco, Antonio Anderson, Kenneth C. Roccaro, Aldo M. Gray, Nathanael S. Ghobrial, Irene M. TI Citron Rho-Interacting Serine/Threonine kinase (CIT) Is a Novel Therapeutic Target in Multiple Myeloma Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kawano, Yawara; Sahin, Ilyas; Moschetta, Michele; Manier, Salomon; Glavey, Siobhan; Mishima, Yuji; Tsukamoto, Shokichi; Sacco, Antonio; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Jinhua; Kokubun, Katsutoshi; Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804210 ER PT J AU Kekre, N Kim, HT Thanarajasingam, G Armand, P Antin, JH Cutler, CS Nikiforow, S Ho, VT Alyea, EP Koreth, J Soiffer, RJ AF Kekre, Natasha Kim, Haesook T. Thanarajasingam, Gita Armand, Philippe Antin, Joseph H. Cutler, Corey S. Nikiforow, Sarah Ho, Vincent T. Alyea, Edwin P. Koreth, John Soiffer, Robert J. TI Immunosuppression Taper to Induce Graft-Verus-Tumor Activity As the Sole Therapy for Early Relapse after Reduced Intensity Allogeneic Hematopoietic Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kekre, Natasha; Armand, Philippe; Antin, Joseph H.; Cutler, Corey S.; Nikiforow, Sarah; Ho, Vincent T.; Alyea, Edwin P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Haesook T.; Koreth, John; Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Thanarajasingam, Gita] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506033 ER PT J AU Kim, E Werner, L Keating, MJ Wierda, WG Ferrajoli, A Estrov, Z Zacharian, G Kipps, TJ Kantarjian, HM Neuberg, D O'Brien, S Burger, JA AF Kim, Ekaterina Werner, Lillian Keating, Michael J. Wierda, William G. Ferrajoli, Alessandra Estrov, Zeev Zacharian, Gracy Kipps, Thomas J. Kantarjian, Hagop M. Neuberg, Donna O'Brien, Susan Burger, Jan A. TI Addition of Rituximab Abrogates Ibrutinib-Induced Lymphocytosis and Promotes More Rapid Decrease in Absolute Lymphocyte Counts in Patients with Relapsed Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kim, Ekaterina; Keating, Michael J.; Wierda, William G.; Ferrajoli, Alessandra; Estrov, Zeev; Zacharian, Gracy; Kantarjian, Hagop M.; O'Brien, Susan; Burger, Jan A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kipps, Thomas J.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505201 ER PT J AU Kim, HT Armand, P Frederick, D Andler, E Cutler, CS Koreth, J Alyea, EP Antin, JH Soiffer, RJ Ritz, J Ho, VT AF Kim, Haesook T. Armand, Philippe Frederick, David Andler, Emily Cutler, Corey S. Koreth, John Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome Ho, Vincent T. TI Absolute Lymphocyte Count Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Clinical Outcome SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kim, Haesook T.; Armand, Philippe; Frederick, David; Andler, Emily; Cutler, Corey S.; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Ritz, Jerome; Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800182 ER PT J AU Klitgaard, JL Magori-Cohen, R Improgo, R Fernandes, SM Tesar, B Hoang, K Kim, HT Brown, JR AF Klitgaard, Josephine L. Magori-Cohen, Reuma Improgo, Reina Fernandes, Stacey M. Tesar, Bethany Hoang, Kevin Kim, Haesook T. Brown, Jennifer R. TI Inhibition of the Notch1 Pathway in Chronic Lymphocytic Leukemia Promotes Apoptosis and Inhibits Proliferation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Klitgaard, Josephine L.; Magori-Cohen, Reuma; Improgo, Reina; Fernandes, Stacey M.; Tesar, Bethany; Hoang, Kevin; Kim, Haesook T.; Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Klitgaard, Josephine L.; Improgo, Reina; Tesar, Bethany; Brown, Jennifer R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Magori-Cohen, Reuma] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805062 ER PT J AU Konopleva, M Pollyea, DA Potluri, J Chyla, BJ Busman, T McKeegan, E Salem, A Zhu, M Ricker, JL Blum, W DiNardo, CD Dunbar, M Kirby, R Falotico, N Leverson, JD Humerickhouse, RA Mabry, M Stone, RM Kantarjian, HM Letai, AG AF Konopleva, Marina Pollyea, Daniel A. Potluri, Jalaja Chyla, Brenda J. Busman, Todd McKeegan, Evelyn Salem, Ahmed Zhu, Ming Ricker, Justin L. Blum, William DiNardo, Courtney D. Dunbar, Martin Kirby, Rachel Falotico, Nancy Leverson, Joel D. Humerickhouse, Rod A. Mabry, Mack Stone, Richard M. Kantarjian, Hagop M. Letai, Anthony G. TI A Phase 2 Study of ABT-199 (GDC-0199) in Patients with Acute Myelogenous Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Konopleva, Marina; DiNardo, Courtney D.; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pollyea, Daniel A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Potluri, Jalaja; Chyla, Brenda J.; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed; Zhu, Ming; Ricker, Justin L.; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel D.; Humerickhouse, Rod A.; Mabry, Mack] AbbVie Inc, N Chicago, IL USA. [Blum, William] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Stone, Richard M.; Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 15 Z9 15 U1 1 U2 4 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807006 ER PT J AU Kopp, N Tschuri, S Haebe, S van Bodegom, D Bird, L Christie, AL Saur, A Christodoulou, AN Tivey, T Kung, AL Weigert, O Weinstock, D AF Kopp, Nadja Tschuri, Sebastian Haebe, Sarah van Bodegom, Diederik Bird, Liat Christie, Amanda L. Saur, Amy Christodoulou, Alexandra N. Tivey, Trevor Kung, Andrew L. Weigert, Oliver Weinstock, David TI Newer-Generation HSP90 Inhibitors Can Overcome Ibrutinib Resistance and Suppress Proliferation in Human Mantle Cell Lymphoma in Vitro and in Vivo SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kopp, Nadja; van Bodegom, Diederik; Bird, Liat; Christie, Amanda L.; Saur, Amy; Christodoulou, Alexandra N.; Tivey, Trevor; Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tschuri, Sebastian; Haebe, Sarah; Weigert, Oliver] Univ Hosp Munich, LMU, Munich, Germany. [Kung, Andrew L.] Columbia Univ Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502011 ER PT J AU Kostadinov, R Scharpf, R Sabunciyan, S Magoon, D Irizarry, R Brown, P AF Kostadinov, Rumen Scharpf, Robert Sabunciyan, Sarven Magoon, Daniel Irizarry, Rafael Brown, Patrick TI Identifying Methylation Changes Driving Evolution of Relapse in MLL-Rearranged Acute Lymphoblastic Leukemias SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kostadinov, Rumen] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Scharpf, Robert] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sabunciyan, Sarven] Johns Hopkins Sch Med, Baltimore, MD USA. [Magoon, Daniel] Johns Hopkins, Baltimore, MD USA. [Irizarry, Rafael] Dana Farber Canc Ctr, Boston, MA USA. [Brown, Patrick] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501102 ER PT J AU Kotini, A Delrow, JJ Graubert, TA Nimer, S Papapetrou, EP AF Kotini, Andriana Delrow, Jeffrey J. Graubert, Timothy A. Nimer, Stephen Papapetrou, Eirini P. TI Functional Dissection of Chromosome 7q Loss and Haploinsufficient Gene Discovery Using iPSC Models of MDS SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kotini, Andriana; Papapetrou, Eirini P.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Delrow, Jeffrey J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Graubert, Timothy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Nimer, Stephen] Univ Miami, Miami, FL USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806082 ER PT J AU Kretz, CA Novakovic, VA Kiseleva, A Cleuren, ACA Khoriaty, R Adams, E Ginsburg, D Gilbert, GE AF Kretz, Colin A. Novakovic, Valerie A. Kiseleva, Anna Cleuren, Audrey C. A. Khoriaty, Rami Adams, Elizabeth Ginsburg, David Gilbert, Gary E. TI TMEM16F Deficiency Causes a Strain-Dependent Lethality in Mice and Reduced Phosphatidylserine Exposure on Heterozygous As Well As Homozygous Deficient Mouse Platelets SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kretz, Colin A.; Khoriaty, Rami; Ginsburg, David] Univ Michigan, Ann Arbor, MI 48109 USA. [Novakovic, Valerie A.; Gilbert, Gary E.] VA Boston Healthcare Syst, Boston, MA USA. [Kiseleva, Anna; Cleuren, Audrey C. A.; Adams, Elizabeth] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Ginsburg, David] Howard Hughes Med Inst, Ann Arbor, MI USA. [Gilbert, Gary E.] Harvard Univ, Sch Med, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506046 ER PT J AU Kritharis, A Kanakry, JA Sehn, LH Feldman, T Kroll, A Gascoyne, RD Petrich, AM Abramson, JS Hernandez-Ilizaliturri, F Al-Mansour, Z Adeimy, C Hemminger, J Bartlett, NL Mato, AR Caimi, P Advani, R Klein, AK Lossos, IS Press, OW Smith, SM Fabregas, JC Nabhan, C Fenske, TS Friedberg, JW Vose, JM Blum, KA Evens, AM AF Kritharis, Athena Kanakry, Jennifer A. Sehn, Laurie H. Feldman, Tatyana Kroll, Aimee Gascoyne, Randy D. Petrich, Adam M. Abramson, Jeremy S. Hernandez-Ilizaliturri, Francisco Al-Mansour, Zeina Adeimy, Camille Hemminger, Jessica Bartlett, Nancy L. Mato, Anthony R. Caimi, Paolo Advani, Ranjana Klein, Andreas K. Lossos, Izidore S. Press, Oliver W. Smith, Sonali M. Fabregas, Jesus C. Nabhan, Chadi Fenske, Timothy S. Friedberg, Jonathan W. Vose, Julie M. Blum, Kristie A. Evens, Andrew M. TI Gray Zone Lymphoma (GZL) with Features Intermediate Between Classical Hodgkin Lymphoma (cHL) and Diffuse Large B-Cell Lymphoma (DLBCL): Analysis of Tumor Immunophenotype (IP) and Critical Examination of Therapy with Associated Impact on Outcome SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kritharis, Athena; Evens, Andrew M.] Tufts Med Ctr, Div Hematol Oncol, Boston, MA USA. [Kanakry, Jennifer A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sehn, Laurie H.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Feldman, Tatyana; Mato, Anthony R.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Kroll, Aimee] Univ Massachusetts, Worcester, MA 01605 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Petrich, Adam M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hernandez-Ilizaliturri, Francisco] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Al-Mansour, Zeina] Univ Massachusetts, Sch Med, Worcester, MA USA. [Adeimy, Camille] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Hemminger, Jessica; Blum, Kristie A.] Ohio State Univ, Columbus, OH 43210 USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Mato, Anthony R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Caimi, Paolo] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Advani, Ranjana] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Klein, Andreas K.] Tufts Med Ctr, Boston, MA USA. [Lossos, Izidore S.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Press, Oliver W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Smith, Sonali M.] Univ Chicago, Chicago, IL 60637 USA. [Fabregas, Jesus C.] Univ Miami, Div Hematol Oncol, Miami, FL USA. [Nabhan, Chadi] Oncol Specialists SC, Park Ridge, IL USA. [Fenske, Timothy S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Friedberg, Jonathan W.] Univ Rochester, Rochester, NY USA. [Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. NR 0 TC 6 Z9 6 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505124 ER PT J AU Kumar, S Berdeja, JG Niesvizky, R Lonial, S Laubach, JP Hamadani, M Stewart, K Hari, PN Roy, V Vescio, R Kaufman, JL Berg, D Liao, E Hui, AM Rajkumar, SV Richardson, PG AF Kumar, Shaji Berdeja, Jesus G. Niesvizky, Ruben Lonial, Sagar Laubach, Jacob P. Hamadani, Mehdi Stewart, Keith Hari, Parameswaran N. Roy, Vivek Vescio, Robert Kaufman, Jonathan L. Berg, Deborah Liao, Eileen Hui, Ai-Min Rajkumar, S. Vincent Richardson, Paul G. TI Long-Term Ixazomib Maintenance Is Tolerable and Improves Depth of Response Following Ixazomib-Lenalidomide-Dexamethasone Induction in Patients (Pts) with Previously Untreated Multiple Myeloma (MM): Phase 2 Study Results SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kumar, Shaji; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Niesvizky, Ruben] Weill Cornell Med Coll, New York, NY USA. [Lonial, Sagar; Kaufman, Jonathan L.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Laubach, Jacob P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hamadani, Mehdi] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Stewart, Keith] Mayo Clin, Scottsdale, AZ USA. [Hari, Parameswaran N.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA. [Vescio, Robert] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Berg, Deborah; Liao, Eileen; Hui, Ai-Min] Takeda Pharmaceut Int Co, Cambridge, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801066 ER PT J AU Kuruvilla, J Byrd, JC Flynn, JM Garzon, R Porcu, P Wagner-Johnston, N Savoie, ML Stone, RM Jacobsen, ED Mau-Sorensen, M Brown, PD Baz, R Shal, B Flinn, I Gabrail, N Kukreti, V Tiedemann, RE Landesman, Y Klebanov, B Shacham, E Saint-Martin, JR Marshall, T McCartney, J McCauley, D Carlson, R Norori, S Savona, MR Rashal, T Mirza, MR Kauffman, M Shacham, S AF Kuruvilla, John Byrd, John C. Flynn, Joseph M. Garzon, Ramiro Porcu, Pierluigi Wagner-Johnston, Nina Savoie, Mary Lynn Stone, Richard M. Jacobsen, Eric D. Mau-Sorensen, Morten Brown, Peter de Nully Baz, Rachid Shal, Bijal Flinn, Ian Gabrail, Nashat Kukreti, Vishal Tiedemann, Rodger E. Landesman, Yosef Klebanov, Boris Shacham, Eran Saint-Martin, Jean-Richard Marshall, Tracey McCartney, John McCauley, Dilara Carlson, Robert Norori, Sasha Savona, Michael R. Rashal, Tami Mirza, Mansoor R. Kauffman, Michael Shacham, Sharon TI The Oral Selective Inhibitor of Nuclear Export ( SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin's Lymphoma (NHL) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Kuruvilla, John] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Flynn, Joseph M.; Garzon, Ramiro] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Wagner-Johnston, Nina] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Savoie, Mary Lynn] Alberta Hlth Serv, Calgary, AB, Canada. [Stone, Richard M.; Jacobsen, Eric D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mau-Sorensen, Morten] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Brown, Peter de Nully] Rigshosp, DK-2100 Copenhagen, Denmark. [Baz, Rachid; Shal, Bijal] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Gabrail, Nashat] Gabrail Canc Ctr, Canton, OH USA. [Kukreti, Vishal; Tiedemann, Rodger E.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Landesman, Yosef; Klebanov, Boris; Shacham, Eran; Saint-Martin, Jean-Richard; Marshall, Tracey; McCartney, John; McCauley, Dilara; Carlson, Robert; Savona, Michael R.; Rashal, Tami; Mirza, Mansoor R.; Kauffman, Michael; Shacham, Sharon] Karyopharm Therapeut Inc, Newton, MA USA. [Norori, Sasha] Ozmosis Res Inc, Toronto, ON, Canada. RI Garzon, Ramiro/E-3104-2011 NR 0 TC 0 Z9 0 U1 0 U2 6 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243508066 ER PT J AU Landau, DA Stewart, C Reiter, JG Lawrence, M Sougnez, C Brown, JR Lopez-Guillermo, A Gabriel, S Lander, E Neuberg, DS Lopez-Otin, C Campo, E Getz, G Wu, CJ AF Landau, Dan A. Stewart, Chip Reiter, Johannes G. Lawrence, Michael Sougnez, Carrie Brown, Jennifer R. Lopez-Guillermo, Armando Gabriel, Stacey Lander, Eric Neuberg, Donna S. Lopez-Otin, Carlos Campo, Elias Getz, Gad Wu, Catherine J. TI Novel Putative Driver Gene Mutations in Chronic Lymphocytic Leukemia (CLL): Results from a Combined Analysis of Whole-Exome Sequencing of 262 Primary CLL Samples SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Landau, Dan A.; Reiter, Johannes G.; Brown, Jennifer R.; Neuberg, Donna S.; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Landau, Dan A.; Lawrence, Michael; Sougnez, Carrie; Gabriel, Stacey; Lander, Eric; Getz, Gad; Wu, Catherine J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Stewart, Chip] Broad Inst, Cambridge, MA USA. [Reiter, Johannes G.] IST Austria, Klosterneuburg, Austria. [Lopez-Guillermo, Armando; Campo, Elias] IDIBAPS, Hosp Clin, Barcelona, Spain. [Lopez-Otin, Carlos] Univ Oviedo, Oviedo, Spain. RI Lopez-Otin, Carlos/C-6657-2013 OI Lopez-Otin, Carlos/0000-0001-6964-1904 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506068 ER PT J AU Landau, DA Tausch, E Taylor-Weiner, AN Bottcher, S Bahlo, J Stewart, C Edelmann, J Kluth, S Mertens, D Kneba, M Kless, S Sougnez, C Fischer, K Ritgen, M Gabriel, S Lander, E Dohner, H Hallek, M Getz, G Neuberg, D Stilgenbauer, S Wu, CJ AF Landau, Dan A. Tausch, Eugen Taylor-Weiner, Amaro N. Bottcher, Sebastian Bahlo, Jasmin Stewart, Chip Edelmann, Jennifer Kluth, Sandra Mertens, Daniel Kneba, Michael Kless, Sabrina Sougnez, Carrie Fischer, Kirsten Ritgen, Matthias Gabriel, Stacey Lander, Eric Dohner, Hartmut Hallek, Michael Getz, Gad Neuberg, Donna Stilgenbauer, Stephan Wu, Catherine J. TI Subclonal Driver Mutations Predict Shorter Progression Free Survival in Chronic Lymphocytic Leukemia Following First-Line Chemo(immuno) Therapy: Results from the CLL8 Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Landau, Dan A.; Taylor-Weiner, Amaro N.; Sougnez, Carrie; Gabriel, Stacey; Lander, Eric; Getz, Gad; Wu, Catherine J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Landau, Dan A.; Neuberg, Donna; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tausch, Eugen; Edelmann, Jennifer; Mertens, Daniel; Kless, Sabrina; Stilgenbauer, Stephan] Univ Ulm, D-89069 Ulm, Germany. [Bottcher, Sebastian; Kneba, Michael; Ritgen, Matthias] Univ Hosp Schleswig Holstein, Kiel, Germany. [Bahlo, Jasmin; Fischer, Kirsten; Hallek, Michael] Univ Cologne, D-50931 Cologne, Germany. [Stewart, Chip] Broad Inst, Cambridge, MA USA. [Kluth, Sandra] Univ Hosp, Cologne, Germany. [Mertens, Daniel] German Canc Res Ctr, Heidelberg, Germany. [Dohner, Hartmut] Univ Hosp Ulm, Ulm, Germany. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505050 ER PT J AU Laubach, JP Raje, NS Yee, AJ Armand, P Schlossman, RL Rosenblatt, J Matous, J Hedlund, J Martin, MG Reynolds, C Shain, KH Zackon, I Stampleman, LV Boswell, EN Chuma, S Liguori, R Mar, S Handisides, D Kroll, S Anderson, KC Richardson, PG Ghobrial, IM AF Laubach, Jacob P. Raje, Noopur S. Yee, Andrew J. Armand, Philippe Schlossman, Robert L. Rosenblatt, Jacalyn Matous, Jeffrey Hedlund, Jacquelyn Martin, Michael G. Reynolds, Craig Shain, Kenneth H. Zackon, Ira Stampleman, Laura V. Boswell, Erica N. Chuma, Stacey Liguori, Rebecca Mar, Stephanie Handisides, Damian Kroll, Stew Anderson, Kenneth C. Richardson, Paul G. Ghobrial, Irene M. TI A Phase 1/2 Trial of TH-302 and Dexamethasone without or with Bortezomib (TBorD) in Patients with Relapsed/Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Laubach, Jacob P.; Armand, Philippe; Schlossman, Robert L.; Boswell, Erica N.; Chuma, Stacey; Anderson, Kenneth C.; Richardson, Paul G.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Laubach, Jacob P.; Armand, Philippe; Schlossman, Robert L.; Rosenblatt, Jacalyn; Matous, Jeffrey; Hedlund, Jacquelyn; Martin, Michael G.; Reynolds, Craig; Zackon, Ira; Stampleman, Laura V.; Boswell, Erica N.; Chuma, Stacey; Liguori, Rebecca; Anderson, Kenneth C.; Richardson, Paul G.; Ghobrial, Irene M.] Blood Canc Res Partnership, Boston, MA USA. [Raje, Noopur S.; Yee, Andrew J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenblatt, Jacalyn] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Matous, Jeffrey] Colorado Blood Canc Inst, Denver, CO USA. [Hedlund, Jacquelyn] New England Canc Specialisits, Scarborough, ME USA. [Martin, Michael G.] Univ Tennessee, Ctr Hlth Sci, West Clin, Memphis, TN 38163 USA. [Reynolds, Craig] Ocala Oncol Ctr, Ocala, FL USA. [Shain, Kenneth H.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Zackon, Ira] New York Oncol Hematol, Albany, NY USA. [Stampleman, Laura V.] Pacific Care Ctr, Salinas, CA USA. [Liguori, Rebecca] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mar, Stephanie; Handisides, Damian; Kroll, Stew] Threshold Pharmaceut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502092 ER PT J AU Lehmann, LE Williams, DA London, WB Agarwal, S AF Lehmann, Leslie E. Williams, David A. London, Wendy B. Agarwal, Suneet TI Full Donor Myeloid Engraftment with Minimal Toxicity in Dyskeratosis Congenita Patients Undergoing Allogeneic Bone Marrow Transplantation without Radiation or Alkylating Agents SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lehmann, Leslie E.; Williams, David A.; London, Wendy B.; Agarwal, Suneet] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lehmann, Leslie E.; Williams, David A.; London, Wendy B.; Agarwal, Suneet] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503181 ER PT J AU Li, A Bendapudi, PK Hamdan, A Makar, RS AF Li, Ang Bendapudi, Pavan K. Hamdan, Ayad Makar, Robert S. TI Moderate Deficiency of ADAMTS13 in Thrombotic Microangiopathy Is Associated with Poor Survival Regardless of Plasma Exchange SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Li, Ang] Massachussetts Gen Hosp, Boston, MA USA. [Bendapudi, Pavan K.; Makar, Robert S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hamdan, Ayad] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807069 ER PT J AU Lindner, JR Widlansky, M Wu, MD Dargatz, J Harmann, LM Belcik, T Neuberg, DS Nathan, DG Linden, J Field, JJ AF Lindner, Jonathan R. Widlansky, Michael Wu, Melinda D. Dargatz, Jillian Harmann, Leanne M. Belcik, Todd Neuberg, Donna S. Nathan, David G. Linden, Joel Field, Joshua J. TI Contrast-Enhanced Ultrasound Detects Differences in Microvascular Blood Flow in Adults with Sickle Cell Disease Administered Regadenoson SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lindner, Jonathan R.; Wu, Melinda D.; Belcik, Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Widlansky, Michael; Harmann, Leanne M.; Field, Joshua J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Dargatz, Jillian; Field, Joshua J.] BloodCtr Wisconsin, Milwaukee, WI USA. [Neuberg, Donna S.; Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Linden, Joel] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807035 ER PT J AU Lindsley, RC Mar, BG Mazzola, E Grauman, P Shareef, S DeAngelo, DJ Neuberg, DS Stone, RM Ebert, BL AF Lindsley, R. Coleman Mar, Brenton G. Mazzola, Emanuele Grauman, Peter Shareef, Sarah DeAngelo, Daniel J. Neuberg, Donna S. Stone, Richard M. Ebert, Benjamin L. TI Ontogeny-Specific Patterns of Genetic Alterations in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lindsley, R. Coleman; Mar, Brenton G.; Mazzola, Emanuele; DeAngelo, Daniel J.; Neuberg, Donna S.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grauman, Peter; Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shareef, Sarah] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500158 ER PT J AU Litzow, MR Wang, XV Carroll, MP Karp, JE Ketterling, R Kaufmann, SH Lazarus, HM Luger, SM Paietta, EM Rowe, JM Altman, JK Pratz, KW Broun, ER Tallman, MS AF Litzow, Mark R. Wang, Xin Victoria Carroll, Martin P. Karp, Judith E. Ketterling, Rhett Kaufmann, Scott H. Lazarus, Hillard M. Luger, Selina M. Paietta, Elisabeth M. Rowe, Jacob M. Altman, Jessica K. Pratz, Keith W. Broun, E. Randolph Tallman, Martin S. TI A Randomized Phase II Trial of Three Novel Regimens for Relapsed/Refractory Acute Myeloid Leukemia (AML) Demonstrates Encouraging Results with a Flavopiridol-Based Regimen: Results of Eastern Cooperative Oncology Group (ECOG) Trial E1906 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Litzow, Mark R.; Ketterling, Rhett; Kaufmann, Scott H.] Mayo Clin, Rochester, MN USA. [Wang, Xin Victoria] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carroll, Martin P.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Karp, Judith E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Altman, Jessica K.] Northwestern Univ, Chicago, IL 60611 USA. [Pratz, Keith W.] Johns Hopkins, Baltimore, MD USA. [Broun, E. Randolph] Oncol Hematol Care Inc, Cincinnati, OH USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505025 ER PT J AU Liu, SY Kharbanda, S Stone, RM AF Liu, Suiyang Kharbanda, Surender Stone, Richard M. TI OncoHist (R), an rh Histone 1.3, Is Cytotoxic to Acute Myeloid Leukemia Cells and Results in Altered Downstream Signaling SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Liu, Suiyang; Kharbanda, Surender; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243507150 ER PT J AU Lobbardi, R Pinder, J Martinez-Pastor, B Blackburn, JS Abdelfattah, N Toiber, D De Waard, M Asara, JM Mostoslavsky, R Dellaire, G Langenau, DM AF Lobbardi, Riadh Pinder, Jordan Martinez-Pastor, Barbara Blackburn, Jessica S. Abdelfattah, Nouran Toiber, Deborah De Waard, Manon Asara, John M. Mostoslavsky, Raul Dellaire, Graham Langenau, David M. TI Thymocyte Selection-Associated High-Mobility Group Box Protein (TOX) Induces Genomic Instability in T-Cell Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Lobbardi, Riadh; Martinez-Pastor, Barbara; Blackburn, Jessica S.; Abdelfattah, Nouran; Mostoslavsky, Raul; Langenau, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lobbardi, Riadh; Blackburn, Jessica S.; Abdelfattah, Nouran; Langenau, David M.] Harvard Stem Cell Inst, Cambridge, MA USA. [Pinder, Jordan; Dellaire, Graham] Dalhousie Univ, Halifax, NS, Canada. [Toiber, Deborah] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [De Waard, Manon] Leiden Univ, Leiden, Netherlands. [Asara, John M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501020 ER PT J AU Loukogeorgakis, SP Li, HY Tang, L Kim, AG Vrecenak, JD Nissim, I Conner, MA Nissim, I De Coppi, P Peranteau, W Irvine, DJ Flake, AW AF Loukogeorgakis, Stavros P. Li, Haiying Tang, Li Kim, Aimee G. Vrecenak, Jesse D. Nissim, Ilana Conner, Michael A. Nissim, Izhtak De Coppi, Paolo Peranteau, William Irvine, Darrell J. Flake, Alan W. TI Cell Engineering with Glycogen Synthase Kinase-3 Beta Inhibitor-Loaded Synthetic Nanoparticles Enhances Hematopoietic Engraftment of Bone Marrow Mononuclear Cells Following in Utero Transplantation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Loukogeorgakis, Stavros P.; Li, Haiying; Kim, Aimee G.; Vrecenak, Jesse D.; Nissim, Ilana; Conner, Michael A.; Nissim, Izhtak; Peranteau, William; Flake, Alan W.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Loukogeorgakis, Stavros P.; De Coppi, Paolo] UCL, London, England. [Tang, Li; Irvine, Darrell J.] MIT, Boston, MA USA. [Nissim, Izhtak] Univ Penn, Philadelphia, PA 19104 USA. [Irvine, Darrell J.] Massachusetts Gen Hosp, MIT, Boston, MA 02114 USA. [Irvine, Darrell J.] Harvard Univ, Boston, MA 02115 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504067 ER PT J AU Luskin, MR Lee, JW Fernandez, HF Lazarus, HM Rowe, JM Tallman, MS Paietta, EM Litzow, M Abdel-Wahab, O Patel, JP Levine, RL Sun, ZX Luger, SM AF Luskin, Marlise R. Lee, Ju-Whei Fernandez, Hugo F. Lazarus, Hillard M. Rowe, Jacob M. Tallman, Martin S. Paietta, Elisabeth M. Litzow, Mark Abdel-Wahab, Omar Patel, Jay P. Levine, Ross L. Sun, Zhuoxin Luger, Selina M. TI High Dose Daunorubicin Improves Survival in AML up to Age 60, Across All Cytogenetic Risk Groups Including Patients with Unfavorable Cytogenetic Risk, and FLT3-ITD Mutant AML: Updated Analyses from Eastern Cooperative Oncology Trial E1900 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Luskin, Marlise R.; Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Lee, Ju-Whei; Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fernandez, Hugo F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Tallman, Martin S.; Abdel-Wahab, Omar; Patel, Jay P.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Litzow, Mark] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505099 ER PT J AU Manier, S Avet-Loiseau, H Campigotto, F Glavey, S Salem, K Huynh, D Boswell, EN Sacco, A Mishima, Y Moschetta, M Reagan, MR Kawano, Y Anderson, KC Roccaro, AM Moreau, P Facon, T Leleu, X Weller, EA Ghobrial, IM AF Manier, Salomon Avet-Loiseau, Herve Campigotto, Federico Glavey, Siobhan Salem, Karma Huynh, Daisy Boswell, Erica N. Sacco, Antonio Mishima, Yuji Moschetta, Michele Reagan, Michaela R. Kawano, Yawara Anderson, Kenneth C. Roccaro, Aldo M. Moreau, Philippe Facon, Thierry Leleu, Xavier Weller, Edie A. Ghobrial, Irene M. TI Prognostic Value of Circulating Exosomal microRNAs in 112 Patients with Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Manier, Salomon; Campigotto, Federico; Glavey, Siobhan; Salem, Karma; Huynh, Daisy; Boswell, Erica N.; Sacco, Antonio; Mishima, Yuji; Moschetta, Michele; Reagan, Michaela R.; Kawano, Yawara; Anderson, Kenneth C.; Roccaro, Aldo M.; Weller, Edie A.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Avet-Loiseau, Herve] Univ Hosp Toulouse, Toulouse, France. [Moreau, Philippe] Univ Hosp Nantes, Nantes, France. [Facon, Thierry; Leleu, Xavier] CHRU Lille, Hop Claude Huriez, F-59037 Lille, France. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015; Reagan, Michaela/E-3549-2017 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501167 ER PT J AU Mantha, S Goldman, D Devlin, SM Lee, JW Zannino, D Douer, D Iland, HJ Litzow, MR Stein, EM Appelbaum, F Larson, RA Rowe, JM Tallman, MS AF Mantha, Simon Goldman, Debra Devlin, Sean M. Lee, Ju-Whei Zannino, Diana Douer, Dan Iland, Harry J. Litzow, Mark R. Stein, Eytan M. Appelbaum, Frederick Larson, Richard A. Rowe, Jacob M. Tallman, Martin S. TI Determinants of Fatal Bleeding during Induction Therapy for Acute Promyelocytic Leukemia in the ATRA Era SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Mantha, Simon; Goldman, Debra; Devlin, Sean M.; Stein, Eytan M.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zannino, Diana] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Douer, Dan] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. [Iland, Harry J.] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Appelbaum, Frederick] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800134 ER PT J AU Marcucci, G Geyer, S Zhao, WQ Caroll, AJ Bucci, D Uy, GL Blum, W Pardee, T Wetzler, M Stock, W Kolitz, JE Eisfeld, AK Bloomfield, CD Stone, RM Larson, RA AF Marcucci, Guido Geyer, Susan Zhao, Weiqiang Caroll, Andrew J. Bucci, Donna Uy, Geoffrey L. Blum, William Pardee, Timothy Wetzler, Meir Stock, Wendy Kolitz, Jonathan E. Eisfeld, Ann-Kathrin Bloomfield, Clara D. Stone, Richard M. Larson, Richard A. TI Adding KIT Inhibitor Dasatinib (DAS) to Chemotherapy Overcomes the Negative Impact of KIT Mutation/over-Expression in Core Binding Factor (CBF) Acute Myeloid Leukemia (AML): Results from CALGB 10801 (Alliance) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Marcucci, Guido] Ohio State Univ, Columbus, OH 43210 USA. [Geyer, Susan] Alliance Clin Trials Oncol Stat & Data Ctr, Rochester, MN USA. [Zhao, Weiqiang; Bucci, Donna; Blum, William; Eisfeld, Ann-Kathrin; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Caroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Uy, Geoffrey L.] Washington Univ, Sch Med, St Louis, MO USA. [Pardee, Timothy] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Stock, Wendy] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Kolitz, Jonathan E.] Monter Canc Ctr, Lake Success, NY USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807159 ER PT J AU Marcucci, G Geyer, S Zhao, W Caroll, AJ Bucci, D Uy, GL Blum, W Pardee, T Wetzler, M Stock, W Kolitz, JE Eisfeld, AK Bloomfield, CD Stone, RM Larson, RA AF Marcucci, Guido Geyer, Susan Zhao, Weiqiang Caroll, Andrew J. Bucci, Donna Uy, Geoffrey L. Blum, William Pardee, Timothy Wetzler, Meir Stock, Wendy Kolitz, Jonathan E. Eisfeld, Ann-Kathrin Bloomfield, Clara D. Stone, Richard M. Larson, Richard A. TI Adding KIT Inhibitor Dasatinib (DAS) to Chemotherapy Overcomes the Negative Impact of KIT Mutation/over-Expression in Core Binding Factor (CBF) Acute Myeloid Leukemia (AML): Results from CALGB 10801 ( Alliance) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Marcucci, Guido] Ohio State Univ, Columbus, OH 43210 USA. [Geyer, Susan] Alliance Clin Trials Oncol Stat & Data Ctr, Rochester, MN USA. [Zhao, Weiqiang; Bucci, Donna; Blum, William; Eisfeld, Ann-Kathrin; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Caroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Uy, Geoffrey L.] Washington Univ, Sch Med, St Louis, MO USA. [Pardee, Timothy] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Stock, Wendy] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Kolitz, Jonathan E.] Monter Canc Ctr, Lake Success, NY USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 1 Z9 1 U1 0 U2 5 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802034 ER PT J AU Marshall, AL Goodarzi, K Kuter, DJ AF Marshall, Ariela L. Goodarzi, Katayoon Kuter, David J. TI Romiplostim in Management of the Thrombocytopenic Surgical Patient SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Marshall, Ariela L.; Goodarzi, Katayoon; Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marshall, Ariela L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808141 ER PT J AU Mattano, LA Devidas, M Friedmann, AM Raetz, EA Loh, M Buckley, P Borowitz, MJ Carroll, AJ Gastier-Foster, J Heerema, NA Kadan-Lottick, N Matloub, Y Marshall, DT Stork, LC Wood, BL Winick, NJ Hunger, S Carroll, WL Maloney, K AF Mattano, Leonard A. Devidas, Meenakshi Friedmann, Alison M. Raetz, Elizabeth A. Loh, Mignon Buckley, Patrick Borowitz, Michael J. Carroll, Andrew J. Gastier-Foster, Julie Heerema, Nyla A. Kadan-Lottick, Nina Matloub, Yousif Marshall, David T. Stork, Linda C. Wood, Brent L. Winick, Naomi J. Hunger, Stephen Carroll, William L. Maloney, Kelly TI Outstanding Outcome for Children with Standard Risk-Low (SR-Low) Acute Lymphoblastic Leukemia (ALL) and No Benefit to Intensified Peg-Asparaginase (PEG-ASNase) Therapy: Results of Children's Oncology Group (COG) Study AALL0331 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Mattano, Leonard A.] Bronson Methodist Hosp, Kalamazoo, MI USA. [Devidas, Meenakshi] Univ Florida, Gainesville, FL USA. [Friedmann, Alison M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raetz, Elizabeth A.] Primary Childrens Med Ctr, Salt Lake City, UT USA. [Loh, Mignon] Dept Pediat Hematol Oncol, San Francisco, CA USA. [Buckley, Patrick] Duke Univ, Med Ctr, Durham, NC USA. [Borowitz, Michael J.] Johns Hopkins Univ, Baltimore, MD USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Gastier-Foster, Julie] Nationwide Childrens Hosp, Columbus, OH USA. [Heerema, Nyla A.] Ohio State Univ, Columbus, OH 43210 USA. [Kadan-Lottick, Nina] Yale Univ, Sch Med, New Haven, CT USA. [Matloub, Yousif] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Marshall, David T.] Med Univ S Carolina, Charleston, SC 29425 USA. [Stork, Linda C.] OR Hlth Sci Univ, Portland, OR USA. [Wood, Brent L.] Seattle Canc Care Alliance, Seattle, WA USA. [Winick, Naomi J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hunger, Stephen] Univ Colorado, Sch Med, Aurora, CO USA. [Hunger, Stephen] Childrens Hosp, Aurora, CO USA. [Carroll, William L.] NYU, Langone Med Ctr, New York, NY USA. [Maloney, Kelly] Childrens Hosp Colorado, Aurora, CO USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505162 ER PT J AU Maxson, JE Melissa, AL Wang, JH Deng, XM Luty, SB Sun, HH Gorenstein, J Middleton, R Gray, NS Druker, BJ Tyner, JW AF Maxson, Julia Elizabeth Melissa, Abel L. Wang, Jinhua Deng, Xianming Luty, Samuel B. Sun, Huahang Gorenstein, Julie Middleton, Richard Gray, Nathanael S. Druker, Brian J. Tyner, Jeffrey W. TI Development and Repurposing of Small-Molecule Kinase Inhibitors to Target Novel Leukemogenic TNK2 Mutations SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Maxson, Julia Elizabeth] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Maxson, Julia Elizabeth; Melissa, Abel L.; Luty, Samuel B.; Tyner, Jeffrey W.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wang, Jinhua; Deng, Xianming; Sun, Huahang; Gorenstein, Julie; Middleton, Richard; Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501148 ER PT J AU McEachern, KA Tron, AE O'Connor, G DuPont, R Gibbons, FD Pablo, L Vishwanathan, K McCoon, P Cortes, JE DeAngelo, DJ Minden, MD Uy, GL Neumann, F Keating, K Huszar, D Pease, JE Brown, J Barrett, JC AF McEachern, Kristen A. Tron, Adriana E. O'Connor, Greg DuPont, Rachel Gibbons, Francis D. Pablo, Lourdes Vishwanathan, Karthick McCoon, Patricia Cortes, Jorge E. DeAngelo, Daniel J. Minden, Mark D. Uy, Geoffrey L. Neumann, Frank Keating, Karen Huszar, Dennis Pease, J. Elizabeth Brown, Jeffrey Barrett, J. Carl TI Preclinical and Clinical Pharmacodynamics of Pan-Pim Inhibition By AZD1208 in Acute Myeloid Leukemia: Assessment of Pim Isoform Dependency for Bad and 4EBP1 Phosphorylation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [McEachern, Kristen A.; Tron, Adriana E.; O'Connor, Greg; DuPont, Rachel; Gibbons, Francis D.; Pablo, Lourdes; Vishwanathan, Karthick; McCoon, Patricia; Neumann, Frank; Keating, Karen; Huszar, Dennis; Pease, J. Elizabeth; Brown, Jeffrey; Barrett, J. Carl] AstraZeneca, Waltham, MA USA. [Cortes, Jorge E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minden, Mark D.] Univ Hlth Network, Toronto, ON, Canada. [Uy, Geoffrey L.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504005 ER PT J AU Melchardt, T Hufnagl, C Weigert, O Weinstock, DM Kopp, N Weiss, L Neureiter, D Trankenschuh, W Hackl, H Greil, R Egle, A AF Melchardt, Thomas Hufnagl, Clemens Weigert, Oliver Weinstock, David M. Kopp, Nadja Weiss, Lukas Neureiter, Daniel Traenkenschuh, Wolfgang Hackl, Hubert Greil, Richard Egle, Alexander TI Clonal Evolution in Relapsed or Refractory Diffuse Large B Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Melchardt, Thomas; Hufnagl, Clemens; Neureiter, Daniel; Traenkenschuh, Wolfgang; Greil, Richard] Paracelsus Med Univ, Salzburg, Austria. [Weigert, Oliver] Univ Hosp Grosshadern LMU, Dept Med 3, Munich, Germany. [Weinstock, David M.; Kopp, Nadja] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weiss, Lukas; Egle, Alexander] Paracelsus Med Univ, Dept Internal Med 3, Salzburg, Austria. [Hackl, Hubert] Med Univ Innsbruck, A-6020 Innsbruck, Austria. RI Greil, Richard/C-7673-2017 OI Greil, Richard/0000-0002-4462-3694 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500033 ER PT J AU Mercier, F Shi, JT Sykes, D Kfoury, YS Yusuf, RZ Miller, E Vasic, R Zhu, A Michor, F Hide, W Scadden, DT AF Mercier, Francois Shi, Jiantao Sykes, David Kfoury, Youmna Sami Yusuf, Rushdia Z. Miller, Elizabeth Vasic, Radovan Zhu, Alex Michor, Franziska Hide, Winston Scadden, David T. TI Identification of a Gene Expression Signature Characterizing Clonal Fitness and Dominance in Vivo in a Murine Model of MLL-AF9 Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Mercier, Francois; Sykes, David; Kfoury, Youmna Sami; Yusuf, Rushdia Z.; Zhu, Alex; Scadden, David T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mercier, Francois; Hide, Winston; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. [Shi, Jiantao] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Yusuf, Rushdia Z.; Scadden, David T.] Harvard Univ, Cambridge, MA 02138 USA. [Miller, Elizabeth] Harvard Univ, Boston, MA 02115 USA. [Vasic, Radovan] Yale Univ, New Haven, CT USA. [Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806028 ER PT J AU Mishima, Y Moschetta, M Shi, JT Mercier, F Manier, S Glavey, S Reagan, MR Kawano, Y Munshi, NC Anderson, KC Roccaro, AM Hide, W Scadden, DT Ghobrial, IM AF Mishima, Yuji Moschetta, Michele Shi, Jiantao Mercier, Francois Manier, Salomon Glavey, Siobhan Reagan, Michaela R. Kawano, Yawara Munshi, Nikhil C. Anderson, Kenneth C. Roccaro, Aldo M. Hide, Winston Scadden, David T. Ghobrial, Irene M. TI Clonal-Heterogeneity and Propensity for Bone Metastasis in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Mishima, Yuji; Moschetta, Michele; Manier, Salomon; Glavey, Siobhan; Reagan, Michaela R.; Kawano, Yawara; Anderson, Kenneth C.; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mishima, Yuji] Japanese Fdn Canc Res, Tokyo, Japan. [Shi, Jiantao] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mercier, Francois] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806156 ER PT J AU Moschetta, M Mishima, Y Kawano, Y Aljawai, Y Paiva, B Palomera, L Calcinotto, A Christine, UL Sahin, I Sacco, A Glavey, S Reagan, MR Manier, S Bergsagel, PL Chesi, M Bellone, M Roccaro, AM Ghobrial, IM AF Moschetta, Michele Mishima, Yuji Kawano, Yawara Aljawai, Yosra Paiva, Bruno Palomera, Luis Calcinotto, Arianna Christine, Unitt L. Sahin, Ilyas Sacco, Antonio Glavey, Siobhan Reagan, Michaela R. Manier, Salomon Bergsagel, Peter Leif Chesi, Marta Bellone, Matteo Roccaro, Aldo M. Ghobrial, Irene M. TI Early Trafficking of Bone Marrow Derived-Endothelial Progenitor Cells Promotes Multiple Myeloma Progression SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Moschetta, Michele; Mishima, Yuji; Kawano, Yawara; Aljawai, Yosra; Sahin, Ilyas; Sacco, Antonio; Glavey, Siobhan; Reagan, Michaela R.; Manier, Salomon; Roccaro, Aldo M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Paiva, Bruno] Univ Navarra Clin, Pamplona, Spain. [Palomera, Luis] Hosp Univ Lozano Bielsa, Zaragoza, Spain. [Calcinotto, Arianna; Bellone, Matteo] Ist Sci San Raffaele, Milan, Italy. [Christine, Unitt L.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Bergsagel, Peter Leif] Mayo Clin, Scottsdale, AZ USA. [Chesi, Marta] Mayo Clin Scottsdale, Scottsdale, AZ USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RI Reagan, Michaela/E-3549-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806167 ER PT J AU Moskowitz, CH Ribrag, V Michot, JM Martinelli, G Zinzani, PL Gutierrez, M De Maeyer, G Jacob, AG Giallella, K Anderson, JW Derosier, M Wang, J Yang, ZJ Rubin, E Rose, S Shipp, MA Armand, P AF Moskowitz, Craig H. Ribrag, Vincent Michot, Jean-Marie Martinelli, Giovanni Zinzani, Pier Luigi Gutierrez, Martin De Maeyer, Guadalupe Jacob, Alexandra G. Giallella, Karen Anderson, Jennifer Weimer Derosier, Martha Wang, Joy Yang, Zijiang Rubin, Eric Rose, Shelonitda Shipp, Margaret A. Armand, Philippe TI PD-1 Blockade with the Monoclonal Antibody Pembrolizumab (MK-3475) in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Preliminary Results from a Phase 1b Study (KEYNOTE-013) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Moskowitz, Craig H.; Jacob, Alexandra G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ribrag, Vincent] Inst Gustave Roussy, Villejuif, France. [Michot, Jean-Marie] Gustave Roussy Canc Ctr, Villejuif, France. [Martinelli, Giovanni] Univ Bologna, Sch Med, Bologna, Italy. [Zinzani, Pier Luigi] Inst Hematol & Med Oncol, Bologna, Italy. [Gutierrez, Martin] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [De Maeyer, Guadalupe; Shipp, Margaret A.; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. [Giallella, Karen; Anderson, Jennifer Weimer; Derosier, Martha; Rose, Shelonitda] Merck & Co Inc, Rahway, NJ 07065 USA. [Wang, Joy] Accenture, Philadelphia, PA USA. [Yang, Zijiang; Rubin, Eric] Merck & Co Inc, N Wales, PA USA. RI Zinzani, Pier Luigi/J-9182-2016 OI Zinzani, Pier Luigi/0000-0002-2112-2651 NR 0 TC 6 Z9 8 U1 2 U2 14 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808074 ER PT J AU Murase, K Kim, HT Hirakawa, M Matos, TR Kawano, Y Ryan, J Matsuoka, KI Koreth, J Soiffer, RJ Letai, AG Kato, J Ritz, J AF Murase, Kazuyuki Kim, Haesook T. Hirakawa, Masahiro Matos, Tiago Reis Kawano, Yutaka Ryan, Jeremy Matsuoka, Ken-Ichi Koreth, John Soiffer, Robert J. Letai, Anthony G. Kato, Junji Ritz, Jerome TI Low-Dose IL-2 Reduces Mitochondrial Priming and Increases Bcl2 Expression in CD4 Memory Regulatory T Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Murase, Kazuyuki; Kim, Haesook T.; Hirakawa, Masahiro; Matos, Tiago Reis; Ryan, Jeremy; Letai, Anthony G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Murase, Kazuyuki; Kawano, Yutaka; Kato, Junji] Sapporo Med Univ, Sch Med, Sapporo, Hokkaido, Japan. [Matsuoka, Ken-Ichi] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. [Koreth, John; Soiffer, Robert J.; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806055 ER PT J AU Natoni, A Moschetta, M Glavey, S Wu, P Morgan, GJ Joshi, L Magnani, JL Ghobrial, IM O'Dwyer, ME AF Natoni, Alessandro Moschetta, Michele Glavey, Siobhan Wu, Ping Morgan, Gareth J. Joshi, Lokesh Magnani, John L. Ghobrial, Irene M. O'Dwyer, Michael E. TI Multiple Myeloma Cells Express Functional E-Selectin Ligands Which Can be Inhibited Both in-Vitro and in-Vivo Leading to Prolongation of Survival in a Murine Transplant Model SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Natoni, Alessandro; Glavey, Siobhan; Joshi, Lokesh; O'Dwyer, Michael E.] Natl Univ Ireland Galway, Galway, Ireland. [Moschetta, Michele; Glavey, Siobhan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Ping] Inst Canc Res, London SW3 6JB, England. [Morgan, Gareth J.] Royal Marsden Hosp, London SW3 6JJ, England. [Magnani, John L.] GlycoMimetics Inc, Gaithersburg, MD USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504045 ER PT J AU Nazha, A Komrokji, RS Garcia-Manero, G Barnard, J Zimmerman, C Najla, AA Roboz, GJ Steensma, DP DeZern, AE Jabbour, E Lee, S Greenberg, MD List, AF Kantarjian, HM Maciejewski, JP Sekeres, MA AF Nazha, Aziz Komrokji, Rami S. Garcia-Manero, Guillermo Barnard, John Zimmerman, Cassie Najla, Al Ali Roboz, Gail J. Steensma, David P. DeZern, Amy E. Jabbour, Elias Lee, Sangmin Greenberg, Molly D. List, Alan F. Kantarjian, Hagop M. Maciejewski, Jaroslaw P. Sekeres, Mikkael A. TI The Efficacy of Current Prognostic Models in Predicting Outcome of Patients with Myelodysplastic Syndromes (MDS) at the Time of Hypomethylating Agent Failure SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Nazha, Aziz; Barnard, John; Zimmerman, Cassie; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Garcia-Manero, Guillermo; Jabbour, Elias; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Najla, Al Ali; List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Roboz, Gail J.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [DeZern, Amy E.] Johns Hopkins Univ, Baltimore, MD USA. [Lee, Sangmin] Weill Cornell New York Presbyterian Hosp, New York, NY USA. [Greenberg, Molly D.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501114 ER PT J AU Nazha, A Sekeres, MA Garcia-Manero, G Barnard, J Al Ali, NH Roboz, GJ Steensma, DP DeZern, AE Zimmerman, C Jabbour, E Greenberg, MD Lee, S List, AF Kantarjian, HM Maciejewski, JP Komrokji, RS AF Nazha, Aziz Sekeres, Mikkael A. Garcia-Manero, Guillermo Barnard, John Al Ali, Najla H. Roboz, Gail J. Steensma, David P. DeZern, Amy E. Zimmerman, Cassie Jabbour, Elias Greenberg, Molly D. Lee, Sangmin List, Alan F. Kantarjian, Hagop M. Maciejewski, Jaroslaw P. Komrokji, Rami S. TI Outcomes of Patients with Myelodysplastic Syndromes (MDS) Who Achieve Stable Disease after Treatment with Hypomethylating Agents (HMA) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Nazha, Aziz; Sekeres, Mikkael A.; Barnard, John; Zimmerman, Cassie; Maciejewski, Jaroslaw P.] Cleveland Clin, Cleveland, OH 44106 USA. [Garcia-Manero, Guillermo; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Al Ali, Najla H.; List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Roboz, Gail J.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [DeZern, Amy E.] Johns Hopkins Univ, Baltimore, MD USA. [Greenberg, Molly D.] Weill Cornell Med Coll, New York, NY USA. [Lee, Sangmin] Weill Cornell New York Presbyterian Hosp, New York, NY USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804071 ER PT J AU Nonami, A Zhao, C Liu, QS Cowens, K Christie, AL Chen, YF Sattler, M Wang, KK Gray, NS Griffin, JD Weisberg, EL AF Nonami, Atsushi Zhao, Chen Liu Qingsong Cowens, Kristen Christie, Amanda L. Chen, Yongfei Sattler, Martin Wang, Kwok-Kin Gray, Nathanael S. Griffin, James D. Weisberg, Ellen L. TI Identification of Wee1 and IGF-1R As Novel Therapeutic Targets for Mutant RAS-Driven Acute Leukemia By Combinatory Chemical Screens SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Nonami, Atsushi; Zhao, Chen; Cowens, Kristen; Christie, Amanda L.; Sattler, Martin; Wang, Kwok-Kin; Gray, Nathanael S.; Griffin, James D.; Weisberg, Ellen L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu Qingsong; Chen, Yongfei] Chinese Acad Sci, Hefei, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808081 ER PT J AU O'Brien, S Jones, JA Coutre, S Mato, AR Hillmen, P Tam, C Osterborg, A Siddiqi, T Thirman, MJ Furman, RR Ilhan, O Keating, M Call, TG Brown, JR Stevens-Brogan, M Li, YF Fardis, M Clow, F James, DF Chu, AD Hallek, M Stilgenbauer, S AF O'Brien, Susan Jones, Jeffrey A. Coutre, Steven Mato, Anthony R. Hillmen, Peter Tam, Constantine Osterborg, Anders Siddiqi, Tanya Thirman, Michael J. Furman, Richard R. Ilhan, Osman Keating, Michael Call, Timothy G. Brown, Jennifer R. Stevens-Brogan, Michelle Li, Yunfeng Fardis, Maria Clow, Fong James, Danelle F. Chu, Alvina D. Hallek, Michael Stilgenbauer, Stephan TI Efficacy and Safety of Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia with 17p Deletion: Results from the Phase II RESONATE (TM)-17 Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [O'Brien, Susan; Keating, Michael] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Jones, Jeffrey A.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Coutre, Steven] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Mato, Anthony R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [Tam, Constantine] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, Constantine] St Vincents Hosp, Melbourne, Vic, Australia. [Osterborg, Anders] Karolinska Univ Hosp, Solna, Sweden. [Siddiqi, Tanya] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Thirman, Michael J.] Univ Chicago Med, Chicago, IL USA. [Furman, Richard R.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Ilhan, Osman] Ankara Univ, Fac Med, TR-06100 Ankara, Turkey. [Call, Timothy G.] Mayo Clin, Rochester, MN USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stevens-Brogan, Michelle; Li, Yunfeng; Fardis, Maria; Clow, Fong; James, Danelle F.; Chu, Alvina D.] Pharmacyclics Inc, Sunnyvale, CA USA. [Hallek, Michael] Univ Cologne, D-50931 Cologne, Germany. [Stilgenbauer, Stephan] Univ Ulm, D-89069 Ulm, Germany. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805131 ER PT J AU O'Donnell, E Laubach, JP Yee, AJ Huff, CA Basile, F Wade, PM Paba-Prada, CE Ghobrial, IM Schlossman, RL Couture, N Doherty, L Lyons, H English, C Munshi, N Anderson, KC Richardson, PG Raje, N AF O'Donnell, Elizabeth Laubach, Jacob P. Yee, Andrew J. Huff, Carol Ann Basile, Frank Wade, Philip M. Paba-Prada, Claudia E. Ghobrial, Irene M. Schlossman, Robert L. Couture, Nicole Doherty, Lauren Lyons, Hannah English, Caroline Munshi, Nikhil Anderson, Kenneth C. Richardson, Paul G. Raje, Noopur TI A Phase II Study of Modified Lenalidomide, Bortezomib, and Dexamethasone (RVD lite) for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [O'Donnell, Elizabeth; Couture, Nicole; Doherty, Lauren; Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Laubach, Jacob P.; Schlossman, Robert L.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yee, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Huff, Carol Ann; English, Caroline] Johns Hopkins Univ, Baltimore, MD USA. [Basile, Frank] Cape Cod Healthcare, Hyannis, MA USA. [Wade, Philip M.] Cape Cod Hosp, Hyannis, MA USA. [Paba-Prada, Claudia E.; Munshi, Nikhil; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Schlossman, Robert L.] Harvard Univ, Boston, MA 02115 USA. [Lyons, Hannah] North Shore Med Ctr, Danvers, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500085 ER PT J AU Odejide, OO Cronin, AM LaCasce, A Abel, GA AF Odejide, Oreofe O. Cronin, Angel M. LaCasce, Ann Abel, Gregory A. TI Predictors of Hospice Utilization Among Patients with Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Odejide, Oreofe O.; Cronin, Angel M.; LaCasce, Ann; Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800069 ER PT J AU Ostro, J Kopolovic, I Lin, YL Dzik, WH Cserti, C Tsubota, H Keir, A Messner, HA DenHollander, N Callum, J AF Ostro, Jackie Kopolovic, Ilana Lin, Yulia Dzik, Walter H. Cserti, Christine Tsubota, Hideki Keir, Amy Messner, Hans A. DenHollander, Neal Callum, Jeannie TI Systematic Review of Cases of Transfusion Associated Graft-Versus-Host-Disease (TA-GVHD): Analysis of Patient Characteristics and Outcomes SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ostro, Jackie; Kopolovic, Ilana] Univ Toronto, Toronto, ON, Canada. [Lin, Yulia; Tsubota, Hideki; Callum, Jeannie] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Dzik, Walter H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cserti, Christine; DenHollander, Neal] Univ Hlth Network, Toronto, ON, Canada. [Keir, Amy] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Messner, Hans A.] Princess Margaret Canc Ctr, Toronto, ON, Canada. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806107 ER PT J AU Ott, CJ Lu, G Reyes, J Lin, CY Kaelin, WG Bradner, JE AF Ott, Christopher J. Lu, Gang Reyes, Jaime Lin, Charles Y. Kaelin, William G. Bradner, James E. TI Disruption of the Ikaros-Mediated Gene Expression Program in Multiple Myeloma with Immunomodulatory Agents SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ott, Christopher J.; Lu, Gang; Reyes, Jaime; Lin, Charles Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaelin, William G.; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806074 ER PT J AU Paba-Prada, C Palumbo, A Mellqvist, UH Voorhees, PM Plesner, T Sonneveld, P Byrne, C Harmenberg, J Nordstrom, E Richardson, PG AF Paba-Prada, Claudia Palumbo, Antonio Mellqvist, Ulf-Henrik Voorhees, Peter M. Plesner, Torben Sonneveld, Pieter Byrne, Catriona Harmenberg, Johan Nordstrom, Eva Richardson, Paul G. TI Determination of the MTD and Encouraging Results in an Ongoing Open-Label Phase 1/2a Study of the Safety and Efficacy of Melflufen and Dexamethasone in Combination for Patients with Relapsed and Relapsed-Refractory Multiple Myeloma (RRMM) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Paba-Prada, Claudia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Palumbo, Antonio] AOU San Giovanni Battista, Turin, Italy. [Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Plesner, Torben] Vejle Hosp, Vejle, Denmark. [Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Byrne, Catriona; Harmenberg, Johan; Nordstrom, Eva] Oncopeptides AB, Stockholm, Sweden. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503128 ER PT J AU Pal, J Shammas, M Kumar, S Gkotzamanidou, M Nanjappa, P Buon, L Munshi, NC AF Pal, Jagannath Shammas, Masood Kumar, Subodh Gkotzamanidou, Maria Nanjappa, Puru Buon, Leutz Munshi, Nikhil C. TI Telomerase-Mediated Repair of Induced DNA Breaks Leads to Increased Genomic Instability in Multiple Myeloma Cells: Possible Mechanism and Translational Significance SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Pal, Jagannath; Shammas, Masood; Kumar, Subodh; Nanjappa, Puru; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Pal, Jagannath; Shammas, Masood; Kumar, Subodh; Nanjappa, Puru; Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Buon, Leutz] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503029 ER PT J AU Park, JH Chung, SS Chung, YR Won, H Kim, E Saven, A Wadleigh, M Stone, RM Barrientos, JC Rai, KR Grever, MR Altman, JK Lacouture, ME Rosen, N Berger, M Levine, RL Abdel-Wahab, O Tallman, MS AF Park, Jae H. Chung, Stephen S. Chung, Young Rock Won, Helen Kim, Eunhee Saven, Alan Wadleigh, Martha Stone, Richard M. Barrientos, Jacqueline C. Rai, Kanti R. Grever, Michael R. Altman, Jessica K. Lacouture, Mario E. Rosen, Neal Berger, Michael Levine, Ross L. Abdel-Wahab, Omar Tallman, Martin S. TI Vemurafenib Has Potent Antitumor Activity in Patients with Relapsed/Refractory BRAF Mutant Hairy Cell Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Park, Jae H.; Chung, Stephen S.; Chung, Young Rock; Won, Helen; Kim, Eunhee; Lacouture, Mario E.; Rosen, Neal; Berger, Michael; Levine, Ross L.; Abdel-Wahab, Omar; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Saven, Alan] Scripps Hlth, La Jolla, CA USA. [Wadleigh, Martha; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Barrientos, Jacqueline C.] North Shore LIJ Canc Inst, Lake Success, NY USA. [Rai, Kanti R.] Hofstra North Shore LIJ Sch Med, New Hyde Pk, NY USA. [Grever, Michael R.] Ohio State Univ, Columbus, OH 43210 USA. [Altman, Jessica K.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803022 ER PT J AU Prabhala, RH Hideshima, T Fulciniti, M Adamia, S Bandi, RL Nanjappa, P Anderson, KC Munshi, NC AF Prabhala, Rao H. Hideshima, Teru Fulciniti, Mariateresa Adamia, Sophia Bandi, Rajya Lakshmi Nanjappa, Puru Anderson, Kenneth C. Munshi, Nikhil C. TI IL-17A-Mediated Notch Signaling in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Prabhala, Rao H.; Anderson, Kenneth C.; Munshi, Nikhil C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Prabhala, Rao H.; Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. [Prabhala, Rao H.; Hideshima, Teru; Fulciniti, Mariateresa; Adamia, Sophia; Bandi, Rajya Lakshmi; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nanjappa, Puru] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806036 ER PT J AU Praditsuktavorn, P Pera, B Kwiatkowski, N Yang, SN Zhang, TH Gray, N Cerchietti, L AF Praditsuktavorn, Pannee Pera, Benet Kwiatkowski, Nicholas Yang, ShaoNing Zhang, Tinghu Gray, Nathanael Cerchietti, Leandro TI Transcription Regulation Targeting in Peripheral T Cell Lymphomas Induces Apoptosis and Sensitization to BCL2 Inhibitors SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Praditsuktavorn, Pannee; Pera, Benet; Yang, ShaoNing; Zhang, Tinghu; Gray, Nathanael; Cerchietti, Leandro] Weill Cornell Med Coll, New York, NY USA. [Kwiatkowski, Nicholas] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805022 ER PT J AU Pyzer, AR Stroopinsky, D Rosenblatt, J Palmer, KA Coll, MD Bar-Natan, M Rajabi, H Somaiya, P Luptakova, K Jain, S McMasters, M Levine, JD Arnason, J Kufe, D Avigan, D AF Pyzer, Athalia Rachel Stroopinsky, Dina Rosenblatt, Jacalyn Palmer, Kristen Anna Coll, Maxwell Douglas Bar-Natan, Michal Rajabi, Hasan Somaiya, Poorvi Luptakova, Katarina Jain, Salvia McMasters, Malgorzata Levine, James D. Arnason, Jon Kufe, Donald Avigan, David TI Myeloid-Derived Suppressor Cells Are Expanded in Patients with AML and Are Dependent on MUC1 Expression SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Pyzer, Athalia Rachel; Stroopinsky, Dina; Rosenblatt, Jacalyn; Palmer, Kristen Anna; Coll, Maxwell Douglas; Bar-Natan, Michal; Somaiya, Poorvi; Luptakova, Katarina; Jain, Salvia; McMasters, Malgorzata; Levine, James D.; Arnason, Jon; Avigan, David] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rajabi, Hasan; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804105 ER PT J AU Rajabi, H Coll, MD Rosenblatt, J Yin, L Stroopinsky, D Luptakova, K Vasir, B Pyzer, AR Palmer, K Bar-Natan, M Jain, S Somaiya, P Arnason, J Kufe, D Avigan, D AF Rajabi, Hasan Coll, Maxwell Douglas Rosenblatt, Jacalyn Yin, Li Stroopinsky, Dina Luptakova, Katarina Vasir, Baldev Pyzer, Athalia Rachel Palmer, Kristen Bar-Natan, Michal Jain, Salvia Somaiya, Poorvi Arnason, Jon Kufe, Donald Avigan, David TI Mucin-1 (MUC1) Oncoprotein in Multiple Myeloma Cells Inhibits the Th1 Responses By Down Regulating the Expression of Mir-200c and up-Regulating the PDL1 Expression SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Rajabi, Hasan; Yin, Li; Vasir, Baldev; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Coll, Maxwell Douglas; Rosenblatt, Jacalyn; Luptakova, Katarina; Pyzer, Athalia Rachel; Palmer, Kristen; Jain, Salvia; Somaiya, Poorvi; Arnason, Jon; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Stroopinsky, Dina] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bar-Natan, Michal] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506100 ER PT J AU Ray, A Das, DS Ravillah, D Song, Y Macri, V Brooks, C Rowinsky, E Richardson, PG Chauhan, D Anderson, KC AF Ray, Arghya Das, Deepika Sharma Ravillah, Durgadevi Song, Yan Macri, Vincent Brooks, Christopher Rowinsky, Eric Richardson, Paul G. Chauhan, Dharminder Anderson, Kenneth C. TI SL-401, a Novel Targeted Therapy Directed to the Interleukin-3 Receptor (IL-3R), Blocks Plasmacytoid Dendritic Cell (pDC)-Triggered Myeloma Cell Growth and Prevents Osteoclastogenesis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ray, Arghya; Das, Deepika Sharma; Ravillah, Durgadevi; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Ray, Arghya; Das, Deepika Sharma; Ravillah, Durgadevi; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Macri, Vincent; Brooks, Christopher; Rowinsky, Eric] Stemline Therapeut Inc, New York, NY USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503129 ER PT J AU Ray, A Ravillah, D Das, DS Song, Y Nordstrom, E Lindberg, J Richardson, PG Chauhan, D Anderson, KC AF Ray, Arghya Ravillah, Durgadevi Das, Deepika Sharma Song, Yan Nordstrom, Eva Lindberg, Jakob Richardson, Paul G. Chauhan, Dharminder Anderson, Kenneth C. TI A Novel Alkylating Agent Melphalan Flufenamide Ethyl Ester Induces an Irreversible DNA Damage in Multiple Myeloma Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Ray, Arghya; Ravillah, Durgadevi; Das, Deepika Sharma; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Ray, Arghya; Ravillah, Durgadevi; Das, Deepika Sharma; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Nordstrom, Eva; Lindberg, Jakob] Oncopeptides AB, Stockholm, Sweden. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807064 ER PT J AU Richardson, PG Jagannath, S Moreau, P Jakubowiak, A Raab, MS Facon, T Vij, R White, D Reece, DE Benboubker, L Zonder, J Tsao, LC Anderson, KC Bleickardt, E Singhal, AK Lonial, S AF Richardson, Paul G. Jagannath, Sundar Moreau, Philippe Jakubowiak, Andrzej Raab, Marc S. Facon, Thierry Vij, Ravi White, Darrell Reece, Donna E. Benboubker, Lotfi Zonder, Jeffrey Tsao, L. Claire Anderson, Kenneth C. Bleickardt, Eric Singhal, Anil K. Lonial, Sagar TI Final Results for the 1703 Phase 1b/2 Study of Elotuzumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul G.; Jagannath, Sundar; Jakubowiak, Andrzej; Vij, Ravi; Zonder, Jeffrey; Anderson, Kenneth C.; Lonial, Sagar] Multiple Myeloma Res Consortium, Norwalk, CT USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Moreau, Philippe] Univ Hosp Nantes, Nantes, France. [Jakubowiak, Andrzej] Univ Chicago Med, Chicago, IL USA. [Raab, Marc S.] Univ Klinikum Heidelberg, Heidelberg, Germany. [Facon, Thierry] Hosp Claude Huriez, Lille, France. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [White, Darrell] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Benboubker, Lotfi] CHU Tours Hop Bretonneau, Tours, France. [Zonder, Jeffrey] Karmanos Canc Inst, Detroit, MI USA. [Tsao, L. Claire; Singhal, Anil K.] AbbVie Biotherapeut Inc ABR, Redwood City, CA USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bleickardt, Eric] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA USA. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505133 ER PT J AU Richardson, PG Kernan, NA Grupp, SA Martin, PL Soiffer, RJ Martin, R Hannah, AL Villa, KF AF Richardson, Paul G. Kernan, Nancy A. Grupp, Stephan A. Martin, Paul L. Soiffer, Robert J. Martin, Richard Hannah, Alison L. Villa, Kathleen F. TI Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease: An Analysis of Clinical Benefit As Determined By Number Needed to Treat (NNT) to Achieve Complete Response and to Improve Survival SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Grupp, Stephan A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Martin, Paul L.] Duke Univ, Med Ctr, Durham, NC USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Richard] EUSA Pharma, Oxford, England. [Hannah, Alison L.; Villa, Kathleen F.] Jazz Pharmaceut Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504189 ER PT J AU Richardson, PG Hungria, VTM Yoon, SS Beksac, M Dimopoulos, MA Elghandour, A Jedrzejczak, WW Guenther, A Nakorn, TN Siritanaratkul, N Schlossman, RL Hou, J Moreau, P Lonial, S Lee, JH Einsele, H Salwender, H Sopala, M Panneerselvam, A Redhu, S Corrado, C Binlich, F San Miguel, JF AF Richardson, Paul G. Hungria, Vania T. M. Yoon, Sung-Soo Beksac, Meral Dimopoulos, Meletios A. Elghandour, Ashraf Jedrzejczak, Wieslaw Wiktor Guenther, Andreas Thanyaphong Na Nakorn Siritanaratkul, Noppadol Schlossman, Robert L. Hou, Jian Moreau, Philippe Lonial, Sagar Lee, Jae Hoon Einsele, Hermann Salwender, Hans Sopala, Monika Panneerselvam, Ashok Redhu, Suman Corrado, Claudia Binlich, Florence San Miguel, Jesus F. TI Characterization of the Incidence and Management of Gastrointestinal Toxicity in the Phase 3 Panorama 1 Study of Panobinostat Plus Bortezomib and Dexamethasone Versus Placebo Plus Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.; Schlossman, Robert L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Hungria, Vania T. M.] Fac Ciencias Med Santa Casa Miserordia Sao Paulo, Disciplina Hematol & Oncol, Sao Paulo, Brazil. [Yoon, Sung-Soo] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Beksac, Meral] Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Elghandour, Ashraf] Univ Alexandria, Alexandria, Egypt. [Jedrzejczak, Wieslaw Wiktor] Med Univ Warsaw, Warsaw, Poland. [Guenther, Andreas] Univ Hosp Kiel, Kiel, Germany. [Thanyaphong Na Nakorn] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Thanyaphong Na Nakorn] Chulalongkorn Univ, Bangkok, Thailand. [Siritanaratkul, Noppadol] Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand. [Hou, Jian] Shanghai Changzheng Hosp, Shanghai, Peoples R China. [Moreau, Philippe] CHU Nantes, F-44035 Nantes 01, France. [Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA USA. [Lee, Jae Hoon] Gachon Univ, Gil Med Ctr, Inchon, South Korea. [Einsele, Hermann] Univ Klinikum, Med Klin 2, Wurzburg, Germany. [Salwender, Hans] Asklepios Klin Altona, Hamburg, Germany. [Sopala, Monika; Corrado, Claudia] Novartis Pharma AG, Basel, Switzerland. [Panneerselvam, Ashok; Redhu, Suman] Novartis Pharmaceut, E Hanover, NJ USA. [Binlich, Florence] Novartis Pharma SAS, Rueil Malmaison, France. [San Miguel, Jesus F.] Univ Navarra Clin, Pamplona, Spain. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501188 ER PT J AU Richardson, PG Smith, AR Triplett, BM Kernan, NA Grupp, SA Arai, S Antin, JH Lehmann, LE Bandiera, V Hume, RL Hannah, AL Nejadnik, B Soiffer, RJ AF Richardson, Paul G. Smith, Angela R. Triplett, Brandon M. Kernan, Nancy A. Grupp, Stephan A. Arai, Sally Antin, Joseph H. Lehmann, Leslie E. Bandiera, Valeria Hume, Robin L. Hannah, Alison L. Nejadnik, Bijan Soiffer, Robert J. CA Defibrotide Study Grp TI Updated Results from a Large, Ongoing, Treatment IND Study Using Defibrotide for Patients with Hepatic Veno-Occlusive Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Smith, Angela R.] Univ Minnesota, Minneapolis, MN USA. [Triplett, Brandon M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Grupp, Stephan A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Arai, Sally] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lehmann, Leslie E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bandiera, Valeria; Defibrotide Study Grp] Gentium SpA, Villa Guardia, Italy. [Hume, Robin L.; Hannah, Alison L.; Nejadnik, Bijan] Jazz Pharmaceut Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804028 ER PT J AU Richardson, PG Lee, JH Majer, I Krishna, A Woodman, RC AF Richardson, Paul G. Lee, Jae Hoon Majer, Istvan Krishna, Arun Woodman, Richard C. TI Efficacy of Treatments in Relapsed or Relapsed and Refractory Multiple Myeloma: An Indirect Treatment Comparison SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Lee, Jae Hoon] Gachon Univ, Gil Med Ctr, Inchon, South Korea. [Majer, Istvan] Pharmerit, Rotterdam, Netherlands. [Krishna, Arun; Woodman, Richard C.] Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800165 ER PT J AU Roberts, AW Ma, S Brander, DM Kipps, TJ Barrientos, JC Davids, MS Anderson, MA Tam, C Mason-Bright, T Rudersdorf, NK Gressick, L Yang, JN Munasinghe, W Zhu, M Cerri, E Enschede, SH Humerickhouse, RA Seymour, JF AF Roberts, Andrew W. Ma, Shuo Brander, Danielle M. Kipps, Thomas J. Barrientos, Jacqueline C. Davids, Matthew S. Anderson, Mary Ann Tam, Constantine Mason-Bright, Tanita Rudersdorf, Nikita K. Gressick, Lori Yang, Jianning Munasinghe, Wijith Zhu, Ming Cerri, Elisa Enschede, Sari H. Humerickhouse, Rod A. Seymour, John F. TI Determination of Recommended Phase 2 Dose of ABT-199 (GDC-0199) Combined with Rituximab (R) in Patients with Relapsed / Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Roberts, Andrew W.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Roberts, Andrew W.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Ma, Shuo] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Brander, Danielle M.] Duke Univ, Med Ctr, Durham, NC USA. [Kipps, Thomas J.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Barrientos, Jacqueline C.] Hofstra North Shore LIJ Sch Med, New Hyde Pk, NY USA. [Davids, Matthew S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Mary Ann] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Tam, Constantine; Seymour, John F.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Mason-Bright, Tanita; Rudersdorf, Nikita K.; Gressick, Lori; Yang, Jianning; Munasinghe, Wijith; Zhu, Ming; Cerri, Elisa; Enschede, Sari H.; Humerickhouse, Rod A.] AbbVie Inc, N Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503159 ER PT J AU Roberts, DA Wadleigh, M McDonnell, A DeAngelo, DJ Stone, RM Steensma, DP AF Roberts, Daniel A. Wadleigh, Martha McDonnell, Anne DeAngelo, Daniel J. Stone, Richard M. Steensma, David P. TI Low Efficacy and High Mortality Associated with Clofarabine Treatment of Patients with Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Roberts, Daniel A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Wadleigh, Martha; DeAngelo, Daniel J.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McDonnell, Anne; Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500061 ER PT J AU Roccaro, AM Sacco, A Moschetta, M Mishima, Y Maiso, P Huynh, D Chiarini, M Cardarelli, PM Cohen, L Kuhne, M Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Moschetta, Michele Mishima, Yuji Maiso, Patricia Huynh, Daisy Chiarini, Marco Cardarelli, Pina M. Cohen, Lewis Kuhne, Michelle Ghobrial, Irene M. TI Novel CXCR4-Targeted Therapy to Inhibit Multiple Myeloma Bone Dissemination SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Roccaro, Aldo M.; Sacco, Antonio; Moschetta, Michele; Mishima, Yuji; Maiso, Patricia; Huynh, Daisy; Chiarini, Marco] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chiarini, Marco] Spedali Civil Brescia, I-25125 Brescia, Italy. [Cardarelli, Pina M.; Kuhne, Michelle] Bristol Myers Squibb Co, Sunnyvale, CA USA. [Cohen, Lewis] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807119 ER PT J AU Rowe, RG Wang, LD Coma, S Ross, S Nguyen, P Pearson, D Wagers, AJ Daley, GQ AF Rowe, Robert G. Wang, Leo D. Coma, Silvia Ross, Samantha Nguyen, Phi Pearson, Daniel Wagers, Amy J. Daley, George Q. TI Inhibition of Let-7 Maturation By Lin28b Controls Timing of Embryonic and Adult Myeloid Progenitor Phenotypes during Development SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Rowe, Robert G.; Wang, Leo D.; Daley, George Q.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Wang, Leo D.; Nguyen, Phi] Joslin Diabet Ctr, Boston, MA 02215 USA. [Coma, Silvia; Ross, Samantha] Childrens Hosp Boston, Boston, MA USA. [Coma, Silvia; Wagers, Amy J.; Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Coma, Silvia; Pearson, Daniel; Daley, George Q.] Harvard Univ, Sch Med, Boston, MA USA. [Wagers, Amy J.] Joslin Diabet Ctr, Harvard Stem Cell Inst, Boston, MA 02215 USA. [Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA USA. [Daley, George Q.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500227 ER PT J AU Samur, MK Rashid, N Cleynen, A Fulciniti, M Sperling, A Minvielle, S Anderson, KC Parmigiani, G Avet-Loiseau, H Munshi, NC AF Samur, Mehmet Kemal Rashid, Naim Cleynen, Alice Fulciniti, Mariateresa Sperling, Adam Minvielle, Stephane Anderson, Kenneth C. Parmigiani, Giovanni Avet-Loiseau, Herve Munshi, Nikhil C. TI Long Intergenic Non-Coding RNAs (lincRNA) Impacts Biology and Clinical Outcome in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Samur, Mehmet Kemal; Rashid, Naim; Fulciniti, Mariateresa; Sperling, Adam] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cleynen, Alice; Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cleynen, Alice] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Minvielle, Stephane] CNRS 6299, Ctr Rech Cancerol Nantes Angers, UMR Inserm 892, Nantes, France. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Avet-Loiseau, Herve] Univ Hosp Nantes, Nantes, France. [Munshi, Nikhil C.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Minvielle, Stephane/K-8251-2015 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800210 ER PT J AU San Miguel, J Hungria, VTM Yoon, SS Beksac, M Dimopoulos, MA Elghandour, A Jedrzejczak, WW Guenther, A Nakorn, TN Siritanaratkul, N Schlossman, RL Hou, J Moreau, P Lonial, S Lee, JH Einsele, H Salwender, H Sopala, M Redhu, S Paul, S Corrado, C Binlich, F Richardson, PG AF San Miguel, Jesus Hungria, Vania T. M. Yoon, Sung-Soo Beksac, Meral Dimopoulos, Meletios A. Elghandour, Ashraf Jedrzejczak, Wieslaw Wiktor Guenther, Andreas Nakorn, Thanyaphong Na Siritanaratkul, Noppadol Schlossman, Robert L. Hou, Jian Moreau, Philippe Lonial, Sagar Lee, Jae-Hoon Einsele, Hermann Salwender, Hans Sopala, Monika Redhu, Suman Paul, Sofia Corrado, Claudia Binlich, Florence Richardson, Paul G. TI Efficacy and Safety Based on Duration of Treatment of Panobinostat Plus Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma in the Phase 3 Panorama 1 Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [San Miguel, Jesus] Univ Navarra, E-31080 Pamplona, Spain. [Hungria, Vania T. M.] Santa Case Misericordia Sao Paulo Hosp, Sao Paulo, Brazil. [Yoon, Sung-Soo] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Beksac, Meral] Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Athens 11528, Greece. [Elghandour, Ashraf] Univ Alexandria, Alexandria, Egypt. [Jedrzejczak, Wieslaw Wiktor] Med Univ Warsaw, Warsaw, Poland. [Guenther, Andreas] Univ Hosp Kiel, Kiel, Germany. [Nakorn, Thanyaphong Na] King Chulalongkorn Mem Hosp, Bangkok, Thailand. [Nakorn, Thanyaphong Na] Chulalongkorn Univ, Bangkok, Thailand. [Siritanaratkul, Noppadol] Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand. [Schlossman, Robert L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Hou, Jian] Shanghai Changzheng Hosp, Shanghai, Peoples R China. [Moreau, Philippe] Univ Hosp Nantes, Nantes, France. [Lonial, Sagar] Emory Univ, Atlanta, GA 30322 USA. [Lee, Jae-Hoon] Gachon Univ, Gil Hosp, Inchon, South Korea. [Einsele, Hermann] Med Klin & Poliklin 2, Wurzburg, Germany. [Salwender, Hans] Asklepios Klin Altona, Hamburg, Germany. [Sopala, Monika; Corrado, Claudia] Novartis Pharma AG, Basel, Switzerland. [Redhu, Suman; Paul, Sofia] Novartis Pharmaceut, E Hanover, NJ USA. [Binlich, Florence] Novartis Pharma SAS, Rueil Malmaison, France. [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 1 Z9 1 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506142 ER PT J AU Sanchez, G Li, A Yellapragada, SV Mims, MP Frolov, A Rahman, E Rivero, GA AF Sanchez, Gabriela Li, Ang Yellapragada, Sarvari Venkata Mims, Martha P. Frolov, Anna Rahman, Effie Rivero, Gustavo A. TI Survival Improvement in Myelodysplastic Syndrome with Refractory Anemia after Treatment with Selective-Serotonin-Reuptake-Inhibitors SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sanchez, Gabriela] St Luke Episcopal Hosp, Houston, TX USA. [Li, Ang] Massachussetts Gen Hosp, Boston, MA USA. [Yellapragada, Sarvari Venkata; Mims, Martha P.; Frolov, Anna; Rahman, Effie] Baylor Coll Med, Houston, TX 77030 USA. [Yellapragada, Sarvari Venkata] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Rivero, Gustavo A.] Michael E DeBakey VAMC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806152 ER PT J AU Sanchez-Guerrero, SA Treon, SP Guevara-Arnal, L Darwich, A Cardenas-Ortega, A Castillo, JJ AF Sanchez-Guerrero, Sergio A. Treon, Steven P. Guevara-Arnal, Luis Darwich, Akram Cardenas-Ortega, Andrea Castillo, Jorge J. TI Bing-Neel Syndrome: A Rare Complication of Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sanchez-Guerrero, Sergio A.; Guevara-Arnal, Luis; Darwich, Akram; Cardenas-Ortega, Andrea] Med Sur, Mexico City, DF, Mexico. [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506217 ER PT J AU Santo, L Ramachandran, J Cirstea, DD Eda, H Nemani, N Hideshima, T Dharminder, C Huszar, D Anderson, KC Raje, N AF Santo, Loredana Ramachandran, Janani Cirstea, Diana D. Eda, Homare Nemani, Neeharika Hideshima, Teru Dharminder, Chauhan Huszar, Dennis Anderson, Kenneth C. Raje, Noopur TI Effect of the Pan-PIM Kinase Inhibitor, AZD1208, Alone and in Combination with Bortezomib in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Santo, Loredana; Ramachandran, Janani; Cirstea, Diana D.; Eda, Homare; Nemani, Neeharika; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Hideshima, Teru; Dharminder, Chauhan; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Huszar, Dennis] AstraZeneca, Waltham, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807029 ER PT J AU Sousa, PSE Lomas, C Shorrock, H Conlan, T Means, TK Plagnol, V Bennett, CL Chakraverty, R AF Santos e Sousa, Pedro Lomas, Cara Shorrock, Hannah Conlan, Thomas Means, Terry K. Plagnol, Vincent Bennett, Clare L. Chakraverty, Ronjon TI A Systems Immunology Approach to Graft-Versus-Host Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Santos e Sousa, Pedro; Lomas, Cara; Shorrock, Hannah; Conlan, Thomas; Plagnol, Vincent; Bennett, Clare L.; Chakraverty, Ronjon] UCL, London, England. [Means, Terry K.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501146 ER PT J AU Seftel, MD Neuberg, D Zhang, MJ Wang, HL Bergeron, J Couban, S DeAngelo, DJ de Lima, MJ Devine, SM Eapen, M Horowitz, MM Pasquini, MC Rizzo, JD Saber, W Sallan, SE Sandmaier, BM Weisdorf, DJ AF Seftel, Matthew D. Neuberg, Donna Zhang, Mei-Jie Wang, Hai-Lin Bergeron, Julie Couban, Stephen DeAngelo, Daniel J. de Lima, Marcos J. Devine, Steven M. Eapen, Mary Horowitz, Mary M. Pasquini, Marcelo C. Rizzo, J. Douglas Saber, Wael Sallan, Stephen E. Sandmaier, Brenda M. Weisdorf, Daniel J. TI Superiority of Pediatric Chemotherapy over Allogeneic Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult ALL in First Complete Remission: A Combined Analysis of Dana-Farber ALL Consortium and CIBMTR Cohorts SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Seftel, Matthew D.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Seftel, Matthew D.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Neuberg, Donna; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Mei-Jie; Wang, Hai-Lin; Eapen, Mary; Horowitz, Mary M.; Pasquini, Marcelo C.; Rizzo, J. Douglas; Saber, Wael] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Bergeron, Julie] Univ Monteal, Hop Maisonneuve Rosemont, Montreal, PQ, Canada. [Couban, Stephen] Dalhousie Univ, Halifax, NS, Canada. [de Lima, Marcos J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Devine, Steven M.] Ohio State Univ, Columbus, OH 43210 USA. [Sallan, Stephen E.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Sandmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503178 ER PT J AU Seymour, JF Dohner, H Butrym, A Wierzbowska, A Selleslag, D Jang, JH Cavenagh, JD Kumar, R Schuh, AC Candoni, A Recher, C Sandhu, I del Castillo, TB Al-Ali, HK Martinelli, G Falantes, J Stone, RM Minden, MD McIntyre, H Songer, S Lucy, LM Beach, CL Dombret, H AF Seymour, John F. Doehner, Hartmut Butrym, Aleksandra Wierzbowska, Agnieszka Selleslag, Dominik Jang, Jun Ho Cavenagh, James D. Kumar, Rajat Schuh, Andre C. Candoni, Anna Recher, Christian Sandhu, Irwindeep Bernal del Castillo, Teresa Al-Ali, Haifa Kathrin Martinelli, Giovanni Falantes, Jose Stone, Richard M. Minden, Mark D. McIntyre, Heidi Songer, Stephen Lucy, Lela M. Beach, C. L. Dombret, Herve TI Azacitidine (AZA) Versus Conventional Care Regimens (CCR) in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (> 30% Bone Marrow Blasts) with Morphologic Dysplastic Changes: A Subgroup Analysis of the AZA-AML-001 Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Seymour, John F.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Doehner, Hartmut] Univ Ulm Klinikum, Ulm, Germany. [Butrym, Aleksandra] Wroclaw Med Univ, Wroclaw, Poland. [Wierzbowska, Agnieszka] Med Univ Lodz, Lodz, Poland. [Selleslag, Dominik] AZ Sint Jan Brugge Oostende, Brugge, Belgium. [Jang, Jun Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Cavenagh, James D.] St Bartholomews Hosp, London, England. [Kumar, Rajat] Canc Care Manitoba, Winnipeg, MB, Canada. [Schuh, Andre C.; Minden, Mark D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Candoni, Anna] Azienda Osped Univ S Maria della Misericordia Udi, Udine, Italy. [Recher, Christian] Inst Univ Canc Toulouse Oncopole, Toulouse, France. [Sandhu, Irwindeep] Univ Alberta, Edmonton, AB, Canada. [Bernal del Castillo, Teresa] Univ Oviedo, Hosp Cent Asturias, E-33080 Oviedo, Spain. [Al-Ali, Haifa Kathrin] Univ Hosp Leipzig, Leipzig, Germany. [Martinelli, Giovanni] Inst Hematol & Med Oncol LeA Seragnoli, Bologna, Italy. [Falantes, Jose] Hosp Univ Virgen del Rocio, Inst BioMed Sevilla, Seville, Spain. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McIntyre, Heidi; Songer, Stephen; Lucy, Lela M.; Beach, C. L.] Celgene Corp, Summit, NJ USA. [Dombret, Herve] Hop St Louis, Paris 10, France. RI Wierzbowska, Agnieszka/S-9449-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506214 ER PT J AU Seymour, JF Dohner, H Butrym, A Wierzbowska, A Selleslag, D Jang, JH Cavenagh, JD Kumar, R Schuh, AC Candoni, A Recher, C Sandhu, I del Castillo, TB Al-Ali, HK Martinelli, G Falantes, J Stone, RM Minden, MD McIntyre, H Songer, S Lucy, LM Beach, CL Dombret, H AF Seymour, John F. Doehner, Hartmut Butrym, Aleksandra Wierzbowska, Agnieszka Selleslag, Dominik Jang, Jun Ho Cavenagh, James D. Kumar, Rajat Schuh, Andre C. Candoni, Anna Recher, Christian Sandhu, Irwindeep del Castillo, Teresa Bernal Al-Ali, Haifa Kathrin Martinelli, Giovanni Falantes, Jose Stone, Richard M. Minden, Mark D. McIntyre, Heidi Songer, Stephen Lucy, Lela M. Beach, C. L. Dombret, Herve TI Azacitidine (AZA) Versus Conventional Care Regimens (CCR) in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (> 30% Bone Marrow Blasts) with Morphologic Dysplastic Changes: A Subgroup Analysis of the AZA-AML-001 Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Seymour, John F.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Doehner, Hartmut] Univ Ulm Klinikum, Ulm, Germany. [Butrym, Aleksandra] Wroclaw Med Univ, Wroclaw, Poland. [Wierzbowska, Agnieszka] Med Univ Lodz, Lodz, Poland. [Selleslag, Dominik] AZ Sint Jan Brugge Oostende, Brugge, Belgium. [Jang, Jun Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Cavenagh, James D.] St Bartholomews Hosp, London, England. [Kumar, Rajat] Canc Care Manitoba, Winnipeg, MB, Canada. [Schuh, Andre C.; Minden, Mark D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Candoni, Anna] Azienda Osped Univ S Maria della Misericordia Udi, Udine, Italy. [Recher, Christian] Inst Univ Canc Toulouse Oncopole, Toulouse, France. [Sandhu, Irwindeep] Univ Alberta, Edmonton, AB, Canada. [del Castillo, Teresa Bernal] Univ Oviedo, Hosp Cent Asturias, E-33080 Oviedo, Spain. [Al-Ali, Haifa Kathrin] Univ Hosp Leipzig, Leipzig, Germany. [Martinelli, Giovanni] Inst Hematol & Med Oncol LeA Seragnoli, Bologna, Italy. [Falantes, Jose] Hosp Univ Virgen del Rocio, Inst BioMed Sevilla, Seville, Spain. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McIntyre, Heidi; Songer, Stephen; Lucy, Lela M.; Beach, C. L.] Celgene Corp, Summit, NJ USA. [Dombret, Herve] Hop St Louis, Paris 10, France. RI Wierzbowska, Agnieszka/S-9449-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506215 ER PT J AU Shank, KR Koppikar, P Bhagwat, N Keller, MD Michor, F Levine, RL Roditi, LD AF Shank, Kaitlyn R. Koppikar, Priya Bhagwat, Neha Keller, Matthew D. Michor, Franziska Levine, Ross L. Roditi, Laura De Vargas TI Mathematical Optimization of JAK Inhibitor Dose and Scheduling for MPN Patients SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Shank, Kaitlyn R.; Koppikar, Priya; Bhagwat, Neha; Keller, Matthew D.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roditi, Laura De Vargas] Eldgenoss Tech Hsch Zurich, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803062 ER PT J AU Sharma, D Ravillah, D Ray, A Song, Y Munshi, NC Richardson, PG Chauhan, D Anderson, KC AF Sharma, Deepika Ravillah, Durgadevi Ray, Arghya Song, Yan Munshi, Nikhil C. Richardson, Paul G. Chauhan, Dharminder Anderson, Kenneth C. TI Anti-Myeloma Activity of a Novel Glutaminase Inhibitor CB-839 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sharma, Deepika; Ravillah, Durgadevi; Ray, Arghya; Song, Yan; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Sharma, Deepika; Ravillah, Durgadevi; Ray, Arghya; Song, Yan; Richardson, Paul G.; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500225 ER PT J AU Shastri, A Schinke, C Yanovsky, AV Bhagat, TD Giricz, O Barreyro, L Boultwood, J Pellagati, A Yu, YT Brown, JR Frank, DA Das, B Kambhampati, S Will, B Steidl, U Verma, A AF Shastri, Aditi Schinke, Carolina Yanovsky, Asya Varshavsky Bhagat, Tushar D. Giricz, Orsolya Barreyro, Laura Boultwood, Jacqueline Pellagati, Andrea Yu, Yiting Brown, Jennifer R. Frank, David A. Das, Bhaskar Kambhampati, Suman Will, Britta Steidl, Ulrich Verma, Amit TI Targeting of MDS and AML Stem Cells Via Inhibition of STAT3 By Pyrimethamine SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Shastri, Aditi; Yanovsky, Asya Varshavsky; Bhagat, Tushar D.; Giricz, Orsolya; Barreyro, Laura; Will, Britta] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Schinke, Carolina] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Boultwood, Jacqueline; Pellagati, Andrea] Univ Oxford, Oxford, England. [Yu, Yiting; Verma, Amit] Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY USA. [Brown, Jennifer R.; Frank, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Das, Bhaskar] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Kambhampati, Suman] Univ Kansas, Ctr Canc, Kansas City, KS USA. [Steidl, Ulrich] Albert Einstein Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502072 ER PT J AU Shi, C Han, LN Tabe, Y Mu, H Wu, SC Zhou, J Zeng, ZH Fruman, DA Tasian, SK Weinstock, DM Konopleva, M AF Shi, Ce Han, Lina Tabe, Yoko Mu, Hong Wu, Shuo-Chieh Zhou, Jin Zeng, Zhihong Fruman, David A. Tasian, Sarah K. Weinstock, David M. Konopleva, Marina TI Dual Targeting of JAK2 Signaling with a Type II JAK2 Inhibitor and of mTOR with a TOR Kinase Inhibitor Induces Apoptosis in CRLF2-Rearranged Ph-like Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Shi, Ce; Han, Lina; Zeng, Zhihong; Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Tabe, Yoko] Juntendo Univ, Sch Med, Tokyo 113, Japan. [Mu, Hong] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Sect Mol Hematol & Therapy, Houston, TX 77030 USA. [Wu, Shuo-Chieh; Weinstock, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhou, Jin] Harbin Med Univ, Hosp Affiliated 1, Harbin, Peoples R China. [Fruman, David A.] Univ Calif Irvine, Irvine, CA USA. [Tasian, Sarah K.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RI Han, Lina/J-5119-2015 OI Han, Lina/0000-0003-1538-1734 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503144 ER PT J AU Shimizu, T Hui, HS Kubovcakova, L Lundberg, P Dirnhofer, S Orkin, SH Grisouard, J Shimizu, Y Pianta, A Szczerba, B Nienhold, R Skoda, RC AF Shimizu, Takafumi Hui Hao-Shen Kubovcakova, Lucia Lundberg, Pontus Dirnhofer, Stephan Orkin, Stuart H. Grisouard, Jean Shimizu, Yukiko Pianta, Annalisa Szczerba, Barbara Nienhold, Ronny Skoda, Radek C. TI JAK2V61 7F and Loss of Ezh2 in Hematopoietic Cells Contribute Synergistically to Myeloproliferative Neoplasm Initiation Potential, and Accelerate Progression of Disease SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Shimizu, Takafumi; Hui Hao-Shen; Kubovcakova, Lucia; Lundberg, Pontus; Grisouard, Jean; Shimizu, Yukiko; Pianta, Annalisa; Szczerba, Barbara; Nienhold, Ronny; Skoda, Radek C.] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Dirnhofer, Stephan] Univ Spital, Basel, Switzerland. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506090 ER PT J AU Siegel, DS Kaufman, JL Raje, NS Mikhael, JR Kapoor, P Treon, SP Castillo, JJ Neuman, LL Lee, JR Ghobrial, I AF Siegel, David S. Kaufman, Jonathan L. Raje, Noopur S. Mikhael, Joseph R. Kapoor, Prashant Treon, Steven P. Castillo, Jorge J. Neuman, Linda L. Lee, Ju RueyJiuan Ghobrial, Irene TI Updated Results from a Multicenter, Open-Label, Dose-Escalation Phase 1b/2 Study of Single-Agent Oprozomib in Patients with Waldenstrom Macroglobulinemia (WM) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Siegel, David S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Kaufman, Jonathan L.] Emory Univ, Atlanta, GA 30322 USA. [Raje, Noopur S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mikhael, Joseph R.] Mayo Clin Arizona, Scottsdale, AZ USA. [Kapoor, Prashant] Mayo Clin, Rochester, MN USA. [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Castillo, Jorge J.; Ghobrial, Irene] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neuman, Linda L.] Onyx Pharmaceut Inc, Redwood City, CA USA. [Lee, Ju RueyJiuan] Onyx Pharmaceut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808148 ER PT J AU Silberstein, L Kharchenko, P Kfoury, Y Mercier, F Osawa, M Hoggatt, J Tate, T Lin, C Scadden, DT AF Silberstein, Lev Kharchenko, Peter Kfoury, Youmna Mercier, Francois Osawa, Masatake Hoggatt, Jonathan Tate, Tiffany Lin, Charles Scadden, David T. TI Proximity-Based Single Cell Analysis of the Bone Marrow Niche Identifies Interleukin-18 As a Quiescence Regulator of Early Hematopoietic Progenitors SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Silberstein, Lev; Kharchenko, Peter; Kfoury, Youmna; Mercier, Francois; Hoggatt, Jonathan; Lin, Charles; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. [Silberstein, Lev; Kfoury, Youmna; Mercier, Francois; Hoggatt, Jonathan; Tate, Tiffany; Lin, Charles; Scadden, David T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kharchenko, Peter] Harvard Ctr Biomed Informat, Boston, MA USA. [Osawa, Masatake] Gifu Univ, Gifu, Japan. [Scadden, David T.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500194 ER PT J AU Skert, C Perucca, S Imberti, L Chiarini, M Malagola, M Fili, C Bergonzi, C Ribolla, R Cancelli, V Turra, A Cattina, F Di Palma, A Russo, D AF Skert, Cristina Perucca, Simone Imberti, Luisa Chiarini, Marco Malagola, Michele Fili, Carla Bergonzi, Cesare Ribolla, Rossella Cancelli, Valeria Turra, Alessandro Cattina, Federica Di Palma, Andrea Russo, Domenico TI Patterns of Lymphocyte Subsets and Index of Bone Marrow Output (KRECs) Correlate Differently with Graft-Versus-Host Disease and Relapse SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Skert, Cristina; Perucca, Simone; Ribolla, Rossella; Turra, Alessandro; Di Palma, Andrea; Russo, Domenico] Univ Brescia, Unit Blood Dis & Stem Cell Transplantat, Chair Hematol, Brescia, Italy. [Imberti, Luisa; Chiarini, Marco] Spedali Civili Brescia, Brescia, Italy. [Chiarini, Marco] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Malagola, Michele] Univ Brescia, Chair Hematol, Brescia, Italy. [Fili, Carla; Bergonzi, Cesare; Cancelli, Valeria; Cattina, Federica] Univ Brescia, Brescia, Italy. [Cattina, Federica] Univ Brescia, Bone Marrow Transplant Unit, Chair Hematol, Brescia, Italy. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803197 ER PT J AU Song, WH Zhang, CL Hu, YG Gkotzamanidou, M Shah, P Shan, WS Yang, G Li, Y Sperling, A Rashid, N Samur, MK Amin, SB Tai, YT Hideshima, T Parmigiani, G Magrangeas, F Minvielle, S Avet-Loiseau, H Anderson, KC Li, C Munshi, NC AF Song, Weihua Zhang, Chaolin Hu, Yiguo Gkotzamanidou, Maria Shah, Parantu Shan, Weisong Yang, Guang Li, Yi Sperling, Adam Rashid, Naim Samur, Mehmet Kemal Amin, Samir B. Tai, Yu-Tzu Hideshima, Teru Parmigiani, Giovanni Magrangeas, Florence Minvielle, Stephane Avet-Loiseau, Herve Anderson, Kenneth C. Li, Cheng Munshi, Nikhil C. TI Bone Marrow Microenvironment Regulates Alternative Splicing Events in Myeloma Cells through Downregulation of RNA Binding Protein Fox2 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Song, Weihua; Hu, Yiguo; Shah, Parantu; Yang, Guang; Li, Yi; Sperling, Adam; Samur, Mehmet Kemal; Amin, Samir B.; Tai, Yu-Tzu; Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Chaolin] Rockefeller Univ, New Yorki City, NY USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Shan, Weisong] McGill Univ, Montreal, PQ, Canada. [Rashid, Naim; Parmigiani, Giovanni; Li, Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Magrangeas, Florence; Minvielle, Stephane] CHU Nantes, F-44035 Nantes 01, France. [Avet-Loiseau, Herve] Univ Hosp Nantes, Nantes, France. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015 NR 0 TC 1 Z9 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233808057 ER PT J AU Sperling, A Rashid, N Bolli, N Wedge, D Van Loo, P Tai, YT Shammas, M Fulciniti, M Samur, MK Richardson, PG Magrangeas, F Minvielle, S Futreal, PA Anderson, KC Avet-Ioiseau, H Campbell, PJ Parmigiani, G Munshi, N AF Sperling, Adam Rashid, Naim Bolli, Niccolo Wedge, David Van Loo, Peter Tai, Yu-Tzu Shammas, Masood Fulciniti, Mariateresa Samur, Mehmet Kemal Richardson, Paul G. Magrangeas, Florence Minvielle, Stephane Futreal, P. Andrew Anderson, Kenneth C. Avet-Ioiseau, Herve Campbell, Peter J. Parmigiani, Giovanni Munshi, Nikhil TI Differential and Limited Expression of Mutant Alleles in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sperling, Adam; Tai, Yu-Tzu; Fulciniti, Mariateresa; Samur, Mehmet Kemal; Anderson, Kenneth C.; Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rashid, Naim] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolli, Niccolo; Campbell, Peter J.] Univ Cambridge, Cambridge, England. [Wedge, David; Van Loo, Peter] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Shammas, Masood; Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Magrangeas, Florence; Minvielle, Stephane] CNRS 6299, UMR Inserm 892, Ctr Rech Cancerol Nantes Angers, Nantes, France. [Futreal, P. Andrew] Wellcome Trust Sanger Inst, Cambridge, England. [Avet-Ioiseau, Herve] Inst Univ Canc, Toulouse, France. [Avet-Ioiseau, Herve] Univ Hosp, Toulouse, France. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015 NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804125 ER PT J AU Stathis, A Freedman, AS Flinn, IW Maddocks, KJ Weitman, S Berdeja, JG Mejia, AV Zucca, E Green, R Romanelli, A Zildjian, SH Ruiz-Soto, R Palomba, L AF Stathis, Anastasios Freedman, Arnold S. Flinn, Ian W. Maddocks, Kami J. Weitman, Steven Berdeja, Jesus G. Mejia, Alex V. Zucca, Emanuele Green, Rebecca Romanelli, Angela Zildjian, Sybil H. Ruiz-Soto, Rodrigo Palomba, Lia TI A Phase I Study of IMGN529, an Antibody-Drug Conjugate (ADC) Targeting CD37, in Adult Patients with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Stathis, Anastasios; Zucca, Emanuele] Oncol Inst Southern Switzerland, Bellinzona, Switzerland. [Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flinn, Ian W.; Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Maddocks, Kami J.] Ohio State Univ, Columbus, OH 43210 USA. [Weitman, Steven; Mejia, Alex V.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Weitman, Steven; Mejia, Alex V.] CTRC Inst Drug Dev, San Antonio, TX USA. [Green, Rebecca; Palomba, Lia] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Romanelli, Angela; Zildjian, Sybil H.; Ruiz-Soto, Rodrigo] ImmunoGen Inc, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506191 ER PT J AU Stein, EM Altman, JK Collins, R DeAngelo, DJ Fathi, AT Flinn, I Frankel, A Levine, RL Medeiros, BC Patel, M Pollyea, DA Roboz, GJ Stone, RM Swords, RT Tallman, MS Agresta, S Fan, B Yang, H Yen, K de Botton, S AF Stein, Eytan M. Altman, Jessica K. Collins, Robert DeAngelo, Daniel J. Fathi, Amir T. Flinn, Ian Frankel, Arthur Levine, Ross L. Medeiros, Bruno C. Patel, Manish Pollyea, Daniel A. Roboz, Gail J. Stone, Richard M. Swords, Ronan T. Tallman, Martin S. Agresta, Sam Fan, Bin Yang, Hua Yen, Katharine de Botton, Stephane TI AG-221, an Oral, Selective, First-in-Class, Potent Inhibitor of the IDH2 Mutant Metabolic Enzyme, Induces Durable Remissions in a Phase I Study in Patients with IDH2 Mutation Positive Advanced Hematologic Malignancies SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Stein, Eytan M.; Levine, Ross L.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Altman, Jessica K.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Collins, Robert; Frankel, Arthur] Univ Texas Southwestern, Dallas, TX USA. [DeAngelo, Daniel J.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Medeiros, Bruno C.] Stanford Univ, Stanford, CA 94305 USA. [Patel, Manish] Florida Canc Specialists, Sarasota, FL USA. [Pollyea, Daniel A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Roboz, Gail J.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Swords, Ronan T.] Univ Miami Hosp, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Agresta, Sam; Fan, Bin; Yang, Hua; Yen, Katharine] Agios Pharmaceut, Cambridge, MA USA. [de Botton, Stephane] Inst Gustave Roussy, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806164 ER PT J AU Stein, EM Stein, A Walter, RB Fathi, AT Lancet, JE Kovacsovics, TJ Advani, AS DeAngelo, DJ O'Meara, MM Zhao, BT Kennedy, DA Erba, HP AF Stein, Eytan M. Stein, Anthony Walter, Roland B. Fathi, Amir T. Lancet, Jeffrey E. Kovacsovics, Tibor J. Advani, Anjali S. DeAngelo, Daniel J. O'Meara, Megan M. Zhao, Baiteng Kennedy, Dana A. Erba, Harry P. TI Interim Analysis of a Phase 1 Trial of SGN-CD33A in Patients with CD33-Positive Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Stein, Eytan M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Stein, Anthony] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Walter, Roland B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Fathi, Amir T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lancet, Jeffrey E.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Kovacsovics, Tibor J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Advani, Anjali S.] Cleveland Clin, Cleveland, OH 44106 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Meara, Megan M.; Zhao, Baiteng; Kennedy, Dana A.] Seattle Genet Inc, Bothell, WA USA. [Erba, Harry P.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805178 ER PT J AU Stock, W Luger, SM Advani, AS Geyer, S Harvey, RC Mullighan, CG Willman, CL Malnassy, G Parker, E Laumann, KM Sanford, B Marcucci, G Paietta, EM Liedtke, M Claxton, DF Foster, MC Appelbaum, FR Erba, H Litzow, MR Tallman, MS Stone, RM Larson, RA AF Stock, Wendy Luger, Selina M. Advani, Anjali S. Geyer, Susan Harvey, Richard C. Mullighan, Charles G. Willman, Cheryl L. Malnassy, Greg Parker, Edy Laumann, Kristina M. Sanford, Ben Marcucci, Guido Paietta, Elisabeth M. Liedtke, Michaela Claxton, David F. Foster, Matthew C. Appelbaum, Frederick R. Erba, Harry Litzow, Mark R. Tallman, Martin S. Stone, Richard M. Larson, Richard A. TI Favorable Outcomes for Older Adolescents and Young Adults (AYA) with Acute Lymphoblastic Leukemia (ALL): Early Results of US Intergroup Trial C10403 SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Stock, Wendy] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Luger, Selina M.] Univ Penn, Philadelphia, PA 19104 USA. [Advani, Anjali S.] Cleveland Clin, Cleveland, OH 44106 USA. [Geyer, Susan; Marcucci, Guido] Ohio State Univ, Columbus, OH 43210 USA. [Geyer, Susan] Alliance Clin Trials Oncol, Stat & Data Ctr, Rochester, MN USA. [Harvey, Richard C.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Mullighan, Charles G.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Willman, Cheryl L.] Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. [Malnassy, Greg; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Parker, Edy; Stone, Richard M.] ALLIANCE, Boston, MA USA. [Laumann, Kristina M.; Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Sanford, Ben] Duke Univ, Med Ctr, Alliance Clin Trials Oncol, Stat & Data Ctr, Durham, NC USA. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Liedtke, Michaela] Stanford Canc Inst, Stanford, CA USA. [Claxton, David F.] Penn State Coll Med, Penn State Hershey Canc Inst, Dept Med Hematol Oncol, Hershey, PA USA. [Foster, Matthew C.] Univ N Carolina, Chapel Hill, NC USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Erba, Harry] Univ Alabama Birmingham, Birmingham, AL USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larson, Richard A.] Alliance Clin Trials Oncol, Boston, MA USA. NR 0 TC 6 Z9 6 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803088 ER PT J AU Stroopinsky, D Pyzer, AR Palmer, KA Coll, MD Bar-Natan, M Rajabi, H Somaiya, P Luptakova, K Jain, S McMasters, M Levine, JD Arnason, J Taverna, P Kufe, D Avigan, D Rosenblatt, J AF Stroopinsky, Dina Pyzer, Athalia Rachel Palmer, Kristen A. Coll, Maxwell D. Bar-Natan, Michal Rajabi, Hasan Somaiya, Poorvi Luptakova, Katarina Jain, Salvia McMasters, Malgorzata Levine, James D. Arnason, Jon Taverna, Pietro Kufe, Donald Avigan, David Rosenblatt, Jacalyn TI Immunomodulatory Effect of SGI-110, a Novel Hypomethylating Agent in Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Stroopinsky, Dina; Pyzer, Athalia Rachel; Palmer, Kristen A.; Coll, Maxwell D.; Bar-Natan, Michal; Somaiya, Poorvi; Luptakova, Katarina; Jain, Salvia; McMasters, Malgorzata; Levine, James D.; Arnason, Jon; Avigan, David; Rosenblatt, Jacalyn] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rajabi, Hasan; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Taverna, Pietro] Astex Pharmaceut Inc, Dublin, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233805189 ER PT J AU Sujobert, P Paubelle, E Grenier, A Zylbersztejn, F Lambert, M Poulain, L Townsend, E Brusq, JM Nicodeme, E Decrooqc, J Nepstad, I Green, A Hospital, MA Jacque, N Hermine, O Foretz, M Viollet, B Lacombe, C Weinstock, DM Mayeux, P Moura, IC Bouscary, D Tamburini, J AF Sujobert, Pierre Paubelle, Etienne Grenier, Adrien Zylbersztejn, Florence Lambert, Mireille Poulain, Laury Townsend, Elizabeth Brusq, Jean-Marie Nicodeme, Edwige Decrooqc, Justine Nepstad, Ina Green, Alexa Hospital, Marie-Anne Jacque, Nathalie Hermine, Olivier Foretz, Marc Viollet, Benoit Lacombe, Catherine Weinstock, David M. Mayeux, Patrick Moura, Ivan C. Bouscary, Didier Tamburini, Jerome TI Co-Activation of AMPK and mTORC1 Is Synthetically Lethal in Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sujobert, Pierre; Grenier, Adrien; Poulain, Laury; Decrooqc, Justine; Jacque, Nathalie; Foretz, Marc; Moura, Ivan C.] Paris Descartes Sorbonne Paris Cite Univ, Paris, France. [Paubelle, Etienne; Hermine, Olivier] Hop Necker Enfants Malad, Paris, France. [Paubelle, Etienne] Univ Paris 05, ICNRS, UMR 8147, Paris, France. [Zylbersztejn, Florence] INSERM, U699, Paris, France. [Lambert, Mireille; Hospital, Marie-Anne] Cochin Hosp, Paris, France. [Townsend, Elizabeth] Harvard Univ, Boston, MA 02115 USA. [Brusq, Jean-Marie; Nicodeme, Edwige] GlaxoSmithKline Res Ctr, Les Ulis, France. [Nepstad, Ina] Univ Bergen, Bergen, Norway. [Green, Alexa; Viollet, Benoit] INSERM, U1016, Paris, France. [Hermine, Olivier] Univ Paris 05, Paris, France. [Lacombe, Catherine] Inst Cochin Genet Mol, F-75014 Paris, France. [Weinstock, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mayeux, Patrick] Inst Cochin Genet Mol, Dept Hematol, F-75014 Paris, France. [Bouscary, Didier] Hop Cochin, APHP, F-75674 Paris, France. [Tamburini, Jerome] Univ Paris 05, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 5 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801168 ER PT J AU Sun, BH Fiskus, W Shah, B Qi, J Devaraj, SGT Iyer, SP Sharma, S Bradner, J Zu, YL Bhalla, KN AF Sun, Baohua Fiskus, Warren Shah, Bhavin Qi, Jun Devaraj, Santhana G. T. Iyer, Swaminathan Padmanabhan Sharma, Sunil Bradner, James Zu, Youli Bhalla, Kapil N. TI Superior Pre-Clinical Activity of BET (Bromodomain and Extra terminal) Protein Antagonist Combined with Ibrutinib, Panobinostat or Carfilzomib Against Human Mantle Cell Lymphoma (MCL) Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sun, Baohua; Fiskus, Warren; Shah, Bhavin; Devaraj, Santhana G. T.; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX USA. [Qi, Jun; Bradner, James] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Iyer, Swaminathan Padmanabhan] Methodist Canc Ctr, Houston, TX USA. [Sharma, Sunil] Huntsman Canc Inst, Salt Lake City, UT USA. [Zu, Youli] Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506010 ER PT J AU Sun, WL Gaynon, PS Sposto, R Bittencourt, H Place, AE Messinger, YH Fraser, C Dalla-Pozza, L van der Giessen, J Eckroth, E Yang, XJ Liang, GN Jones, PA Wayne, AS Cooper, T AF Sun, Weili Gaynon, Paul S. Sposto, Richard Bittencourt, Henrique Place, Andrew E. Messinger, Yoav H. Fraser, Chris Dalla-Pozza, Luciano van der Giessen, Jeannette Eckroth, Elena Yang, Xiaojing Liang, Gangning Jones, Peter A. Wayne, Alan S. Cooper, Todd TI A Phase 1 Study of Azacitidine (AZA) in Combination with Fludarabine and Cytarabine in Relapse/Refractory Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Sun, Weili; Wayne, Alan S.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Gaynon, Paul S.; Sposto, Richard; van der Giessen, Jeannette; Eckroth, Elena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Bittencourt, Henrique] Univ Montreal, St Justine Univ Hosp, Montreal, PQ, Canada. [Place, Andrew E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Messinger, Yoav H.] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Fraser, Chris] Royal Childrens Hosp, Brisbane, Qld, Australia. [Dalla-Pozza, Luciano] Childrens Hosp Westmead, Sydney, NSW, Austria. [Yang, Xiaojing; Liang, Gangning; Jones, Peter A.] Univ So Calif, Los Angeles, CA USA. [Jones, Peter A.] Van Andel Res Inst, Grand Rapids, MI USA. [Cooper, Todd] Emory Univ, Aflac Canc Ctr, Atlanta, GA 30322 USA. [Cooper, Todd] Emory Univ, Blood Disorders Serv, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243503202 ER PT J AU Usmani, SZ Sexton, R Ailawadhi, S Shah, JJ Callander, NS Zimmerman, T Valent, J Rosenzweig, M Lipe, BC Zonder, J Fredette, S Durie, BGM Hoering, A Rajkumar, SV Richardson, PG Orlowski, RZ AF Usmani, Saad Z. Sexton, Rachael Ailawadhi, Sikander Shah, Jatin J. Callander, Natalie S. Zimmerman, Todd Valent, Jason Rosenzweig, Michael Lipe, Brea C. Zonder, Jeffrey Fredette, Sandi Durie, Brian G. M. Hoering, Antje Rajkumar, S. Vincent Richardson, Paul G. Orlowski, Robert Z. TI SWOG 1211: Initial Report on PHASE I Trial of RVD-Elotuzumab for NEWLY Diagnosed High Risk Multiple Myeloma (HRMM) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Usmani, Saad Z.] Levine Canc Inst, Charlotte, NC USA. [Sexton, Rachael; Hoering, Antje] Canc Res & Biostat, Seattle, WA USA. [Ailawadhi, Sikander] Mayo Clin, Jacksonville, FL 32224 USA. [Shah, Jatin J.; Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Callander, Natalie S.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Callander, Natalie S.] Univ Wisconsin, Madison, WI USA. [Zimmerman, Todd] Univ Chicago Med, Chicago, IL USA. [Valent, Jason] Cleveland Clin, Cleveland, OH 44106 USA. [Rosenzweig, Michael] City Hope Natl Med Ctr, Duarte, CA USA. [Lipe, Brea C.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Zonder, Jeffrey] Karmanos Canc Inst, Detroit, MI USA. [Fredette, Sandi] SWOG Operat, San Antonio, TX USA. [Durie, Brian G. M.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804025 ER PT J AU van der Hulle, T den Exter, PL Meyer, G Planquette, B Soler, S Monreal, M Jimenez, D Portillo, AK O'Connell, C Liebman, H Shteinberg, M Adir, Y Tiseo, M Bersanelli, M Abdel-Razeq, HN Mansour, AH Donnelly, OG Radhakrishna, G Ramasamy, S Bozas, G Maraveyas, A Shinagare, AB Hatabu, H Nishino, M Huisman, MV Klok, FA AF van der Hulle, T. den Exter, P. L. Meyer, G. Planquette, B. Soler, S. Monreal, M. Jimenez, D. Portillo, A. K. O'Connell, C. Liebman, H. Shteinberg, M. Adir, Y. Tiseo, M. Bersanelli, M. Abdel-Razeq, H. N. Mansour, A. H. Donnelly, O. G. Radhakrishna, G. Ramasamy, S. Bozas, G. Maraveyas, A. Shinagare, A. B. Hatabu, H. Nishino, M. Huisman, M. V. Klok, F. A. TI Risk of Recurrent Venous Thromboembolism and Major Bleeding in Cancer-Associated Incidental Pulmonary Embolism Amongst Treated and Untreated Patients: A Pooled Analysis of 926 Patients SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [van der Hulle, T.; den Exter, P. L.; Huisman, M. V.; Klok, F. A.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Meyer, G.; Planquette, B.] Univ Paris 05, Hop Europeen Georges Pompidou, Paris, France. [Soler, S.] Hosp St Jaume, Olot, Gerona, Spain. [Monreal, M.] Hosp Badalona Germans Trias & Pujol, Barcelona, Spain. [Jimenez, D.; Portillo, A. K.] IRYCIS, Ramon & Cajal Hosp, Madrid, Spain. [Jimenez, D.; Portillo, A. K.] Univ Alcala de Henares, Madrid, Spain. [O'Connell, C.; Liebman, H.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Shteinberg, M.; Adir, Y.] Technion Israel Inst Technol, Fac Med, Carmel Med Ctr, Haifa, Israel. [Tiseo, M.; Bersanelli, M.] Univ Hosp Parma, Parma, Italy. [Abdel-Razeq, H. N.; Mansour, A. H.] King Hussein Canc Ctr, Amman, Jordan. [Donnelly, O. G.] Univ Leeds, Leeds, W Yorkshire, England. [Donnelly, O. G.; Radhakrishna, G.; Ramasamy, S.] St James Inst Oncol, Leeds, W Yorkshire, England. [Bozas, G.; Maraveyas, A.] Hull & East Yorkshire Hosp NHS Trust, Castle Hill Hosp, Cottingham, Yorks, England. [Maraveyas, A.] Hull York Med Sch, Cottingham, Yorks, England. [Shinagare, A. B.; Hatabu, H.; Nishino, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shinagare, A. B.; Hatabu, H.; Nishino, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804063 ER PT J AU Varga, C Laubach, JP Ghobrial, IM Weinstock, M Paba-Prada, CE Schlossman, RL Munshi, N Xie, W Weller, EA Anderson, KC Mitsiades, CS Richardson, PG AF Varga, Cindy Laubach, Jacob P. Ghobrial, Irene M. Weinstock, Matthew Paba-Prada, Claudia E. Schlossman, Robert L. Munshi, Nikhil Xie, Wanling Weller, Edie A. Anderson, Kenneth C. Mitsiades, Constantine S. Richardson, Paul G. TI Time to Development of Treatment-Emergent Extramedullary and Osseous Plasmacytomas in the Era of Novel Agents: An Analysis of Upfront Regimens in Newly Diagnosed MM Incorporating Lenalidomide and Bortezomib SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Varga, Cindy; Paba-Prada, Claudia E.; Schlossman, Robert L.; Munshi, Nikhil; Weller, Edie A.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Laubach, Jacob P.; Xie, Wanling] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Weinstock, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802019 ER PT J AU Verstovsek, S Mesa, RA Foltz, LM Gupta, V Mascarenhas, JO Ritchie, EK Hoffman, R Silver, RT Kremyanskaya, M Pozdnyakova, O Hasserjian, RP Trehu, E Kantarjian, HM Gotlib, JR AF Verstovsek, Srdan Mesa, Ruben A. Foltz, Lynda M. Gupta, Vikas Mascarenhas, John O. Ritchie, Ellen K. Hoffman, Ronald Silver, Richard T. Kremyanskaya, Marina Pozdnyakova, Olga Hasserjian, Robert P. Trehu, Elizabeth Kantarjian, Hagop M. Gotlib, Jason R. TI Phase 2 Trial of PRM-151, an Anti-Fibrotic Agent, in Patients with Myelofibrosis: Stage 1 Results SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Verstovsek, Srdan; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Mesa, Ruben A.] Mayo Clin Canc Ctr, Scottsdale, AZ USA. [Foltz, Lynda M.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. [Foltz, Lynda M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Gupta, Vikas] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Mascarenhas, John O.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Ritchie, Ellen K.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Hoffman, Ronald] Ichan Sch Med Mt Sinai, Div Hematol Oncol, Tisch Canc Inst, Dept Med,Myeloproliferat Disorders Res Consortium, New York, NY USA. [Silver, Richard T.] Weill Cornell New York Presbyterian Hosp, New York, NY USA. [Kremyanskaya, Marina] Icahn Schoool Med Mt Sinai, New York, NY USA. [Pozdnyakova, Olga] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Trehu, Elizabeth] Promedior Inc, Lexington, MA USA. [Gotlib, Jason R.] Stanford Canc Inst, Stanford, CA USA. [Gotlib, Jason R.] Stanford Univ Sch Med, Stanford, CA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9HU UT WOS:000349233804115 ER PT J AU Viel, KR Kim, B Tejero, ME Cole, SS Howard, TE Ortiz, AS AF Viel, Kevin R. Kim, Benjamin Elizabeth Tejero, Maria Cole, Shelley S. Howard, Tom E. Santamaria Ortiz, Amparo TI The Spectrum of Amino Acid Substitutions Resulting from Single Nucleotide Substitutions in the Coagulation Biosystem: Impact on Identification By Mass Spectrometry SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Viel, Kevin R.] Histonis Inc, Atlanta, GA USA. [Kim, Benjamin] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Elizabeth Tejero, Maria] Inst Nacl Med Genom, Mexico City, DF, Mexico. [Cole, Shelley S.] Texas Biomed Res Inst, San Antonio, TX USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Santamaria Ortiz, Amparo] Hosp Valle De Hebron, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502119 ER PT J AU Vij, R Huff, CA Bensinger, WI Siegel, DS Jagannath, S Berdeja, J Lendvai, N Lebovic, D Anderson, LD Costello, CL Stockerl-Goldstein, KE Laubach, JP Elias, L Clow, F Fardis, M Graef, T Bilotti, E Richardson, PG AF Vij, Ravi Huff, Carol Ann Bensinger, William I. Siegel, David S. Jagannath, Sundar Berdeja, Jesus Lendvai, Nikoletta Lebovic, Daniel Anderson, Larry D. Costello, Caitlin L. Stockerl-Goldstein, Keith E. Laubach, Jacob P. Elias, Laurence Clow, Fong Fardis, Maria Graef, Thorsten Bilotti, Elizabeth Richardson, Paul G. TI Ibrutinib, Single Agent or in Combination with Dexamethasone, in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Phase 2 Results SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Vij, Ravi; Stockerl-Goldstein, Keith E.] Washington Univ, Sch Med, St Louis, MO USA. [Huff, Carol Ann] Johns Hopkins Univ, Baltimore, MD USA. [Bensinger, William I.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Berdeja, Jesus] Sarah Cannon Res Inst, Nashville, TN USA. [Lendvai, Nikoletta] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lendvai, Nikoletta] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Lebovic, Daniel] Univ Michigan, Ann Arbor, MI 48109 USA. [Anderson, Larry D.] UT Southwestern Med Ctr, Simmons Comprehens Canc Ctr, Dallas, TX USA. [Costello, Caitlin L.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Laubach, Jacob P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elias, Laurence; Clow, Fong; Fardis, Maria; Graef, Thorsten; Bilotti, Elizabeth] Pharmacyclics Inc, Sunnyvale, CA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506005 ER PT J AU Vij, R Savona, M Siegel, DS Kaufman, JL Badros, A Ghobrial, IM Paner, A Jagannath, S Jakubowiak, A Mikhael, JR Kapoor, P Neuman, LL Lee, JR Berdeja, JG AF Vij, Ravi Savona, Michael Siegel, David S. Kaufman, Jonathan L. Badros, Ashraf Ghobrial, Irene M. Paner, Agne Jagannath, Sundar Jakubowiak, Andrzej Mikhael, Joseph R. Kapoor, Prashant Neuman, Linda L. Lee, Ju RueyJiuan Berdeja, Jesus G. TI Clinical Profile of Single-Agent Oprozomib in Patients (Pts) with Multiple Myeloma (MM): Updated Results from a Multicenter, Open-Label, Dose Escalation Phase 1b/2 Study SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Savona, Michael] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Siegel, David S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Kaufman, Jonathan L.] Emory Univ, Atlanta, GA 30322 USA. [Badros, Ashraf] Univ Maryland, Baltimore, MD 21201 USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Paner, Agne] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Jagannath, Sundar] Mt Sinai Hosp, New York, NY 10029 USA. [Jakubowiak, Andrzej] Univ Chicago Med, Chicago, IL USA. [Mikhael, Joseph R.] Mayo Clin Arizona, Scottsdale, AZ USA. [Kapoor, Prashant] Mayo Clin, Rochester, MN USA. [Neuman, Linda L.] Onyx Pharmaceut Inc, Redwood City, CA USA. [Lee, Ju RueyJiuan] Onyx Pharmaceut Inc, San Francisco, CA USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504031 ER PT J AU Vij, R Hars, V Blum, W Shore, TB Rapoport, AP Shea, TC Hoke, E Stone, RM Friedman, P Owzar, K Devine, SM AF Vij, Ravi Hars, Vera Blum, William Shore, Tsiporah B. Rapoport, Aaron P. Shea, Thomas C. Hoke, Eva Stone, Richard M. Friedman, Paula Owzar, Kouros Devine, Steven M. TI CALGB 100801 (Alliance): A Phase II Multi-Center NCI Cooperative Group Study of the Addition of Azacitidine (AZA) to Reduced-Intensity Conditioning (RIC) Allogeneic Transplantation for High Risk Myelodysplasia (MDS) and Older Patients with Acute Myeloid Leukemia (AML): Results of a "test dose" Strategy to Target Busulfan Exposure SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Hars, Vera] Duke Univ, Med Ctr, Durham, NC USA. [Blum, William; Devine, Steven M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Shore, Tsiporah B.] New York Hosp, New York, NY 10021 USA. [Rapoport, Aaron P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Shea, Thomas C.] Univ N Carolina, Chapel Hill, NC USA. [Hoke, Eva] Duke Univ, Med Ctr, Alliance Clin Trials Oncol Stat & Data Ctr, Durham, NC USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Friedman, Paula] Univ Chicago, Chicago, IL 60637 USA. [Owzar, Kouros] Canc & Leukemia Grp B, Boston, MA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806177 ER PT J AU Vogl, DT Raje, N Hari, P Jones, SS Supko, JG Leone, G Wheeler, C Orlowski, RZ Richardson, PG Lonial, S Tamang, D Jagannath, S AF Vogl, Dan T. Raje, Noopur Hari, Parameswaran Jones, Simon S. Supko, Jeffrey G. Leone, Gina Wheeler, Catherine Orlowski, Robert Z. Richardson, Paul G. Lonial, Sagar Tamang, David Jagannath, Sundar TI Phase 1B Results of Ricolinostat (ACY-1215) Combination Therapy with Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Vogl, Dan T.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Raje, Noopur; Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hari, Parameswaran] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jones, Simon S.; Leone, Gina; Wheeler, Catherine; Tamang, David] Acetylon Pharmaceut Inc, Boston, MA USA. [Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505209 ER PT J AU Voorhees, PM Schlossman, RL Gasparetto, CJ Berdeja, JG Morris, J Jacobstein, DA Anderson, KC Mitsiades, CS Laubach, JP Richardson, PG AF Voorhees, Peter M. Schlossman, Robert L. Gasparetto, Cristina J. Berdeja, Jesus G. Morris, John Jacobstein, Douglas A. Anderson, Kenneth C. Mitsiades, Constantine S. Laubach, Jacob P. Richardson, Paul G. TI An Open-Label, Dose Escalation, Multi-Center Phase 1 Study of PRLX 93936, an Agent Synthetically Active Against the Activated Ras Pathway, in the Treatment of Relapsed or Relapsed and Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Schlossman, Robert L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gasparetto, Cristina J.] Duke Univ, Med Ctr, Durham, NC USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Morris, John] Univ Cincinnati, Inst Canc, Cincinnati, OH USA. [Jacobstein, Douglas A.] Prolexys Pharmaceut Inc, Columbia, MD USA. [Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Mitsiades, Constantine S.; Laubach, Jacob P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500015 ER PT J AU Wagers, AJ AF Wagers, Amy J. TI Stem Cell Rejuvenation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wagers, Amy J.] Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 8 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243501074 ER PT J AU Wagner, DD AF Wagner, Denisa D. TI Neutrophil Extracellular Traps and von Willebrand Factor in Thrombosis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9HU UT WOS:000349233802013 ER PT J AU Walter, RB Othus, M Paietta, EM Racevskis, J Fernandez, HF Lee, JW Sun, ZX Tallman, MS Patel, JP Gonen, M Abdel-Wahab, O Levine, RL Estey, EH AF Walter, Roland B. Othus, Megan Paietta, Elisabeth M. Racevskis, Janis Fernandez, Hugo F. Lee, Ju-Whei Sun, Zhuoxin Tallman, Martin S. Patel, Jay P. Goenen, Mithat Abdel-Wahab, Omar Levine, Ross L. Estey, Elihu H. TI Effect of Genetic Profiling on Prediction of Therapeutic Resistance and Survival in Adult Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Walter, Roland B.; Estey, Elihu H.] Univ Washington, Seattle, WA 98195 USA. [Walter, Roland B.; Othus, Megan; Estey, Elihu H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Paietta, Elisabeth M.; Racevskis, Janis] Montefiore Med Ctr, Bronx, NY 10467 USA. [Fernandez, Hugo F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Lee, Ju-Whei; Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tallman, Martin S.; Patel, Jay P.; Goenen, Mithat; Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233807082 ER PT J AU Wang, HF Yashiro-Ohtani, Y Zang, CZ Wong, YJ Bailis, W Knoechel, B Bernstein, B Blacklow, S Liu, XS Pear, WS Aster, JC AF Wang, Hongfang Yashiro-Ohtani, Yumi Zang, Chongzhi Wong, Yinling Joey Bailis, Will Knoechel, Birgit Bernstein, Bradley Blacklow, Steve Liu, X. Shirley Pear, Warren S. Aster, Jon C. TI Alternative Super-Enhancer States Determine MYC Sensitivity to Notch and Brd4 Inhibitors in T Lymphoblastic Leukemia/Lymphoma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Hongfang; Wong, Yinling Joey; Aster, Jon C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yashiro-Ohtani, Yumi; Bailis, Will; Pear, Warren S.] Univ Penn, Philadelphia, PA 19104 USA. [Zang, Chongzhi; Liu, X. Shirley] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zang, Chongzhi; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Knoechel, Birgit] Boston Childrens Hosp, Boston, MA USA. [Bernstein, Bradley] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. [Blacklow, Steve] Harvard Univ, Sch Med, Boston, MA USA. RI Zang, Chongzhi/D-1445-2011 NR 0 TC 0 Z9 0 U1 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803096 ER PT J AU Wang, LD Nguyen, P Ficarro, SB Hutchinson, J Hofmann, O Marto, JA Wagers, AJ AF Wang, Leo D. Phi Nguyen Ficarro, Scott B. Hutchinson, John Hofmann, Oliver Marto, Jarrod A. Wagers, Amy J. TI Small-Scale Mass Spectrometry-Based Phosphoproteomic Analysis of Primary Hematopoietic Stem and Progenitor Cells to Identify Critical Regulators of HSPC Mobilization and Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Leo D.; Phi Nguyen] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wang, Leo D.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Wang, Leo D.; Phi Nguyen; Hutchinson, John; Hofmann, Oliver] Harvard Stem Cell Inst, Cambridge, MA USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hutchinson, John; Hofmann, Oliver] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wagers, Amy J.] Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA USA. [Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243504093 ER PT J AU Wang, LD Nguyen, P Rowe, RG Rao, TN Daley, GQ Wagers, AJ AF Wang, Leo D. Phi Nguyen Rowe, Robert G. Rao, Tata Nageswara Daley, George Q. Wagers, Amy J. TI Ectopic Expression of Lin28 Biases Myeloid Differentiation to Promote an Immature Mast Cell State and Is Implicated in Aggressive Mastocytosis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Leo D.; Rowe, Robert G.; Daley, George Q.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Wang, Leo D.; Phi Nguyen; Rao, Tata Nageswara] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy J.] Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500114 ER PT J AU Wang, LL Kotliar, D Fan, J Li, SQ Grimsby, J Landau, DA Brown, JR Lennon, N Neuberg, D Livak, KJ Wu, CJ AF Wang, Lili Kotliar, Dylan Fan, Jean Li, Shuqiang Grimsby, Jonna Landau, Dan A. Brown, Jennifer R. Lennon, Niall Neuberg, Donna Livak, Kenneth J. Wu, Catherine J. TI Integrated Single-Cell Detection of Genotype and Phenotype in SF3B1-Mutated Chronic Lymphocytic Leukemia Cells SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Lili; Landau, Dan A.; Brown, Jennifer R.; Neuberg, Donna; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Lili; Kotliar, Dylan; Fan, Jean; Landau, Dan A.; Wu, Catherine J.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Shuqiang; Livak, Kenneth J.] Fluidigm Co, San Francisco, CA USA. [Grimsby, Jonna; Lennon, Niall] Broad Inst, Cambridge, MA USA. [Landau, Dan A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Brown, Jennifer R.; Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803145 ER PT J AU Weinacht, KG AF Weinacht, Katja G. TI Linking Oxidative Stress to Cell Fate-Ipsc-Based Disease Modeling Identifies New Therapeutic Target in Reticular Dysgenesis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Weinacht, Katja G.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 2 WC Hematology SC Hematology GA CA9HU UT WOS:000349233800093 ER PT J AU Weinstock, M Aljawai, Y Ghobrial, IM Morgan, EA Laubach, JP Roccaro, AM Varga, C Gannon, M Paba-Prada, CE Schlossman, RL Munshi, N Anderson, KC Richardson, PG Mitsiades, CS AF Weinstock, Matthew Aljawai, Yosra Ghobrial, Irene M. Morgan, Elizabeth A. Laubach, Jacob P. Roccaro, Aldo M. Varga, Cindy Gannon, Muriel Paba-Prada, Claudia E. Schlossman, Robert L. Munshi, Nikhil Anderson, Kenneth C. Richardson, Paul G. Mitsiades, Constantine S. TI Incidence and Clinical Features of Extramedullary Multiple Myeloma in Patients Who Underwent Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Weinstock, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Aljawai, Yosra; Roccaro, Aldo M.; Varga, Cindy; Paba-Prada, Claudia E.; Munshi, Nikhil; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ghobrial, Irene M.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Morgan, Elizabeth A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Laubach, Jacob P.; Gannon, Muriel] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlossman, Robert L.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233803129 ER PT J AU Whitlock, J Pozza, LD Goldberg, JM Silverman, LB Ziegler, DS Attarbaschi, A Brown, P Gardner, RA Gaynon, PS Hutchinson, RJ Marcus, LJ Messinger, YH Schultz, KR Vandergiessen, J Eckroth, E Locatelli, F Zwaan, CM Wood, BL Sposto, R Gore, L AF Whitlock, James Pozza, Luciano dalla Goldberg, John M. Silverman, Lewis B. Ziegler, David S. Attarbaschi, Andishe Brown, Patrick Gardner, Rebecca A. Gaynon, Paul S. Hutchinson, Raymond J. Marcus, Leigh J. Messinger, Yoav H. Schultz, Kirk R. Vandergiessen, Jeannette Eckroth, Elena Locatelli, Franco Zwaan, C. Michel Wood, Brent L. Sposto, Richard Gore, Lia TI Nelarabine in Combination with Etoposide and Cyclophosphamide Is Active in First Relapse of Childhood T-Acute Lymphocytic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LL) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Whitlock, James] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Pozza, Luciano dalla] Childrens Hosp Westmead, Sydney, NSW, Australia. [Goldberg, John M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Goldberg, John M.] Sylvester Comprehens Canc Ctr, Miami, FL USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ziegler, David S.] Sydney Childrens Hosp, Sydney, NSW, Australia. [Attarbaschi, Andishe] St Anna Childrens Hosp, A-1090 Vienna, Austria. [Brown, Patrick] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Gardner, Rebecca A.] Seattle Childrens Hosp, Seattle, WA USA. [Gaynon, Paul S.; Vandergiessen, Jeannette; Eckroth, Elena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Hutchinson, Raymond J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Marcus, Leigh J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Messinger, Yoav H.] Childrens Hosp & Clin, St Paul, MN USA. [Schultz, Kirk R.] Univ British Columbia, BC Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. [Locatelli, Franco] Univ Pavia, IRCCS Bambino Gesu Childrens Hosp Rome, Rome, Italy. [Zwaan, C. Michel] Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands. [Wood, Brent L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sposto, Richard] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. [Gore, Lia] Univ Colorado, Ctr Canc, Aurora, CO USA. NR 0 TC 3 Z9 3 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243502167 ER PT J AU Xu, J Shao, Z Li, D Xie, HF Kim, W Huang, JL Pinello, L Glass, K Yuan, GC Orkin, SH AF Xu, Jian Shao, Zhen Li, Dan Xie, Huafeng Kim, Woojin Huang, Jialiang Pinello, Luca Glass, Kimberly Yuan, Guo-Cheng Orkin, Stuart H. TI Developmental Control of Polycomb Subunit Composition Mediates a Switch to Non-Canonical Functions during Hematopoiesis SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Xu, Jian; Shao, Zhen; Xie, Huafeng; Kim, Woojin; Huang, Jialiang; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp, Boston, MA 02115 USA. [Xu, Jian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Shao, Zhen] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Shanghai, Peoples R China. [Li, Dan] Harvard Univ, Boston, MA USA. [Pinello, Luca; Glass, Kimberly; Yuan, Guo-Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233801222 ER PT J AU Yee, AJ Voorhees, PM Bensinger, W Berdeja, JG Supko, JG Richardson, PG Tamang, D Jones, SS Patrick, G Wheeler, C Raje, N AF Yee, Andrew J. Voorhees, Peter M. Bensinger, William Berdeja, Jesus G. Supko, Jeffrey G. Richardson, Paul G. Tamang, David Jones, Simon S. Patrick, Gretchen Wheeler, Catherine Raje, Noopur TI Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Yee, Andrew J.; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Voorhees, Peter M.] Univ N Carolina, Chapel Hill, NC USA. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA. [Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richardson, Paul G.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Tamang, David; Jones, Simon S.; Patrick, Gretchen; Wheeler, Catherine] Acetylon Pharmaceut Inc, Boston, MA USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505057 ER PT J AU Zeidan, AM Sekeres, MA Garcia-Manero, G Barnard, J Al Ali, NH Zimmerman, C Roboz, GJ Steensma, DP DeZern, AE Jabbour, E Kantarjian, H Zell, K Wang, QQ Gore, SD Nazha, A Maciejewski, JP List, AF Komrokji, RS AF Zeidan, Amer M. Sekeres, Mikkael A. Garcia-Manero, Guillermo Barnard, John Al Ali, Najla H. Zimmerman, Cassie Roboz, Gail J. Steensma, David P. DeZern, Amy E. Jabbour, Elias Kantarjian, Hagop Zell, Katrina Wang, Quiqing Gore, Steven D. Nazha, Aziz Maciejewski, Jaroslaw P. List, Alan F. Komrokji, Rami S. TI The Prognostic Utility of the Current Risk Models in Predicting Outcomes of Patients (pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agents (HMA) SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zeidan, Amer M.; Gore, Steven D.] Yale Univ, Yale Canc Ctr, New Haven, CT USA. [Sekeres, Mikkael A.; Barnard, John; Zimmerman, Cassie; Zell, Katrina; Wang, Quiqing; Nazha, Aziz; Maciejewski, Jaroslaw P.] Cleveland Clin, Cleveland, OH 44106 USA. [Garcia-Manero, Guillermo; Jabbour, Elias; Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Al Ali, Najla H.; List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Roboz, Gail J.] Weill Cornell Med Coll, New York, NY USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [DeZern, Amy E.] Johns Hopkins Univ, Baltimore, MD USA. [Komrokji, Rami S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 4 WC Hematology SC Hematology GA CA9KX UT WOS:000349243505131 ER PT J AU Zhang, HJ Kozono, D O'Connor, K Vidal-Cardenas, S Hamilton, A Gaudiano, E Greenberger, JS Grompe, M Parmar, K D'Andrea, AD AF Zhang, Haojian Kozono, David O'Connor, Kevin Vidal-Cardenas, Sofia Hamilton, Abigail Gaudiano, Emily Greenberger, Joel S. Grompe, Markus Parmar, Kalindi D'Andrea, Alan D. TI Bone Marrow Failure in Fanconi Anemia from Hyperactive TGF-beta Signaling SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhang, Haojian; Kozono, David; O'Connor, Kevin; Vidal-Cardenas, Sofia; Hamilton, Abigail; Gaudiano, Emily; Parmar, Kalindi; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Greenberger, Joel S.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Grompe, Markus] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506220 ER PT J AU Zhang, QS Benedetti, E Deater, M Schubert, K Major, A Pelz, C Impey, S Marquez-Loza, L Rathbun, K Kato, S Bagby, GC Grompe, M AF Zhang, Qingshuo Benedetti, Eric Deater, Matthew Schubert, Kathryn Major, Angela Pelz, Carl Impey, Soren Marquez-Loza, Laura Rathbun, Keaney Kato, Shigeaki Bagby, Grover C. Grompe, Markus TI Oxymetholone Therapy of Fanconi Anemia Induces Hematopoietic Stem Cell Cycling By Suppressing Osteopontin Transcription SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhang, Qingshuo; Benedetti, Eric; Deater, Matthew; Schubert, Kathryn; Pelz, Carl; Impey, Soren; Marquez-Loza, Laura; Grompe, Markus] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Major, Angela] Texas Childrens Hosp, Houston, TX 77030 USA. [Rathbun, Keaney; Bagby, Grover C.] Portland VA Med Ctr, Portland, OR USA. [Kato, Shigeaki] Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9HU UT WOS:000349233806030 ER PT J AU Zhou, Z Rademaker, AW Gordon, LI LaCasce, AS Crosby-Thompson, A Vanderplas, A Abel, GA Rodriguez, MA Nademanee, A Kaminski, M Czuczman, MS Millenson, MM Niland, J Zelenetz, AD Friedberg, JW Winter, JN AF Zhou, Zheng Rademaker, Alfred W. Gordon, Leo I. LaCasce, Ann S. Crosby-Thompson, Allison Vanderplas, Ann Abel, Gregory A. Rodriguez, Maria A. Nademanee, Auayporn Kaminski, Mark Czuczman, Myron S. Millenson, Michael M. Niland, Joyce Zelenetz, Andrew D. Friedberg, Jonathan W. Winter, Jane N. TI High Body Mass Index (BMI) in North American Elderly Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Rituximab (R)-CHOP Compensates for Negative Impact of Male Gender SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhou, Zheng] Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Chicago, IL 60611 USA. [Rademaker, Alfred W.; Gordon, Leo I.; Winter, Jane N.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [LaCasce, Ann S.; Crosby-Thompson, Allison; Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vanderplas, Ann; Niland, Joyce] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Rodriguez, Maria A.] UT MD Anderson Canc Ctr, Houston, TX USA. [Nademanee, Auayporn] City Hope Natl Med Ctr, Duarte, CA USA. [Kaminski, Mark] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Friedberg, Jonathan W.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243506118 ER PT J AU Zweidler-McKay, PA DeAngelo, DJ Douer, D Dombret, H Ottmann, OG Vey, N Thomas, DA Zhu, LL Huang, F Bajaj, G Fischer, BS AF Zweidler-McKay, Patrick A. DeAngelo, Daniel J. Douer, Dan Dombret, Herve Ottmann, Oliver G. Vey, Norbert Thomas, Deborah A. Zhu, Lili Huang, Fei Bajaj, Gaurav Fischer, Bruce S. TI The Safety and Activity of BMS-906024, a Gamma Secretase Inhibitor (GSI) with Anti-Notch Activity, in Patients with Relapsed T-Cell Acute Lymphoblastic Leukemia (T-ALL): Initial Results of a Phase 1 Trial SO BLOOD LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2014 CL San Francisco, CA SP Amer Soc Hematol C1 [Zweidler-McKay, Patrick A.; Thomas, Deborah A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Douer, Dan] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, New York, NY 10021 USA. [Dombret, Herve] Hop St Louis, AP HP, Paris, France. [Ottmann, Oliver G.] Goethe Univ Hosp, Frankfurt, Germany. [Vey, Norbert] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Zhu, Lili; Huang, Fei; Bajaj, Gaurav; Fischer, Bruce S.] Bristol Myers Squibb Co, Princeton, NJ USA. RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 0 TC 5 Z9 5 U1 0 U2 1 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 DEC 6 PY 2014 VL 124 IS 21 PG 3 WC Hematology SC Hematology GA CA9KX UT WOS:000349243500196 ER PT J AU Kling, S Akca, IB Chang, EW Scarcelli, G Bekesi, N Yun, SH Marcos, S AF Kling, Sabine Akca, Imran B. Chang, Ernest W. Scarcelli, Giuliano Bekesi, Nandor Yun, Seok-Hyun Marcos, Susana TI Numerical model of optical coherence tomographic vibrography imaging to estimate corneal biomechanical properties SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE non-contact; corneal biomechanical properties; vibrography; corneal natural frequencies ID CROSS-LINKING; AIR-PUFF; TONOMETRY; DEFORMATION; MICROSCOPY; THICKNESS AB Most techniques measuring corneal biomechanics in vivo are biased by side factors. We demonstrate the ability of optical coherence tomographic (OCT) vibrography to determine corneal material parameters, while reducing current prevalent restrictions of other techniques (such as intraocular pressure (IOP) and thickness dependency). Modal analysis was performed in a finite-element (FE) model to study the oscillation response in isolated thin corneal flaps/eye globes and to analyse the dependency of the frequency response function on: corneal elasticity, viscoelasticity, geometry (thickness and curvature), IOP and density. The model was verified experimentally in flaps from three bovine corneas and in two enucleated porcine eyes using sound excitation (100-110 dB) together with a phase-sensitive OCT to measure the frequency response function (range 50-510 Hz). Simulations showed that corneal vibration in flaps is sensitive to both, geometrical and biomechanical parameters, whereas in whole globes it is primarily sensitive to corneal biomechanical parameters only. Calculations based on the natural frequency shift revealed that flaps of the posterior cornea were 0.8 times less stiff than flaps from the anterior cornea and cross-linked corneas were 1.6 times stiffer than virgin corneas. Sensitivity analysis showed that natural vibration frequencies of whole globes were nearly independent from corneal thickness and IOP within the physiological range. OCT vibrography is a promising non-invasive technique to measure corneal elasticity without biases from corneal thickness and IOP. C1 [Kling, Sabine; Bekesi, Nandor; Marcos, Susana] CSIC, Inst Opt, E-28006 Madrid, Spain. [Akca, Imran B.; Chang, Ernest W.; Scarcelli, Giuliano; Yun, Seok-Hyun] Wellman Ctr Photomed, Boston, MA USA. [Akca, Imran B.; Chang, Ernest W.; Scarcelli, Giuliano; Yun, Seok-Hyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kling, S (reprint author), CSIC, Inst Opt, Serrano 121, E-28006 Madrid, Spain. EM kling.sabine@gmail.com; susana@io.cfmac.csic.es RI Bekesi, Nandor/A-6812-2010 OI Bekesi, Nandor/0000-0001-7532-9589 FU European Research Council under the European Union [294099]; Spanish Government, MINECO [FIS2011-25637, FPI-BES-2009-024560]; Harvard Clinical and Translational Science Center [NIH UL1-RR025758]; NIH [P41-EB015903]; NSF [CBET-1264356]; Comunidad de Madrid; EU [FP7/2007-2013/REA 291820] FX The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP7/2007-2013)/ERC grant agreement no. 294099 and furthermore from the Spanish Government, MINECO, FIS2011-25637, FPI-BES-2009-024560, Harvard Clinical and Translational Science Center (NIH UL1-RR025758), NIH grant no. P41-EB015903, NSF grant no. CBET-1264356; Comunidad de Madrid and EU (FP7/2007-2013/REA 291820). NR 28 TC 9 Z9 9 U1 1 U2 10 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD DEC 6 PY 2014 VL 11 IS 101 AR UNSP 20140920 DI 10.1098/rsif.2014.0920 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AR6DF UT WOS:000343672800016 PM 25320067 ER PT J AU Li, W Long, JA Watts, LT Jiang, Z Shen, Q Li, YX Duong, TQ AF Li, Wei Long, Justin Alexander Watts, Lora Talley Jiang, Zhao Shen, Qiang Li, Yunxia Duong, Timothy Q. TI A Quantitative MRI Method for Imaging Blood-Brain Barrier Leakage in Experimental Traumatic Brain Injury SO PLOS ONE LA English DT Article ID REPERFUSION INJURY; MODEL SELECTION; PATLAK PLOTS; RAT MODEL; GD-DTPA; PERMEABILITY; STROKE; PARAMETERS; DIFFUSION; BREAKDOWN AB Blood-brain barrier (BBB) disruption is common following traumatic brain injury (TBI). Dynamic contrast enhanced (DCE) MRI can longitudinally measure the transport coefficient K-trans which reflects BBB permeability. K-trans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of K-trans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B-1 field) and magnetization (M-0) distributions. A series of T-1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI), and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T-2 contrast showing cerebral edema, K-trans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T-2. This improved K-trans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI. C1 [Li, Wei; Long, Justin Alexander; Watts, Lora Talley; Jiang, Zhao; Shen, Qiang; Li, Yunxia; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Li, Wei; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Watts, Lora Talley] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Watts, Lora Talley; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Li, W (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. EM liw5@uthscsa.edu; duongt@uthscsa.edu RI Shen, Qiang/B-8784-2008 OI Shen, Qiang/0000-0002-4287-3403 FU NIH/NINDS [R01 NS45879, UL1 TR001119, TL1TR001119, KL2 TR001118]; NIH/NINDS via the Clinical Translational Science Awards (CTSA) [TL1TR001119, UL1TR001119, 8UL1TR000149] FX The study was supported in part by grants from NIH/NINDS R01 NS45879 (TQD), UL1 TR001119 (WL), TL1TR001119 (JAL), and KL2 TR001118 (LTW) via the Clinical Translational Science Awards (CTSA, parent grant UL1TR001119, 8UL1TR000149, and TL1TR001119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 7 Z9 9 U1 2 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2014 VL 9 IS 12 AR e114173 DI 10.1371/journal.pone.0114173 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX4MS UT WOS:000346907200050 PM 25478693 ER PT J AU Lahav, A Skoe, E AF Lahav, Amir Skoe, Erika TI An acoustic gap between the NICU and womb: a potential risk for compromised neuroplasticity of compromised neuroplasticity of the auditory system in preterm infants SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE auditory development; NICU; preterm infants; noise exposure; high frequency ID NEONATAL INTENSIVE-CARE; BRAIN-STEM; HEARING-LOSS; TRAINING INFLUENCES; SOUND ENVIRONMENT; CRITICAL PERIOD; NOISE EXPOSURE; FETAL HEARING; SPEECH SOUNDS; HUMAN COCHLEA AB The intrauterine environment allows the fetus to begin hearing low-frequency sounds in a protected fashion, ensuring intial optimal development of the peripheral and central auditory system. However, the auditory nursery provided by the womb vanishes once the preterm newborn enters the high-frequency (HF) noisy environment of the neonatal intensive care unit (NICU). The present article draws a concerning line between auditory system development and HF noise in the NICU, which we argue is not necessarily conductive to fostering this development. Overexposure to HF noise during critical periods disrupts the functional organization of auditory cortical cicuits. As a result, we theorize that the ability to tune out noise and extract acoustic information in a noisy environment may be impaired, leading to increased risks for a variety of auditory, language, and attention disorders. Additionally, HF noise in the NICU often masks human speech sounds, further limitting quality exposure to linguistic stimuli. Understanding the impact of the sound environment on the developing auditory system is an important first step in meeting the development demands of preterm newborns undergoing intensive care. C1 [Lahav, Amir] Brigham & Womens Hosp, Dept Pediat & Newborn Med, Boston, MA 02115 USA. [Lahav, Amir] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. [Skoe, Erika] Univ Connecticut, Dept Speech Language & Hearing Sci, Dept Psychol Affiliate, Cognit Sci Program Affiliate, Storrs, CT USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, Dept Pediat & Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM amir_lahav@hms.harvard.edu FU Charles H. Hood Foundation; Peter and Elizabeth C. Tower Foundation; Gerber Foundation; Little Giraffe Foundation; Hailey's Hope Foundation; Jackson L. Graves Foundation; TripAdvisor Fund FX We gratefully thank Linda Malie for assisting with graphic design of Figure 1 and Parker Tichko for comments on the manuscript. We are also grateful for the generous support Amir Lahav received from the Charles H. Hood Foundation, Peter and Elizabeth C. Tower Foundation, Gerber Foundation, Little Giraffe Foundation, Hailey's Hope Foundation, Jackson L. Graves Foundation, and TripAdvisor Fund. NR 108 TC 7 Z9 8 U1 3 U2 15 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD DEC 5 PY 2014 VL 8 AR 381 DI 10.3389/fnins.2014.00381 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AW9DA UT WOS:000346556600001 PM 25538543 ER PT J AU Wang, Y AF Wang, Yu TI RING Finger Protein 4 (RNF4) Derepresses Gene Expression from DNA Methylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE DNA Methylation; Protein Turnover; RING Finger Protein 4 (RNF4); Transcription; Ubiquitylation (Ubiquitination); Methyl CpG-binding Protein 2 (MeCP2) ID MAMMALIAN DNA; TET PROTEINS; 5-METHYLCYTOSINE; DEMETHYLATION; 5-HYDROXYMETHYLCYTOSINE; 5-CARBOXYLCYTOSINE; IDENTIFICATION; TRANSCRIPTION; COREGULATOR; CONVERSION AB Background: RNF4 is a transcription activator, yet the mechanism is unknown. Results: RNF4 mediates ubiquitination and turnover of MeCP2 and thus derepresses transcription from DNA methylation. Conclusion: RNF4 regulates transcription by creating a permissive epigenetic environment. Significance: This study lays the basis for better understanding the role of RNF4 in epigenetics and transcription. RNF4 is an E3 ubiquitin ligase originally identified as a transcription co-activator. The mechanism by which RNF4 promotes transcription remains unclear. In this study, I found that RNF4 antagonizes transcriptional repression mediated by DNA methylation. RNF4 does not promote DNA demethylation, but mediates the ubiquitination of MeCP2, a methyl-CpG-binding domain (MBD) protein. Removal of MeCP2 from gene promoters activates transcription. This study thus not only uncovers how RNF4 functions as a transcription activator, but also reveals the mechanism by which MeCP2 protein stability is regulated. C1 [Wang, Yu] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wang, Yu] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Wang, Y (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, WAB 164,200 Longwood Ave, Boston, MA 02115 USA. EM yu.wang@childrens.harvard.edu FU American Heart Association FX Supported by a postdoctoral fellowship from American Heart Association. To whom correspondence should be addressed: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, WAB-164, 200 Longwood Ave., Boston, MA 02115. E-mail: yu.wang@childrens.harvard.edu. NR 21 TC 1 Z9 1 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 2014 VL 289 IS 49 BP 33808 EP 33813 DI 10.1074/jbc.C114.611558 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW1UZ UT WOS:000346077600008 PM 25355316 ER PT J AU Woody, G Bruce, D Korthuis, PT Chhatre, S Hillhouse, M Jacobs, P Sorensen, J Saxon, AJ Poole, S Metzger, D Ling, W AF Woody, George Bruce, Douglas Korthuis, P. Todd Chhatre, Sumedha Hillhouse, Maureen Jacobs, Petra Sorensen, James Saxon, Andrew J. Poole, Sabrina Metzger, David Ling, Walter TI Authors' Reply: "Risk Reduction With Buprenorphine-Naloxone and Methadone: Patient's Choice" SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Woody, George; Chhatre, Sumedha; Poole, Sabrina; Metzger, David] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woody, George; Chhatre, Sumedha; Jacobs, Petra; Metzger, David] Treatment Res Inst, Philadelphia, PA USA. [Bruce, Douglas] Yale Univ, Sch Med, New Haven, CT USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Hillhouse, Maureen; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA. [Sorensen, James] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Woody, G (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RI Metzger, David/D-9499-2012 FU NIAID NIH HHS [P30 AI045008]; NIDA NIH HHS [K05 DA-17009, K05 DA017009, U10 DA-13043, U10 DA013043, U10 DA013714, U10-DA013714, UG1 DA013714]; NIMH NIH HHS [P30 MH097488] NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 5 PY 2014 VL 67 IS 5 BP E142 EP E143 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AT2NW UT WOS:000344772300003 PM 25243431 ER PT J AU Kapoor, R Saint, S Kapoor, JR Johnson, RA Dhaliwal, G AF Kapoor, Roger Saint, Sanjay Kapoor, John R. Johnson, Richard A. Dhaliwal, Gurpreet TI D Is for Delay SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PELLAGRA; SKIN C1 [Kapoor, Roger] Beloit Hlth Syst, Dept Med, Beloit, WI 53511 USA. [Kapoor, Roger] Univ Illinois, Coll Med, Rockford, IL 61107 USA. [Kapoor, John R.] Chicago Med Sch, Dept Med, Chicago, IL USA. [Saint, Sanjay] Ann Arbor Vet Affairs VA Med Ctr, Ann Arbor, MI USA. [Saint, Sanjay] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Johnson, Richard A.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Kapoor, R (reprint author), Beloit Hlth Syst, Dept Med, 1969 W Hart Rd, Beloit, WI 53511 USA. EM rogerkapoor@gmail.com FU Doximity; Jvion FX Dr. Saint reports receiving fees for board membership from Doximity and Jvion. No other potential conflict of interest relevant to this article was reported. NR 13 TC 3 Z9 3 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2218 EP 2223 DI 10.1056/NEJMcps1212211 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700012 PM 25470698 ER PT J AU Sahay, T Ananthakrishnan, AN AF Sahay, Tanya Ananthakrishnan, Ashwin N. TI Vitamin D deficiency is associated with community-acquired clostridium difficile infection: a case-control study SO BMC INFECTIOUS DISEASES LA English DT Article DE C difficile; Vitamin D; Community-acquired; Infection; Cathelicidin ID INFLAMMATORY-BOWEL-DISEASE; BINDING PROTEIN; REDUCED RISK; CATHELICIDIN; PLASMA; REPRODUCIBILITY; EPIDEMIOLOGY; HOSPITALS; DIARRHEA; BURDEN AB Background: Clostridium difficile infection (CDI) is increasingly recognized as an important community acquired pathogen causing disease (CA-CDI). Vitamin D [25(OH)D] has immune modulatory effects and plays an important role in intestinal immunity. The role of vitamin D in CA-CDI has not been examined previously. Methods: This was a single referral center case-control study. Cases comprised of all patients with CA-CDI who had a serum 25(OH)D measured within 12 months prior to infection. Controls were drawn from patients who had 25(OH)D checked and matched based on age, gender, race and health status. Serum 25(OH)D was stratified as < 15 ng/ mL, 15-30 ng/ mL or > 30 ng/ mL. Regression models adjusting for potential confounders were used to define independent association between vitamin D and CA-CDI. Results: We identified 58 matched case-control pairs (66% women; 85% Caucasian). The mean age was 62 years. The mean serum 25(OH)D level was significantly lower in CA-CDI cases compared to controls (28.5 ng/ mL vs. 33.8 ng/ mL, p = 0.046). Cases had higher rate of antibiotic exposure and more comorbidity. Serum 25(OH) D < 15 ng/ mL was associated with an increased risk of CA-CDI on univariate (Odds ratio (OR) 5.10, 95% confidence interval (CI) 1.51 - 17.24) and multivariate analysis (OR 3.84, 95% CI 1.10 - 13.42). Vitamin D levels between 15-30 ng/ mL did not modify disease risk. Conclusions: Low serum 25(OH)D < 15 ng/mL was associated with increased risk of CA-CDI. This suggests vitamin D may have a role in determining susceptibility to CA-CDI. C1 [Sahay, Tanya] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU National Institutes of Health [DK097142] FX Dr. Ananthakrishnan is supported by a grant from the National Institutes of Health (DK097142). NR 45 TC 3 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD DEC 4 PY 2014 VL 14 AR 661 DI 10.1186/s12879-014-0661-6 PG 6 WC Infectious Diseases SC Infectious Diseases GA AX6CR UT WOS:000347011600001 PM 25471926 ER PT J AU Batista, PJ Molinie, B Wang, JK Qu, K Zhang, JJ Li, LJ Bouley, DM Lujan, E Haddad, B Daneshvar, K Carter, AC Flynn, RA Zhou, C Lim, KS Dedon, P Wernig, M Mullen, AC Xing, Y Giallourakis, CC Chang, HY AF Batista, Pedro J. Molinie, Benoit Wang, Jinkai Qu, Kun Zhang, Jiajing Li, Lingjie Bouley, Donna M. Lujan, Ernesto Haddad, Bahareh Daneshvar, Kaveh Carter, Ava C. Flynn, Ryan A. Zhou, Chan Lim, Kok-Seong Dedon, Peter Wernig, Marius Mullen, Alan C. Xing, Yi Giallourakis, Cosmas C. Chang, Howard Y. TI m(6)A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells SO CELL STEM CELL LA English DT Article ID LONG NONCODING RNA; MESSENGER-RNA; LINEAGE SPECIFIERS; SACCHAROMYCES-CEREVISIAE; POSTNATAL-DEVELOPMENT; NUCLEAR-RNA; PLURIPOTENCY; MOUSE; METHYLATION; REVEALS AB N6-methyl-adenosine (m(6)A) is the most abundant modification on messenger RNAs and is linked to human diseases, but its functions in mammalian development are poorly understood. Here we reveal the evolutionary conservation and function of m(6)A by mapping the m(6)A methylome in mouse and human embryonic stem cells. Thousands of messenger and long noncoding RNAs show conserved m(6)A modification, including transcripts encoding core pluripotency transcription factors. m(6)A is enriched over 30 untranslated regions at defined sequence motifs and marks unstable transcripts, including transcripts turned over upon differentiation. Genetic inactivation or depletion of mouse and human Mettl3, one of the m(6)A methylases, led to m(6)A erasure on select target genes, prolonged Nanog expression upon differentiation, and impaired ESC exit from self-renewal toward differentiation into several lineages in vitro and in vivo. Thus, m(6)A is a mark of transcriptome flexibility required for stem cells to differentiate to specific lineages. C1 [Batista, Pedro J.; Qu, Kun; Zhang, Jiajing; Li, Lingjie; Carter, Ava C.; Flynn, Ryan A.; Chang, Howard Y.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Batista, Pedro J.; Qu, Kun; Zhang, Jiajing; Li, Lingjie; Carter, Ava C.; Flynn, Ryan A.; Chang, Howard Y.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA. [Molinie, Benoit; Daneshvar, Kaveh; Zhou, Chan; Mullen, Alan C.; Giallourakis, Cosmas C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Zhang, Jiajing; Xing, Yi] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Bouley, Donna M.] Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA. [Lujan, Ernesto; Haddad, Bahareh; Wernig, Marius] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Lujan, Ernesto; Haddad, Bahareh; Wernig, Marius] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Lujan, Ernesto] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Lim, Kok-Seong; Dedon, Peter] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Mullen, Alan C.; Giallourakis, Cosmas C.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Xing, Y (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. EM yxing@ucla.edu; cgiallourakis@mgh.harvard.edu; howchang@stanford.edu RI Qu, Kun/G-3359-2012; Wang, Jinkai/H-1750-2015; Fang, Fengqin/F-4387-2016; ZHOU, Chan/A-7110-2009; OI ZHOU, Chan/0000-0002-0351-6235; Daneshvar, Kaveh/0000-0002-7863-0489; Flynn, Ryan/0000-0001-5013-0442 FU California Institute for Regenerative Medicine; NIH [R01-CA118750, DK090122]; MGH Start-Up Funds; MGH ECOR [2013A051178]; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Research Award FX We thank C. He, C. Mason, S. Schwartz, A. Regev, J.M. Claycomb, N. Van Wittenberghe, B.D. Howard, and members of the Chang and Giallourakis labs for discussions and assistance. We thank H.E. Arda and S.K. Kim for help with FACS analysis and A. Memmelaar for his expertise in graphic arts. This work was supported by the California Institute for Regenerative Medicine and NIH R01-CA118750 (H.Y.C.), the MGH Start-Up Funds and MGH ECOR grant 2013A051178 (C.C.G.), NIH grant DK090122 (A.C.M.), and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Research Award (Y.X.). P.J.B. is the Kenneth G. and Elaine A. Langone Fellow of the Damon Runyon Cancer Research Foundation. Y.X. is an Alfred Sloan Foundation Research Fellow. H.Y.C. is an Early Career Scientist of the Howard Hughes Medical Institute. NR 44 TC 76 Z9 82 U1 5 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 4 PY 2014 VL 15 IS 6 BP 707 EP 719 DI 10.1016/j.stem.2014.09.019 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AX8QS UT WOS:000347174300010 PM 25456834 ER PT J AU Cuiffo, BG Campagne, A Bell, GW Lembo, A Orso, F Lien, EC Bhasin, MK Raimo, M Hanson, SE Marusyk, A El-Ashry, D Hematti, P Polyak, K Mechta-Grigoriou, F Mariani, O Volinia, S Vincent-Salomon, A Taverna, D Kamoub, AE AF Cuiffo, Benjamin G. Campagne, Antoine Bell, George W. Lembo, Antonio Orso, Francesca Lien, Evan C. Bhasin, Manoj K. Raimo, Monica Hanson, Summer E. Marusyk, Andriy El-Ashry, Dorraya Hematti, Peiman Polyak, Kornelia Mechta-Grigoriou, Fatima Mariani, Odette Volinia, Stefano Vincent-Salomon, Anne Taverna, Daniela Kamoub, Antoine E. TI MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis SO CELL STEM CELL LA English DT Article ID MESENCHYMAL STEM-CELLS; HUMAN OVARIAN-CANCER; EXPRESSION SIGNATURE; TUMOR PROGRESSION; EMERGING ROLES; SURVIVAL; GROWTH; CARCINOGENESIS; TUMORIGENESIS; TRANSITION AB Mesenchymal stem/stromal cells (MSCs) are progenitor cells shown to participate in breast tumor stroma formation and to promote metastasis. Despite expanding knowledge of their contributions to breast malignancy, the underlying molecular responses of breast cancer cells (BCCs) to MSC influences remain incompletely understood. Here, we show that MSCs cause aberrant expression of microRNAs, which, led by microRNA-199a, provide BCCs with enhanced cancer stem cell (CSC) properties. We demonstrate that such MSC-deregulated microRNAs constitute a network that converges on and represses the expression of FOXP2, a forkhead transcription factor tightly associated with speech and language development. FOXP2 knockdown in BCCs was sufficient in promoting CSC propagation, tumor initiation, and metastasis. Importantly, elevated microRNA-199a and depressed FOXP2 expression levels are prominent features of malignant clinical breast cancer and are associated significantly with poor survival. Our results identify molecular determinants of cancer progression of potential utility in the prognosis and therapy of breast cancer. C1 [Cuiffo, Benjamin G.; Campagne, Antoine; Lien, Evan C.; Kamoub, Antoine E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Campagne, Antoine; Mechta-Grigoriou, Fatima; Mariani, Odette; Vincent-Salomon, Anne] Inst Curie, F-75248 Paris 05, France. [Bell, George W.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lembo, Antonio; Orso, Francesca; Raimo, Monica; Taverna, Daniela] Univ Turin, Dept Mol Biotechnol & Hlth Sci, I-10126 Turin, Italy. [Lembo, Antonio; Orso, Francesca; Raimo, Monica; Taverna, Daniela] MBC, I-10126 Turin, Italy. [Bhasin, Manoj K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Hanson, Summer E.; Hematti, Peiman] Univ Wisconsin, Sch Med & Publ Hlth, Carbone Canc Ctr, Madison, WI 53792 USA. [Marusyk, Andriy; Polyak, Kornelia] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. [Marusyk, Andriy; Polyak, Kornelia] Harvard Univ, Dept Med, Sch Med, Boston, MA 02215 USA. [El-Ashry, Dorraya] Univ Miami, Miller Sch Med, Dept Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Volinia, Stefano] Univ Ferrara, Human Anat Branch, Dept Morphol Surg & Expt Med, I-44121 Ferrara, Italy. [Kamoub, Antoine E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Kamoub, Antoine E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Kamoub, AE (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. EM akarnoub@bidmc.harvard.edu RI taverna, daniela/J-8358-2016; Orso, Francesca/B-1985-2014; MECHTA-GRIGORIOU, Fatima/C-5253-2017; OI taverna, daniela/0000-0002-6365-527X; MECHTA-GRIGORIOU, Fatima/0000-0002-3751-6989; Lien, Evan/0000-0001-7866-4761; Volinia, Stefano/0000-0003-0910-3893 FU BIDMC; Sidney Kimmel Cancer Research Foundation; Susan G. Komen For The Cure; AIRC [IG14201]; Compagnia di San Paolo [2008.1054]; Progetto Ricerca Ateneo Torino; BIDMC Prostate and Breast Cancer Research Program FX We thank J. Love, J.-A. Kwon, and S. Gupta for miRNA profiling data analysis; A. Contreras for assistance in animal studies; K. Groglio and M. Fahlberg for FACS sorting assistance; D. Louvard for assistance in clinical specimen procurement; and P. Pandolfi and P. Provero for helpful discussions. This work was supported by start-up funds from BIDMC (A.E.K.), the Sidney Kimmel Cancer Research Foundation (A.E.K.), the Susan G. Komen For The Cure (A.E.K.), AIRC IG14201 (D.T.), Compagnia di San Paolo, 2008.1054 (D.T.), and Progetto Ricerca Ateneo Torino (D.T.). Human BM-MSCs were provided by the Texas A&M Health Science Center (CMI for Regenerative Medicine at Scott & White) through NIH P40RR017447. B.G.C. is a 2012 American Cancer Society Postdoctoral Fellow. F.O. is a recipient of FIRB giovani 2008 (RBFR08F2FS-276 002). A.E.K. is a 2010 Kimmel Scholar, a recipient of a Career Development Award from the BIDMC Prostate and Breast Cancer Research Program, and a recipient of a 2012 Career Catalyst Research Award from Susan G. Komen For The Cure. NR 65 TC 25 Z9 26 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 4 PY 2014 VL 15 IS 6 BP 762 EP 774 DI 10.1016/j.stem.2014.10.001 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AX8QS UT WOS:000347174300014 PM 25515522 ER PT J AU Bruedigam, C Bagger, FO Heidel, FH Kuhn, CP Guignes, S Song, A Austin, R Vu, T Lee, E Riyat, S Moore, AS Lock, RB Bullinger, L Hill, GR Armstrong, SA Williams, DA Lane, SW AF Bruedigam, Claudia Bagger, Frederik O. Heidel, Florian H. Kuhn, Catherine Paine Guignes, Solene Song, Axia Austin, Rebecca Vu, Therese Lee, Erwin Riyat, Sarbjit Moore, Andrew S. Lock, Richard B. Bullinger, Lars Hill, Geoffrey R. Armstrong, Scott A. Williams, David A. Lane, Steven W. TI Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse following Chemotherapy SO CELL STEM CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL; COMMITTED PROGENITOR; GENE-EXPRESSION; DNA-DAMAGE; LIFE-SPAN; MICE; TRANSFORMATION; MUTATIONS; HIERARCHY AB Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. C1 [Bruedigam, Claudia; Kuhn, Catherine Paine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Hill, Geoffrey R.; Lane, Steven W.] QIMR Berghofer Med Res Inst, Div Immunol, Brisbane, Qld 4006, Australia. [Bagger, Frederik O.] Univ Copenhagen, Finsen Lab, Bioinformat Ctr, Dept Biol, DK-1165 Copenhagen, Denmark. [Bagger, Frederik O.] Univ Copenhagen, BRIC, DK-1165 Copenhagen, Denmark. [Heidel, Florian H.] Otto Von Guericke Univ, Univ Hosp, Dept Hematol & Oncol, D-39120 Magdeburg, Germany. [Lee, Erwin; Lock, Richard B.] Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst Australia, Sydney, NSW 2052, Australia. [Riyat, Sarbjit; Hill, Geoffrey R.; Lane, Steven W.] Royal Brisbane & Womens Hosp, Dept Haematol, Brisbane, Qld 4006, Australia. [Moore, Andrew S.] Queensland Childrens Med Res Inst, Brisbane, Qld 4029, Australia. [Moore, Andrew S.; Hill, Geoffrey R.; Lane, Steven W.] Univ Queensland, Brisbane, Qld 4072, Australia. [Bullinger, Lars] Univ Hosp Ulm, Dept Hematol & Oncol, D-89081 Ulm, Germany. [Armstrong, Scott A.] Mem Sloan Kettering Leukemia Ctr, Dept Pediat, New York, NY 10065 USA. [Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol & Oncol, Cambridge, MA 02138 USA. [Williams, David A.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Lane, SW (reprint author), QIMR Berghofer Med Res Inst, Div Immunol, Brisbane, Qld 4006, Australia. EM steven.lane@qimrberghofer.edu.au RI Lock, Richard/G-4253-2013; Moore, Andrew/I-6275-2012; Hill, Geoffrey/O-2630-2016; OI Moore, Andrew/0000-0001-8062-1779; Hill, Geoffrey/0000-0003-2994-0429; Otzen Bagger, Frederik/0000-0003-0636-8845 FU Leukaemia Foundation of Queensland; National Health and Medical Research Council; In Vitro Technologies; Pfizer Cancer Research Grant; Rio Tinto Ride to Conquer Cancer; NIH [CA66996, CA140575] FX We acknowledge the generous contribution of imetelstat, provided by Geron Corporation. We gratefully acknowledge the technical assistance of Amity Roberts, Glen Boyle, Grace Chojnowski, and Paula Hall (flow cytometry) and the members of the QIMR-Berghofer Animal House. We thank Stephen Sykes, Mark Smyth, Kelli MacDonald, and members of their laboratories for their helpful discussion. S.W.L. and G.R.H. have received funding from the Leukaemia Foundation of Queensland and the National Health and Medical Research Council. S.W.L. is the recipient of the Rhys Pengelly Fellowship in Leukaemia Research from In Vitro Technologies and Pfizer Cancer Research Grant. C.B., G.R.H., and S.W.L. have received funding from the Rio Tinto Ride to Conquer Cancer. S. A. A. acknowledges funding from the NIH (CA66996 and CA140575). NR 47 TC 17 Z9 20 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 4 PY 2014 VL 15 IS 6 BP 775 EP 790 DI 10.1016/j.stem.2014.11.010 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AX8QS UT WOS:000347174300015 PM 25479751 ER PT J AU Kumar, RM Cahan, P Shalek, AK Satija, R DaleyKeyser, A Li, H Zhang, J Pardee, K Gennert, D Trombetta, JJ Ferrante, TC Regev, A Daley, GQ Collins, JJ AF Kumar, Roshan M. Cahan, Patrick Shalek, Alex K. Satija, Rahul DaleyKeyser, Ajay Li, Hu Zhang, Jin Pardee, Keith Gennert, David Trombetta, John J. Ferrante, Thomas C. Regev, Aviv Daley, George Q. Collins, James J. TI Deconstructing transcriptional heterogeneity in pluripotent stem cells SO NATURE LA English DT Article ID SELF-RENEWAL; RNA-SEQ; GENE-EXPRESSION; GROUND-STATE; MICRORNA; NOISE; GENERATION; NANOG; BIOLOGY; DIFFERENTIATION AB Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs. C1 [Kumar, Roshan M.; DaleyKeyser, Ajay; Pardee, Keith; Ferrante, Thomas C.; Collins, James J.] Harvard Univ, Wyss lnst Biologically Inspired Engn, Boston, MA 02115 USA. [Kumar, Roshan M.; Pardee, Keith; Collins, James J.] Boston Univ, Ctr Synthet Biol, Dept Biomed Engn, Howard Hughes Inst, Boston, MA 02215 USA. [Cahan, Patrick; Zhang, Jin; Daley, George Q.] Boston Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA. [Cahan, Patrick; Daley, George Q.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Dept Biol Chem & Mol Pharma, Boston, MA 02115 USA. [Shalek, Alex K.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Shalek, Alex K.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Satija, Rahul; Gennert, David; Trombetta, John J.; Regev, Aviv] Harvard Univ, MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Li, Hu] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Ctr Individualized Med, Rochester, MN 55905 USA. [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02140 USA. RP Daley, GQ (reprint author), Harvard Univ, Sch Med,Manton Ctr Orphan Dis Res, Harvard Stem Cell Inst,Howard Hughes Med Inst, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; jcollins@bu.edu OI Shalek, Alex K./0000-0001-5670-8778; Cahan, Patrick/0000-0003-3652-2540 FU NIH [R24DK092760, R01GM107536, P50HG005550]; HHMI; Broad Institute; Klarman Cell Observatory at the Broad Institute; NIH CEGS [1P50HG006193-01]; NIH Pioneer Award [DP1OD003958-01]; Wyss Institute; NIDDK [K01DK096013]; NHLBI [T32HL066987, T32HL007623]; Manton Center for Orphan Disease Research; NIH Postdoctoral Fellowship [1F32HD075541-01]; Mayo Clinic Center for Individualized Medicine; [NIH-P30-HD18655] FX We thank members of the Collins and Daley laboratories for discussions. J.J.C. is supported by NIH grant R24DK092760 and the HHMI. G.Q.D. is supported by grants from the NIH (R01GM107536, R24DK092760, P50HG005550) and is an affiliate member of the Broad Institute and an investigator of the Manton Center for Orphan Disease Research and the Howard Hughes Medical Institute. A.R. is supported by the Broad Institute, the Klarman Cell Observatory at the Broad Institute, an NIH CEGS (1P50HG006193-01), an NIH Pioneer Award (DP1OD003958-01) and the HHMI. R.M.K. is supported by the Wyss Institute. P.C. is supported by NIDDK (K01DK096013) and received support from NHLBI (T32HL066987 and T32HL007623) and the Manton Center for Orphan Disease Research. R.S. was supported by an NIH Postdoctoral Fellowship (1F32HD075541-01). H.L. is supported by the Mayo Clinic Center for Individualized Medicine. Sequencing was performed by the Broad Institute Genomics Platform. Flow cytometry was performed in the Hematologic Neoplasia Flow Cytometry Facility at the Dana-Farber Cancer Institute and the BCH IDDRC Stem Cell Core Facility at Boston Children's Hospital supported by NIH-P30-HD18655. Single-cell qPCR experiments were performed at the BCH IDDRC Molecular Genetics Core Facility at Children's Hospital Boston supported by NIH-P30-HD18655. Fludigm C1 experiments were performed at the Broad Institute and the Biopolymers Facility at Harvard Medical School. NR 69 TC 86 Z9 86 U1 5 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 4 PY 2014 VL 516 IS 7529 BP 56 EP U112 DI 10.1038/nature13920 PG 26 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AW5JD UT WOS:000346310800037 PM 25471879 ER PT J AU Duan, JB Shi, JX Fiorentino, A Leites, C Chen, XN Moy, W Chen, JC Alexandrov, BS Usheva, A He, DL Freda, J O'Brien, NL McQuillin, A Sanders, AR Gershon, ES DeLisi, LE Bishop, AR Gurling, HMD Pato, MT Levinson, DF Kendler, KS Pato, CN Gejman, PV AF Duan, Jubao Shi, Jianxin Fiorentino, Alessia Leites, Catherine Chen, Xiangning Moy, Winton Chen, Jingchun Alexandrov, Boian S. Usheva, Anny He, Deli Freda, Jessica O'Brien, Niamh L. McQuillin, Andrew Sanders, Alan R. Gershon, Elliot S. DeLisi, Lynn E. Bishop, Alan R. Gurling, Hugh M. D. Pato, Michele T. Levinson, Douglas F. Kendler, Kenneth S. Pato, Carlos N. Gejman, Pablo V. CA MGS GPC TI A Rare Functional Noncoding Variant at the GWAS-Implicated MIR137/MIR2682 Locus Might Confer Risk to Schizophrenia and Bipolar Disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; MACULAR DEGENERATION; COMMON VARIANTS; PSYCHIATRIC-DISORDERS; TRANSCRIPTION FACTOR; REGULATORY ELEMENTS; LOW-FREQUENCY; STEM-CELLS; MIR137 AB Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and M1R2682 (miR2682), two microRNA genes important for neuronal function. We sequenced -6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 x 10(-4) ). We further identified its risk allele Tin 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression. C1 [Duan, Jubao; Leites, Catherine; Moy, Winton; He, Deli; Freda, Jessica; Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Ctr Psychiat Genet, Evanston, IL 60201 USA. [Duan, Jubao; Sanders, Alan R.; Gershon, Elliot S.; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fiorentino, Alessia; O'Brien, Niamh L.; McQuillin, Andrew; Gurling, Hugh M. D.] UCL, Mol Psychiat Lab, Div Psychiat, London WC1E 6JJ, England. [Chen, Xiangning; Chen, Jingchun; Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Alexandrov, Boian S.; Usheva, Anny] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alexandrov, Boian S.; Bishop, Alan R.] Los Alamos Natl Lab, Los Alamos, NM 87544 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Pato, Michele T.; Pato, Carlos N.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Levinson, Douglas F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94305 USA. RP Duan, JB (reprint author), NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Ctr Psychiat Genet, Evanston, IL 60201 USA. EM jduan@uchicago.edu RI Macciardi, Fabio/N-3768-2014; McQuillin, Andrew/C-1623-2008; OI Macciardi, Fabio/0000-0003-0537-4266; McQuillin, Andrew/0000-0003-1567-2240; Nicolini, Humberto/0000-0003-2494-0067; Alexandrov, Boian/0000-0001-8636-4603 FU Wellcome Trust [WT091310]; NIH [R01MH067257, R01MH059588, R01MH059565, R01MH059587, R01MH060870, R01MH059566, R01MH059586, R01MH061675, R01MH060879, U01MH046276, U01MH079470]; MRC [G1000708]; National Nuclear Security Administration of the US Department of Energy; LANL, LDRD [20110516ECR]; National Institutes of Health (NIH) [R21MH102685]; NorthShore University HealthSystem Research Career Development Award; [R01MH059571]; [R01MH081800]; [U01MH079469]; [MH085548]; [MH085542] FX We thank the study participants of MGS, CNG, ICCSS, ISHDSF, UCL, GPC, NIME-BP collections. This study also makes use of whole-genome sequencing data (TwinsUK) generated by the UK10K Consortium. A full list of the investigators who contributed to the generation of the data is available from UK10K Project homepage. Wellcome Trust award WT091310 provided funding for UK10K. We also thank K. Fang and N. Park (Illinois Mathematics and Science Academy) for their technical help with the 3C experiment. This work was primarily supported by R01MH059571, R01MH081800, and U01MH079469 (to P.V.G.) and other NIH grants for MGS (R01MH067257 to N.G.B., R01MH059588 to B.J.M., R01MH059565 to R.F., R01MH059587 to F.A., R01MH060870 to W.F.B., R01MH059566 to D.W.B., R01MH059586 to J.M.S., R01MH061675 to D.F.L., R01MH060879 to C.R.C., U01MH046276 to C.R.C., and U01MH079470 to D.F.L). GPC was supported by MH085548 and MH085542 (to C.N.P and M.T.P). UCL genotyping was supported by MRC grant G1000708 (to H.M.D.G. and A.M.). The computational modeling of transcription factor binding at Los Alamos National Laboratory was carried out under the auspices of the National Nuclear Security Administration of the US Department of Energy and was supported by the LANL, LDRD, 20110516ECR grant (to B.S.A.). This work was also partially supported by National Institutes of Health (NIH) grant R21MH102685 and NorthShore University HealthSystem Research Career Development Award (to J.D.). NR 76 TC 17 Z9 17 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC 4 PY 2014 VL 95 IS 6 BP 744 EP 753 DI 10.1016/j.ajhg.2014.11.001 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AX0DH UT WOS:000346623100011 PM 25434007 ER PT J AU Duan, B Cheng, LZ Bourane, S Britz, O Padilla, C Garcia-Campmany, L Krashes, M Knowlton, W Velasquez, T Ren, XY Ross, SE Lowell, BB Wang, Y Goulding, M Ma, QF AF Duan, Bo Cheng, Longzhen Bourane, Steeve Britz, Olivier Padilla, Christopher Garcia-Campmany, Lidia Krashes, Michael Knowlton, Wendy Velasquez, Tomoko Ren, Xiangyu Ross, Sarah E. Lowell, Bradford B. Wang, Yun Goulding, Martyn Ma, Qiufu TI Identification of Spinal Circuits Transmitting and Gating Mechanical Pain SO CELL LA English DT Article ID SUBSTANTIA-GELATINOSA NEURONS; SUPERFICIAL DORSAL-HORN; NEUROPATHIC PAIN; MARGINAL ZONE; SOMATIC SENSATIONS; GABAERGIC NEURONS; THERMAL STIMULI; SENSORY NEURONS; CELLULAR BASIS; NERVE INJURY AB Pain information processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and A beta mechanoreceptors, with A beta inputs gated through feed-forward activation of spinal inhibitory neurons (INs). Here, we used intersectional genetic manipulations to identify these critical components of pain transduction. Marking and ablating six populations of spinal excitatory and inhibitory neurons, coupled with behavioral and electrophysiological analysis, showed that excitatory neurons expressing somatostatin (SOM) include T-type cells, whose ablation causes loss of mechanical pain. Inhibitory neurons marked by the expression of dynorphin (Dyn) represent INs, which are necessary to gate A beta fibers from activating SOM+ neurons to evoke pain. Therefore, peripheral mechanical nociceptors and A beta mechanoreceptors, together with spinal SOM+ excitatory and Dyn(+) inhibitory neurons, form a microcircuit that transmits and gates mechanical pain. C1 [Duan, Bo; Cheng, Longzhen; Knowlton, Wendy; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Duan, Bo; Cheng, Longzhen; Knowlton, Wendy; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Bourane, Steeve; Britz, Olivier; Padilla, Christopher; Garcia-Campmany, Lidia; Velasquez, Tomoko; Goulding, Martyn] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. [Garcia-Campmany, Lidia; Krashes, Michael; Lowell, Bradford B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. [Garcia-Campmany, Lidia; Krashes, Michael; Lowell, Bradford B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Ross, Sarah E.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Ross, Sarah E.] Univ Pittsburgh, Pain Ctr, Pittsburgh, PA 15213 USA. [Cheng, Longzhen; Wang, Yun] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Cheng, Longzhen; Wang, Yun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. RP Goulding, M (reprint author), Salk Inst Biol Studies, Mol Neurobiol Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA. EM goulding@salk.edu; Qiufu_Ma@dfci.harvard.edu FU NIH [R01NS086372, NS047710, P01 NS072040, R01 NS 080586, P01 NS072031, R01 AR063772, R21 AR064445, R01 DK075632, R37 DK053477, R01 DK071051, R01 DK089044, R01 DK096010, P30 DK057521, P30 DK046200, F32 DK089710]; National Natural Science Foundation of China [81171224, 81100815] FX We thank Dr. Z. Josh Huang and the Jackson laboratory for the SOM-IRES-Cre and Calb2-IRES-Cre mice, GENSAT and MMRRC at University of California, Davis, for the NPY-Cre mice, the Allen Brain Institute, and the Jackson Laboratory for the Rosa26LSL-tdTomato mice, and Dr. Susan Dymecki for the ROSA26CAG-FRT-STOP-FRT-GFP mice. We thank Drs. Yan Lu, Clifford Woolf, and Fu-Chia Yang for critical comments on the manuscript; Dr Yan Lu for his advice on spinal cord slice recording; and Dr. Enrique Jose Cobos for providing the scoring system in measuring dynamic allodynia. The Ma lab was supported by NIH grants (R01NS086372, NS047710, and P01 NS072040), the Goulding lab is supported by NIH grants (R01NS086372, R01 NS 080586, and P01 NS072031), the Ross lab is supported by NIH grants (R01 AR063772 and R21 AR064445), and the Lowell lab was supported by NIH grants (R01 DK075632, R37 DK053477, R01 DK071051, R01 DK089044, R01 DK096010, P30 DK057521, and P30 DK046200). M.K. was supported by F32 DK089710. L.C. and Y.W. were supported by grants from the National Natural Science Foundation of China (81171224 and 81100815). NR 69 TC 58 Z9 58 U1 10 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 4 PY 2014 VL 159 IS 6 BP 1417 EP 1432 DI 10.1016/j.cell.2014.11.003 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AX0PA UT WOS:000346652900019 PM 25467445 ER PT J AU Sulahian, R Casey, F Shen, J Qian, ZR Shin, H Ogino, S Weir, BA Vazquez, F Liu, XS Hahn, WC Bass, AJ Chan, V Shivdasani, RA AF Sulahian, R. Casey, F. Shen, J. Qian, Z. R. Shin, H. Ogino, S. Weir, B. A. Vazquez, F. Liu, X. S. Hahn, W. C. Bass, A. J. Chan, V. Shivdasani, R. A. TI An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer SO ONCOGENE LA English DT Article DE transcriptional control of cancer; synexpression groups; somatic copy number alterations; ChIP-seq; GATA transcription factors ID LINEAGE-SURVIVAL ONCOGENE; GENE-EXPRESSION; STEM-CELLS; DIFFERENTIATION; ADENOCARCINOMA; PATTERNS; STOMACH; GENOME; AMPLIFICATION; INTESTINE AB Lineage-restricted transcription factors (TFs) are frequently mutated or overexpressed in cancer and contribute toward malignant behaviors; however, the molecular bases of their oncogenic properties are largely unknown. As TF activities are difficult to inhibit directly with small molecules, the genes and pathways they regulate might represent more tractable targets for drug therapy. We studied GATA6, a TF gene that is frequently amplified or overexpressed in gastric, esophageal and pancreatic adenocarcinomas. GATA6-overexpressing gastric cancer cell lines cluster in gene expression space, separate from non-overexpressing lines. This expression clustering signifies a shared pathogenic group of genes that GATA6 may regulate through direct cis-element binding. We used chromatin immunoprecipitation and sequencing (ChIP-seq) to identify GATA6-bound genes and considered TF occupancy in relation to genes that respond to GATA6 depletion in cell lines and track with GATA6 mRNA (synexpression groups) in primary gastric cancers. Among other cellular functions, GATA6-occupied genes control apoptosis and govern the M-phase of the cell cycle. Depletion of GATA6 reduced the levels of the latter transcripts and arrested cells in G2 and M phases of the cell cycle. Synexpression in human tumor samples identified likely direct transcriptional targets substantially better than consideration only of transcripts that respond to GATA6 loss in cultured cells. Candidate target genes responded to the loss of GATA6 or its homolog GATA4 and even more to the depletion of both proteins. Many GATA6-dependent genes lacked nearby binding sites but several strongly dependent, synexpressed and GATA6-bound genes encode TFs such as MYC, HES1, RARB and CDX2. Thus, many downstream effects occur indirectly through other TFs and GATA6 activity in gastric cancer is partially redundant with GATA4. This integrative analysis of locus occupancy, gene dependency and synexpression provides a functional signature of GATA6-overexpressing gastric cancers, revealing both limits and new therapeutic directions for a challenging and frequently fatal disease. C1 [Sulahian, R.; Qian, Z. R.; Ogino, S.; Weir, B. A.; Vazquez, F.; Hahn, W. C.; Bass, A. J.; Shivdasani, R. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sulahian, R.; Hahn, W. C.; Bass, A. J.; Shivdasani, R. A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Casey, F.; Shen, J.; Chan, V.] Novartis Inst Biomed Res, Emeryville, CA USA. [Qian, Z. R.; Ogino, S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. [Qian, Z. R.; Ogino, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shin, H.; Liu, X. S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Hahn, W. C.; Bass, A. J.; Shivdasani, R. A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ramesh_shivdasani@dfci.harvard.edu FU Dana-Farber Cancer Institute-Novartis Drug Discovery Program; National Institutes of Health [R01CA151993, R01HG4069, K08CA134931]; SPORE program in GI cancers [P50 CA127003] FX This study was supported by the Dana-Farber Cancer Institute-Novartis Drug Discovery Program and National Institutes of Health awards R01CA151993 (SO), R01HG4069 (XSL), K08CA134931 (AJB) and the SPORE program in GI cancers P50 CA127003. Data associated with this study are available in the GEO, GSE51936. NR 49 TC 13 Z9 13 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD DEC 4 PY 2014 VL 33 IS 49 BP 5637 EP 5648 DI 10.1038/onc.2013.517 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AW1ZW UT WOS:000346088700008 PM 24317510 ER PT J AU Sequist, TD Taveras, EM AF Sequist, Thomas D. Taveras, Elsie M. TI Clinic-Community Linkages for High-Value Care SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Sequist, Thomas D.] Harvard Univ, Brigham & Womens Hosp, Partners HealthCare Syst, Dept Hlth Care Policy,Med Sch,Div Gen Med, Boston, MA 02115 USA. [Taveras, Elsie M.] Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA. RP Sequist, TD (reprint author), Harvard Univ, Brigham & Womens Hosp, Partners HealthCare Syst, Dept Hlth Care Policy,Med Sch,Div Gen Med, Boston, MA 02115 USA. NR 4 TC 8 Z9 8 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2148 EP 2150 DI 10.1056/NEJMp1408457 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700002 PM 25470692 ER PT J AU Mauri, L Kereiakes, DJ Yeh, RW Driscoll-Shempp, P Cutlip, DE Steg, PG Normand, SLT Braunwald, E Wiviott, SD Cohen, DJ Holmes, DR Krucoff, MW Hermiller, J Dauerman, HL Simon, DI Kandzari, DE Garratt, KN Lee, DP Pow, TK Lee, PV Rinaldi, MJ Massaro, JM AF Mauri, Laura Kereiakes, Dean J. Yeh, Robert W. Driscoll-Shempp, Priscilla Cutlip, Donald E. Steg, P. Gabriel Normand, Sharon-Lise T. Braunwald, Eugene Wiviott, Stephen D. Cohen, David J. Holmes, David R., Jr. Krucoff, Mitchell W. Hermiller, James Dauerman, Harold L. Simon, Daniel I. Kandzari, David E. Garratt, Kirk N. Lee, David P. Pow, Thomas K. Lee, Peter Ver Rinaldi, Michael J. Massaro, Joseph M. CA DAPT Study Investigators TI Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES; RANDOMIZED-TRIAL; HEART-ASSOCIATION; CLOPIDOGREL; ASPIRIN; EVENTS; IMPLANTATION; DEFINITIONS AB BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain. METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding. RESULTS A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P = 0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P = 0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. C1 [Mauri, Laura; Yeh, Robert W.; Driscoll-Shempp, Priscilla; Cutlip, Donald E.; Massaro, Joseph M.] Harvard Clin Res Inst, Boston, MA USA. [Mauri, Laura; Braunwald, Eugene; Wiviott, Stephen D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mauri, Laura; Yeh, Robert W.; Cutlip, Donald E.; Normand, Sharon-Lise T.; Braunwald, Eugene; Wiviott, Stephen D.] Harvard Univ, Sch Med, Boston, MA USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Kereiakes, Dean J.] Christ Hosp, Heart & Vasc Ctr, Cincinnati, OH 45219 USA. [Kereiakes, Dean J.] Lindner Ctr Res & Educ, Cincinnati, OH USA. [Steg, P. Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ Fibrosis, INSERM,U1148, F-75877 Paris, France. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Steg, P. Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Natl Heart & Lung Inst, Inst Cardiovasc Med & Sci, London, England. [Cohen, David J.] Univ Missouri, Sch Med, St Lukes Mid Amer Heart Inst, Kansas City, MO 64108 USA. [Holmes, David R., Jr.] Mayo Clin, Rochester, MN USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Durham, NC USA. [Rinaldi, Michael J.] Carolinas HealthCare Syst, Sanger Heart & Vasc Inst, Charlotte, NC USA. [Hermiller, James] St Vincent Heart Ctr, Indianapolis, IN USA. [Dauerman, Harold L.] Univ Vermont, Burlington, VT USA. [Simon, Daniel I.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Kandzari, David E.] Piedmont Heart Inst, Atlanta, GA USA. [Garratt, Kirk N.] Lenox Hill Hosp, New York, NY 10021 USA. [Lee, David P.] Stanford Univ, Stanford, CA 94305 USA. [Pow, Thomas K.] Great Lakes Heart & Vasc Inst, St Joseph, MI USA. [Lee, Peter Ver] Eastern Maine Med Ctr, Bangor, ME USA. RP Mauri, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM lmauri1@partners.org FU Abbott; Boston Scientific; Cordis; Medtronic; Bristol-Myers Squibb-Sanofi Pharmaceuticals; Eli Lilly; Daiichi Sankyo; Department of Health and Human Services [1RO1FD003870-01] FX Supported by Abbott, Boston Scientific, Cordis, and Medtronic, Bristol-Myers Squibb-Sanofi Pharmaceuticals Partnership, Eli Lilly, and Daiichi Sankyo, and by a grant (1RO1FD003870-01) from the Department of Health and Human Services. NR 35 TC 435 Z9 447 U1 5 U2 35 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2155 EP 2166 DI 10.1056/NEJMoa1409312 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700004 PM 25399658 ER PT J AU Smith, PK Puskas, JD Ascheim, DD Voisine, P Gelijns, AC Moskowitz, AJ Hung, JW Parides, MK Ailawadi, G Perrault, LP Acker, MA Argenziano, M Thourani, V Gammie, JS Miller, MA Page, P Overbey, JR Bagiella, E Dagenais, F Blackstone, EH Kron, IL Rose, EA Moquete, EG Jeffries, N Gardner, TJ O'Gara, PT Alexander, JH Michler, RE AF Smith, P. K. Puskas, J. D. Ascheim, D. D. Voisine, P. Gelijns, A. C. Moskowitz, A. J. Hung, J. W. Parides, M. K. Ailawadi, G. Perrault, L. P. Acker, M. A. Argenziano, M. Thourani, V. Gammie, J. S. Miller, M. A. Page, P. Overbey, J. R. Bagiella, E. Dagenais, F. Blackstone, E. H. Kron, I. L. Rose, E. A. Moquete, E. G. Jeffries, N. Gardner, T. J. O'Gara, P. T. Alexander, J. H. Michler, R. E. CA Cardiothoracic Surg Trials Network TI Surgical Treatment of Moderate Ischemic Mitral Regurgitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; HEART-FAILURE; THORACIC SURGEONS; CLINICAL-TRIALS; SURVIVAL; REVASCULARIZATION; ECHOCARDIOGRAPHY; ASSOCIATION; DETERMINANT; MECHANISM AB BACKGROUND Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitralvalve repair to coronary-artery bypass grafting (CABG) are uncertain. METHODS We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure). The primary end point was the left ventricular end-systolic volume index (LVESVI), a measure of left ventricular remodeling, at 1 year. This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank. RESULTS At 1 year, the mean LVESVI among surviving patients was 46.1+/-22.4 ml per square meter of body-surface area in the CABG-alone group and 49.6+/-31.5 ml per square meter in the combined-procedure group (mean change from baseline, -9.4 and -9.3 ml per square meter, respectively). The rate of death was 6.7% in the combined-procedure group and 7.3% in the CABG-alone group (hazard ratio with mitral-valve repair, 0.90; 95% confidence interval, 0.38 to 2.12; P = 0.81). The rank-based assessment of LVESVI at 1 year (incorporating deaths) showed no significant between-group difference (z score, 0.50; P = 0.61). The addition of mitral-valve repair was associated with a longer bypass time (P<0.001), a longer hospital stay after surgery (P = 0.002), and more neurologic events (P = 0.03). Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group (11.2% vs. 31.0%, P<0.001). There were no significant between-group differences in major adverse cardiac or cerebrovascular events, deaths, readmissions, functional status, or quality of life at 1 year. CONCLUSIONS In patients with moderate ischemic mitral regurgitation, the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling. Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events. Thus, at 1 year, this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG. Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit. C1 [Smith, P. K.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Alexander, J. H.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Puskas, J. D.; Rose, E. A.] Icahn Sch Med Mt Sinai, Mt Sinai Hlth Syst, Dept Cardiac Surg, New York, NY 10029 USA. [Ascheim, D. D.; Gelijns, A. C.; Moskowitz, A. J.; Parides, M. K.; Overbey, J. R.; Bagiella, E.; Moquete, E. G.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Int Ctr Hlth Outcomes & Innovat Res, New York, NY 10029 USA. [Argenziano, M.] Columbia Univ, Coll Phys & Surg, Dept Surg, Dept Cardiothorac Surg, New York, NY USA. [Michler, R. E.] Albert Einstein Coll Med, Monash Med Ctr, Dept Cardiothorac & Vasc Surg, New York, NY USA. [Voisine, P.; Dagenais, F.] Hop Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada. [Perrault, L. P.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Page, P.] Hop Sacre Coeur, Dept Surg, Montreal, PQ H4J 1C5, Canada. [Hung, J. W.] Massachusetts Gen Hosp, Echocardiog Core Lab, Boston, MA 02114 USA. [O'Gara, P. T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Ailawadi, G.; Kron, I. L.] Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA. [Acker, M. A.] Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Thourani, V.] Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA. [Gammie, J. S.] Univ Maryland, Baltimore, MD 21201 USA. [Miller, M. A.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Jeffries, N.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Blackstone, E. H.] Cleveland Clin Fdn, Dept Thorac & Cardiovasc Surg, Cleveland, OH USA. [Gardner, T. J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA. RP Gelijns, AC (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA. EM annetine.gelijns@mssm.edu RI Stevens, Louis-Mathieu/E-6453-2016; OI Stevens, Louis-Mathieu/0000-0003-3372-3419; Moskowitz, Alan/0000-0002-4412-9450; Browndyke, Jeffrey/0000-0002-8573-7073 FU National Heart, Lung, and Blood Institute [U01 HL088942]; National Institute of Neurological Disorders and Stroke; Canadian Institutes of Health Research; Thoratec and HeartWare; Edwards Lifesciences; St. Jude Medical; Sorin Medical FX Supported by a cooperative agreement (U01 HL088942) with the National Heart, Lung, and Blood Institute, including funding by the National Institute of Neurological Disorders and Stroke and the Canadian Institutes of Health Research.; Dr. Acker reports receiving consulting fees from Thoratec and HeartWare. Dr. Gelijns reports holding equity in MERS International. Dr. Thourani reports receiving grant support from Edwards Lifesciences, St. Jude Medical, and Sorin Medical. No other potential conflict of interest relevant to this article was reported. NR 42 TC 93 Z9 96 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2178 EP 2188 DI 10.1056/NEJMoa1410490 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700006 PM 25405390 ER PT J AU Sundt, TM AF Sundt, Thoralf M. TI Surgery for Ischemic Mitral Regurgitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VALVE; REVASCULARIZATION; SURVIVAL; REPAIR C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. NR 10 TC 6 Z9 7 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 4 PY 2014 VL 371 IS 23 BP 2228 EP 2229 DI 10.1056/NEJMe1412045 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AW0IY UT WOS:000345976700015 PM 25405391 ER PT J AU Pan, H He, MH Liu, RX Brecha, NC Yu, ACH Pu, ML AF Pan, Hong He, Meihua Liu, Ruixing Brecha, Nicholas C. Yu, Albert Cheung Hoi Pu, Mingliang TI Sulforaphane Protects Rodent Retinas against Ischemia-Reperfusion Injury through the Activation of the Nrf2/HO-1 Antioxidant Pathway SO PLOS ONE LA English DT Article ID NRF2-DEPENDENT PHASE-2 ENZYME; OXIDATIVE STRESS; HEME OXYGENASE-1; ISCHEMIA/REPERFUSION INJURY; PHARMACOLOGICAL INDUCTION; CALCIUM DOBESILATE; RESPONSE ELEMENT; KAPPA-B; CELLS; GENE AB Retinal ischemia-reperfusion (I/R) injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF), which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2)-mediated induction of heme oxygenase-1 (HO-1). This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p.) injected with SF (12.5 mg/kg) or vehicle (corn oil) once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP) to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II) (ZnPP, 30 mg/kg, i.p.) treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs) and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL), and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway. C1 [Pan, Hong; Yu, Albert Cheung Hoi] Peking Univ, Neurosci Res Inst, Dept Neurobiol, Sch Basic Med Sci, Beijing 100871, Peoples R China. [Pan, Hong; He, Meihua; Liu, Ruixing; Pu, Mingliang] Peking Univ, Dept Anat Embryol, Sch Basic Med Sci, Beijing 100871, Peoples R China. [Pan, Hong] Binzhou Med Coll, Dept Phys, Yantai, Shandong, Peoples R China. [Pan, Hong; He, Meihua; Liu, Ruixing; Pu, Mingliang] Peking Univ, Key Lab Machine Percept, Minist Educ, Beijing 100871, Peoples R China. [Pan, Hong; He, Meihua; Liu, Ruixing; Pu, Mingliang] Peking Univ, Key Lab Visual Impairment & Restorat, Minist Educ, Beijing 100871, Peoples R China. [Brecha, Nicholas C.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med Los Angeles, Jules Stein Eye Inst,CURE Digest Dis Res Ctr,Dept, Los Angeles, CA 90024 USA. [Brecha, Nicholas C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. RP Pu, ML (reprint author), Peking Univ, Dept Anat Embryol, Sch Basic Med Sci, Beijing 100871, Peoples R China. EM mpu@hsc.pku.edu.cn RI He, Meihua/D-4312-2017 FU National Basic Research Program of China (973 Program) [2011CB510206]; National Science Foundation of China [30831160516, 81200691]; Ministry of Education of China [20090001120075]; Azalea Endowment Fund; Fundamental Research Fund for the Central Universities [21609101]; NIH [EY04067]; VA Merit Review FX This study was supported by grants obtained from the National Basic Research Program of China (973 Program, 2011CB510206 [MP]), the National Science Foundation of China (30831160516 [MP] and 81200691 [MH]), the Ministry of Education of China (20090001120075 [MH]), Azalea (1972) Endowment Fund (KS & RC), and the Fundamental Research Fund for the Central Universities (21609101, KS), NIH EY04067 (NCB) and VA Merit Review (NB). NCB is a VA Career Research Scientist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 14 Z9 16 U1 3 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 3 PY 2014 VL 9 IS 12 AR e114186 DI 10.1371/journal.pone.0114186 PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CA7WS UT WOS:000349128700082 PM 25470382 ER PT J AU de Lima-Pardini, AC Coelho, DB Silva, MB Azzi, NM Martinelli, AR Horak, FB Teixeira, LA AF de Lima-Pardini, Andrea Cristina Coelho, Daniel Boari Silva, Marina Brito Azzi, Nametala Maia Martinelli, Alessandra Rezende Horak, Fay Bahling Teixeira, Luis Augusto TI Aging increases flexibility of postural reactive responses based on constraints imposed by a manual task SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE postural control; manual constraint; dual task; elderly; postural adaptation; balance control ID AGE-RELATED-CHANGES; PARKINSONIAN SUBJECTS; FALLS PREVENTION; BALANCE CONTROL; GRIP FORCE; LIFE-SPAN; COORDINATION; MOVEMENT; SET; ATTENTION AB This study compared the effect of stability constraints imposed by a manual task on the adaptation of postural responses between 16 healthy elderly (7.38) and 16 healthy young (mean age = 22.94 years, SD = 4.82) individuals. Postural stability was perturbed through unexpected release of a load attached to the participant's trunk while performing two versions of a voluntary task: holding a tray with a cylinder placed with its flat side down (low constraint) or with its rolling round side down (high constraint). Low and high constraint tasks were performed in alternate blocks of trials. Results showed that young participants adapted muscular activation and kinematics of postural responses in association with previous experience with the first block of manual task constraint, whereas the elderly modulated postural responses based on the current manual constraint. This study provides evidence for flexibility of postural strategies in the elderly to deal with constraints imposed by a manual task. C1 [de Lima-Pardini, Andrea Cristina] Univ Sao Paulo, Fac Med, Inst Radiol, Lab Med Invest LIM44, BR-05403900 Sao Paulo, Brazil. [Coelho, Daniel Boari; Silva, Marina Brito; Azzi, Nametala Maia; Martinelli, Alessandra Rezende; Teixeira, Luis Augusto] Univ Sao Paulo, Sch Phys Educ & Sport, Dept Human Movement Biodynam, Human Motor Syst Lab, BR-05403900 Sao Paulo, Brazil. [Horak, Fay Bahling] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Horak, Fay Bahling] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Balance Disorders Lab, Portland, OR 97201 USA. RP de Lima-Pardini, AC (reprint author), Univ Sao Paulo, Fac Med, Inst Radiol, Lab Med Invest LIM44, Av Dr Eneas de Carvalho Aguiar,S-N Rua1, BR-05403900 Sao Paulo, Brazil. EM aclfisio@yahoo.com.br RI Coelho, Daniel/I-9369-2012; OI Coelho, Daniel/0000-0001-8758-6507; Teixeira, Luis/0000-0003-4132-0484 FU Coordination for the Improvement of Higher Level Personnel (CAPES, Brazil); Foundation for Research Advancement of the State of Sao Paulo (FAPESP, Brazil) [2009/11319-2]; Brazilian Council for Scientific and Technological Development (CNPq, Brazil) [200321/2010-2] FX We thank Coordination for the Improvement of Higher Level Personnel (CAPES, Brazil) for a studentship granted to the first author, the Foundation for Research Advancement of the State of Sao Paulo (FAPESP, Brazil), process number 2009/11319-2, and the Brazilian Council for Scientific and Technological Development (CNPq, Brazil), process number 200321/2010-2, for funding this research. We are also thankful to the great contribution in the review process given by the professor Kim Barrett from the University of California San Diego, USA, and to the participants of this study. NR 48 TC 2 Z9 2 U1 1 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD DEC 3 PY 2014 VL 6 AR 327 DI 10.3389/fnagi.2014.00327 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY9RN UT WOS:000347888100001 PM 25520656 ER PT J AU Dilisio, MF Miller, LR Warner, JJP Higgins, LD AF Dilisio, Matthew F. Miller, Lindsay R. Warner, Jon J. P. Higgins, Laurence D. TI Arthroscopic Tissue Culture for the Evaluation of Periprosthetic Shoulder Infection SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID POSITIVE INTRAOPERATIVE CULTURES; PROPIONIBACTERIUM-ACNES; ARTHROPLASTY; REVISION; PROSTHESIS; MANAGEMENT; SERIES AB Background: Periprosthetic shoulder infections can be difficult to diagnose. The purpose of this study was to investigate the utility of arthroscopic tissue culture for the diagnosis of infection following shoulder arthroplasty. Our hypothesis was that culture of arthroscopic biopsy tissue is a more reliable method than fluoroscopically guided shoulder aspiration for diagnosing such infection. Methods: A retrospective review identified patients who had undergone culture of arthroscopic biopsy tissue during the evaluation of a possible chronic periprosthetic shoulder infection. The culture results of the arthroscopic biopsies were compared with those of fluoroscopically guided glenohumeral aspiration and open tissue biopsy samples obtained at the time of revision surgery. Results: Nineteen patients had undergone arthroscopic biopsy to evaluate a painful shoulder arthroplasty for infection. All subsequently underwent revision surgery, and 41% of those with culture results at that time had a positive result, which included Propionibacterium acnes in each case. All arthroscopic biopsy culture results were consistent with the culture results obtained during the revision surgery, yielding 100% sensitivity, specificity, positive predictive value, and negative predictive value. In contrast, fluoroscopically guided glenohumeral aspiration yielded a sensitivity of 16.7%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 58.3%. Conclusions: Arthroscopic tissue biopsy is a reliable method for diagnosing periprosthetic shoulder infection and identifying the causative organism. C1 [Dilisio, Matthew F.; Miller, Lindsay R.; Warner, Jon J. P.; Higgins, Laurence D.] Harvard Univ, Sch Med, Boston Shoulder Inst, Brigham & Womens Hosp,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dilisio, MF (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed, 75 Francis St, Boston, MA 02115 USA. EM ldhiggins@partners.org NR 29 TC 8 Z9 8 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC 3 PY 2014 VL 96A IS 23 BP 1952 EP 1958 DI 10.2106/JBJS.M.01512 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AW7WC UT WOS:000346471300009 PM 25471909 ER PT J AU Bharadwaj, R Peter, CJ Jiang, Y Roussos, P Vogel-Ciernia, A Shen, EY Mitchell, AC Mao, WJ Whittle, C Dincer, A Jakovcevski, M Pothula, V Rasmussen, TP Giakoumaki, SG Bitsios, P Sherif, A Gardner, PD Ernst, P Ghose, S Sklar, P Haroutunian, V Tamminga, C Myers, RH Futai, K Wood, MA Akbarian, S AF Bharadwaj, Rahul Peter, Cyril J. Jiang, Yan Roussos, Panos Vogel-Ciernia, Annie Shen, Erica Y. Mitchell, Amanda C. Mao, Wenjie Whittle, Catheryne Dincer, Aslihan Jakovcevski, Mira Pothula, Venu Rasmussen, Theodore P. Giakoumaki, Stella G. Bitsios, Panos Sherif, Ajfar Gardner, Paul D. Ernst, Patricia Ghose, Subroto Sklar, Pamela Haroutunian, Vahram Tamminga, Carol Myers, Richard H. Futai, Kensuke Wood, Marcelo A. Akbarian, Schahram TI Conserved Higher-Order Chromatin Regulates NMDA Receptor Gene Expression and Cognition SO NEURON LA English DT Article ID DE-NOVO MUTATIONS; GENOME-WIDE; SYNAPTIC-TRANSMISSION; SCHIZOPHRENIA RISK; PREFRONTAL CORTEX; ENERGY-METABOLISM; MAMMALIAN GENOMES; ENHANCER FUNCTION; SUBUNIT GENES; CYTOCHROME-C AB Three-dimensional chromosomal conformations regulate transcription by moving enhancers and regulatory elements into spatial proximity with target genes. Here we describe activity-regulated long-range loopings bypassing up to 0.5 Mb of linear genome to modulate NMDA glutamate receptor GRIN2B expression in human and mouse prefrontal cortex. Distal intronic and 3' intergenic loop formations competed with repressor elements to access promoter-proximal sequences, and facilitated expression via a "cargo'' of AP-1 and NRF-1 transcription factors and TALE-based transcriptional activators. Neuronal deletion or overexpression of Kmt2a/Mll1 H3K4-and Kmt1e/Setdb1 H3K9-methyl-transferase was associated with higher-order chromatin changes at distal regulatory Grin2b sequences and impairments in working memory. Genetic polymorphisms and isogenic deletions of loop-bound sequences conferred liability for cognitive performance and decreased GRIN2B expression. Dynamic regulation of chromosomal conformations emerges as a novel layer for transcriptional mechanisms impacting neuronal signaling and cognition. C1 [Bharadwaj, Rahul; Peter, Cyril J.; Jiang, Yan; Roussos, Panos; Shen, Erica Y.; Mitchell, Amanda C.; Dincer, Aslihan; Pothula, Venu; Sherif, Ajfar; Sklar, Pamela; Haroutunian, Vahram; Akbarian, Schahram] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Bharadwaj, Rahul; Peter, Cyril J.; Jiang, Yan; Roussos, Panos; Shen, Erica Y.; Mitchell, Amanda C.; Dincer, Aslihan; Pothula, Venu; Sherif, Ajfar; Sklar, Pamela; Haroutunian, Vahram; Akbarian, Schahram] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Roussos, Panos; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY 10029 USA. [Roussos, Panos; Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Mao, Wenjie; Whittle, Catheryne; Gardner, Paul D.; Futai, Kensuke] Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA. [Bitsios, Panos] Fdn Res & Technol Hellas, Inst Comp Sci, Computat Med Lab, Iraklion 71003, Greece. [Rasmussen, Theodore P.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Rasmussen, Theodore P.] Univ Connecticut, Univ Conn Stem Cell Inst, Storrs, CT 06269 USA. [Jakovcevski, Mira] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Giakoumaki, Stella G.; Bitsios, Panos] Univ Crete, Dept Psychiat, Iraklion 71003, Greece. [Giakoumaki, Stella G.] Univ Crete, Dept Psychol, Iraklion 71003, Greece. [Ernst, Patricia] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Genet, Hanover, NH 03755 USA. [Ernst, Patricia] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Microbiol & Immunol, Hanover, NH 03755 USA. [Ghose, Subroto; Tamminga, Carol] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Myers, Richard H.] Boston Univ, Dept Neurol, Boston, MA 02118 USA. [Vogel-Ciernia, Annie; Wood, Marcelo A.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. RP Akbarian, S (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. EM schahram.akbarian@mssm.edu RI Dincer, Aslihan/N-4435-2015; Ghose, Subroto/J-6732-2016; Roussos, Panos/J-7090-2013; OI Dincer, Aslihan/0000-0002-4971-1597; Roussos, Panos/0000-0002-4640-6239; Peter, Cyril/0000-0001-9190-8724 FU National Institute of Mental Health [R01 MH086509, P50 MH096890]; National Institute of Neurological Disorders and Stroke [R01 NS073947-04]; National Institute of Drug Abuse [R01 DA036984]; NIH Brain and Tissue Repository grant [HHSN271201300031C]; VA; Veterans Affairs Merit grant [BX002395]; BBRF; APA-Merck & Co. Early Academic Career Research Award; Connecticut State Stem Cell Research Program [09-SCB-UCON-18]; Whitehall Foundation; University of Crete Research Funds Account [E.L.K.E. 1348] FX This work was supported by National Institute of Mental Health grants R01 MH086509 and P50 MH096890 (S.A.); National Institute of Neurological Disorders and Stroke grant R01 NS073947-04 (R.H.M.); National Institute of Drug Abuse grant R01 DA036984 (M.A.W. and S.A.); NIH Brain and Tissue Repository grant HHSN271201300031C and the VA, and Veterans Affairs Merit grant BX002395, BBRF, the APA-Merck & Co. Early Academic Career Research Award (P.R.); the Connecticut State Stem Cell Research Program (09-SCB-UCON-18) (T.P.R.); the Whitehall Foundation (K.F.); and the University of Crete Research Funds Account (E.L.K.E. 1348). The authors thank the participants and the personnel of the Military Training Camp of Candidate, Supply Army officers (SEAP) in Heraklion, Crete, for their help with the LOGOS study. NR 74 TC 13 Z9 13 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD DEC 3 PY 2014 VL 84 IS 5 BP 997 EP 1008 DI 10.1016/j.neuron.2014.10.032 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW9JW UT WOS:000346574300012 PM 25467983 ER PT J AU Albertsson, AM Zhang, XL Leavenworth, J Bi, D Nair, S Qiao, LL Hagberg, H Mallard, C Cantor, H Wang, XY AF Albertsson, Anna-Maj Zhang, Xiaoli Leavenworth, Jianmei Bi, Dan Nair, Syam Qiao, Lili Hagberg, Henrik Mallard, Carina Cantor, Harvey Wang, Xiaoyang TI The effect of osteopontin and osteopontin-derived peptides on preterm brain injury SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Preterm; Brain injury; Osteopontin; Hypoxia; Ischemia ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LATE OLIGODENDROCYTE PROGENITORS; NEONATAL ISCHEMIC BRAIN; DEVELOPING MOUSE-BRAIN; CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER INJURY; HYPOXIA-ISCHEMIA; DENDRITIC CELLS; INTRANASAL DELIVERY; MULTIPLE-SCLEROSIS AB Background: Osteopontin (OPN) is a highly phosphorylated sialoprotein and a soluble cytokine that is widely expressed in a variety of tissues, including the brain. OPN and OPN-derived peptides have been suggested to have potential neuroprotective effects against ischemic brain injury, but their role in preterm brain injury is unknown. Methods: We used a hypoxia-ischemia (HI)-induced preterm brain injury model in postnatal day 5 mice. OPN and OPN-derived peptides were given intracerebroventricularly and intranasally before HI. Brain injury was evaluated at 7 days after the insults. Results: There was a significant increase in endogenous OPN mRNA and OPN protein in the mouse brain after the induction of HI at postnatal day 5. Administration of full-length OPN protein and thrombin-cleaved OPN did not affect preterm brain injury. This was demonstrated with both intracerebroventricular and intranasal administration of OPN as well as in OPN-deficient mice. Interestingly, both N134-153 and C154-198 OPN-derived peptides increased the severity of brain injury in this HI-induced preterm brain injury model. Conclusions: The neuroprotective effects of OPN are age-dependent, and, in contrast to the more mature brain, OPN-derived peptides potentiate injury in postnatal day 5 mice. Intranasal administration is an efficient way of delivering drugs to the central nervous system (CNS) in neonatal mice and is likely to be an easy and noninvasive method of drug delivery to the CNS in preterm infants. C1 [Albertsson, Anna-Maj; Zhang, Xiaoli; Bi, Dan; Nair, Syam; Qiao, Lili; Hagberg, Henrik; Wang, Xiaoyang] Univ Gothenburg, Sahlgrenska Acad, Dept Neurosci & Physiol, Perinatal Ctr, SE-40530 Gothenburg, Sweden. [Zhang, Xiaoli; Bi, Dan; Wang, Xiaoyang] Zhengzhou Univ, Affiliated Hosp 3, Dept Pediat, Zhengzhou 450052, Peoples R China. [Leavenworth, Jianmei; Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Leavenworth, Jianmei; Cantor, Harvey] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Qiao, Lili] Song Jiang Cent Hosp, Dept Pediat, Shanghai 201600, Peoples R China. [Hagberg, Henrik] Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynecol, Perinatal Ctr, S-41685 Gothenburg, Sweden. [Hagberg, Henrik] St Thomas Hosp, Kings Hlth Partners, Div Imaging Sci & Biomed Engn, Kings Coll London,Dept Perinatal Imaging & Hlth, London SE1 7EH, England. RP Wang, XY (reprint author), Univ Gothenburg, Sahlgrenska Acad, Dept Neurosci & Physiol, Perinatal Ctr, Box 432, SE-40530 Gothenburg, Sweden. EM xiaoyang.wang@fysiologi.gu.se RI Albertsson, Ann-Christine /Q-6107-2016; OI Albertsson, Ann-Christine /0000-0001-8696-9143; Hagberg, Henrik/0000-0003-3962-1448 NR 65 TC 6 Z9 7 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD DEC 3 PY 2014 VL 11 AR 197 DI 10.1186/s12974-014-0197-0 PG 13 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA AW6LM UT WOS:000346381000001 PM 25465048 ER PT J AU Deo, RC Musso, G Tasan, M Tang, P Poon, A Yuan, C Felix, JF Vasan, RS Beroukhim, R De Marco, T Kwok, PY MacRae, CA Roth, FP AF Deo, Rahul C. Musso, Gabriel Tasan, Murat Tang, Paul Poon, Annie Yuan, Christiana Felix, Janine F. Vasan, Ramachandran S. Beroukhim, Rameen De Marco, Teresa Kwok, Pui-Yan MacRae, Calum A. Roth, Frederick P. TI Prioritizing causal disease genes using unbiased genomic features SO GENOME BIOLOGY LA English DT Article AB Background: Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits. Results: To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM. Conclusion: Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature. C1 [Deo, Rahul C.; Yuan, Christiana; Kwok, Pui-Yan] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA. [Deo, Rahul C.; De Marco, Teresa] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Deo, Rahul C.; Tang, Paul; Poon, Annie; Kwok, Pui-Yan] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA. [Deo, Rahul C.] Calif Inst Quantitat Biosci, San Francisco, CA 94143 USA. [Deo, Rahul C.; Musso, Gabriel; Tasan, Murat; MacRae, Calum A.; Roth, Frederick P.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Musso, Gabriel; Beroukhim, Rameen] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5G 1X5, Canada. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada. [Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5G 1X5, Canada. [Tasan, Murat; Roth, Frederick P.] Mt Sinai Hosp, Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Felix, Janine F.] Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA 01702 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Roth, Frederick P.] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. [Roth, Frederick P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Roth, Frederick P.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada. RP Deo, RC (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.; Deo, RC (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM rahul.deo@ucsf.edu; fritz.roth@utoronto.ca OI Roth, Frederick/0000-0002-6628-649X FU NIH awards [K08 HL098361, DP2 OD017483, U01 HL107440-03]; NIH/NHGRI Center of Excellence in Genomic Science (CEGS) grant [P50 HG004233]; NIH/NHGRI grant [HG001715]; Ontario Research Fund Research Excellence Award; Krembil Foundation; Avon Foundation; Canada Excellence Research Chairs Program FX The work was funded by NIH awards K08 HL098361 (RCD), DP2 OD017483 (RCD), U01 HL107440-03 (RCD and FPR), and by an NIH/NHGRI Center of Excellence in Genomic Science (CEGS) grant (P50 HG004233) (FPR). FPR was also supported by NIH/NHGRI grant HG001715, an Ontario Research Fund Research Excellence Award, the Krembil Foundation, the Avon Foundation and by the Canada Excellence Research Chairs Program. NR 76 TC 6 Z9 6 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PD DEC 3 PY 2014 VL 15 AR 534 DI 10.1186/s13059-014-0534-8 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V45YL UT WOS:000209851800001 PM 25633252 ER PT J AU Knights, D Silverberg, MS Weersma, RK Gevers, D Dijkstra, G Huang, HL Tyler, AD van Sommeren, S Imhann, F Stempak, JM Huang, H Vangay, P Al-Ghalith, GA Russell, C Sauk, J Knight, J Daly, MJ Huttenhower, C Xavier, RJ AF Knights, Dan Silverberg, Mark S. Weersma, Rinse K. Gevers, Dirk Dijkstra, Gerard Huang, Hailiang Tyler, Andrea D. van Sommeren, Suzanne Imhann, Floris Stempak, Joanne M. Huang, Hu Vangay, Pajau Al-Ghalith, Gabriel A. Russell, Caitlin Sauk, Jenny Knight, Jo Daly, Mark J. Huttenhower, Curtis Xavier, Ramnik J. TI Complex host genetics influence the microbiome in inflammatory bowel disease SO GENOME MEDICINE LA English DT Article ID POUCH-ANAL ANASTOMOSIS; CROHNS-DISEASE; PHENOTYPE; DIVERSITY; CORRELATE; ECOLOGY; GENOME; ALTERS AB Background: Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually. Recent findings point to interactions between host genetics and microbial exposures as important contributors to disease risk in IBD. These include evidence of the partial heritability of the gut microbiota and the conferral of gut mucosal inflammation by microbiome transplant even when the dysbiosis was initially genetically derived. Although there have been several tests for association of individual genetic loci with bacterial taxa, there has been no direct comparison of complex genome-microbiome associations in large cohorts of patients with an immunity-related disease. Methods: We obtained 16S ribosomal RNA (rRNA) gene sequences from intestinal biopsies as well as host genotype via Immunochip in three independent cohorts totaling 474 individuals. We tested for correlation between relative abundance of bacterial taxa and number of minor alleles at known IBD risk loci, including fine mapping of multiple risk alleles in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene exon. We identified host polymorphisms whose associations with bacterial taxa were conserved across two or more cohorts, and we tested related genes for enrichment of host functional pathways. Results: We identified and confirmed in two cohorts a significant association between NOD2 risk allele count and increased relative abundance of Enterobacteriaceae, with directionality of the effect conserved in the third cohort. Forty-eight additional IBD-related SNPs have directionality of their associations with bacterial taxa significantly conserved across two or three cohorts, implicating genes enriched for regulation of innate immune response, the JAK-STAT cascade, and other immunity-related pathways. Conclusions: These results suggest complex interactions between genetically altered host functional pathways and the structure of the microbiome. Our findings demonstrate the ability to uncover novel associations from paired genome-microbiome data, and they suggest a complex link between host genetics and microbial dysbiosis in subjects with IBD across independent cohorts. C1 [Knights, Dan] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA. [Knights, Dan; Gevers, Dirk; Daly, Mark J.; Huttenhower, Curtis; Xavier, Ramnik J.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Knights, Dan; Russell, Caitlin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Knights, Dan; Russell, Caitlin; Sauk, Jenny; Daly, Mark J.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Knights, Dan] Univ Minnesota, Inst Biotechnol, St Paul, MN 55108 USA. [Silverberg, Mark S.; Tyler, Andrea D.; Stempak, Joanne M.] Univ Toronto, Zane Cohen Ctr Digest Dis, Mt Sinai Hosp, IBD Grp, Toronto, ON M5G 1X5, Canada. [Weersma, Rinse K.; Dijkstra, Gerard; van Sommeren, Suzanne; Imhann, Floris] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, NL-9700 RB Groningen, Netherlands. [Huang, Hailiang] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [van Sommeren, Suzanne; Imhann, Floris] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Huang, Hu; Vangay, Pajau; Al-Ghalith, Gabriel A.] Univ Minnesota, Minneapolis, MN 55455 USA. [Russell, Caitlin; Sauk, Jenny; Xavier, Ramnik J.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Knight, Jo] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Knights, D (reprint author), Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA. EM dknights@umn.edu; xavier@molbio.mgh.harvard.edu RI Silverberg, Mark/B-4183-2008; OI Huang, Hailiang/0000-0003-1461-5762; Knight, Joanne/0000-0002-7148-1660 FU VIDI grant from the Netherlands Organization for Scientific Research (NWO); Dutch Digestive Foundation [WO 11-72]; NIH [R01HG005969]; NSF [DBI-1053486]; ARO [W911NF-11-1-0473]; Gale and Graham Wright Research Chair in Digestive Disease; Crohn's and Colitis Foundation of Canada; Crohn's and Colitis Foundation of America, NIH [U54 DE023798, R01 DK092405] FX We thank the patients who donated samples for this study, and the health professionals who collected them. We thank Tjasso Blokzijl for technical assistance and Levi Waldron for power analysis code. We thank Aylwin Ng and Moran Yassour for critical review of the manuscript. We thank Timothy Tickle and Tonya Ward for helpful discussions regarding methods. RKW is supported by a VIDI grant from the Netherlands Organization for Scientific Research (NWO) and the Dutch Digestive Foundation (WO 11-72). CH is partially supported by NIH R01HG005969, NSF DBI-1053486, and ARO W911NF-11-1-0473. MSS is partially supported by the Gale and Graham Wright Research Chair in Digestive Disease. Partial funding for sample collection for Toronto samples provided by the Crohn's and Colitis Foundation of Canada. Work was supported by grants from the Crohn's and Colitis Foundation of America, NIH grants U54 DE023798, and R01 DK092405 (RJX, CH, DG). JK is the Joanne Murphy Professor in Behavioural Science. NR 42 TC 53 Z9 54 U1 4 U2 29 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD DEC 2 PY 2014 VL 6 AR 107 DI 10.1186/s13073-014-0107-1 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AZ3ZD UT WOS:000348161400001 PM 25587358 ER EF